1. Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice
- Author
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Aurélie Waget, Matteo Serino, Jean-Claude Thiers, Gaelle Payros, Rémy Burcelin, Amélie Lacombe, Serge Luquet, Jessica Denom, Myriam Masseboeuf, Catherine Kabani, Céline Cruciani-Guglielmacci, Nicolas Marsollier, Anne Nègre-Salvayre, Christophe Magnan, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), RB is the recipient of a grant from the European Association for the Study of Diabetes (EASD) and Amylin. CM is the recipient of funding from the 'Agence Nationale de la Recherche' (France): ANR-07-PHYSIO, Simon, Marie Francoise, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
- Subjects
Central Nervous System ,Anatomy and Physiology ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Guanidines ,Jejunum ,Lipid peroxidation ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Endocrinology ,Integrative Physiology ,Glucose homeostasis ,Homeostasis ,Insulin ,Intestinal Mucosa ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,Multidisciplinary ,Intestines ,medicine.anatomical_structure ,Medicine ,Research Article ,medicine.medical_specialty ,Science ,Endocrine System ,Biology ,Neurological System ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,medicine ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Obesity ,030304 developmental biology ,Nutrition ,Diabetic Endocrinology ,Endocrine Physiology ,medicine.disease ,Vagus nerve ,Oxidative Stress ,Glucose ,chemistry ,Metabolic Disorders ,Duodenum ,Lipid Peroxidation ,Insulin Resistance ,Physiological Processes ,Digestive System ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; BACKGROUND: Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice. METHODOLOGY/PRINCIPAL FINDINGS: An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity. CONCLUSIONS/SIGNIFICANCE: Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity.
- Published
- 2011