Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids.
Administration of triamcinolone or dexamethasone to rats led to a prompt, marked and persistent rise in liver acetyl-CoA carboxylase activity. The activity of fatty acid synthetase increased to a lesser extent and after a more prolonged glucocorticoid treatment, whereas the changes in that of NADP-malate dehydrogenase and ATP-citrate lyase were not appreciable. The overall channeling of [1-14-C]acetyl-CoA to fatty acids was enhanced. The triamcinolone effect on acetyl-CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan-diabetic rats, whereas the alanine-aminotransferase-inducing effect of this hormone was additive to that of insulin deficiency. In adipose tissue triamcinolone treatment caused a reduction in the activity of all lipogenesis enzymes and blunted their response to insulin administration. The antagonism of glucocorticoids toward insulin, selectively modulating the responses of the insulin-sensitive enzymes in liver and adipose tissue is discussed. The rise in hepatic lipogenic capacity, through the retention of the ability of insulin to induce acetyl-CoA carboxylase, may be physiologically important in restraining the ketogenesis from acetyl-CoA despite the increased fat utilization during glucocorticoid excess.
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000410:Alanine Transaminase / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D064429:Fatty Acid Synthases / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008025:Ligases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008297:Male; D007652:Oxo-Acid-Lyases / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014221:Triamcinolone / Q000494:pharmacology*
D007328:Insulin; D014221:Triamcinolone; D003907:Dexamethasone; D008291:Malate Dehydrogenase; D064429:Fatty Acid Synthases; D001275:ATP Citrate (pro-S)-Lyase; D000410:Alanine Transaminase; D007652:Oxo-Acid-Lyases; D008025:Ligases; D000103:Acetyl-CoA Carboxylase