Effects of adrenalectomy and dexamethasone on hepatic lipid metabolism

The influence of adrenalectomy and dexamethasone on hepatic free fatty acid metabolism was studied in isolated perfused livers from male rats. Adrenalectomy 1 week prior to perfusion did not affect uptake of oleate, output of triglyceride, or rate of ketogenesis compared to sham-operated match-fed controls. Livers from dexamethasone-treated rats (0-2 mg/kg per day for 7 days) removed less oleate from the perfusate, esterified more to total and very low density lipoprotein (VLDL) triglyceride, and oxidized less to ketone bodies, compared to match fed controls; additional studies with [1-(14)C]oleate confirmed these findings. The output of glucose by livers from dexamethasone-treated rats was also stimulated. The output of VLDL triglyceride was correlated with output of total perfusate triglyceride (r = 0.77, P < 0.001). Prior to perfusion, dexamethasone livers accumulated more triglyceride than did control livers. Adrenalectomy did not affect the concentration of plasma free fatty acid or blood ketones and glucose; however, the plasma concentration of triglyceride was elevated. Dexamethasone increased the concentration of plasma free fatty acid, total triglyceride, and VLDL protein, triglyceride, phospholipid, and free cholesterol. No changes were observed in the concentration or composition of plasma low density lipoprotein (LDL) lipids. The concentration of plasma high density lipoprotein (HDL) protein and lipid, and plasma apoA-I, tended to increase; the ratio of total HDL cholesterol to LDL cholesterol was elevated with dexamethasone treatment. These observations suggest that augmented synthesis and secretion of VLDL triglyceride contribute to glucocorticoid-induced hyper-triglyceridemia.-Cole, T. G., H. G. Wilcox, and M. Heimberg. Effects of adrenalectomy and dexamethasone on hepatic lipid metabolism.