LIVER/INTESTINAL METABOLISM OF BILE ACIDS AND LIPIDS

肝肠脂质计划项目(LILPP)由一个 一组密切相关的研究项目，都与研究有关 胆汁酸、胆固醇、磷脂和甘油三酯 肝脏或肠道的新陈代谢和运输。建议数 计划项目由七项个人拨款申请组成，由 独立调查人员，长期在 类固醇、胆汁酸和/或其他脂类的代谢。四 该方案项目的成员来自 胃肠病学和其他四个来自基础学院 健康科学。该计划项目的总体目标是 将个人调查人员的资源和人才集中在 为了加深我们对肝脏和肠道的了解 脂类的代谢。这项建议的具体目标是 目的：a)阐明胆汁酸的调节机制 合成和分泌；b)确定调节因素 人体内游离胆固醇“代谢活性池”的大小 肝脏是胆汁酸合成的前体来源， 胆汁胆固醇排泄；c)提供动力学定义 血浆中游离和酯化胆固醇的贡献 不同脂蛋白组分对胆汁酸合成和胆汁的影响 男性的胆固醇分泌(正常受试者和 不同类型的高脂血症)；d)描述其机制 磷脂和甘油三酯合成的调节 肝脏；e)描述激素在胆汁调节中的作用 肝脏中盐分的运输和分泌；f)确定其作用 胆盐在肠道钙、铁吸收中的作用 钙离子对回肠胆盐吸收及携带的影响 胆汁酸肠道微生物代谢的基础研究。 细胞培养-分子生物学核心实验室，在 Hylemon博士的导演，将在这个项目中发挥关键作用 项目。这个核心实验室将提供现代技术，而不是 可供多名调查人员使用。LILPP的这一方面将 允许一些P.I.S在他们的研究中采取更深入的方法。 不同研究人员之间的广泛合作研究 已经启动，还有一些其他项目正在规划中 相位。

The Liver-Intestinal Lipid Program Project (LILPP) consists of a group of closely related research projects all dealing with studies of bile acids, cholesterol, phospholipid and triglyceride metabolism and transport by the liver or intestines. The proposed program project consists of seven individual grant applications by independent investigators, with long standing interests in the metabolism of sterols, bile acids and/or other lipids. Four members of the program project are from the Division of Gastroenterology and the other four are from the School of Basic Health Sciences. The overall objective of the program project is to pool the resources and talents of individual investigators in order to further our understanding of hepatic and intestinal metabolism of lipids. The specific objectives of this proposal are to: a) elucidate the mechanisms of regulation of bile acid synthesis and secretion; b) determine the factors which regulate the size of "metabolically active pool" of free cholesterol in the liver, which is the precursor source for bile acid synthesis and biliary cholesterol excretion; c) to provide a kinetic definition of the contribution of plasma free and esterified cholesterol from different lipoprotein fractions to bile acid synthesis and biliary cholesterol secretion in man (normal subjects and patients with different types of hyperlipidemia); d) to describe the mechanism of regulation of phospholipid and triglyceride synthesis in the liver; e) describe the role of hormones in the regulation of bile salt transport and secretion in the liver; f) to determine the role of bile salt in the intestinal absorption of Ca++ and Fe++ and effects of Ca++ on ileal bile salt absorption and g) to carry outbasic studies of intestinal microbial metabolism of bile acids. The Cell Culture-Molecular Biology Core laboratory, under the direction of Dr. Hylemon, will play a pivotal role in this program project. This core laboratory will offer modern technology not available to several investigators. This aspect of the LILPP will permit a number of P.I.'s a more indepth approach in their studies. Extensive collaborative studies between different investigators have already been initiated and a number of others are in planning phase.