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Am J Physiol Regul Integr Comp Physiol. 2011 Dec;301(6):R1738-47. doi: 10.1152/ajpregu.00235.2011. Epub 2011 Sep 7.

Interactions between CD36 and global intestinal alkaline phosphatase in mouse small intestine and effects of high-fat diet.

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  • 1Department of Biology, Boston University, Boston, Massachusetts 02215, USA.


The mechanisms of the saturable component of long-chain fatty acid (LCFA) transport across the small intestinal epithelium and its regulation by a high-fat diet (HFD) are uncertain. It is hypothesized here that the putative fatty acid translocase/CD36 and intestinal alkaline phosphatases (IAPs) function together to optimize LCFA transport. Phosphorylated CD36 (pCD36) was expressed in mouse enterocytes and dephosphorylated by calf IAP (CIAP). Uptake of fluorescently tagged LCFA into isolated enteroctyes was increased when cells were treated with CIAP; this was blocked with a specific CD36 inhibitor. pCD36 colocalized in enterocytes with the global IAP (gIAP) isozyme and, specifically, coimmunoprecipitated with gIAP, but not the duodenal-specific isozyme (dIAP). Purified recombinant gIAP dephosphorylated immunoprecipitated pCD36, and antiserum to gIAP decreased initial LCFA uptake in enterocytes. Body weight, adiposity, and plasma leptin and triglycerides were significantly increased in HFD mice compared with controls fed a normal-fat diet. HFD significantly increased immunoreactive CD36 and gIAP, but not dIAP, in jejunum, but not duodenum. Uptake of LCFA was increased in a CD36-dependent manner in enterocytes from HFD mice. It is concluded that CD36 exists in its phosphorylated and dephosphorylated states in mouse enterocytes, that pCD36 is a substrate of gIAP, and that dephosphorylation by IAPs results in increased LCFA transport capability. HFD upregulates CD36 and gIAP in parallel and enhances CD36-dependent fatty acid uptake. The interactions between these proteins may be important for efficient fat transport in mouse intestine, but whether the changes in gIAP and CD36 in enterocytes contribute to HFD-induced obesity remains to be determined.

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