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3,5‐Diiodo‐L‐thyronine prevents high‐fat‐diet‐induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations
Author(s) -
Moreno Maria,
Silvestri Elena,
De Matteis Rita,
Lange Pieter,
Lombardi Assunta,
Glinni Daniela,
Senese Rosalba,
Cioffi Federica,
Salzano Anna Maria,
Scaloni Andrea,
Lanni Antonia,
Goglia Fernando
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-181982
Subject(s) - endocrinology , medicine , thyronine , glycolysis , phosphofructokinase , skeletal muscle , insulin resistance , insulin , hormone , chemistry , triiodothyronine , metabolism
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.—Moreno, M., Silvestri, E., De Matteis, R., de Lange, P., Lombardi, A., Glinni, D., Senese, R., Cioffi, F., Salzano, A. M., Scaloni, A., Lanni, A., Goglia, F. 3,5‐Diiodo‐L‐thyronine prevents high‐fat diet‐induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations. FASEB J. 25, 3312–3324 (2011). www.fasebj.org