| 19116374 |
Lombardi A, de Lange P, Silvestri E, Busiello RA, Lanni A, Goglia F, Moreno M: 3,5-Diiodo-L-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement. Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E497-502. Epub 2008 Dec 30.
Triiodothyronine regulates energy metabolism and thermogenesis. Among triiodothyronine derivatives, 3,5-diiodo-l-thyronine (T (2)) has been shown to exert marked effects on energy metabolism by acting mainly at the mitochondrial level. Here we investigated the capacity of T (2) to affect both skeletal muscle mitochondrial substrate oxidation and thermogenesis within 1 h after its injection into hypothyroid rats. Administration of T (2) induced an increase in mitochondrial oxidation when palmitoyl-CoA (+104%), palmitoylcarnitine (+80%), or succinate (+30%) was used as substrate, but it had no effect when pyruvate was used. T (2) was able to 1) activate the AMPK-ACC-malonyl-CoA metabolic signaling pathway known to direct lipid partitioning toward oxidation and 2) increase the importing of fatty acids into the mitochondrion. These results suggest that T (2) stimulates mitochondrial fatty acid oxidation by activating several metabolic pathways, such as the fatty acid import/beta-oxidation cycle/FADH (2)-linked respiratory pathways, where fatty acids are imported. T (2) also enhanced skeletal muscle mitochondrial thermogenesis by activating pathways involved in the dissipation of the proton-motive force not associated with ATP synthesis ("proton leak"), the effect being dependent on the presence of free fatty acids inside mitochondria. We conclude that skeletal muscle is a target for T (2), and we propose that, by activating processes able to enhance mitochondrial fatty acid oxidation and thermogenesis, T (2) could play a role in protecting skeletal muscle against excessive intramyocellular lipid storage, possibly allowing it to avoid functional disorders. |
1(0,0,0,1) |