CD36 and Intestinal Fat Absorption

描述（由申请人提供）：1993年，我们发现膜蛋白CD36是长链脂肪酸（FA）的转运体。大量的证据

DESCRIPTION (provided by applicant): In 1993 we identified the membrane protein CD36 as a transporter for long-chain fatty acids (FA). A wealth of evidence supporting such a role was subsequently obtained by us and by others. Recent work with animal models of CD36 deficiency or overexpression documented that, in vivo, CD36 mediates greater than 60 percent of FA transport in key tissues. In humans, CD36 deficiency was linked to defects of myocardial FA uptake and to hypertrophic cardiomyopathy. This proposal is based on the hypothesis that CD36 plays an important role in lipid absorption in the small intestine, based on several pieces of evidence. First, CD36 has been documented to facilitate FA uptake and esterification in key tissues where it is highly expressed and its expression levels in the intestine are very high. Second, in the small intestine CD36 is highest in the jejunum and is localized apically in the upper two thirds of microvilli enterocytes, where most FA are absorbed. Third, our preliminary data indicate that CD36 null mice exhibit a delayed and low response of plasma triglycerides (TG) after an oral fat load. Our aims are to define the defect in absorption and chylomicron production in CD36 null mice. The importance of CD36 to fat absorption and energy metabolism overall will be assessed from examining susceptibility of CD36 null and wild type mice, where intestinal CD36 will be specifically inhibited, to high fat diet-induced obesity. Other studies with CD36 null mice and with Caco 2 cells infected with an adenoviral construct containing CD26, will explore the role of Cd36 in directing the FA to chylomicron production and in determining polarity of FA metabolism in the enterocyte. The work will contribute to the understanding of intestinal FA absorption and of FA metabolism in enterocytes. It may help design new approaches aimed at preventing the obesity induced by consumption of high dietary fat.