Regulation of hepatic fatty acid-synthesizing enzymes of diabetic animals by thyroid-hormone

Subcutaneous administration of l-triiodothyronine (T₃) to diabetic rats restored hepatic acetyl-CoA carboxylase and fatty acid synthetase enzymes to normal levels. T₃ stimulated the fatty acid-synthesizing enzymes of diabetic animals by two different mechanisms. Between 4 and 12 h after T₃ administration, carboxylase and synthetase increased slowly, after which both the enzyme activities increased at faster rate. Carboxylase and synthetase induction could be inhibited by cycloheximide or actinomycin D during the first 12 h. The incorporation of [¹⁴C]pantothenate into the fatty acid synthetase during 4–12 h followed the same pattern as the development of the enzyme activity. Moreover, liver supernatants from T₃-treated diabetic rats were able to compete with pure fatty acid synthetase for antibody binding sites, the degree of competition increased with increasing period of T₃ treatment. The results suggest that enzymatically inactive precursors of synthetase in the diabetic livers are converted to enzymatically active enzyme as a result of T₃ treatment. The second part of T₃-mediated stimulation (24 to 72 h following T₃ treatment) was inhibited by cycloheximide and actinomycin D. Antibody-antigen titration and measurement of rate of protein synthesis suggest that the increased activity of hepatic synthetase is due to enhanced synthesis of the enzyme for that period. These results indicate that T₃ might play a significant regulatory role in hepatic fatty acid synthesis.