Fatty acid inhibition of hormonal induction of acetyl-coenzyme A carboxylase in hepatocyte monolayers

Arch Biochem Biophys. 1986 Apr;246(1):82-9. doi: 10.1016/0003-9861(86)90451-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyl-CoA Carboxylase / biosynthesis*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Cells, Cultured
  • Dexamethasone / antagonists & inhibitors*
  • Dexamethasone / pharmacology
  • Enzyme Induction / drug effects
  • Fatty Acids / biosynthesis
  • Fatty Acids / pharmacology*
  • Fatty Acids, Nonesterified / pharmacology
  • Glucagon / pharmacology
  • Insulin / pharmacology
  • Insulin Antagonists*
  • Ligases / biosynthesis*
  • Liver / enzymology*
  • Male
  • Rats
  • Rats, Inbred Strains
  • Triiodothyronine / pharmacology

Substances

  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Insulin
  • Insulin Antagonists
  • Triiodothyronine
  • Dexamethasone
  • Adenosine Triphosphate
  • Glucagon
  • Ligases
  • Acetyl-CoA Carboxylase