CD36 and Intestinal Fat Absorption

描述(申请人提供)：1993年，我们鉴定了膜蛋白CD36是长链脂肪酸(FA)的转运体。丰富的证据 随后，我们和其他国家获得了支持这样一个角色。近期 对CD36缺乏或过度表达的动物模型的研究证明， 在体内，CD36介导了超过60%的FA在关键组织中的转运。 在人类中，CD36缺乏与心肌FA摄取缺陷和 肥厚型心肌病。这一提议是基于CD36的假设 在小肠的脂肪吸收中起着重要的作用，基于 几件证据。首先，CD36已被记录为促进FA 在其高表达的关键组织中的摄取和酯化及其 在肠道中的表达水平非常高。第二，在小范围内 肠CD36在空肠中最高，位于顶部 2/3的微绒毛细胞，大部分FA被吸收。第三，我们的 初步数据表明，CD36缺失的小鼠表现出延迟和低水平 口服脂肪负荷后血浆甘油三酯(TG)的反应。我们的目标是 明确CD36基因缺失小鼠在吸收和乳糜粒产生方面的缺陷。 CD36对脂肪吸收和能量代谢的整体重要性将是 通过检测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缺失小鼠和感染了CD36基因的CCO2细胞进行的其他研究 一个含有CD26的腺病毒载体，将探索CD36在 指导乳酸菌生产和确定乳酸菌的极性 肠道细胞的新陈代谢。这项工作将有助于理解 肠道FA吸收及肠道细胞FA代谢。这可能会有帮助 设计新的方法，旨在预防因食用 高脂肪饮食。

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.