PMID:21670063

Citation	Moreno, M, Silvestri, E, De Matteis, R, de Lange, P, Lombardi, A, Glinni, D, Senese, R, Cioffi, F, Salzano, AM, Scaloni, A, Lanni, A and Goglia, F (2011) 3,5-Diiodo-L-thyronine prevents high-fat-diet-induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations. FASEB J. 25:3312-24
Abstract	The worldwide prevalence of obesity-associated pathologies, including type 2 diabetes, requires thorough investigation of mechanisms and interventions. Recent studies have highlighted thyroid hormone analogs and derivatives as potential agents able to counteract such pathologies. In this study, in rats receiving a high-fat diet (HFD), we analyzed the effects of a 4-wk daily administration of a naturally occurring iodothyronine, 3,5-diiodo-L-thyronine (T2), on the gastrocnemius muscle metabolic/structural phenotype and insulin signaling. The HFD-induced increases in muscle levels of fatty acid translocase (3-fold; P<0.05) and TGs (2-fold, P<0.05) were prevented by T2 (each; P<0.05 vs. HFD). T2 increased insulin-stimulated Akt phosphorylation levels (∼2.5-fold; P<0.05 vs. HFD). T2 induced these effects while sparing muscle mass and without cardiac hypertrophy. T2 increased the muscle contents of fast/glycolytic fibers (2-fold; P<0.05 vs. HFD) and sarcolemmal glucose transporter 4 (3-fold; P<0.05 vs. HFD). Adipocyte differentiation-related protein was predominantly present within the slow/oxidative fibers in HFD-T2. In T2-treated rats (vs. HFD), glycolytic enzymes and associated components were up-regulated (proteomic analysis, significance limit: 2-fold; P<0.05), as was phosphofructokinase activity (by 1.3-fold; P<0.05), supporting the metabolic shift toward a more glycolytic phenotype. These results highlight T2 as a potential therapeutic approach to the treatment of diet-induced metabolic dysfunctions.
Links	PubMed Online version:10.1096/fj.11-181982
Keywords	Animals; Antigens, CD36/metabolism; Dietary Fats/administration & dosage; Dietary Fats/adverse effects; Diiodothyronines/metabolism; Diiodothyronines/pharmacology; Gene Expression Regulation/physiology; Glucose Transporter Type 4/metabolism; Insulin/metabolism; Insulin Resistance/physiology; Lipids/chemistry; Lipids/physiology; Male; Membrane Proteins/genetics; Membrane Proteins/metabolism; Muscle Fibers, Skeletal/classification; Muscle, Skeletal/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Rats; Rats, Wistar; Sarcolemma/metabolism; Signal Transduction; Triglycerides/metabolism
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