Experimental hyperlipidemia in rats.

Abstract

Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The concentrations of the serum lipoproteins were significantly increased, while, only small changes in the distribution of the serum lipids and the composition of the lipoproteins were observed. Following stimulation of isolated adipose tissue cells with ACTH, the lipolytic response and the accumulation of cyclic AMP was higher in cells derived from the rats with the tumor, although the accumulation of cyclic GMP was not different from control adipocytes. Further, when the isolated adipose tissue cells were stimulated with dibutyryl cyclic AMP no difference was observed between the control and tumor bearing groups. Clofibrate administered in the diet resulted in a complete elimination of the tumor effect on serum triglycerides and to a great extent prevented the rise in serum cholesterol. The tumor-induced increase in the concentration of the high density lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was not affected, but the elevation of the d less than 1.063 lipoproteins was partially reversed. The increased lipolytic response and accumulation of cyclic AMP following stimulation by ACTH was not altered in adipocytes derived from tumor bearing rats. However, clofibrate treatment resulted in a significantly greater accumulation of cyclic GMP in fat cells stimulated with ACTH from both control and tumor bearing rats. Clofibrate in the diet did not alter the levels of GH or prolactin or serum lipids in the control rats nor were the elevated hormone levels of the tumor bearing rats changed.