CD36 and Intestinal Fat Absorption

CD36 与肠道脂肪吸收

• 批准号: 6650779
• 负责人: Nada A. Abumrad
• 金额: $ 32.17万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650779
• 关键词: SDS polyacrylamide gel electrophoresis; bioenergetics; chylomicrons; density gradient ultracentrifugation; dietary lipid; fatty acid metabolism; gastrointestinal absorption /transport; gastrointestinal nutrient absorption; high performance liquid chromatography; immunoprecipitation; laboratory mouse; long chain fatty acid; membrane proteins; microarray technology; nutrition related tag; obesity; polymerase chain reaction; small intestines; thin layer chromatography; triglycerides

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.

描述（由申请人提供）：1993年，我们鉴定出膜蛋白CD36作为长链脂肪酸（FA）的转运蛋白。丰富的证据 我们和其他人随后获得了对这一角色的支持。最近的 对 CD36 缺乏或过度表达的动物模型的研究表明， 在体内，CD36 介导关键组织中 60% 以上的 FA 转运。 在人类中，CD36 缺乏与心肌 FA 摄取缺陷和 肥厚型心肌病。该提议基于 CD36 的假设 在小肠的脂质吸收中起重要作用 几件证据。首先，CD36已被记录以方便FA 在其高度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。其次，在小 肠 CD36 在空肠中最高，位于顶部 三分之二的微绒毛肠细胞，大部分 FA 在这里被吸收。三、我们的 初步数据表明 CD36 缺失小鼠表现出延迟和低 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 CD36 缺失小鼠的吸收和乳糜微粒产生缺陷。 CD36 对脂肪吸收和能量代谢的重要性 通过检查 CD36 缺失和野生型小鼠的敏感性进行评估，其中 肠道CD36会被特异性抑制，对高脂肪饮食诱发 肥胖。对 CD36 缺失小鼠和感染了 CD36 的 Caco 2 细胞进行的其他研究 含有 CD26 的腺病毒构建体将探索 Cd36 在 引导 FA 产生乳糜微粒并确定 FA 的极性 肠上皮细胞中的代谢。这项工作将有助于理解 肠道 FA 吸收和肠上皮细胞 FA 代谢。它可能有帮助 设计新方法旨在预防因消费而引起的肥胖 高膳食脂肪。