Short-Term Stimulation of Lipogenesis by 3,5-l-Diiodothyronine in Cultured Rat Hepatocytes

Short-term effects of 3,5-L-diiodothyronine (T2) on lipid biosynthesis were studied in cultured hepatocytes from hypothyroid rats. A comparison with the effects of T3was routinely carried out. After T2 addition to cell cultures, a distinct stimulation of fatty acid and cholesterol syntheses, measured as incorporation of [1- 14 C]acetate into these lipid fractions, was observed. The T2 dose-dependent effect on both metabolic pathways, already detectable at 10 8 -10 9 M, reached a 2-fold stimulationat10 5 MT2.Atthisconcentration,thestimulatory effect was evident withi n1ho f T2 addition to the hepatocytes and increased with time up to the length of the experimental period of 4 h. T2 stimulation of lipogenesis was also confirmed by incubating hepatocytes with [ 3 H]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 thatT2additiontothecellsproducedasignificantstimulation oftheincorporationofnewlysynthesizedfattyacidsintoboth neutral and polar lipids. By comparing the effects induced by T2 with those seen in the presence of T3, it appeared that T2 was able to mimic T3 effects. Experiments conducted in the presence of cycloheximide, a protein synthesis inhibitor, indicated that the T2 stimulatory effect on fatty acid and cholesterol synthesis was essentially independent of protein synthesis. (Endocrinology 146: 3959–3966, 2005)