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International audience; Les activités spécifiques des lipases gastriques et pancréatiques ont été mesurées à l'aide de triacylglycérols (TAG) issus d'huile de colza, de 1,3-sn-DAG et de 1,2(2,3)-sn-DAG purifiés produits à partir de cette huile, ainsi que d'une huile de colza huile enrichie à 40% w/w DAG (DAGOIL). La lipase gastrique était plus active sur le 1,3 --DAG et le TAG, tandis que la lipase pancréatique présentait une sélectivité inverse avec une activité plus élevée sur le TAG que sur le DAG pris comme substrats initiaux. Cependant, dans les deux cas, les activités les plus élevées étaient affichées sur DAGOIL. Ces résultats montrent que le DAG mélangé au TAG, comme au cours de la digestion, est un meilleur substrat pour les lipases que le TAG. Les mêmes acylglycérols d'huile de colza ont été utilisés pour étudier l' absorption des graisses intestinales - sn -DAG que sur 1,2(2,3) -snchez le rat avec canulation du canal lymphatique mésentérique. Les taux de TAG synthétisés dans l'intestin et la concentration en acides gras totaux dans la lymphe n'étaient pas différents lorsque les rats recevaient des quantités identiques d'huile de colza TAG, de 1,2(2,3)-- DAG ou de DAGOIL. Depuis la lipolyse du 1,3- sn -DAG, 1,3- sn sn-DAG par les lipases digestives conduit au glycérol et non au 2-sn-monoacylglycérol (2- sn - MAG) comme la lipolyse des TAG, ces résultats suggèrent que la re-synthèse des TAG dans les entérocytes peut se faire entièrement via le « glycérol-3-phosphate ». (G3P) », avec la même efficacité que la voie 2- sn -MAG majoritairement impliquée dans l'absorption des graisses intestinales. Ces découvertes apportent un nouvel éclairage sur le rôle joué par les DAG en tant que produits intermédiaires de lipolyse. Selon leur structure, 1,2(2,3) -sn - DAG versus 1,3 - sn -DAG, les DAG peuvent contrôler la voie (2- sn -MAG ou G3P) par laquelle les TAG sont resynthétisés dans les entérocytes .

International audience; Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.

Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (−57.0 ± 2.6% to −83.9 ± 1.6%) and cholesterol (−35.3 ± 4.4% to −60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (−41.5 ± 3.7% to −97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.

International audience

Oxylipins and endocannabinoids (eCBs) both belong to superclasses of lipid mediators with potent inflammation modulatory activities. The adipose tissue (AT) plays a key role in metabolic syndrome-related inflammation, via altered adipocyte physiology, infiltrated macrophages and altered profile of eCBs. We previously reported that DHA is more potent than EPA at modulating systemic inflammation, but the underlying mechanisms remain unclear. The objective of this study was to compare the individual effect of high-dose DHA and of EPA on circulating lipid mediators, i.e. plasma oxylipins and eCBs, and AT-related inflammation. In a randomized double-blind crossover trial, 154 volunteers with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1- EPA (2.7 g/d); 2- DHA (2.7 g/d); 3- corn oil (control), each separated by a 9-wk washout. Supplements were provided as re-esterified triacylglycerols. Profiling of plasma oxylipins and eCBs was performed on 58 subjects after each phase. Abdominal subcutaneous AT biopsies were also obtained from 13 individuals after each phase. Plasma DHA-, EPA-, arachidonic acid-derived oxylipins were analyzed by LC-MS. eCBs and some of their bioactive congeners were analyzed in plasma and AT by LC-APCI-MS. Adipocyte diameter was determined by histological analysis and AT macrophage infiltration was quantified by double immunofluorescence. Compared with EPA, DHA increased plasma levels of hydroxy-docosahexaenoic acids (7-, 11-, 14-, 4-, 17-HDOHE; P < 0.0001) and palmitoylethanolamide (PEA; P = 0.04). Compared with DHA, EPA led to higher plasma level of hydroxy-eicosapentaenoic acids (12-, 15-, 5-HEPE; P < 0.0001). In the AT, EPA increased the level of oleoylethanolamide (OEA; P = 0.01) compared with DHA, but no other difference was observed between treatments in adipose eCBs and eCB-related lipids. DHA and EPA did not differentially modify adipocyte size distributions (P > 0.50) and proportions of M1-type and M2-type macrophages (P > 0.30). In conclusion, increased plasma levels of anti-inflammatory DHA-derived oxylipins and plasma PEA may be responsible, at least to some extent, for the more potent anti-inflammatory effects of DHA compared with EPA observed in the ComparED study. Conversely, subcutaneous AT does not seem to be involved in explaining such differences between EPA and DHA.

