CD36 and Intestinal Fat Absorption

描述（由申请人提供）：1993年，我们鉴定了膜蛋白 CD36作为长链脂肪酸（FA）的转运蛋白。大量证据 我们和其他国家随后获得了支持这一作用的支持。最近 对CD36缺陷或过度表达的动物模型的研究证明， 在体内，CD36介导了关键组织中超过60%的FA转运。 在人类中，CD36缺乏与心肌FA摄取缺陷和心肌FA摄取缺陷有关。 肥厚型心肌病这一提议是基于这样的假设，即CD36 在小肠的脂质吸收中起重要作用，基于 几个证据。首先，CD36已被证明有助于FA 在其高度表达的关键组织中的摄取和酯化， 在肠中的表达水平非常高。第二，在小 肠CD 36在空肠中最高，并且位于上部的顶部。 三分之二的微绒毛肠上皮细胞，其中大部分FA被吸收。三是我们 初步数据表明，CD36缺失小鼠表现出延迟的和低的免疫应答。 口服脂肪负荷后血浆甘油三酯（TG）的反应。我们的目标是 定义了CD36缺失小鼠中吸收和乳糜微粒产生的缺陷。 CD36对脂肪吸收和能量代谢的重要性将在 通过检查CD36缺失和野生型小鼠的易感性进行评估，其中 肠道CD36会被特异性抑制，以高脂饮食诱导 肥胖用CD36缺失小鼠和用Caco 2细胞感染的其他研究 一种含有CD 26的腺病毒构建体，将探索CD 36在 指导FA产生乳糜微粒和确定FA的极性 肠上皮细胞中的代谢。这项工作将有助于了解 肠FA吸收和肠细胞中FA代谢。它可能有助于 设计新的方法，旨在预防因食用 高脂肪食物。

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.