The effects of nutrients and hormones on transcriptional and post-transcriptional regulation of acetyl-CoA carboxylase in rat liver were investigated following a cDNA cloning. After refeeding a carbohydrate/protein diet to fasted rats, the transcriptional rate was increased 2.5-fold in only 1 h. The mRNA concentration reached a maximal level of 9-12-fold increase in 8-16 h, and the enzyme induction increased 10-fold in 48 h. By a carbohydrate diet without protein, the transcriptional rate, mRNA concentration and enzyme induction were similarly increased to the levels in the carbohydrate/protein diet. It appears that protein feeding is not necessary to induce acetyl-CoA carboxylase. Corn oil feeding decreased the transcriptional rate. In diabetic rats, the transcriptional rate, mRNA concentration and enzyme induction were very low in comparison with the normal. After insulin treatment, the transcriptional rate was increased 2-fold (the normal level) in 2 h in diabetic rats. By fructose feeding to diabetic rats, the transcriptional rate and mRNA concentration were increased similarly to the levels reached by insulin treatment, while the enzyme induction was increased by only 60%. Thus, it is suggested that insulin is importantly involved in the transcription and also translation of acetyl-CoA carboxylase. On the other hand, triiodothyronine treatment increased the mRNA and enzyme levels in diabetic and normal rats, and somewhat increased the transcriptional rate only in diabetic rats. Triiodothyronine appears to stabilize the mRNA besides having an insulin-like action in acetyl-CoA carboxylase transcription.The first step in the pathway of long-chain fatty acid biosynthesis is mediated by acetyl-CoA carboxylase, which catalyzes the carboxylation of acetyl-CoA to form malonylCoA. It is known that acetyl-CoA carboxylase plays a critical role in the regulation of this biosynthetic process. It is also known that the cellular content of the enzyme varies with different nutritional, hormonal and genetic conditions, and the catalytic activity of the enzyme is modulated by a number of metabolites and by phosphorylation/dephosphorylation of the enzyme [l, 21. However, very little information on regulation of gene expression of acetyl-CoA carboxylase is available at the present time [3-51. Pape et al. [4] reported that the amounts of acetyl-CoA carboxylase mRNA in liver and epididymal adipose tissue of rats were very low in fasted and diabetic states, and increased by refeeding a fat-free diet and by insulin treatment, respectively. The mRNA amounts of acetyl-CoA carboxylase corresponded to changes in the activity and amount of the enzyme. Takai et al.[5] reported the developmental changes of the content of acetyl-CoA carboxylase mRNA in chicken liver. However, the transcriptional and post-transcriptional regulation of acetyl-CoA carboxylase is still not clear. In the present study, we have isolated cDNA clones for rat liver acetyl-CoA carboxylase and investigated the transcriptional and post-transcriptional regulation of ...