International audience; Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-alpha-tocopherol) and alpha-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus alpha-tocopherol acetate by measuring the plasma concentrations of alpha-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and alpha-tocopherol acetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; alpha-tocopherol acetate, 11.4%). Plasma concentrations of alpha-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.

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.

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.

International audience; Donor human milk, pasteurised for safety reasons, is the first alternative for feeding preterm infants when mothers' own milk is unavailable. Breastmilk pasteurisation impact on lipid digestion and absorption was evaluated by a static in vitro digestion model for preterm infants coupled with intestinal absorption using Caco-2/TC7 cells. Lipid absorption was quantified by digital image analysis of lipid droplets, by measurement of basolateral triglyceride concentration and by analysing the expression of major genes involved. After in vitro digestion, lipolysis extent was 13% lower in pasteurised human milk (PHM) than in raw human milk (RHM). In Caco-2/TC7 cells, the number of lipid droplets was identical for both milk types, while the mean droplet area was 17% smaller with PHM. Altogether, pasteurisation decreased the pre-lipolysis of human milk. This initial difference in free fatty acid amount was only partially buffered by the subsequent processes of in vitro digestion and cellular lipid absorption.

Insulin resistance (IR) favors the progression of metabolic syndrome (MetS) and increases the risk of type 2 diabetes. IR results from metabolic dysfunctions, oxidative stress and inflammation caused by ectopic fat depots. We studied the effect of canola oil enriched with micronutrients naturally present in canola seed on IR and MetS during a high fat (HF)-challenge. Rats were fed with a HF diet containing 30% of lipids, mainly derived from palm oil (diet P), or from a mixture of palm and canola oils (60:40, diet C). In 2 groups of animals, diet C was further supplemented with alpha tocopherol, CoQ with or without Canolol, (diets CMC & CM respectively). Insulin sensitivity and glucose tolerance were assessed after 10 weeks. HF animals were compared to control animals receiving a standard diet. All groups receiving a HF diet gained significantly more weight compared to control. Similar results were obtained for fat depots. Glucose tolerance was altered in P and C groups and improved in CM and CMC. Insulin sensitivity was not different between control and P groups, but was higher in CMC group compared to controls. A reduced activation of PDK4 and Srebp1c expression was observed in skeletal muscle in CM group. In conclusion, the proportion of AGPI could not prevent metabolic disturbance induced by a HF meal. Enrichment with natural micronutrients could prevent insulin resistance and glucose intolerance which could be mediated by a better glucose oxidation in skeletal muscle

The identification of natural bioactive compounds aimed at promoting optimal gut health and improving lipid metabolism is paramount in the prevention of chronic disease. In this review, we summarize basic science and clinical research examining the protective properties of milk sphingomyelin (SM) against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. Dietary SM dose-dependently reduces the intestinal absorption of cholesterol, triglycerides, and fatty acids in cell culture and rodent studies. Overall, rodent feeding studies show dietary milk SM, milk polar lipid mixtures, and milk fat globule membrane reduce serum and hepatic lipid concentrations. Furthermore, these hypolipidemic effects are observed in some supplementation studies in humans, although the extent of reductions in serum cholesterol is typically smaller and only one trial was conducted with purified SM. Dietary milk SM has been reported to affect the gut microbiota in rodent studies and its hydrolytic product, sphingosine, displays bactericidal activity in vitro. Milk SM may also improve gut barrier function to prevent the translocation of inflammatory gut bacteria-derived molecules. Current evidence from pre-clinical studies indicates that dietary milk SM has protective properties against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. The hypolipidemic effects of milk SM observed in animal studies have been reported in some human studies, although the magnitude of such effects is typically smaller. More research is warranted to clearly define how dietary milk SM influences lipid metabolism, gut microbiota, and inflammation in humans.

