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1. Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans.

Author

David Patsouris, Jingwei-Ji Cao, Guillaume Vial, Amelie Bravard, Etienne Lefai, Annie Durand, Christine Durand, Marie-Agnés Chauvin, Fabienne Laugerette, Cyrille Debard, Marie-Caroline Michalski, Martine Laville, Hubert Vidal, and Jennifer Rieusset

Subjects
Medicine, Science
Abstract

Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.

Published
2014
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2. Lipopolysaccharide-Binding Protein, Soluble CD14, and the Long-Term Risk of Alzheimer’s Disease: A Nested Case-Control Pilot Study of Older Community Dwellers from the Three-City Cohort

Author

Cécilia Samieri, Jean-François Dartigues, Charline Buisson, Catherine Féart, Perrine André, Fabienne Laugerette, Catherine Helmer, Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), U 897 Department of Nutritional Epidemiology, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Fondation pour la Recherche Medicale, Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Région Bourgogne-Franche-Comté, Région Nouvelle-Aquitaine, Fondation de France, Ministry of Research-INSERM Program Cohortes et collections de données biologiques, Fondation Plan Alzheimer, Caisse Nationale pour la Solidarité et l'Autonomie (CNSA), and ITMO Santé Publique - Alliance nationale pour les sciences de la vie et de la sante (AVIESAN) [ISP05 2014]

Subjects
Male, 0301 basic medicine, endotoxins, Urban Population, [SDV]Life Sciences [q-bio], Lipopolysaccharide Receptors, Pilot Projects, Disease, soluble cluster, neuroinflammation, Pathogenesis, serum-levels, 0302 clinical medicine, oxidative stress, Aged, 80 and over, education.field_of_study, Membrane Glycoproteins, biology, Incidence, General Neuroscience, lipopolysaccharide, General Medicine, Alzheimer's disease, metabolic endotoxemia, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Cohort, Female, France, Independent Living, medicine.symptom, Lipopolysaccharide binding protein, lipopolysaccharide-binding protein, Population, Inflammation, 03 medical and health sciences, Alzheimer Disease, medicine, Humans, Dementia, education, Aged, lps, business.industry, interleukin-6, of differentiation-14, medicine.disease, 030104 developmental biology, inflammation, Case-Control Studies, Nested case-control study, Immunology, biology.protein, cells, beta, Neurosciences & Neurology, Geriatrics and Gerontology, Carrier Proteins, tumor-necrosis-factor, business, 030217 neurology & neurosurgery, Acute-Phase Proteins, dementia
Abstract

Background Identifying the mechanisms involved in the pathogenesis of Alzheimer's disease (AD) remains crucially important. Chronic age-related low-grade inflammation is considered to be one such mechanism, although its causes are unclear. Lipopolysaccharide (LPS)-type endotoxins, a major component of the outer membrane of Gram-negative bacteria, are known as potent pro-inflammatory molecules. Therefore, we hypothesized that greater exposure to circulating LPS, potentially mediated by the inflammatory pathway, would be a key step of the onset of AD. Objective The aim of this study was to investigate the link between plasma endotoxin-exposure, inflammation, and AD. Methods Applying a nested case-control design, we evaluated the associations among baseline plasma endotoxin-exposure (assessed by measuring LPS-binding protein (LBP) and soluble cluster of differentiation-14 (sCD14) levels), inflammation (assessed by measuring interleukin-6 (IL6) levels), and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 incident cases of AD were matched with 424 controls without dementia with regard to age, gender, and education level. Results After adjusting for a large set of confounders, including the use of anti-inflammatory drugs, only higher LBP levels were significantly associated with a 30% higher odds of developing AD over 12 years (OR 1.30, 95% CIs [1.07-1.59]), regardless of IL6 levels. Conclusion This large case-control study provides preliminary results concerning plasma endotoxin-exposure among the elderly and suggests that higher LBP levels, an acute-phase reactant involved in the pro-inflammatory response to LPS, are associated with higher odds of developing AD.

Published
2019

3. Impact of Rapeseed and Soy Lecithin on Postprandial Lipid Metabolism, Bile Acid Profile, and Gut Bacteria in Mice

Author

Chloé Robert, Hélène Abrous, Carole Vaysse, Lydie Humbert, Charline Buisson, Maria C. Urdaci, Benjamin Van Dorsselaer, Dominique Rainteau, Fabienne Laugerette, François Caillet, Marie-Caroline Michalski, Emmanuelle Loizon, Emmanuelle Meugnier, Justine Vande Weghe, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe Nutrition, Santé et Biochimie des Lipides (ITERG), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Microbiologie et Biochimie appliquée, Université de Bordeaux (UB), Bordeaux Sciences Agro [Gradignan], and Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)

Subjects
Male, 0301 basic medicine, food.ingredient, medicine.drug_class, Phospholipid, Gut flora, Lecithin, Bile Acids and Salts, Mice, 03 medical and health sciences, chemistry.chemical_compound, food, Lecithins, medicine, Animals, Food science, intestine, phospholipid, food additive, 030109 nutrition & dietetics, biology, Bile acid, Chemistry, Brassica napus, Clostridium leptum, alpha-Linolenic Acid, Lipid metabolism, Lipid Metabolism, Postprandial Period, biology.organism_classification, medicine.disease, Lipids, Gastrointestinal Microbiome, nutrition, 030104 developmental biology, Postprandial, Soybeans, Metabolic syndrome, absorption, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science, Biotechnology
Abstract

Scope Synthetic emulsifiers have recently been shown to promote metabolic syndrome and considerably alter gut microbiota. Yet, data is lacking regarding the effects of natural emulsifiers, such as plant lecithins rich in essential α-linolenic acid (ALA), on gut and metabolic health. Methods and results For 5 days, male Swiss mice were fed diets containing similar amounts of ALA and 0, 1, 3 or 10% rapeseed lecithin (RL) or 10% soy lecithin (SL). Following an overnight fast, they were force-fed the same oil mixture and euthanised after 90min. The consumption of lecithin significantly increased faecal levels of Clostridium leptum (p = 0.0004), regardless of origin or dose, without altering hepatic or intestinal expression of genes of lipid metabolism. 10%-RL increased ALA abundance in plasma triacylglycerols at 90min, reduced caecal bile acid hydrophobicity and increased their sulfatation, as demonstrated by the increased hepatic RNA expression of Sult2a1 (p = 0.037) and caecal CA-7S concentration (p = 0.05) versus 0%-lecithin. Conclusion After only 5 days, nutritional doses of RL and SL modified gut bacteria in mice, by specifically increasing Clostridium leptum group. RL also increased postprandial ALA abundance and induced beneficial modifications of the bile acid profile. ALA-rich lecithins, especially RL, may then appear as promising natural emulsifiers. This article is protected by copyright. All rights reserved.

Published
2021

4. Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes

Author

Laurent Genser, Doriane Aguanno, Joe-Elie Salem, Liping Dong, Philippe Wind, Fabienne Laugerette, Laurence Trystram, Jean-Christophe Vaillant, Karen E. Assmann, Armelle Leturque, Jean-Michel Oppert, Sophie Thenet, Christine Poitou, Hédi Soula, Marie-Caroline Michalski, Karine Clément, Monique Rousset, and Edith Brot-Laroche

Subjects
0301 basic medicine, medicine.medical_specialty, Intestinal permeability, Ussing chamber, business.industry, Zonulin, Inflammation, Systemic inflammation, Occludin, medicine.disease, 3. Good health, Pathology and Forensic Medicine, 03 medical and health sciences, 030104 developmental biology, Endocrinology, Internal medicine, medicine, medicine.symptom, business, Barrier function, Ex vivo
Abstract

Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2018

5. Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets

Author

Manon Lecomte, Emmanuelle Loizon, Carole Vaysse, Pascale Plaisancié, Alain Géloën, Annie Durand, Marie-Caroline Michalski, Leslie Couëdelo, Florent Joffre, Emmanuelle Meugnier, Fabienne Laugerette, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut des Corps Gras (ITERG), ITERG, Université Panthéon-Sorbonne - UFR d'Économie (UP1 UFR02), Université Panthéon-Sorbonne (UP1), ITERG (ITERG), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Covalab-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Oméga 21, and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Male, 0301 basic medicine, endotoxin, Panniculitis, huile de palme, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Lipopolysaccharide Receptors, tissu adipeux, Adipose tissue, White adipose tissue, endotoxine, Biochemistry, Lecithin, chemistry.chemical_compound, 0302 clinical medicine, Food science, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, palm oil, Membrane Glycoproteins, Nutrition and Dietetics, alpha-Linolenic acid, Fatty Acids, adipose tissue, Liver, lipide polaire, medicine.symptom, Lipopolysaccharide binding protein, food.ingredient, Dietary lipid, 030209 endocrinology & metabolism, Inflammation, Biology, Diet, High-Fat, 03 medical and health sciences, food, medicine, Animals, soja, Molecular Biology, soya bean, huile de lin, Fatty acid, linseed oil, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Dietary Supplements, biology.protein, Soybeans, Carrier Proteins, Acute-Phase Proteins
Abstract

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoiins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as alpha-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.

