This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Dietary cholesterol increases plasma total and LDL-cholesterol concentration and accelerates the development of atherosclerosis. Within populations, serum cholesterol is poorly correlated with dietary cholesterol and fat composition when minor dietary changes are made since most subjects appear to compensate for dietary manipulations. Evidence has been presented that the population-based variations may occur at the level of cholesterol absorption.The intraluminal environment within the intestine has profound effects on cholesterol absorption. Specifically, biliary bile acid composition and concentration may alter cholesterol absorption substantially. Secondly, dietary fatty acid composition may affect cholesterol absorption. Finally, other factors affecting cholesterol absorption may be genetically determined (regulation of expression of a putative cholesterol transport protein), and may have substantial effects on cholesterol absorption. This study proposal will address only aim 2.
Aims 1 and 3 have been completed.Hypothesis 2: Cholesterol absorption will be significantly altered by the composition of dietary fat. Specifically, a high polyunsaturated/saturated (P/S) fat diet will cause a reduction in cholesterol absorption and consequently result in increased cholesterol FSR and HMG CoA reductase and LDL-receptor mRNA levels.
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