Table S1. FA composition in retroperitoneal adipose tissue. (*P

International audience

Introduction et but de l’etude L’hyperlipemie postprandiale et l’alteration de la beta-oxydation des lipides sont des facteurs de risque metaboliques lies a l’obesite et en lien direct avec l’apport alimentaire en lipides. La quantite et la taille des chylomicrons sont connus pour conditionner leur elimination et sont capables de moduler la repartition finale des acides gras (AG) alimentaires entre beta-oxydation et stockage. Cependant, l’influence de la quantite de matiere grasse ingeree sur la lipemie postprandiale et le devenir metabolique des AG alimentaires chez les sujets obeses reste a elucider. Materiel et methodes Dans une etude en chasse croise randomise, 18 hommes sains normo-ponderes (NP) et obeses ont consomme des repas tests contenant soit 10 g soit 40 g de matiere grasse marquee au carbone 13 (13C) a l’aide de traceurs isotopiques. La teneur en triglycerides et la taille des chylomicrons ont ete mesurees pendant 8 h apres le petit-dejeuner. Les concentrations plasmatiques en 13C-palmitate et 13C-oleate ont aussi ete mesurees pendant 8 h ainsi que leur perte fecale sur 72 h. Un test respiratoire au 13CO2 couple a de la calorimetrie indirecte pendant 8 h a permis de calculer le devenir metabolique des AG exogenes. Resultats et analyse statistique Les triglycerides des chylomicrons ont augmente chez tous les sujets proportionnellement a la dose ingeree de lipides (p Conclusion Le profil de lipemie postprandiale apres un repas realiste riche en lipides est altere chez les hommes obeses. Meme si la reduction de la quantite de lipides ingeres semble normaliser le devenir postprandial des acides gras ingeres chez les sujets obeses, d’autres recherches sont necessaires pour mieux comprendre les mecanismes d’alteration du metabolisme postprandial des lipides en situation d’obesite.

Introduction et but de l’etude Les regimes occidentaux sont impliques dans le developpement des maladies metaboliques, dont la composante inflammatoire peut etre due a une alteration de la barriere intestinale. Les produits laitiers contiennent naturellement la matiere grasse sous forme de globule gras, constitues (i) d’un cœur de triglycerides (98 % des lipides) et (ii) d’une membrane biologique riche en lipides mineurs bioactifs, les lipides polaires (2 % des lipides) incluant de maniere specifique la sphingomyeline (SM, ∼ 25 % des lipides polaires). Les composes alimentaires peuvent affecter la barriere intestinale en influencant l’organisation des proteines des jonctions serrees qui sont impliquees dans les transports paracellulaires entre la lumiere intestinale et la circulation. Notre hypothese est que la matiere grasse laitiere exerce certains de ses effets benefiques par l’intermediaire de la SM, notamment sur l’integrite de la barriere intestinale qui pourraient reduire une inflammation. Nous avons teste in vitro l’hypothese que l’interleurkine-8 (IL-8), impliquee dans la maturation de l’epithelium intestinal [1] , serait un acteur des modifications intestinales en reponse aux lipides polaires laitiers. Materiel et methodes Des cellules Caco-2/TC7 cultivees sur filtre Transwell® (modele d’epithelium intestinal) ont ete incubees avec des micelles mixtes lipidiques enrichies ou non en SM laitiere (0 mM, 0,2 mM et 0,4 mM). L’expression genique des proteines impliquees dans les jonctions serrees (Occludine, claudine et JAM-1, des proteines transmembranaires, et ZO-1, proteine intracellulaire) et la concentration d’IL-8 (au pole apical et basolateral) ont ete etudies ainsi que plusieurs marqueurs inflammatoires. Nous avons dans un deuxieme temps incube les cellules avec l’IL-8 recombinante humaine en apical et/ou en basolateral afin d’observer l’impact sur l’expression genique des proteines de jonctions serrees. Resultats et analyse statistique Apres 24 h d’incubation avec des micelles enrichies avec 0,4 mM de SM, nous avons observe une surexpression de l’occludine (p Conclusion Nos resultats revelent un impact de la SM laitiere sur la modulation de l’expression des proteines des jonctions serrees et de l’IL-8, ainsi que de sa concentration. Apres incubation avec l’IL-8 recombinante, nous avons demontre que les modifications induites par la SM sur les jonctions serrees peuvent etre expliquees au moins en partie par l’action de l’IL-8.

