Fatty acid inhibition of hormonal induction of acetyl-coenzyme A carboxylase in hepatocyte monolayers.
Primary cultures of adult rat hepatocytes were utilized to ascertain the impact of free fatty acids on the insulin plus dexamethasone induction of acetyl-CoA carboxylase. Lipogenesis was induced threefold by the combination of insulin and dexamethasone. The rise in fatty acid synthesis was accompanied by a comparable increase in the rate-determining enzyme acetyl-CoA carboxylase. Dexamethasone was required for the insulin induction of acetyl-CoA carboxylase. Under the permissive action of glucocorticoid, 10(-7) M insulin maximally increased enzyme activity. Half-maximum stimulation occurred with 5 X 10(-9) M insulin. Media containing 0.2 mM palmitate, oleate, linoleate, arachidonate, or docosahexaenoate significantly suppressed the hormonal induction of acetyl-CoA carboxylase. The extent of suppression was only 30-35% and did not vary with chain length or degree of unsaturation. Carboxylase activity was not suppressed further by raising the concentration of linoleate to 0.5 mM; however, 0.5 mM palmitate depleted the cells of ATP and abolished acetyl-CoA carboxylase activity. Therefore, based upon the inhibitory characteristics of the various fatty acids and the lack of a concentration dependency of the fatty acid inhibition, it would appear that fatty acid inhibition of the induction of acetyl-CoA carboxylase activity may not be a direct, physiological regulatory mechanism.
Salati
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Clarke
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D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005227:Fatty Acids / Q000096:biosynthesis / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists; D008025:Ligases / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007329:Insulin Antagonists; D014284:Triiodothyronine; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D005934:Glucagon; D008025:Ligases; D000103:Acetyl-CoA Carboxylase