Liver lipid metabolism and effect of cholesterol-lowering agents in the hyperlipidemia induced in rats by implantation of the pituitary-derived MtT-F4 tumor

Abstract

Subcutaneous implantation of the transplantable pituitary tumor MtT-F4, which secretes large amounts of prolactin, growth hormone, and ACTH, produces hyperlipidemia in less than 30 days in the Fisher 344 rat. Further characterization of this new experimental model of endogenous hyperlipidemia showed that, at the 35th day after implantation, the hypertriglyceridemia may begin to subside while the elevation of plasma cholesterol progresses. At this time, acetate incorporation by liver slices into cholesterol is increased 27-fold while incorporation into fatty acids is 9 times as high as in sham-operated rats. Three drugs, probucol, hydroxymethylglutaric acid, and clofibrate, capable of lowering plasma cholesterol in these animals, also reduced the tumor-induced effect on cholesterol synthesis by about 60%. Only the latter two drugs, however, suppressed fatty acid synthesis to a similar extent. These experiments suggest that enhanced hepatic synthesis of cholesterol is in part responsible for the tumor-induced hypercholesterolemia.