Introduction et but de l’etude La denutrition represente un surcout eleve hospitalier meme dans les pays industrialises. La denutrition a un impact important sur la croissance infantile. La presence d’un microbiote intestinal est indispensable au maintien d’une croissance juvenile. En situation de denutrition chez l’animal, certaines souches de lactobacillus plantarum ont montre un effet promoteur sur la croissance. Le Lactobacillus Fermentum CECT5716 (LfCECT5716) est une souche isolee du lait de mere qui est deja utilisee en nutrition pediatrique. Le but de cette etude est de rechercher si l’ajout de LfCECT5716 induit un effet promoteur de croissance sur un modele de drosophile axenique en situation de denutrition ; et si cet effet est accompagne d’une modulation de l’absorption lipidique enterocytaire. Materiel et methodes Des larves de drosophiles axeniques de type yellow white ont ete incubees en presence du LfCECT5716 en situation de denutrition proteique. Apres 7 jours d’incubation, la taille des larves de drosophiles etait mesuree et comparee au groupe temoins de larves steriles et de deux souches temoins positives pour la croissance juvenile (Lactobacilus plantarum NIZO21 et WJL). L’effet d’une incorporation de la souche LfCECT5716 dans une formulation infantile a ete egalement teste. Le temps de maturation des larves a ete surveille a 21 jours d’incubation. Enfin, des cellules enterocytaires humaines Caco/TC7 ont ete incubees en presence de LfCECT5716 et de micelles lipidiques postprandiaux marques a l’oleate C13 afin d’etudier la modulation de l’absorption lipidique. Resultats et analyse statistique Les larves incubees en presence de LfCECT5716 etaient statistiquement plus grandes (3,7 mm ; 2,2–5,4 ; p Conclusion Le LfCECT5716 est capable de restaurer la croissance juvenile en situation de denutrition chez la drosophile axenique sans augmenter les apports nutritifs du milieu. Cet effet est conserve lorsque le LfCECT5716 est incorpore dans une formule infantile. Enfin le LfCECT5716 semble moduler l’absorption lipidique enterocytaire.

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.

Resume La composante inflammatoire des maladies metaboliques fait l’objet de nombreux travaux, avec les notions d’inflammation metabolique concernant le phenomene chronique de bas grade, ou encore d’inflammation postprandiale pour le phenomene transitoire observe suite a un repas. De nombreux biomarqueurs sont utilises et l’endotoxemie fait partie des facteurs d’interet. Le role des lipides alimentaires dans l’inflammation est tres discute. Les produits laitiers sont souvent decries pour leur teneur en acides gras satures susceptibles de favoriser l’inflammation. A ce jour, l’impact de ces produits sur l’inflammation postprandiale dependrait avant tout de la quantite consommee, et ce au meme titre que d’autres sources de lipides. De plus, aucun effet negatif de la consommation de produits laitiers sur l’inflammation chronique n’est a ce jour decrit ; trois etudes soulignent meme un effet protecteur chez des sujets minces a obeses. Dans une approche de nutrition preventive, l’etiologie de l’inflammation metabolique doit donc etre placee dans un contexte d’equilibre des regimes alimentaires.

Beyond fatty acid composition of milk fat that can impact the health of consumers, interest is growing regarding the importance of the supramolecular structure of milk lipids on their nutritional properties. Indeed, milk fat is found naturally under the form of an emulsion of lipid droplets called the milk fat globule (MFG) composed of a triglyceride core stabilized by a complex trilayered membrane called the MFG membrane. Recent researches have highlighted that this unique structure and the presence of bioactive lipids such as sphingomyelin could have a beneficial metabolic impact on lipid metabolism and contribute to intestinal and systemic health. The purpose of this chapter is to provide a focused overview on the composition of milk lipids, their organization as MFG and, their impact on lipid digestion and postprandial lipemia. In addition, the long-term effect on lipid metabolism and related metabolic players such as inflammation and gut microbiota are discussed.

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.

Humans spend more than three-quarters of their lives in the postprandial state. Although the link between metabolic and cardiovascular diseases and fasting lipid and carbohydrate metabolism has been extensively studied and illustrated on the basis of conventional parameters (cholesterol, triglycerides, glucose, insulin, etc), it is equally legitimate and important to examine the role of these metabolic parameters in lipotoxicity and glucotoxicity occurring during the postprandial phase. However, studies of postprandial excursions, peaks and 2-hour post-meal follow-up are not sufficient to characterize integrative metabolic responses during the postprandial phase. Studies of the modulation of postprandial hyperlipidemia and hyperglycemia, using integrated kinetic monitoring and stable isotope tracers, are of prime importance to highlight the metabolic phenomena underlying lipemic and glycemic responses and to better characterize their long-term metabolic consequences.

