This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The role of variations in cholesterol absorption on plasma lipids, cholesterol synthesis and the development of atherosclerosis is poorly studied in humans. Although there is known to be tremendous variation in cholesterol absorption amongst certain populations, little study has been undertaken to understand the underlying mechanisms of these variations. The purpose of this study is to assess the effects of differing biliary bile acid composition, differing dietary fatty acid composition and differences in plasma cholesterol concentration on cholesterol absorption, cholesterol synthesis and factors responsible for cholesterol metabolism in adults and a group of children and adults with inborn errors of bile acid metabolism. This outpatient study involves feeding subjects a standardized meal for 20 days with collection of blood samples to assess plasma lipids and factors that might influence cholesterol metabolism, a collection of bile after a meal stimulus to study events within the intestine involved with cholesterol absorption, a measurement of cholesterol synthesis using a stable isotope technique and finally the measurement of cholesterol synthesis using a novel technique that measures stable isotope incorporation into red blood cells.
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