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.

3,5-Diiodo-L-thyronine prevents high-fat-diet-induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations.

DE MATTEIS, RITA;
2011

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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2512714
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 69
  • ???jsp.display-item.citation.isi??? 66
social impact