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.

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.

Lipid metabolism studies focus mainly on oxidation and storage but rarely on faecal elimination, which is needed to assess total lipid distribution during the postprandial period. The purpose of the present work was to set up and validate the analysis of lipid tracers in stools, with an aim of later using this methodology in studies of postprandial lipid tracer metabolism. Eight subjects received a mixture of [1,1,1-(13)C3]tripalmitin and [1,1,1-(13)C3]triolein with a fat-rich meal. The nature and amounts of (13)C lipids excreted in stools during 3 days post-dose were determined by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis of fatty acid methyl esters (FAMEs) from total fatty acid (TFA), free fatty acid (FFA) and triacylglycerol (TAG) fractions. The results were expressed as the Cumulative Tracer Recovery of the administered dose (CTR%). The quantities and labelling of FAMEs were higher in FFA than in TAG, indicating that label loss was not due to a lack of digestive lipase activity. The labelling was higher for C16:0 than for C18:1. The CTRs were 7.03 ± 0.77% and 6.87 ± 0.91%, respectively, in TFA and FFA for [1-(13)C] C16:0, while they were 0.60 ± 0.15% and 0.51 ± 0.11% for [1-(13)C] C18:1 (mean ± sem). By studying the kinetics of lipid excretion from subjects, two groups emerged. The first one showed rapid excretion in stool #1, whereas the second showed slower excretion in stools #2-#3. A significant difference was found in the FFA in stool #1 for C16:0 (p < 0.01) and C18:1 (p < 0.05). Individual excretion kinetics showed marked variability. Nevertheless, the CTR over the 3-day study period was substantial and homogenous for all subjects. These results confirm that the assessment of faecal elimination is of great importance when establishing total lipid distribution during the postprandial period and validate the analysis of cumulative tracer loss during 72 h post-tracer ingestion.

The purpose of the study was to characterise the phospholipid and sterol composition in four French breast milk samples, with an aim to highlight molecular lipid species of possible nutritional significance for infants. Main PL species were phosphatidylethanolamine (PE, 21.3 ± 4.7%), phosphatidylcholine (19.0 ± 2.2%) and sphingomyelin (43.3 ± 2.6%). PE contained more arachidonic acid (4.8%) than did other PL species (P

International audience; Background: The 2 major dietary sources of trans fatty acids (TFAs) are partially hydrogenated oils and ruminant-derived products. Epidemiologic data suggest that chronic consumption of industrial sources of TFAs could be damaging to insulin sensitivity, but intervention studies on this issue have remained inconclusive. Objective: The trial was designed to compare the effects of dairy compared with industrial sources of TFAs on insulin sensitivity in overweight women. Design: Sixty-three healthy women with abdominal obesity [waist circumference > 88 cm and a body mass index (in kg/m(2)) > 28] were recruited. After a run-in period, the volunteers were randomly assigned to consume 1 of 3 four-week diets: 60 g low-TFA lipids/d (0.54 g/d; n = 21), ruminant TFA-rich lipids (4.86 g/d; n = 21), or industrial TFA-rich lipids (5.58 g/d; n = 21). Changes in peripheral insulin sensitivity were assessed by using hyperinsulinemiceuglycemic clamps. Results: After the intervention period, fasting glycemia and insulinemia and insulin sensitivity were not significantly modified in either group (P > 0.05). Conclusions: These data indicate that consumption of dairy- and industrial-source TFAs for 4 wk at nutritional levels do not impair peripheral insulin sensitivity in insulin-resistant women. Our study may not preassess the effects of TFAs in normal insulin-sensitive individuals. This trial was registered at clinicaltrials.gov as NCT00617435. Am J Clin Nutr 2009;90:88-94.

In milk fat, fatty acids are located at specific positions on the triacylglycerol backbone. The sn-2 position contains most saturated long-chain fatty acids, while the sn-3 position contains short-chain fatty acids. Moreover, these triacylglycerols are structured as milk fat globules surrounded by their native membrane containing phospholipids. This native structure can be modified by the dairy processes to generate various possible colloidal structures with milk fat. The structure of triacylglycerols and the milk fat ultrastructure can impact on fatty acid digestion and absorption, which has a potential effect on cardiovascular risk factors linked to postprandial hypertriglyceridemia. The review points out the impact of the triacylglycerol structure and the ultrastructure of milk fat on these risk factors.

