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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/E497    most recent 90642.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lombardi, A. Articles by Moreno, M. Search for Related Content PubMed PubMed Citation Articles by Lombardi, A. Articles by 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

¹Dipartimento delle Scienze Biologiche, Università degli Studi di Napoli "Federico II", Via Mezzocannone, Napoli; ²Dipartimento di Scienze della Vita, Seconda Università degli Studi di Napoli, Via Vivaldi, Caserta; and ³Dipartimento delle Scienze Biologiche ed Ambientali, Via Port'Arsa, Benevento, Italy

Submitted 30 July 2008 ; accepted in final form 23 December 2008

Triiodothyronine regulates energy metabolism and thermogenesis. Among triiodothyronine derivatives, 3,5-diiodo-L-thyronine (T₂) has been shown to exert marked effects on energy metabolism by acting mainly at the mitochondrial level. Here we investigated the capacity of T₂ to affect both skeletal muscle mitochondrial substrate oxidation and thermogenesis within 1 h after its injection into hypothyroid rats. Administration of T₂ 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. T₂ 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 T₂ stimulates mitochondrial fatty acid oxidation by activating several metabolic pathways, such as the fatty acid import/β-oxidation cycle/FADH₂-linked respiratory pathways, where fatty acids are imported. T₂ 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 T₂, and we propose that, by activating processes able to enhance mitochondrial fatty acid oxidation and thermogenesis, T₂ could play a role in protecting skeletal muscle against excessive intramyocellular lipid storage, possibly allowing it to avoid functional disorders.

adenosine 5'-monophosphate; thyroid hormone; mitochondria

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