Cholesterol absorption plays a key role in cholesterol homeostasis and is a major determinant in plasma cholesterol concentrations.
The aims of the present study are three fold: (1) to determine how enrichment of the bile acid pool with exogenous bile acids (cholic, ursodeoxycholic, chenodeoxycholic, and deoxycholic acids) regulates cholesterol absorption and leads to alterations in cholesterol synthesis and LDL- receptor mRNA levels in normal adults and children and adults with inborn errors of bile acid metabolism. (2) To determine the effect of increased dietary polyunsaturated fat on cholesterol absorption and consequent changes in cholesterol synthesis and LDL-receptor mRNA levels in healthy adults. (3) To determine the relationship between cholesterol absorption and plasma cholesterol concentrations in women with high and low decile plasma cholesterol concentrations and whether differences in synthesis and LDL-receptor mRNA levels are similarly related to plasma cholesterol levels. For each of these aims, subjects will be studied will consuming cell controlled diets as outpatients. Techniques employed for these studies will include state of the art techniques utilizing stable isotopes and isotope ration mass spectroscopy , gas chromatography, and RTPCR. Integration of studies from this project with other laboratory analyses will help to better characterize the role of modifications of biliary bile acid compositions, cholesterol solubilization, phospholipid content, and pancreatic enzyme concentrations in the regulation of human cholesterol absorption and synthesis.
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