title: 3,5-Diiodo-L-thyronine prevents high-fat-diet-induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations.
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.
authors.affiliation: Dipartimento di Scienze per la Biologia, la Geologia e l'Ambiente, Università degli Studi del Sannio, via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Elena
authors.initials: E
authors.lastname: Silvestri
authors.forename: Rita
authors.initials: R
authors.lastname: De Matteis
authors.forename: Pieter
authors.initials: P
authors.lastname: de Lange
authors.forename: Assunta
authors.initials: A
authors.lastname: Lombardi
authors.forename: Daniela
authors.initials: D
authors.lastname: Glinni
authors.forename: Rosalba
authors.initials: R
authors.lastname: Senese
authors.forename: Federica
authors.initials: F
authors.lastname: Cioffi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Salzano
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Antonia
authors.initials: A
authors.lastname: Lanni
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D004104:Diiodothyronines / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000737:chemistry / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000145:classification; D018482:Muscle, Skeletal / Q000378:metabolism*; D000070780:Perilipin-2; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D004041:Dietary Fats; D004104:Diiodothyronines; D051275:Glucose Transporter Type 4; D007328:Insulin; D008055:Lipids; D008565:Membrane Proteins; D000070780:Perilipin-2; C495694:Slc2a4 protein, rat; D014280:Triglycerides; C030103:3,5-diiodothyronine; D051057:Proto-Oncogene Proteins c-akt