Effects of dietary lipids on hepatic cholesterol homeostasis in F1B hamsters

Chang, Chih-Kai (2007) Effects of dietary lipids on hepatic cholesterol homeostasis in F1B hamsters. Masters thesis, Memorial University of Newfoundland.

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Abstract

The regulation of cholesterol homeostatsis is of considerable interest because of the host of studies that show a clear positive relationship between plasma cholesterol levels and the risk of coronary heart disease. It has become apparent that plasma cholesterol levels are affected by a number of life style factors including the amount and type of fat in the diet. However, the mechanisms whereby dietary fat affects plasma cholesterol remain unclear. In this study we have investigated the effects of the levels and types of dietary fat on the cholesterol homeostasis. We used the FIB strain of hamster as a model as this strain has been shown to be sensitive to dietary fat induced atherosclerosis. We propose that this sensitivity reflects differences in the regulation of lipid metabolism between the F1B and the parent strain of hamsters. -- Cholesterol homeostasis in the liver is tightly regulated by several sterol-sensitive regulatory proteins and receptors, including LDL receptor, HMG-CoA reductase, ACAT, CYP7, and SREBPs. It is postulated that the ER cholesterol is the cholesterol regulatory pool plays a major role in the regulation of these enzymes of the whole cell. -- We examined the effect of different dietary fats on the activity or expression of these proteins and observed that the activities of these enzymes are not directly regulated by the fats and cholesterol in the diet; instead, they appear more responsive to changes in the lipid environment of the microsome in the F1B hamster liver. Both the HMG-CoA reductase and the ACAT activity are positively correlated with the level of n-3 fatty acids in the microsome, and ACAT activity also depend on the content of microsomal cholesterol. -- We suggested that the levels of n-3 fatty acids and cholesterol in the diets may change the lipid composition microsomal membranes. This might alter membrane fluidity or the distribution of the key enzymes and regulatory proteins in the membrane of the ER. We suggest that the formation of microdomains (rafts) may sequester much of the cholesterol into pools that are separate from the cholesterol regulatory pool in the ER. However, further studies on the lipid composition of these microdomains are needed for clarify our hypothesis.

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