Published
2017

6. Milk Polar Lipids in a High-Fat Diet Can Prevent Body Weight Gain: Modulated Abundance of Gut Bacteria in Relation with Fecal Loss of Specific Fatty Acids

Author

David Cheillan, Marie-Caroline Michalski, Karène Bertrand, Charline Buisson, Marine Milard, Pascale Plaisancié, Laure B. Bindels, Florent Joffre, Sébastien Viel, Valérie Sauvinet, Nathalie M. Delzenne, Audrey M. Neyrinck, Emmanuelle Loizon, Lydie Humbert, Annie Durand, Corinne Louche-Pelissier, Emmanuelle Meugnier, Dominique Rainteau, Fabienne Laugerette, Lorna Garnier, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), Louvain Drug Research Institute, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Corps Gras (ITERG), ITERG, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition and Metabolism Research Group (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL), French Ministry for Higher Education and Research via EDISS, Universite Claude Bernard Lyon 1, CNIEL (French Dairy Interbranch Organization), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Michalski, Marie-Caroline

Subjects
Male, 0301 basic medicine, obesity, sphingomyeline, [SDV]Life Sciences [q-bio], Ingénierie des aliments, Gut flora, Weight Gain, [SDV.IDA]Life Sciences [q-bio]/Food engineering, adiposity, bile salts, feces, gut barrier, microbiota, milk fat globule membrane, phospholipids, sphingomyelin, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, biology, acide gras, Chemistry, Fatty Acids, sel biliaire, Lipids, Sphingomyelins, Bifidobacterium animalis, obésité, Milk, Liver, medicine.symptom, Sphingomyelin, Biotechnology, phospholipide, medicine.medical_specialty, Crypt, Inflammation, Diet, High-Fat, 03 medical and health sciences, microbiote, lipid, Internal medicine, medicine, Food engineering, Animals, Feces, lipide, 030109 nutrition & dietetics, Macrophages, barrière intestinale, biology.organism_classification, medicine.disease, Obesity, Gastrointestinal Microbiome, Lactobacillus reuteri, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Intestinal Absorption, fatty acid, Food Science
Abstract

Scope Enhanced adiposity and metabolic inflammation are major features of obesity associated with altered gut microbiota and intestinal barrier. How these metabolic outcomes can be impacted by milk polar lipids (MPL), naturally containing 25% of sphingomyelin, is investigated in mice fed a mixed high-fat (HF) diet . Methods and results Male C57Bl/6 mice receive a HF-diet devoid of MPL (21% fat, mainly palm oil, in chow), or supplemented with 1.1% or 1.6% of MPL (HF-MPL1; HF-MPL2) via a total-lipid extract from butterserum concentrate for 8 weeks. HF-MPL2 mice gain less weight versus HF (p < 0.01). Diets do not impact plasma markers of inflammation but in the liver, HF-MPL2 tends to decrease hepatic gene expression of macrophage marker F4/80 versus HF-MPL1 (p = 0.06). Colonic crypt depth is the maximum in HF-MPL2 (p < 0.05). In cecal microbiota, HF-MPL1 increases Bifidobacterium animalis versus HF (p < 0.05). HF-MPL2 decreases Lactobacillus reuteri (p < 0.05), which correlates negatively with the fecal loss of milk sphingomyelin-specific fatty acids (p < 0.05). Conclusion In mice fed a mixed HF diet, MPL can limit HF-induced body weight gain and modulate gut physiology and the abundance in microbiota of bacteria of metabolic interest. This supports further exploration of how residual unabsorbed lipids reaching the colon can impact HF-induced metabolic disorders.

Published
2019

7. Metabolic endotoxemia: a potential underlying mechanism of the relationship between dietary fat intake and risk for cognitive impairments in humans?

Author

Catherine Féart, Perrine André, Fabienne Laugerette, Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and Andre, Perrine

Subjects
Male, microbiome, Bioinformatics, Metabolic endotoxemia, Cognition, 0302 clinical medicine, Risk Factors, Medicine, high-fat, 10. No inequality, Cognitive impairment, humans, 2. Zero hunger, matière grasse alimentaire, Nutrition and Dietetics, endotoxemia, Communication, lipopolysaccharide, Age Factors, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, maladie d'alzheimer, facteur de risque, nutrition, dietary fat, Host-Pathogen Interactions, Alimentation et Nutrition, Female, lcsh:Nutrition. Foods and food supply, Nutritive Value, Alzheimer’s disease, Adult, lcsh:TX341-641, 030209 endocrinology & metabolism, valeur nutritive, Risk Assessment, personne âgée, Young Adult, 03 medical and health sciences, Healthy food, Alzheimer's disease, dementia, Dementia, Food and Nutrition, Cognitive Dysfunction, Aged, Bacteria, démence, business.industry, Mechanism (biology), interaction hôte pathogène, lipopolisaccharide, medicine.disease, Dietary Fats, Gastrointestinal Microbiome, Dietary fat intake, Cognitive Aging, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Healthy ageing, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Food Science
Abstract

(1) Background: Nutrition is a major lifestyle factor that can prevent the risk of cognitive impairment and dementia. Diet-induced metabolic endotoxemia has been proposed as a major root cause of inflammation and these pathways emerge as detrimental factors of healthy ageing. The aim of this paper was to update research focusing on the relationship between a fat-rich diet and endotoxemia, and to discuss the potential role of endotoxemia in cognitive performances. (2) Methods: We conducted a non-systematic literature review based on the PubMed database related to fat-rich meals, metabolic endotoxemia and cognitive disorders including dementia in humans. A total of 40 articles out of 942 in the first screening met the inclusion criteria. (3) Results: Evidence suggested that a fat-rich diet, depending on its quality, quantity and concomitant healthy food components, could influence metabolic endotoxemia. Since only heterogeneous cross-sectional studies are available, it remains unclear to what extent endotoxemia could be associated or not with cognitive disorders and dementia. (4) Conclusions: A fat-rich diet has the capability to provide significant increases in circulating endotoxins, which highlights nutritional strategies as a promising area for future research on inflammatory-associated diseases. The role of endotoxemia in cognitive disorders and dementia remains unclear and deserves further investigation.

