CD36 Displays Features of a Lipid-Sensor Involved in Chylomicron Processing in the Rodent Small Intestine

Abstract : The membrane glycoprotein CD36 binds nanomolar concentrations of long-chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into the potential underlying mechanisms. Our in vivo data demonstrated that CD36 gene deletion in mice did not affect LCFA uptake and their subsequent esterification into triglycerides by the intestinal mucosa at micellar LCFA concentrations prevailing in the intestine. In rodents, CD36 protein early disappeared from the luminal side of intestinal villi during the post-prandial period but only when the diet contained lipids. This drop was significant 1 h after a lipid supply and was associated with an ubiquitination of CD36 as reported during the ligand receptor desensitization process. Using CHO cells expressing CD36, it is shown that the digestion products, LCFA and diglycerides, triggered the CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevented the lipid-mediated degradation of CD36 and the up-regulation of L-FABP, a key gene implicated in the formation and secretion of large chylomicrons. Since the L-FABP up-regulation by lipids remained abolished in CD36-null mice with and without MG132, CD36 degradation appears to be linked to the chylomicron formation. Therefore, intestinal CD36 displays features of a lipid sensor involving in the adaptation of enterocyte metabolism to the post-prandial lipid challenge by producing large triglyceride-rich lipoproteins rapidly cleared in blood. This finding raises the possibility of alternative therapeutic approaches to reduce the post-prandial hypertriglyceridemia and prevent cardiovascular risks.
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Submitted on : Thursday, November 8, 2018 - 3:07:07 PM
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Thi Thu Trang Tran, Hélène Poirier, Lionel C. Clément, Fatiha Nassir, Pelsers M.M.A.L., et al.. CD36 Displays Features of a Lipid-Sensor Involved in Chylomicron Processing in the Rodent Small Intestine. ''Atherosclerosis Supplements'', 2010, 11 (1), pp.82 - 83. ⟨10.1016/j.atherosclerosissup.2010.04.040⟩. ⟨hal-01916507⟩

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