TRIIODOTHYRONINE STIMULATES AND GLUCAGON INHIBITS TRANSCRIPTION OF THE ACETYL-COA CARBOXYLASE GENE IN CHICK-EMBRYO HEPATOCYTES - GLUCOSE AND INSULIN AMPLIFY THE EFFECT OF TRIIODOTHYRONINE

The mechanisms by which triiodothyronine (T3), glucose, insulin, and g lucagon regulate acetyl-CoA carboxylase expression in primary cultures of chick embryo hepatocytes have been investigated. Incubating hepato cytes with T3 in the absence of glucose caused a fourfold increase in acetyl-CoA carboxylase activity. Addition of glucose (20 mM) enhanced the T3-induced increase in acetyl-CoA carboxylase activity by threefol d but had no effect on enzyme activity in the absence of T3. The effec ts of T3 and glucose on acetyl-CoA carboxylase activity were accompani ed by similar changes in acetyl-CoA carboxylase mRNA levels, indicatin g that regulation occurred at a pretranslational step. Xylitol mimicke d the effect of glucose on acetyl-CoA carboxylase mRNA abundance, sugg esting that an intermediate(s) of the nonoxidative branch of the pento se phosphate pathway may be involved in mediating this response. Insul in accelerated the accumulation of acetyl-CoA carboxylase mRNA abundan ce caused by T3 and glucose but had no effect on steady-state levels o f acetyl-CoA carboxylase mRNA in the absence or presence of T3. Glucag on caused a 65% decrease in the accumulation of acetyl-CoA carboxylase mRNA in hepatocytes incubated with T3 and glucose. The effects of T3, glucose, insulin, and glucagon on the abundance of acetyl-CoA carboxy lase mRNA were accounted for by changes in the transcription rate of t he acetyl-CoA carboxylase gene. These data support the hypothesis that T3, glucose, insulin, and glucagon play a role in mediating the effec ts of nutritional manipulation on transcription of acetyl-CoA carboxyl ase in liver. (C) 1997 Academic Press.