Published
2019

8. Metabolic effects in mice of cream formulation: Addition of both thickener and emulsifier does not alter lipid metabolism but modulates mucus cells and intestinal endoplasmic reticulum stress

Author

Charline Buisson, Pascale Plaisancié, S. Bugeat, Marion Létisse, Emmanuelle Loizon, Alain Géloën, S. Serieye, Emmanuelle Meugnier, Marie-Caroline Michalski, Annie Durand, Fabienne Laugerette, Marine Milard, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Spectrochimie Infrarouge et Raman - UMR 8516 (LASIR), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Laboratoire d'ingénierie circulation transports (LICIT), Institut National de Recherche sur les Transports et leur Sécurité (INRETS)-École Nationale des Travaux Publics de l'État (ENTPE), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Sodiaal Union, Partenariat industriel : SODIAAL-CANDIA R&D; Sodiaal-Candia RD, Sodiaal-Candia RI, CNIEL (French Dairy Interbranch Organization, Paris, France), Nutricia Research (Utrecht, the Netherlands), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ProdInra, Migration

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Duodenum, [SDV]Life Sciences [q-bio], cow milk, Fatty Acids, Nonesterified, dairy matrix, Mice, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, Intestine, Small, Genetics, medicine, Animals, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Intestinal permeability, Chemistry, Endoplasmic reticulum, Intestinal lipid absorption, Lipid metabolism, Endoplasmic Reticulum Stress, Lipid Metabolism, medicine.disease, Mucus, Small intestine, 3. Good health, Carrageenan, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Milk, nutrition, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Liver, Emulsifying Agents, carrageenan, Cattle, Food Additives, Animal Science and Zoology, Dairy Products, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract

International audience; Additives stabilize or improve the organoleptic or functional properties (or both) of many dairy products including whipping cream. Their influence on the metabolic effect of dairy cream is scarcely known. We tested the hypothesis that added emulsifier (lactic acid esters of mono- and diglycerides; MAG/DAG), thickener (carrageenan, CGN), or both, could modify the metabolic effect, notably in the intestine and liver. Nine-week-old male C57Bl/6J mice were fed UHT cream (indirect treatment) mixed with nonlipidic powder (final: 13% milkfat) for 1 or 4 wk. We compared creams (1) without additive (Ctl), (2) with thickener (Th), 0.02% of κ-CGN, and (3) with both thickener and emulsifier, 0.1% of MAG/DAG esters (Th/Em). We analyzed plasma parameters, intestine, and liver. Fasting glycemia, insulinemia, triglyceridemia, nonesterified fatty acids, body weight gain, and liver weight did not differ among groups. After 1 wk, Th/Em had higher expression in the duodenum of some of the genes involved in (1) intestinal lipid absorption and (2) tight junction proteins versus Ctl and Th. After 4 wk, mucus cell number in the small intestine was higher in Th/Em versus Ctl and Th. Genes involved in endoplasmic reticulum (ER) stress in the duodenum were more expressed in Th/Em after 1 wk. After 4 wk, in the colon, a higher expression of ER stress genes was observed for Th versus Th/Em and Ctl. Liver damage score was not altered by additives. Adding both CGN (0.02%) and MAG/DAG esters (0.1%) in dairy cream did not result in deleterious outcomes in mice after 4 wk regarding lipid metabolism, intestinal permeability, and liver disorders. The longer term effect of intestinal ER stress modulation deserves further investigation.

Published
2018

9. Metabolic effects in mice of cream processing: Direct ultra-high-temperature process lowers high-fat-induced adipose tissue inflammation

Author

Marie-Caroline Michalski, Alain Géloën, Emmanuelle Meugnier, Charline Buisson, Pascale Plaisancié, Marion Létisse, Emmanuelle Loizon, S. Serieye, S. Bugeat, Fabienne Laugerette, Annie Durand, Marine Milard, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Sodiaal Union, Partenariat industriel : SODIAAL-CANDIA R&D; Sodiaal-Candia R&I (Research & Innovation Department, Paris, France), Sodiaal-Candia RI, CNIEL (French Dairy Interbranch Organization, Paris, France), and Nutricia Research (Utrecht, the Netherlands)

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Hot Temperature, cow milk, Adipose tissue, Inflammation, dairy matrix, Fatty acid-binding protein, Fats, Butterfat, Mice, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, Genetics, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Epididymis, 2. Zero hunger, 030109 nutrition & dietetics, Chemistry, Lipid metabolism, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Carrageenan, Intestines, Mice, Inbred C57BL, Milk, nutrition, Endocrinology, Adipose Tissue, Zonula Occludens-1 Protein, Microsome, Cattle, Animal Science and Zoology, Dairy Products, medicine.symptom, food process, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract

International audience; Although UHT heat treatment is being optimized to improve the stability and functional properties of dairy products, its metabolic effects remain scarcely known. As such, we studied the effect of the type of UHT process on lipid metabolism, intestinal barrier, and inflammation in mice. Nine-week-old male C57Bl/6J mice were fed a diet composed of nonlipidic powder mixed with different UHT dairy creams (final: 13% milkfat) for 1 or 4 wk. All creams contained 0.02% of thickener (carrageenan) and were treated via either (1) classical indirect heating process (Th), (2) indirect process at higher temperature (Th+), or (3) direct process by steam injection (ThD). Plasma, epididymal adipose tissue (EAT), and intestine were analyzed. Multivariate principal component analyses were used to identify differential effects of processes. Th+ differed by a globally higher liver damage score compared with that of the other creams. After 4 wk, the duodenal expression of lipid absorption genes fatty acid binding protein 4 (Fatp4) and microsomal triglycerides transfer protein (Mttp) was lower in the Th+ versus Th group. Expression in the colon of tight junction protein zonula occludens 1 (Zo-1) and of some endoplasmic reticulum stress markers was lower in both Th+ and ThD versus the Th group. In EAT, ThD had lower gene expression of several inflammatory markers after 4 wk. Some differential effects may be related to heat-induced physicochemical changes of creams. The type of cream UHT process differentially affected metabolic parameters in mice after a 4-wk fat-rich diet, partly due to cream structure. Altogether, direct steam injection process induced the lowest early markers of high-fat-induced metabolic inflammation in EAT.

Published
2018

10. Milk Polar Lipids Affect In Vitro Digestive Lipolysis and Postprandial Lipid Metabolism in Mice

Author

David Cheillan, Armelle Penhoat, Marie-Caroline Michalski, Emmanuelle Loizon, Gaëlle Pineau, Manon Lecomte, Michèle Trauchessec, Alain Géloën, Fabienne Laugerette, Emmanuelle Meugnier, Claire Bourlieu, Olivia Ménard, Mathilde Claude, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hereditary Metabolic Diseases Department, East Medical Group, Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
émulsion, medicine.medical_specialty, sphingomyéline, Lipolysis, aliment, Medicine (miscellaneous), digestion, Mice, chemistry.chemical_compound, Internal medicine, Intestine, Small, Lecithins, [SDV.IDA]Life Sciences [q-bio]/Food engineering, lipemie, medicine, Animals, Nutrition and Dietetics, Triglyceride, Intestinal lipid absorption, Lipid metabolism, Lipid Metabolism, Postprandial Period, Lipids, lait, Milk, nutrition, Postprandial, Chylomicron assembly, Endocrinology, Gene Expression Regulation, chemistry, Emulsifying Agents, Female, lipids (amino acids, peptides, and proteins), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Lipid digestion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Chylomicron
Abstract

Background: Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism, but focused studies on postprandial lipemia are lacking. Objective: We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro. Methods:Female Swiss mice were gavaged with 150 mL of an oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase‐quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. Results: In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 mg/mL vs. 90 mg/mL; P= 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 mg/mL vs. 44 mg/mL; P< 0.05). The opposite was observed after 4 h with lower TGs (21 mg/mL vs. 35 mg/mL; P < 0.01) and NEFAs (20 mg/mL vs. 32 mg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B (Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B (Sar1b), in the duodenum of MPL mice compared with SPL mice (P < 0.05). In vitro, during the intestinal phase, TGs were hydrolyzed more in the MPL emulsion than in the SPL emulsion (decremental AUCs were 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipid absorption and sharper kinetics of lipemia. Conclusions: Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partly through differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism. J Nutr 2015;145:1770‐7.

