title: Link between intestinal CD36 ligand binding and satiety induced by a high protein diet in mice.
abstract: CD36 is a ubiquitous membrane glycoprotein that binds long-chain fatty acids. The presence of a functional CD36 is required for the induction of satiety by a lipid load and its role as a lipid receptor driving cellular signal has recently been demonstrated. Our project aimed to further explore the role of intestinal CD36 in the regulation of food intake. Duodenal infusions of vehicle or sulfo-N-succinimidyl-oleate (SSO) was performed prior to acute infusions of saline or Intralipid (IL) in mice. Infusion of minute quantities of IL induced a decrease in food intake (FI) compared to saline. Infusion of SSO had the same effect but no additive inhibitory effect was observed in presence of IL. No IL- or SSO-mediated satiety occurred in CD36-null mice. To determine whether the CD36-mediated hypophagic effect of lipids was maintained in animals fed a satietogen diet, mice were subjected to a High-Protein diet (HPD). Concomitantly with the satiety effect, a rise in intestinal CD36 gene expression was observed. No satiety effect occurred in CD36-null mice. HPD-fed WT mice showed a diminished FI compared to control mice, after saline duodenal infusion. But there was no further decrease after lipid infusion. The lipid-induced decrease in FI observed on control mice was accompanied by a rise in jejunal oleylethanolamide (OEA). Its level was higher in HPD-fed mice than in controls after saline infusion and was not changed by lipids. Overall, we demonstrate that lipid binding to intestinal CD36 is sufficient to produce a satiety effect. Moreover, it could participate in the satiety effect induced by HPD. Intestine can modulate FI by several mechanisms including an increase in OEA production and CD36 gene expression. Furthermore, intestine of mice adapted to HPD have a diminished capacity to modulate their food intake in response to dietary lipids.
authors.affiliation: Inserm, U855, Lyon, France. danielle.naville@inserm.fr
authors.forename: Danielle
authors.initials: D
authors.lastname: Naville
authors.forename: Adeline
authors.initials: A
authors.lastname: Duchampt
authors.forename: Michèle
authors.initials: M
authors.lastname: Vigier
authors.forename: Delphine
authors.initials: D
authors.lastname: Oursel
authors.forename: René
authors.initials: R
authors.lastname: Lessire
authors.forename: Hélène
authors.initials: H
authors.lastname: Poirier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Niot
authors.forename: Martine
authors.initials: M
authors.lastname: Bégeot
authors.forename: Philippe
authors.initials: P
authors.lastname: Besnard
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009829:Oleic Acids / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D012528:Satiety Response / Q000187:drug effects; D013388:Succinimides / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D008024:Ligands; D009829:Oleic Acids; C440229:Oleylethanolamide; D013388:Succinimides; C120556:sulfo-N-succinimidyl oleate