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.
Highlights
CD36 is a multifunctional plasma membrane glycoprotein expressed by a broad variety of tissues [1,2]
To further explore the intestinal CD36 implication either as a AGLC transporter [19] or a putative receptor [13] in the lipidmediated control of food intake, pharmacological manipulation of the ligand binding site of CD36 was performed using an infusion of the sulfosuccinimidyl-oleate (SSO) into the duodenal lumen prior to IL or saline treatment in wild-type and CD36-null mice
Our data show that the binding of intestinal CD36 with the pharmacogical drug SSO is sufficient to reproduce this lipid-mediated regulation
Summary
CD36 is a multifunctional plasma membrane glycoprotein expressed by a broad variety of tissues [1,2] This receptor-like protein is able to bind multiple compounds such as oxidized LDL [3], collagen [4] or thrombospondin [5]. CD36 generally plays a specific role in a given cell type It is involved in collagen-mediated cytoadhesion in platelets, whereas it mediates LCFA uptake in myocytes. Its localization is strictly restricted to the brush border membrane of differentiated enterocytes [10,12,13] This location raises the possibility of an involvement in lipid uptake by intestinal cells, the specific role of CD36 in the small intestine is not yet fully understood. It has been demonstrated that intestinal CD36 exerts a role of lipid receptor, driving cellular signals stimulating chylomicron synthesis [13]
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