Published
2015

11. Emulsifying dietary fat modulates postprandial endotoxemia associated with chylomicronemia in obese men: a pilot randomized crossover study

Author

Martine Laville, Hubert Vidal, Cécile Vors, Jocelyne Drai, Fabienne Laugerette, Gaëlle Pineau, Marie-Caroline Michalski, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA), Centre National Interprofessionnel de l'Economie Laitiere (CNIEL, French Dairy Board), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
0301 basic medicine, Male, IMPACT, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, endotoxine, hyperlipemie, 0302 clinical medicine, Endocrinology, Ingestion, lcsh:RC620-627, 2. Zero hunger, Meal, Cross-Over Studies, digestive, oral, and skin physiology, Postprandial Period, homme, 3. Good health, lcsh:Nutritional diseases. Deficiency diseases, obésité, Postprandial, facteur de risque, Alimentation et Nutrition, Hyperlipoproteinemia Type I, TRIAL, MEAL, Lipidology, Adult, medicine.medical_specialty, Short Report, 030209 endocrinology & metabolism, Clinical nutrition, 03 medical and health sciences, Insulin resistance, INFLAMMATION, Internal medicine, medicine, Humans, Food and Nutrition, Obesity, 030109 nutrition & dietetics, business.industry, LIPOPOLYSACCHARIDES, Biochemistry (medical), medicine.disease, Crossover study, Dietary Fats, Endotoxemia, business, graisse alimentaire
Abstract

Postprandial hyperlipemia is recognized as a major cardio-metabolic risk factor, recently linked to the co-absorption of pro-inflammatory lipopolysaccharides with dietary lipids. This causes endotoxemia that is involved in the pathophysiology of obesity and insulin resistance, but to date the impact of food formulation is unknown. We tested a novel concept that endotoxin absorption can be modulated by fat emulsified structure in the meal, and potentially differently in obese vs. lean men. In a randomized controlled crossover study, eight normal-weight and eight obese age-matched healthy men ingested two isocaloric, isolipidic breakfasts of identical composition including 40 g of milk fat that was emulsified or unemulsified. Plasma- and chylomicron-endotoxemia and chylomicron-triglycerides were measured during 8 h after breakfast ingestion. After emulsion consumption, parallel to an enhanced chylomicronemia, obese subjects presented an early and sharp increase in chylomicron-endotoxemia at 60 min (P time = 0.02), which was higher than (i) after spread fat in obese subjects (P

Published
2017

12. Overfeeding increases postprandial endotoxemia in men: Inflammatory outcome may depend on LPS transporters LBP and sCD14

Author

Stéphanie Lambert-Porcheron, Hubert Vidal, Marie-Caroline Michalski, Jean-Philippe Bastard, Jocelyne Drai, Martine Laville, Fabienne Laugerette, Maud Alligier, Emilie Chanseaume, Béatrice Morio, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), French National Research Agency (ANR) [ANR-07-PNRA-0007, ANR-06-PNRA-0007], INRA, and ALFEDIAM-SFD

Subjects
Male, [SDV]Life Sciences [q-bio], Lipopolysaccharide Receptors, Body Mass Index, Cohort Studies, Medicine, Membrane Glycoproteins/*blood, Membrane Glycoproteins, CD14/*blood, Acute-phase protein, Postprandial Period, Postprandial, Endotoxins/blood, Waist Circumference, medicine.symptom, Biotechnology, Adult, medicine.medical_specialty, High-Fat/adverse effects, Endotoxemia/*blood/etiology, Inflammation, Hyperphagia, Diet, High-Fat, Internal medicine, Humans, Antigens, Hyperphagia/*complications, Cluster of differentiation, Interleukin-6, business.industry, Body Weight, Transporter, medicine.disease, Obesity, Endotoxemia, Diet, Inflammation/*blood/etiology, Endotoxins, Endocrinology, Interleukin-6/blood, Carrier Proteins, business, Weight gain, Body mass index, Biomarkers/blood, Carrier Proteins/*blood, Biomarkers, Acute-Phase Proteins, Food Science
Abstract

International audience; SCOPE: Low-grade inflammation is a recognized hallmark of obesity. Endotoxins absorbed after high-fat meals have recently been implicated. Plasma lipopolysaccharides binding protein (LBP) and soluble cluster of differentiation 14 (sCD14) have also been suggested as clinical markers of endotoxemia. In mice, the ratio LBP/sCD14 has been associated with high fat diet induced inflammation. We tested the hypothesis that healthy subjects develop inflammation differently during weight gain according to changes of LBP/sCD14 ratio. METHODS AND RESULTS: Eighteen healthy men were overfed during 8 wk (+760 kcal/day). Endotoxemia, sCD14, LBP, and IL-6 were measured before and after overfeeding (OF) at fasting (n = 18) and postprandially (subcohort, n = 8). OF did not modify fasting IL-6 but increased the LBP/sCD14 ratio (P = 0.017). Subjects were categorized into tertiles for LBP/sCD14 ratio variation. Subjects in the highest tertile (+90% LBP/sCD14) increased plasma IL-6 (+26%) versus the lowest tertile due to a decrease of sCD14 associated with high LBP. The postprandial accumulation of endotoxins increased after OF (+160%). However, only four responding subjects presented increased postprandial IL-6 accumulation. CONCLUSION: OF increases postprandial endotoxemia but the inflammatory outcome may be modulated by endotoxin handling in plasma. This study supports a new concept whereby inflammation setup during the initial phase of weight gain is linked to the relative variations of LBP and sCD14.

Published
2014

13. P4-418: PLASMA ENDOTOXEMIA, INFLAMMATION AND LONG-TERM RISK OF ALZHEIMER'S DISEASE AMONG ELDERLY COMMUNITY-DWELLERS

Author

Charline Buisson, Jean-François Dartigues, Catherine Helmer, Cécilia Samieri, Perrine André, Fabienne Laugerette, and Catherine Féart

Subjects
medicine.medical_specialty, Community dwellers, Epidemiology, business.industry, Health Policy, Inflammation, Disease, Long term risk, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, Intensive care medicine, business
Published
2019

14. Western-diet consumption induces alteration of barrier function mechanisms in the ileum that correlates with metabolic endotoxemia in rats

Author

Marie-Caroline Michalski, Mathilde Guerville, Gaëlle Boudry, Annaëlle Sinquin, Fabienne Laugerette, Anaïs Leroy, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Jonchère, Laurent, and Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Lipopolysaccharides, Male, Physiology, Endocrinology, Diabetes and Metabolism, endotoxine, Eating, Intestinal mucosa, Gene expression, rat, Intestinal Mucosa, Barrier function, Cells, Cultured, Bifidobacterium, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, chemistry.chemical_classification, digestive, oral, and skin physiology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, foie, metabolic endotoxemia, Intestine, obésité, régime alimentaire, medicine.anatomical_structure, Alimentation et Nutrition, medicine.medical_specialty, Ileum, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Permeability, 03 medical and health sciences, Organ Culture Techniques, microbiote, [SDV.CAN] Life Sciences [q-bio]/Cancer, intestin, Physiology (medical), Internal medicine, medicine, Food and Nutrition, Animals, Secretion, Obesity, Rats, Wistar, lps, Feeding Behavior, biology.organism_classification, Mucus, Endotoxemia, Rats, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Enzyme, Endocrinology, chemistry, Diet, Western, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Obesity and its related disorders have been associated with the presence in the blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad libitum or pair-fed to match the caloric intake of C rats for the first week, then fed ad libitum for the remaining 5 wk. Six-week WD feeding led to a mild obese phenotype with increased adiposity and elevated serum LPS-binding protein (LBP) levels relative to C rats, irrespective of initial energy intake. Serum LPS was not different between dietary groups but exhibited strong variability. Disrupted ileal mucus secretion and decreased ileal Reg3-γ and -β gene expression along with high ileal permeability to LPS were observed in WD compared with C-fed rats. Ileal and cecal intestinal alkaline phosphatase (IAP) activity as well as Verrucomicrobia and Bifidobacterium cecal levels were increased in WD-fed rats compared with C-fed rats. WD consumption did not impact mRNA levels of LPS-handling hepatic enzymes. Correlation analysis revealed that ileal passage of LPS, IAP activity, Proteobacteria levels and hepatic aoah gene expression correlated with serum LPS and LBP, suggesting that ileal mucosal defense impairment induced by WD feeding contribute to metabolic endotoxemia.

