LIVER/INTESTINAL METABOLISM OF BILE ACIDS AND LIPIDS

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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.