Short-term stimulation of lipogenesis by 3,5-L-diiodothyronine in cultured rat hepatocytes

Short-term effects of 3,5-L-diiodothyronine (T-2) on lipid biosynthesis were studied in cultured hepatocytes from hypothyroid rats. A comparison with the effects of T-3 was routinely carried out. After T-2 addition to cell cultures, a distinct stimulation of fatty acid and cholesterol syntheses, measured as incorporation of [1-C-14] acetate into these lipid fractions, was observed. The T-2 dose-dependent effect on both metabolic pathways, already detectable at 10(-8)-10(-9) M, reached a 2-fold stimulation at 10(-5) MT2. At this concentration, the stimulatory effect was evident within 1 h of T-2 addition to the hepatocytes and increased with time up to the length of the experimental period of 4 h. T-2 stimulation of lipogenesis was also confirmed by incubating hepatocytes with [H-3] H2O, used as an independent index of lipogenic activity. The effects of T2 are rather specific as 3,3',5,5'-tetraiodo-D-thyronine and 3,5-diiodo-L-tyrosine were practically ineffective on both fatty acid and cholesterol synthesis. Analysis of various lipid fractions showed that T-2 addition to the cells produced a significant stimulation of the incorporation of newly synthesized fatty acids into both neutral and polar lipids. By comparing the effects induced by T-2 with those seen in the presence of T-3, it appeared that T-2 was able to mimic T-3 effects. Experiments conducted in the presence of cycloheximide, a protein synthesis inhibitor, indicated that the T-2 stimulatory effect on fatty acid and cholesterol synthesis was essentially independent of protein synthesis.