Published
2016

15. Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice

Author

Annie Durand, Carole Vaysse, Marion Létisse, Pascale Plaisancié, Gaëlle Pineau, Armelle Penhoat, Alain Géloën, Marie-Caroline Michalski, Florent Joffre, Manon Lecomte, Fabienne Laugerette, Leslie Couëdelo, Laure Gabert, Emmanuelle Meugnier, Bérengère Benoit, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Region Rhone-Alpes ARC1, Lipides pour l'Industrie et la Sante, Societe Francophone du Diabete, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut des Corps Gras (ITERG), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Panthéon-Sorbonne - UFR d'Économie (UP1 UFR02), Université Panthéon-Sorbonne (UP1), ITERG (ITERG), ITERG, Régulations métaboliques, nutrition et diabètes (RMND), Oméga 21, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), and Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Panniculitis, [SDV]Life Sciences [q-bio], Adipose tissue, Metabolic disease, White adipose tissue, chemistry.chemical_compound, Feces, Intestinal mucosa, Gut barrier, Lecithins, Diet, Fat-Restricted, ComputingMilieux_MISCELLANEOUS, Adiposity, 2. Zero hunger, chemistry.chemical_classification, Leptin, Lipids, 3. Good health, Phospholipid, Milk, Liver, Tumor necrosis factor alpha, Goblet Cells, medicine.symptom, Biotechnology, medicine.medical_specialty, Colon, Adipose Tissue, White, Inflammation, Biology, Diet, High-Fat, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, 030109 nutrition & dietetics, Fatty acid, Caco-2, Mice, Inbred C57BL, Endocrinology, chemistry, Emulsifying Agents, Immunology, Soybeans, Caco-2 Cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract

International audience; SCOPE: Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. METHODS AND RESULTS: Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p \textless 0.05), with larger adipocytes (p \textless 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p \textless 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p \textless 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p \textless 0.05), and more goblet cells in the colon (p \textless 0.05). CONCLUSIONS: Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak.

Published
2016

16. Inside front cover: Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice

Author

Gaëlle Pineau, Carole Vaysse, Leslie Couëdelo, Alain Géloën, Armelle Penhoat, Emmanuelle Meugnier, Pascale Plaisancié, Laure Gabert, Florent Joffre, Manon Lecomte, Bérengère Benoit, Marion Létisse, Annie Durand, Marie-Caroline Michalski, and Fabienne Laugerette

Subjects
0404 agricultural biotechnology, Front cover, Chemistry, medicine, Inflammation, 04 agricultural and veterinary sciences, Food science, medicine.symptom, 040401 food science, High fat fed, Food Science, Biotechnology
Published
2016

17. Dietary lipid emulsions and endotoxemia

Author

Marie-Caroline Michalski, Fabienne Laugerette, Manon Lecomte, Cécile Vors, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre Européen pour la Nutrition et la Santé (CENS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), ProdInra, Archive Ouverte, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, medicine.medical_specialty, obesity, [SDV]Life Sciences [q-bio], Dietary lipid, lcsh:TP670-699, 030209 endocrinology & metabolism, Inflammation, Biology, oil, Biochemistry, Intestinal absorption, fat, emulsifier, inflammation, nutrition, Metabolic endotoxemia, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, pétrole, medicine, human nutrition, 2. Zero hunger, petroleum, 030109 nutrition & dietetics, Intestinal lipid absorption, émulsifiant, Transporter, medicine.disease, graisse, 3. Good health, [SDV] Life Sciences [q-bio], obésité, Postprandial, Endocrinology, Immunology, lipids (amino acids, peptides, and proteins), lcsh:Oils, fats, and waxes, medicine.symptom, Agronomy and Crop Science, nutrition humaine, Food Science
Abstract

The low-grade inflammation observed in obesity is a risk factor for cardiovascular diseases and insulin resistance. Among factors triggering such inflammation, recent works revealed the role of bacterial lipopolysaccharides (LPS), so-called endotoxins. LPS are naturally present in the gut via the intestinal microbiota. Recent studies show that they can induce in plasma a metabolic endotoxemia after the consumption of unbalanced hyperlipidic meals. This article reviews recent knowledge gained on the role of intestinal lipid absorption and the composition of dietary lipids on: (i) the induction of metabolic endotoxemia, (ii) the types of plasma transporters of LPS and (iii) associated low-grade inflammation. Notably, lipids are present in foods under various physicochemical structures and notably in emulsified form. Our recent works reveal that such structure and the type of emulsifier can modulate postprandial lipemia; recent results on the possible consequences on metabolic endotoxemia will be discussed.

Published
2016

18. Reduction of endoplasmic reticulum stress using chemical chaperones or Grp78 overexpression does not protect muscle cells from palmitate-induced insulin resistance

Author

Marie-Agnès Chauvin, Marie-Caroline Michalski, Jennifer Rieusset, Hubert Vidal, Fabienne Laugerette, Annie Durand, Amélie Bravard, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, medicine.medical_treatment, Muscle Fibers, Skeletal, Palmitates, Adipose tissue, MESH: Heat-Shock Proteins, Biochemistry, Mice, 0302 clinical medicine, MESH: Endoplasmic Reticulum Stress, Insulin, Myocyte, MESH: Animals, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins, 0303 health sciences, MESH: Muscle Fibers, Skeletal, biology, Tunicamycin, Endoplasmic Reticulum Stress, MESH: Insulin Resistance, medicine.anatomical_structure, MESH: Dietary Fats, medicine.medical_specialty, Biophysics, 030209 endocrinology & metabolism, MESH: Insulin, Butylamines, Taurochenodeoxycholic Acid, 03 medical and health sciences, Insulin resistance, MESH: Diet, MESH: Mice, Inbred C57BL, Internal medicine, medicine, MESH: Butylamines, MESH: Taurochenodeoxycholic Acid, Animals, MESH: Mice, Molecular Biology, 030304 developmental biology, MESH: Tunicamycin, Endoplasmic reticulum, Skeletal muscle, Cell Biology, MESH: Palmitates, medicine.disease, Dietary Fats, MESH: Male, Diet, Mice, Inbred C57BL, Insulin receptor, Endocrinology, biology.protein, Unfolded protein response, Insulin Resistance, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Endoplasmic reticulum (ER) stress is proposed as a novel link between elevated fatty acids levels, obesity and insulin resistance in liver and adipose tissue. However, it is unknown whether ER stress also contributes to lipid-induced insulin resistance in skeletal muscle, the major tissue responsible of insulin-stimulated glucose disposal. Here, we investigated the possible role of ER stress in palmitate-induced alterations of insulin action, both in vivo, in gastrocnemius of high-palm diet fed mice, and in vitro, in palmitate-treated C(2)C(12) myotubes. We demonstrated that 8 weeks of high-palm diet increased the expression of ER stress markers in muscle of mice, whereas ex-vivo insulin-stimulated PKB phosphorylation was not altered in this tissue. In addition, exposure of C(2)C(12) myotubes to either tuncamycine or palmitate induced ER stress and altered insulin-stimulated PKB phosphorylation. However, alleviation of ER stress by either TUDCA or 4-PBA treatments, or by overexpressing Grp78, did not restore palmitate-induced reduction of insulin-stimulated PKB phosphorylation in C(2)C(12) myotubes. This work highlights that, even ER stress is associated with palmitate-induced alterations of insulin signaling, ER stress is likely not the major culprit of this effect in myotubes, suggesting that the previously proposed link between ER stress and insulin resistance is less important in skeletal muscle than in adipose tissue and liver.

