Accumulation of adipocyte cholesterol during hypolipidemic drug treatment in cholesterol-fed rats

An attempt was made to mobilize adipose tissue cholesterol independently of triacylglycerol by feeding cholesterol to intact Fischer 344 rats to 'load' adipocytes followed by hypolipidemic drug treatment in order to lower plasma cholesterol and, hence, adipocyte cholesterol. In this strain of rat, body weight and adipocyte sizes remain relatively constant after 1 year of age. Therefore, alterations in adipocyte cholesterol can be ascribed to factors other than cell size. Both oxandrolone and combined cholestyramine/clofibrate treatment caused significant reductions in plasma cholesterol in cholesterol-fed rats, but cholesterol concentrations in liver were reduced only by cholestyramine/clofibrate treatment. Oxandrolone enhanced the development of liver fatty liver in the cholesterol-fed rats, but cholestyramine/clofibrate significantly reduced liver triacylglycerol concentrations. Adipocyte cholesterol in the epididymal depot was significantly elevated, not lowered, in both concentrations. Adipocyte cholesterol in the epididymal depot was significantly elevated, not lowered, in both groups of drug-treated animals. Subcutaneous adipocytes from rats receiving drug treatment also contained more cholesterol, especially in rats given oxandrolone. Increments in adipocyte cholesterol were associated with decreases in the absolute amounts of apolipoproteins, A-I and A-IV, as measured by densitometric scanning of electrophoretic gels. Under the present experimental conditions, changes in plasma cholesterol scanning of electrophoretic gels. Under the present experimental conditions, changes in plasma cholesterol concentration did not adequately reflect the cholesterol content of either liver or adipose tissue.