Stimulation by acetoacetate of hepatic triacylglycerol synthesis.
The factors responsible for the huge accumulation of hepatic triacylglycerols in the ketotic diabetic state are not established. Our earlier work suggested a role for ketone bodies in the increased hepatic triacylglycerol synthesis observed in the ketotic diabetic state. Isolated hepatocytes obtained from normal fed rats were incubated with sodium acetoacetate or sodium chloride (control) and [1-14C]palmitate in Krebs-albumin buffer. Acetoacetate stimulated triacylglycerol synthesis in a concentration-dependent manner without increasing palmitate uptake or inhibiting palmitate oxidation. Beta hydroxybutyrate showed no effect on palmitate esterification to triacylglycerols. Isolated hepatocytes of normal fed rats were incubated with either sodium acetoacetate or sodium chloride and the nuclear-free homogenate was incubated with [U-14C]glycero-3-phosphate and cofactors. The synthesis of triacylglycerol and the activity of the cytosolic phosphatidate phosphohydrolase were increased in the cells pre-incubated with acetoacetate. The results of this study demonstrate that the increases in triacylglycerol synthesis and the cytosolic activity of phosphatidate phosphohydrolase previously observed by us in the ketotic diabetic liver, could be reproduced in normal fed rat liver cells by incubating them with acetoacetate. The results identify acetoacetate as a potential factor, in the regulation of hepatic triacylglycerol synthesis and for hepatic accumulation of triacylglycerols observed in the ketotic diabetic state.
D000090:Acetoacetates / Q000494:pharmacology*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004951:Esterification; D007657:Ketone Bodies / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010168:Palmitates / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D014280:Triglycerides / Q000096:biosynthesis*
D000090:Acetoacetates; D007657:Ketone Bodies; D010168:Palmitates; D014280:Triglycerides; C016635:acetoacetic acid; D010711:Phosphatidate Phosphatase