Published
2012

19. Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial

Author

Gaëlle Pineau, Hubert Vidal, Emmanuelle Meugnier, Martine Laville, Jocelyne Drai, Sandra Pesenti, Fabienne Laugerette, Corinne Malpuech-Brugère, Cécile Vors, Marie-Caroline Michalski, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre National Interprofessionnel de l'Economie Laitiere (CNIEL), INRA, Ezus-Lyon1, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Lipopolysaccharides, Male, Blood Glucose, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Biochemistry, Intestinal absorption, Body Mass Index, Endocrinology, Membrane Glycoproteins/blood, Chylomicrons, Insulin, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Carrier Proteins/blood, Membrane Glycoproteins, Cross-Over Studies, Lipopolysaccharides/*blood, Postprandial Period, Obesity/*blood, 3. Good health, Postprandial, Endotoxemia/*blood, lipids (amino acids, peptides, and proteins), medicine.symptom, Drug, Adult, medicine.medical_specialty, Context (language use), Inflammation, Dose-Response Relationship, Postprandial Period/*physiology, Internal medicine, Diabetes mellitus, medicine, Humans, Obesity, Chylomicrons/*blood, Dose-Response Relationship, Drug, business.industry, Biochemistry (medical), medicine.disease, Dietary Fats, Endotoxemia, business, Carrier Proteins, Insulin/blood, Body mass index, Dyslipidemia, Chylomicron, Acute-Phase Proteins
Abstract

International audience; CONTEXT: Postprandial endotoxemia is a metabolic risk factor, which has been shown to originate from the intestinal absorption of gut lipopolysaccharides (LPS) using nonphysiological high-fat tests. OBJECTIVE: This study aimed to determine whether different realistic fat amounts can modulate postprandial dynamics and handling of LPS by varying postprandial lipidemia in humans of different body mass indices. DESIGN, SETTING, AND PARTICIPANTS: In a randomized, controlled, cross-over study in nutrition research center, eight normal-weight (NW) and eight obese age-matched men, without diabetes nor dyslipidemia, ingested breakfasts containing 10 vs 40 g fat. Blood samples, leukocytes, and chylomicron-rich fractions were obtained during 8 h. Plasma and chylomicron-endotoxemia, plasma LPS transporters (LBP, sCD14) and IL-6, nuclear factor kappaB (NF-kappaB) translocation, and IL-6 gene expression of immune cells were measured. MAIN OUTCOME: The postprandial fatty acid handling after ingesting 40 g fat was previously published as primary outcome. The secondary outcomes were inflammatory ones including postprandial endotoxemia, LPS handling, and plasma markers of inflammation after ingesting 10 or 40 g fat. RESULTS: Chylomicronemia increased in all subjects according to ingested fat amount (P \textless .01), but only obese had higher postprandial endotoxemia after 40 g (P \textless .05). Obese subject chylomicrons were more enriched with LPS compared with NW (PBMI \textless .01). We observed neither NF-kappaB translocation, nor variation of IL-6 expression in leukocytes. In both groups, fat amount did not modify postprandial response of plasma IL-6. However, the area under the curve (AUC) of IL-6 in obese was higher than in NW (P \textless .05) parallel to higher fasting LPS-binding protein (LBP; P \textless .05). AUC of IL-6 was correlated with LBP (P \textless .01). CONCLUSION: Postprandial endotoxemia is modulated by ingested fat amount in obese men. LPS handling in plasma through chylomicrons and LBP seems critical in driving the acute inflammatory response. The pathophysiological importance of repeated postprandial endotoxemia excursions and their contribution to a vicious cycle of LBP-driven low-grade inflammation deserve further investigation in the nutritional management of cardio-metabolic risk prevention.

Published
2015

20. Increasing fat content from 20 to 45 wt% in a complex diet induces lower endotoxemia in parallel with an increased number of intestinal goblet cells in mice

Author

Alain Géloën, Hubert Vidal, Gaëlle Pineau, Fabienne Laugerette, Marie-Caroline Michalski, Pascale Plaisancié, Annick Bernalier-Donadille, Monique Estienne, Bérengère Benoit, Jacques Bodennec, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
Leptin, Lipopolysaccharides, Male, Intestines/cytology/metabolism, Dietary Fats/*administration & dosage, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Adipose tissue, White adipose tissue, Mucin 2, Inbred C57BL, Weight Gain, Mice, Endocrinology, Zonula Occludens-1 Protein/metabolism, Fat-Restricted, Intestinal Mucosa, Diet, Fat-Restricted, 2. Zero hunger, Nutrition and Dietetics, food and beverages, Colon/metabolism, 3. Good health, Intestines, White/metabolism, Triglycerides/blood, Goblet Cells/*metabolism, Liver, Adipose Tissue, lipids (amino acids, peptides, and proteins), Adiponectin, Goblet Cells, Adiponectin/blood, medicine.symptom, Liver/metabolism, medicine.medical_specialty, Colon, Adipose Tissue, White, Dietary lipid, Adipokine, Inflammation, Biology, Diet, High-Fat, Occludin, Internal medicine, medicine, Animals, Occludin/metabolism, Triglycerides, Interleukin-6, Inflammation/*physiopathology, Dietary Fats, Endotoxemia, Diet, Mice, Inbred C57BL, High-Fat, Leptin/blood, Immunology, Zonula Occludens-1 Protein, Interleukin-6/blood, Endotoxemia/*physiopathology
Abstract

International audience; The impacts of high-fat diets (HFDs) on the onset of metabolic endotoxemia and low-grade inflammation are well established in rodent models. However, the dose-effect of dietary lipid intakes on these parameters is not known. We hypothesized that increasing dietary lipid amounts could be linked to parallel increases of endotoxemia, low-grade inflammation, and metabolic and intestinal alterations. Six-week-old male C57BL/6J mice were fed a low-fat diet (LFD, 2.6 wt% of lipids), a moderate HFD (mHFD, 22 wt% of lipids), or a very HFD (vHFD, 45 wt% of lipids) formulated mainly using chow ingredients and milk fat. After 12 weeks, white adipose tissues, liver, intestine, distal colon contents, and plasma were collected. Only vHFD mice significantly increased body weight and fat mass vs LFD mice. This was associated with increases of plasma concentrations of triglycerides, leptin and adiponectin, and liver lipids. No such differences were observed between LFD and mHFD mice. However, mHFD developed metabolic endotoxemia and inflammation, unlike vHFD mice. In turn, vHFD mice showed more goblet cells in all intestine segments vs both other groups and a decrease of Bacteroides-Prevotella in their microbiota vs LFD mice. Finally, mHFD mice colon exhibited a decrease in lactobacilli and in the levels of occludin phosphorylation. Altogether, using complex HFD, no associations were observed between dietary lipid amounts and the magnitude of endotoxemia, inflammation, and physiological alterations developed. These results reveal the impact of the diet composition on intestinal goblet cells and mucus coat, bringing new insights about further consequences on HFD-induced metabolic disorders.

Published
2015

21. CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions

Author

Bruno Patris, Maria Febbraio, Jean-Pierre Montmayeur, Isabelle Niot, Fabienne Laugerette, Patricia Passilly-Degrace, Philippe Besnard, Laboratoire de Physiologie de la Nutrition, and Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)

Subjects
CD36 Antigens, medicine.medical_specialty, CD36, Appetite, 03 medical and health sciences, 0302 clinical medicine, Tongue, Internal medicine, medicine, Animals, Humans, Lingual papilla, 030304 developmental biology, Dietary lipids, chemistry.chemical_classification, 0303 health sciences, biology, Fatty acid, Transporter, General Medicine, Taste Buds, Dietary Fats, Endocrinology, medicine.anatomical_structure, Biochemistry, chemistry, biology.protein, Pancreas, Ligation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Immunostaining, Research Article
Abstract

International audience; Rats and mice exhibit a spontaneous attraction for lipids. Such a behavior raises the possibility that an orosensory system is responsible for the detection of dietary lipids. The fatty acid transporter CD36 appears to be a plausible candidate for this function since it has a high affinity for long-chain fatty acids (LCFAs) and is found in lingual papillae in the rat. To explore this hypothesis further, experiments were conducted in rats and in wild-type and CD36-null mice. In mice, RT-PCR experiments with primers specific for candidate lipid-binding proteins revealed that only CD36 expression was restricted to lingual papillae although absent from the palatal papillae. Immunostaining studies showed a distribution of CD36 along the apical side of circumvallate taste bud cells. CD36 gene inactivation fully abolished the preference for LCFA-enriched solutions and solid diet observed in wild-type mice. Furthermore, in rats and wild-type mice with an esophageal ligation, deposition of unsaturated LCFAs onto the tongue led to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions. These findings demonstrate that CD36 is involved in oral LCFA detection and raise the possibility that an alteration in the lingual fat perception may be linked to feeding dysregulation.

