Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats stimulates bioenergetic parameters in liver mitochondria

摘要

The role of 3,5-diiodo-L-thyronine (T-2), initially considered only a 3,3',5-triiodo-L-thyronine (T-3) catabolite, in the bioenergetic metabolism is of growing interest. In this study we investigated the acute effects (within 1 h) of T-2 administration to hypothyroid rats on liver mitochondria fatty acid uptake and beta-oxidation rate, mitochondrial efficiency (by measuring proton leak) and mitochondrial oxidative damage (by determining H2O2 release). Fatty acid uptake into mitochondria was measured assaying carnitine palmitoyl transferase (CPT) I and II activities, and fatty acid beta-oxidation using palmitoyl-CoA as a respiratory substrate. Mitochondrial fatty acid pattern was defined by gas-liquid chromatography. In hypothyroid + T-2 vs hypothyroid rats we observed a raise in the serum level of nonesterified fatty acids (NEFA), in the mitochondrial CPT system activity and in the fatty acid beta-oxidation rate. A parallel increase in the respiratory chain activity, mainly from succinate, occurs. When fatty acids are chelated by bovine serum albumin, a T-2-induced increase in both state 3 and state 4 respiration is observed, while, when fatty acids are present, mitochondrial uncoupling occurs together with increased proton leak, responsible for mitochondrial thermogenesis. T-2 administration decreases mitochondrial oxidative stress as determined by lower H2O2 production. We conclude that in rat liver mitochondria T-2 acutely enhances the rate of fatty acid beta-oxidation, and the activity of the downstream respiratory chain. The T-2-induced increase in proton leak may contribute to mitochondrial thermogenesis and to the reduction of oxidative stress. Our results strengthen the previously reported ability of T-2 to reduce adiposity, dyslipidemia and to prevent liver steatosis.