Origin and pattern of glucocorticoid-induced hyperlipidemia in rats. Dose-dependent bimodal changes in serum lipids and lipoproteins in relation to hepatic lipogenesis and tissue lipoprotein lipase activity.
Rats maintained for five days on a low dose of triamcinolone (0.5 mg/kg) showed a 2-fold increase in serum triacylglycerol concentration, paralleled by a rise in all very low density lipoprotein (VLDL) components but no significant change in serum cholesterol or high density lipoproteins (HDL). In contrast, a high dose of triamcinolone (12.5 mg/kg) produced a fall in triacylglycerol and VLDL to the range of control levels coincident with doubling in serum cholesterol and HDL. The rise in VLDL was attributed in a large part to enhanced hepatic fatty acid synthesis as evident from the marked rises in activity of rate-limiting enzymes of lipogenesis and in 3H incorporation into liver and serum fatty acids from in vivo administered 3H2O. The induction of fatty acid synthesis was linked to pronounced hyperinsulinemia, elicited by the triamcinolone treatment, to which the liver remained selectively responsive, contrary to the general insulin antagonism in peripheral tissues. Triamcinolone treatment also resulted in small rises in serum glucagon but these changes did not appear to be of importance for the observed bimodal serum lipoprotein perturbations. Dexamethasone, prednisolone and cortisol, administered in doses equipotent to 0.5 mg/kg triamcinolone, produced similar changes in the levels of serum triacylglycerol and insulin and activities of hepatic enzymes of lipogenesis.
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000378:metabolism; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism*; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D010730:Phosphoenolpyruvate Carboxylase / Q000378:metabolism; D051381:Rats; D014221:Triamcinolone; D014280:Triglycerides / Q000378:metabolism
D008074:Lipoproteins; D014280:Triglycerides; D014221:Triamcinolone; D002784:Cholesterol; D008291:Malate Dehydrogenase; D064429:Fatty Acid Synthases; D008071:Lipoprotein Lipase; D010730:Phosphoenolpyruvate Carboxylase; D000103:Acetyl-CoA Carboxylase