Published
2005

22. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation

Author

Marie-Caroline Michalski, Cécile Vors, Noël Peretti, Fabienne Laugerette, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Fabienne Laugerette acknowledges grants from Institut Benjamin Delessert and Société Française de Nutrition. Cécile Vors is a recipient of doctoral grand from INRA & CNIEL. Marie-Caroline Michalski acknowledges a grant from ALFEDIAM., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Vericel, Evelyne, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
MESH: Inflammation, Metabolic inflammation, 030309 nutrition & dietetics, Endogeny, MESH: Metabolic Diseases, Biochemistry, Mice, MESH: Endotoxins, MESH: Obesity, MESH: Animals, Intestinal Mucosa, Subclinical infection, MESH: Lipid Metabolism, 0303 health sciences, General Medicine, 3. Good health, Intestines, MESH: Insulin Resistance, MESH: Dietary Fats, lipids (amino acids, peptides, and proteins), medicine.symptom, Digestion, Lipid digestion, MESH: Intestines, medicine.medical_specialty, MESH: Rats, Inflammation, Biology, 03 medical and health sciences, Insulin resistance, Metabolic Diseases, Internal medicine, medicine, Animals, Humans, Obesity, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Metagenome, medicine.disease, Lipid Metabolism, Dietary Fats, Endotoxemia, Rats, Endotoxins, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, MESH: Endotoxemia, Metagenome, Insulin Resistance, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.

Published
2011

23. Pasture v. standard dairy cream in high-fat diet-fed mice: improved metabolic outcomes and stronger intestinal barrier

Author

Alain Géloën, Bérengère Benoit, Hubert Vidal, Cyrille Debard, Jacques Bodennec, Olivier Cousin, Monique Estienne, Emmanuelle Loizon, Fabienne Laugerette, Pascale Plaisancié, Emmanuelle Meugnier, Marie-Caroline Michalski, Patricia Daira, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Sodiaal-Candia RD, Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Covalab-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Sodiaal Candia R&D, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Sciences Po Bordeaux - Institut d'études politiques de Bordeaux (IEP Bordeaux), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Covalab

Subjects
Male, Panniculitis, Milk/adverse effects/chemistry/secretion, 030309 nutrition & dietetics, Conjugated linoleic acid, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Adipose tissue, White adipose tissue, Inbred C57BL, Jejunum, chemistry.chemical_compound, Mice, Random Allocation, Functional Food, Lactation, Food science, Intestinal Mucosa, Animal Husbandry, ComputingMilieux_MISCELLANEOUS, Intestinal Mucosa/immunology/metabolism/pathology/physiopathology, 2. Zero hunger, Hypertriglyceridemia, 0303 health sciences, Nutrition and Dietetics, Hypertriglyceridemia/etiology/prevention & control, Chemistry, Aerial/chemistry/growth & development, Intestinal epithelium, Poaceae/chemistry/growth & development, medicine.anatomical_structure, Milk, Liver, Adipose Tissue, Female, Cattle/*physiology, Liver/metabolism, medicine.medical_specialty, Adipose Tissue, White, High-Fat/adverse effects, Context (language use), Diet, High-Fat, Poaceae, Functional Food/analysis, Dairy Products/adverse effects/analysis, 03 medical and health sciences, Internal medicine, medicine, Panniculitis/etiology/*prevention & control, Diet/*veterinary, Animals, Obesity, 030304 developmental biology, Dietary Fats/adverse effects/analysis/metabolism/*therapeutic use, Plant Components, Aerial, Dietary Fats, Small intestine, Diet, Mice, Inbred C57BL, Endocrinology, White/immunology/metabolism/pathology, Obesity/immunology/metabolism/pathology/*physiopathology, Cattle, Dairy Products, Plant Components
Abstract

Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepaticPPARαmRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.

Published
2014

24. Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans

Author

Amélie Bravard, Jennifer Rieusset, Jingwei-Ji Cao, Etienne Lefai, Hubert Vidal, Annie Durand, David Patsouris, Fabienne Laugerette, Marie-Agnès Chauvin, Martine Laville, Christine Durand, Guillaume Vial, Marie-Caroline Michalski, Cyrille Debard, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Patsouris, David

Subjects
Male, Chemokine, Muscle Physiology, Physiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Skeletal/*immunology/metabolism/pathology"*"Myositis/*immunology/metabolism, Mice, Obese, lcsh:Medicine, White adipose tissue, chémokine, Cell Movement, Immune Physiology, lcsh:Science, Immune Response, Chemokine CCL2, Obese"*"Mice, Innate Immune System, Multidisciplinary, biology, Myogenesis, muscle squelettique, medicine.anatomical_structure, Endocrinologie et métabolisme, Tumor necrosis factor alpha, medicine.symptom, Research Article, medicine.medical_specialty, diabète de type 2, Immunology, Inflammation, Mice, Transgenic, macrophage, Cell Line, Insulin resistance, Internal medicine, medicine, Animals, Humans, Transgenic"*"Muscle, Muscle, Skeletal, résistance à l'insuline, Nutrition, Endocrinology and metabolism, Endocrine Physiology, Myositis, Insulin, Macrophages, lcsh:R, Skeletal muscle, Biology and Life Sciences, Animals"*"Cell Line"*"Cell Movement"*"Chemokine CCL2/*physiology"*"Diabetes Mellitus, Nutrients, Type 2/immunology/metabolism"*"Humans"*"Insulin Resistance/*immunology"*"Macrophages/*immunology"*"Male"*"Mice, medicine.disease, Nutritional Diseases, Diet, Mice, Inbred C57BL, Endocrinology, Diabetes Mellitus, Type 2, Immune System, biology.protein, Inbred C57BL"*"Mice, lcsh:Q, Insulin Resistance
Abstract

International audience; Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFalpha expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.

Published
2014

25. Identification of new binding partners of the chemosensory signaling protein Gγ13 expressed in taste and olfactory sensory cells

Author

Sylvie Grall, Claire Fenech, Esmerina Tili, Fabienne Laugerette, Zhenhui Liu, Xavier Grosmaitre, Anna Wiencis, Jean-Pierre Montmayeur, Hervé Cadiou, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Ohio State University [Columbus] (OSU), Montmayeur, Jean-Pierre, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Ohio State University [Columbus] ( OSU )

Subjects
Taste, G protein, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, PDZ domain, Sensory system, Biology, taste bud, zo-1, gy13, pdz, olfactory sensory neurons, mpdz, gopc, lcsh:RC321-571, Cellular and Molecular Neuroscience, Taste receptor, Taste bud, medicine, GOPC, Food and Nutrition, PDZ, Original Research Article, Receptor, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, ZO-1, HEK 293 cells, Neurosciences, Olfactory sensory neurons, medicine.anatomical_structure, MPDZ, Neurons and Cognition, Alimentation et Nutrition, Gγ13, Neuroscience, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Tastant detection in the oral cavity involves selective receptors localized at the apical extremity of a subset of specialized taste bud cells called taste receptor cells (TRCs). The identification of the genes coding for the taste receptors involved in this process have greatly improved our understanding of the molecular mechanisms underlying detection. However, how these receptors signal in TRCs, and whether the components of the signaling cascades interact with each other or are organized in complexes is mostly unexplored. Here we report on the identification of three new binding partners for the mouse G protein gamma 13 subunit (Gγ13), a component of the bitter taste receptors signaling cascade. For two of these Gγ13 associated proteins, namely GOPC and MPDZ, we describe the expression in taste bud cells for the first time. Furthermore, we demonstrate by means of a yeast two-hybrid interaction assay that the C terminal PDZ binding motif of Gγ13 interacts with selected PDZ domains in these proteins. In the case of the PDZ domain-containing protein zona occludens-1 (ZO-1), a major component of the tight junction defining the boundary between the apical and baso-lateral region of TRCs, we identified the first PDZ domain as the site of strong interaction with Gγ13. This association was further confirmed by co-immunoprecipitation experiments in HEK 293 cells. In addition, we present immunohistological data supporting partial co-localization of GOPC, MPDZ, or ZO-1, and Gγ13 in taste buds cells. Finally, we extend this observation to olfactory sensory neurons (OSNs), another type of chemosensory cells known to express both ZO-1 and Gγ13. Taken together our results implicate these new interaction partners in the sub-cellular distribution of Gγ13 in olfactory and gustatory primary sensory cells.

