1. Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats stimulates bioenergetic parameters in liver mitochondria.
- Author
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Cavallo, Alessandro, Taurino, Federica, Damiano, Fabrizio, Siculella, Luisa, Sardanelli, Anna, and Gnoni, Antonio
- Subjects
HYPOTHYROIDISM diagnosis ,HYPOTHYROIDISM treatment ,LIVER mitochondria ,THYRONINES ,FATTY acid oxidation ,LABORATORY rats ,THERAPEUTICS - Abstract
The role of 3,5-diiodo-L-thyronine (T), initially considered only a 3,3′,5-triiodo-L-thyronine (T) catabolite, in the bioenergetic metabolism is of growing interest. In this study we investigated the acute effects (within 1 h) of T administration to hypothyroid rats on liver mitochondria fatty acid uptake and β-oxidation rate, mitochondrial efficiency (by measuring proton leak) and mitochondrial oxidative damage (by determining HO release). Fatty acid uptake into mitochondria was measured assaying carnitine palmitoyl transferase (CPT) I and II activities, and fatty acid β-oxidation using palmitoyl-CoA as a respiratory substrate. Mitochondrial fatty acid pattern was defined by gas-liquid chromatography. In hypothyroid + T 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 β-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-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 administration decreases mitochondrial oxidative stress as determined by lower HO production. We conclude that in rat liver mitochondria T acutely enhances the rate of fatty acid β-oxidation, and the activity of the downstream respiratory chain. The T-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 to reduce adiposity, dyslipidemia and to prevent liver steatosis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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