INCREASED HEPATIC PYRUVATE-DEHYDROGENASE KINASE-ACTIVITY IN FED HYPERTHYROID RATS - STUDIES IN-VIVO AND WITH CULTURED-HEPATOCYTES

Experimental hyperthyroidism induced by the administration of tri-iodo thyronine (T3; 100 mu g/100 g body wt; 3 days) increased plasma non-es terified fatty acids in the fed state in the rat. At the same time, he patic PDH kinase responded with a persistent (1.6-fold) increase in ac tivity. The exposure of hepatocytes from fed euthyroid rats to T3 (100 nM) in culture for 21 h increased PDH kinase activity to an extent co mparable to that observed in vivo in response to hyperthyroidism. The in vitro increase in PDH kinase activity was suppressed by insulin (10 0 mu U/ml) and by inhibition of mitochondrial fatty acid oxidation. Th e results demonstrate a direct hepatic action of T3 to increase PDH ki nase activity, which is mediated by intramitochondrial fatty acyl-CoA or a product of beta-oxidation, and facilitated by hepatic insulin res istance.