Published
2012

26. CLA-Enriched Diet Containing t10,c12-CLA Alters Bile Acid Homeostasis and Increases the Risk of Cholelithiasis in Mice

Author

Amaia Zabala Letona, Maria P. Portillo, Marie-Claude Monnot, Fabienne Laugerette, Hélène Poirier, Philippe Besnard, Isabelle Niot, Anne Athias, Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) (NUTox), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Santé - STIC, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Enterohepatic circulation, medicine.medical_specialty, medicine.drug_class, Linoleic acid, [SDV]Life Sciences [q-bio], Blotting, Western, Medicine (miscellaneous), 030209 endocrinology & metabolism, Cholesterol 7 alpha-hydroxylase, Polymerase Chain Reaction, Bile Acids and Salts, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Cholelithiasis, Internal medicine, Hyperinsulinémie, medicine, Hyperinsulinemia, Animals, Homeostasis, 030304 developmental biology, 0303 health sciences, Nutrition and Dietetics, Bile acid, integumentary system, Cholesterol, alpha-Linolenic Acid, food and beverages, medicine.disease, Dietary Fats, Bile Salt Export Pump, Mice, Inbred C57BL, Cholesterol 7-alpha hydroxylase, Endocrinology, Metabolism, Liver, chemistry, Nutrient physiology, Female, lipids (amino acids, peptides, and proteins), Steatosis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the entero-hepatic circulation of BA was altered due to greater BA synthesis and ileal reclamation. This resulted from higher hepatic cholesterol 7α-hydroxylase (CYP7A1) and ileal apical sodium BA transporter expressions in CLA-fed mice. Furthermore, hepatic Na+/taurocholate co-transporting polypeptide (NTCP) (−52%) and bile salt export pump (BSEP) (−77%) protein levels were lower in CLA-fed mice than in controls, leading to a greater accumulation of BA in the plasma (+500%); also, the cholesterol saturation index and the concentration of hydrophobic BA in the bile were greater in CLA-fed mice, changes associated with the presence of cholesterol crystals. Expt. 2 suggests that CLA-mediated changes were caused by hyperinsulinemia, which occurred after 6 d of the CLA diet before NTCP and BSEP mRNA downregulation (10 d). Expt. 3 demonstrated that only t10,c12-CLA altered NTCP and BSEP mRNA levels. In conclusion, t10,c12-CLA alters BA homeostasis and increases the risk of cholelithiasis in mice.

Published
2011

27. The gustatory pathway is involved in CD36-mediated orosensory perception of long-chain fatty acids in the mouse

Author

Philippe Besnard, Aziz Hichami, Nicolas Darcel, Dany Gaillard, Patricia Passilly-Degrace, Jean-Pierre Montmayeur, Fabienne Laugerette, Naim Akhtar Khan, Abdelghani El-Yassimi, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Institut de signalisation, biologie du développement et cancer (ISBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût (CSG), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Lipides et signalisation cellulaire, Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût ( CSG ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Université de Bourgogne ( UB ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut National de la Recherche Agronomique (INRA), and Institut National de la Recherche Agronomique (INRA)-AgroParisTech

Subjects
CD36 Antigens, medicine.medical_specialty, Taste, CD36, Linoleic acid, Palmitic Acid, Succinimides, Oleic Acids, Context (language use), Biochemistry, Calcium in biology, Linoleic Acid, Food Preferences, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tongue, Taste receptor, Internal medicine, Avoidance Learning, Solitary Nucleus, Genetics, medicine, Animals, Molecular Biology, Glossopharyngeal Nerve, 030304 developmental biology, 0303 health sciences, biology, [SCCO.NEUR]Cognitive science/Neuroscience, Fatty Acids, Solitary tract, Genes, fos, Taste Buds, Dietary Fats, Mice, Inbred C57BL, Endocrinology, medicine.anatomical_structure, chemistry, [ SCCO.NEUR ] Cognitive science/Neuroscience, biology.protein, Conditioning, Operant, Calcium, Chorda Tympani Nerve, 030217 neurology & neurosurgery, Biotechnology
Abstract

International audience; The sense of taste informs the body about the quality of ingested foods. Tastant-mediated signals are generated by a rise in free intracellular calcium levels ([Ca(2+)]i) in the taste bud cells and then are transferred to the gustatory area of brain via connections between the gustatory nerves (chorda tympani and glossopharyngeal nerves) and the nucleus of solitary tract in the brain stem. We have recently shown that lingual CD36 contributes to fat preference and early digestive secretions in the mouse. We show here that 1) the induction of an increase in [Ca(2+)]i by linoleic acid is CD36-dependent in taste receptor cells, 2) the spontaneous preference for or conversely conditioned aversion to linoleic acid requires intact gustatory nerves, and 3) the activation of gustatory neurons in the nucleus of the solitary tract elicited by a linoleic acid deposition on the tongue in wild-type mice cannot be reproduced in CD36-null animals. We conclude that the CD36-mediated perception of long-chain fatty acids involves the gustatory pathway, suggesting that the mouse may have a "taste" for fatty foods. This system would constitute a potential physiological advantage under conditions of food scarcity by leading the mouse to select and absorb fatty foods. However, it might also lead to a risk of obesity and associated diseases in a context of constantly abundant food.

Published
2008

28. P198 Low-grade inflammatory response to overfeeding is linked to the relative variations of sCD14 and LBP in healthy men

Author

Marie-Caroline Michalski, Jean-Philippe Bastard, Fabienne Laugerette, Maurice Laville, Hubert Vidal, and Maud Alligier

Subjects
medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Inflammatory response, Inflammation, General Medicine, Overweight, medicine.disease, Obesity, Pathophysiology, Endocrinology, Postprandial, Internal medicine, Cohort, Internal Medicine, medicine, medicine.symptom, business, Weight gain
Abstract

Introduction Low-grade inflammation is now recognized as a hallmark of obesity pathophysiology. Recent interest has focused on the role of endotoxins absorbed during high fat meals. LBP and sCD14 have also been suggested as clinical markers of endotoxemia and in mice, the ratio LBP/sCD14 has been associated with high-fat diet induced inflammation. We tested the hypothesis that healthy subjects develop inflammation differently during overfeeding-induced weight gain according to the changes of LBP/sCD14 ratio in plasma. Patients et methodes Eighteen lean to overweight subjects were submitted to overfeeding (OF) during 8 weeks (+ 760 kcal/day). Endotoxemia, sCD14, LBP and IL-6 were measured before and after OF at fasting (n = 18), and in the postprandial phase after an 882-kcal test meal in a subcohort (n = 8). Resultats In the cohort, no effect of OF was observed on fasting IL-6 but OF induced an increase of LBP/sCD14 ratio (P = 0,017). Subjects were divided into tertiles regarding their variation of LBP/sCD14 ratio due to OF. Subjects in the highest tertile (+ 90 % of LBP/sCD14 ratio) increased plasma IL-6 (+ 26%) compared with the lowest tertile (no increase of LBP/sCD14 ratio ; − 31 % of plasma IL-6 ; P Conclusion Overfeeding increases postprandial endotoxemia but the inflammatory outcome appears to be modulated by the handling of endotoxins by different transporters in plasma. This study supports a new concept whereby the setup of low-grade inflammation during the initial phase of weight gain is linked to the relative variations of LBP and sCD14.

Published
2014

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