Resume Le lait maternel est riche en acides gras polyinsatures (AGPI), tres sensibles a l’oxydation. Nous avons donc mesure des marqueurs finaux 1) global (le MDA) et 2) specifiques de la peroxydation des AGPI des series n – 6 et n – 3 : le 4-hydroxynonenal (4-HNE) et le 4-hydroxyhexenal (4-HHE), respectivement, a partir de 7 echantillons de lait maternel. Les analyses ont ete effectuees dans le lait frais ou conserve 1 jour a 18 °C ou 7 jours a 4 °C. Dix formules lactees, en poudre ou liquides, supplementees ou non en AGPI a longue chaine, ont aussi ete etudiees. Le rapport [4-HHE/AGPI n – 3] etait 20 fois superieur dans les formules lactees liquides par rapport au lait maternel (0,19 ± 0,01 μg.g −1 ) ( P n – 6] etait 300 fois superieur dans les formules lactees en poudre par rapport au lait maternel (0,004 ± 0,000 μg.g −1 ) ( P

Native milk fat globules of various mean diameters, ranging from d 43 = = 2.3 μm to 8.0 μm, were obtained using microfiltration of raw whole milk. After milk fat globule washing, the milk fat globule membrane (MFGM) was separated by manual churning. After total lipid extraction and separation of polar lipids, their phospholipid (PL) and sterol composition was measured using thin-layer chromatography, methyl ester analyses by gas chromatography, and gas chromatography coupled to mass spectrometry. The main PL species were phosphatidylethanolamine, phosphatidylcholine and sphingomyelin. The respective fatty acid composition of each PL species was measured. Many different minor bioactive sterols were detected in the MFGM, e.g. lanosterol, lathosterol, desmosterol, stigmasterol and β-sitosterol. No significant differences in the PL and sterol profile were found between MFGM extracted from small and large milk fat globule fractions.

The aim of this study was to characterize differences in the thermal and structural behavior between different sized native milk fat globules. A novel microfiltration process permits the selection of native small fat globules (SFG, 1-3 microm) and large fat globules (LFG,5 microm) in raw milk, that were analyzed by X-ray diffraction (XRD) coupled to differential scanning calorimetry (DSC). There were no major differences in triglyceride crystalline structures between SFG and LFG, after eliminating thermal history and the influence of cooling rates. The three main 3L and 2L crystalline structures appearing under slow cooling existed regardless of globule size. The supercooling increased for the SFG, mainly due to heterogeneous nucleation in winter milk, and also to compositional variations in spring milk. Differences appeared regarding stabilized crystalline forms at 20 degrees C and subsequent cooling: the SFG contained less 2L triglyceride structures than the LFG. These results can be important in dairy manufactures using tempering periods.

Introduction et but de l’etude En situation d’obesite, l’exposition par voie orale aux matieres grasses alimentaires peut moduler la digestion et l’absorption des lipides. Cependant, les mecanismes oraux sous-jacents n’ont pas ete clairement identifies. Nous avons teste l’hypothese que des composants de la salive impliques dans la sensibilite orale aux lipides alimentaires seraient differents selon l’indice de masse corporelle (IMC) et le metabolisme lipidique postprandial des individus. Materiel et methodes La salive a ete recueillie a jeun chez neuf sujets de poids normal (IMC = 22,3 ± 0,5 kg/m2) et neuf individus obeses (IMC = 31,7 ± 0,3 kg/m2) pour la mesure des parametres suivants : flux, teneur en proteines, lipolyse, amylase, proteolyse, pouvoir antioxydant, lysozyme, teneurs en lipocaline 1 et en anhydrase carbonique-VI (CAVI). Ce recueil a ete realise avant la consommation d’un repas contenant 40 g de matiere grasse, suivie d’un test d’exploration metabolique de 8 h, au cours duquel les sujets obeses ont revele un metabolisme lipidique postprandial retarde. Resultats et analyse statistique Nous avons montre que la lipolyse salivaire est plus faible chez les sujets obeses par rapport aux individus de poids normal alors que la proteolyse et la teneur en CAVI sont plus elevees ( Tableau 1 ). Par analyse multivariee et par test de Mann-Whitney, nous observons que ces differences de lipolyse et de proteolyse sont liees a des differences de metabolisme lipidique incluant l’absorption postprandiale des acides gras exogenes et leur beta oxydation. Conclusion Ces resultats suggerent un role de la salive sur le metabolisme lipidique postprandial. Ils amenent de nouvelles hypotheses causales sur les liens entre la composition de la salive, la sensibilite orale aux graisses alimentaires et le metabolisme lipidique postprandial en fonction de l’IMC.

