Modulation by glycerol of hepatic glycero-3-phosphate concentration, ketogenesis, and output of triglyceride and glucose in perfused livers from hyperthyroid and euthyroid rats.

Decreased glycero-3-phosphate (glycero-3-P) concentration, decreased output of triglyceride and glucose, increased output of apolipoprotein A-I, and increased ketogenesis were observed with isolated perfused livers from triiodothyronine-treated rats in comparison to livers from euthyroid animals. Infusion of glycerol produced a concentration-dependent accumulation of glycero-3-P in perfused livers from hyperthyroid and euthyroid rats, which was considerably enhanced in the euthyroid group. The antiketogenic effect of glycerol in livers from triiodothyronine-treated rats was accompanied by increased output of glucose and triglyceride, while no change in the output of apolipoprotein A-I was observed. The reduction of ketogenesis (49%) in euthyroid livers by glycerol was not accompanied by increased triglyceride output, while with the largest amount of glycerol infused, decreased output of apolipoprotein A-I was seen. Output of triglycerides by livers from hyperthyroid rats correlated with hepatic concentration of glycero-3-P and was maximal at a glycero-3-P concentration (0.5 mumol/g), similar to that observed in livers from euthyroid rats in the absence of glycerol. Availability of glycero-3-P appears to be rate-limiting for synthesis and secretion of triglyceride by livers from hyperthyroid animals, whereas the glycero-3-P concentrations in euthyroid livers were sufficient to support maximal production of triglyceride limited only by the supply of free fatty acid.