Native milk fat globules of various mean diameters, ranging from d 43 = 1.5 to 7.3 pm, were obtained using microfiltration of raw whole milk acquired in winter and spring. After total lipid extraction, fatty acid composition was characterized by methyl and butyl ester analysis using gas chromatography. The oleic and linoleic acid content of milk obtained in winter increased with fat globule size, whereas myristic and palmitic acid decreased. There was significantly more lauric, myristic and palmitoleic acid, and less stearic acid in small fat globules compared to large fat globules in milk obtained in both winter and spring. The relative content of oleic and linoleic acids were found to depend on fat globule size and season. Results are interpreted on the basis of the relative content of milk fat globule membrane depending on fat globule size, and on consequences of compositional variations on milk fat globule melting behavior.

The apparent ζ -potential ( ζ ap ) of raw milk fat globules, either natural or mechanically damaged by homogenization or shear, was measured by laser Doppler electrophoresis. Upon homogenization, ζ ap increased in a non-linear way as a function of the surface coverage of the milk fat globule membrane (MFGM) with casein micelles and whey proteins (from −13.5±0.9 mV for natural globules to −20±1 mV for strongly homogenized ones). A model was calculated to estimate the MFGM deteriorations after mechanical stress, using ζ ap measurements. This new method to assess technological damages to raw milk fat globules can be considered as simple when comparing particle size distributions is not possible.

The stability and conformation of tripalmitin (TP) and triolein (TO) Langmuir-Blodgett (LB) monolayers on glass were investigated using Atomic Force Microscopy (AFM). Compression isotherms revealed that TP reached the solid state at 15 mN m -1 , with a trident conformation. LB deposition of the monolayer on the glass surface was performed at the solid state (30 mN m -1 ) with a transfer ratio close to 1. The TO monolayer collapsed in the liquid-expanded phase at 13 mN m -1 . LB deposition was performed at 11 mN m -1 with a transfer ratio of 1.4. The LB films were imaged by AFM (tapping mode). The TO monolayer collapsed in amorphous droplets. TP presented tiny amorphous drops plus crystalline shapes with unit layers of a thickness of 40-46 A, corresponding to the long spacing of the β and a polymorphic forms. TP monolayer thus collapsed in aggregates to form crystalline structures. The thickness of the first step was mostly 86 A, but sometimes 68 A steps were observed, while the transferred monolayer generally reorganizes as a tuning fork in a regular crystalline unit, but can also remain as a trident, providing a hydrophobic support for upper layers. This findings supply backing for technical processes such as the interpretation of fat fractionation by microfiltration membranes, based on triglyceride/solid interaction statements. La stabilite et la conformation de monocouches de Langmuir-Blodgett de tripalmitine (TP) et de trioleine (TO) deposees sur du verre sont etudiees par microscopie a force atomique. Lors du depot sur substrat de verre, il se produit un collapse du reseau bidimensionnel en une structure tridimensionnelle qui indique que les interactions entre molecules sont plus fortes que celles entre les molecules et la surface de verre.

Triglyceride wetting properties on solid surfaces of different hydro-phobicities were investigated using three different methods, namely, the sessile drop method for static contact angle measurements, the Wilhelmy method for dynamic contact angle measurements, and the captive bubble method to investigate thin triglyceride film stability. For solid surfaces having a surface free energy higher than the surface tension of triglycerides (tributyrin, tricaprylin, and triolein), a qualitative correlation was observed between wetting and solid/triglyceride relative hydrophobicities. On surfaces presenting extreme hydrophobic or hydrophilic properties, medium-chain triglycerides had a behavior similar to that of long-chain unsaturated ones. On a high-energy surface (glass), tricaprylin showed an autophobic effect subsequent to molecular adsorption in trident conformation on the solid, observed with the three methods. Thin triglyceride films between an air bubble and a solid surface were stable for a short time, for solids with a surface free energy larger than the triglyceride surface tension. If the solid surface had a lower surface free energy, the thin film collapsed after a time interval which increased with triglyceride viscosity. Copyright 2000 Academic Press.

The surface free energy of polymeric films of polyvinylchloride (PVC) + poly(ethylene-co-vinylacetate) (EVA) blends was calculated using the van Oss treatment (Lifshitz and electron donor-electron acceptor components of surface free energy) and the Owens-Wendt treatment (dispersive and nondispersive components of surface free energy). Surface free energy results were found to be greatly dependent on the calculation method and on the number of standard liquids used for contact angle measurements. The nondispersive/donor-acceptor surface free energy component and the total surface free energy of polymeric films were always higher when the van Oss treatment was used compared to the Owens-Wendt treatment. Conversely, both methods led to similar apolar/Lifshitz components. All the calculation methods were in good agreement for the surface free energy of PVC; however, a discrepancy between the methods arose as EVA content in the blends increased. It seems that there is not yet a definite solution for the calculation of solid surface free energy. Further developments of existing models are needed in order to gain consistency when calculating this important physicochemical quantity. Copyright 1998 Academic Press.

Introduction Les maladies metaboliques d'origine nutritionnelle sont caracterisees par un metabolisme des lipides perturbe incluant une hyperlipemie postprandiale. Dans ce contexte, un interet se developpe autour des effets des lipides polaires (LP), agents de texture largement utilises dans l'industrie alimentaire. Nous etudions donc l'impact de LP de differentes sources alimentaires (vegetal vs animal) sur la lipemie postprandiale. Materiels et methodes Des souris ont ete gavees avec 2 types d'emulsions, dont les gouttelettes de matiere grasse etaient recouvertes de LP laitiers ou de LP de soja. Le plasma et l'intestin grele ont ete collectes au cours de la digestion. Des cellules intestinales Caco-2/TC7 ont ete incubees 24 heures avec des micelles lipidiques contenant differents L P, phosphatidylcholine ou sphingomyeline (specifique des LP laitiers) pour analyse des chylomicrons secretes. Resultats Une heure apres gavage, les LP Laitiers induisent des concentrations plasmatiques de triglycerides et d'acides gras libres plus elevees que les LP de soja. L'effet inverse est observe apres 4 heures. Ces lipemies differentes sont associees a une moindre expression genique de proteines impliquees dans la secretion des chylomicrons, dans le duodenum du groupe LP laitiers a 4 heures. Ceci suggere que l'absorption et la metabolisation des lipides dependent du type de LP utilise, notamment via une modulation des genes dans l'enterocyte. In vitro , la presence de sphin-gomyeline dans les micelles induit une secretion plus importante de triglycerides sous la forme de plus petits chylomicrons. Ainsi, les effets observes in vivo sont probablement dus a la teneur elevee des LP laitiers en sphingomyeline. Conclusion Ces resultats suggerent que la qualite des lipides polaires utilises pour stabiliser une emulsion influence le metabolisme postprandial des lipides. Ces nouvelles connaissances pourraient servir a la mise en place de formulations alimentaires optimisees. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Adhesion of oils and fatty food products to packages is an important storage problem, because it increases product-package interactions that alter quality. Reducing such adhesion would also allow savings in recycling and cleaning processes. The aim of our work was to test if some thermodynamical adhesion models were correlated to edible oils’ bulk adhesion as measured experimentally. Food-contact surfaces were low-density polyethylene, polyethylene teraphthalate, stainless steel, and glass. The Young-Dupre equation and five models of adhesion from the literature were used to calculate solids’ surface tension and the thermodynamical work of adhesion (Wa). The dispersive, polar, acid-base, and hydrogen surface tension components of oils and solids were calculated. The experimental adhesion, or amount of edible oils remaining on solid surfaces after contact, was found to be correlated to Young-Dupre Wa, involving contact angle measured by specially designed image analysis technique. Two models, involving, respectively, surface tension’s hydrogen component and a linear dependence of Wap on the liquid polar surface tension component, fitted best with oil bulk adhesion as measured experimentally. Our theoretical approach to fatty food material adhesion seems, so far, consistent to predict global residues of edible oils on solid surfaces.