3,5‐Diiodo‐L‐thyronine prevents high‐fat‐diet‐induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations
Open accessAbstract
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
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3,5-T2 prevents insulin resistance in skeletal muscle of rats fed a high-fat diet and increases GLUT4 protein expression and insulin-induced Akt phosphorylation.
“These results are in accordance with the finding that 3,5-T2 prevents insulin resistance in the skeletal muscle of rats fed on a high-fat diet and increases GLUT4 (SLC2A4) protein expression and insulin-induced Akt phosphorylation (Moreno et al. 2011).”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Moreno et al. 2011
Prolonged high-fat diet exposure gradually decreases the early oxidative adaptation, ultimately resulting in fiber type shift toward glycolytic fibers and eventual development of insulin resistance.
“This adaptation, however, gradually decreases with prolonged high-fat diet exposure, ultimately resulting in fiber type shift towards glycolytic fibers and the eventual development of insulin resistance [8, 9].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [8]
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- Authors
- 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.
- Affiliations
- Dipartimento di Scienze per la Biologia, la Geologia e l'Ambiente Università degli Studi del Sannio Benevento Italy
- University of Sannio (IT)
- Dipartimento di Scienze Biomolecolari Università di Urbino Carlo Bo Urbino Italy
- Dipartimento di Scienze della Vita Seconda Università degli Studi di Napoli Caserta Italy
- University of Naples Federico II (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Istituto per il Sistema Produzione Animale in Ambiente Mediterraneo (IT)
- Corresponding author
- Goglia, Fernando
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2011-06-13
- Volume
- 25
- Issue
- 10
- Pages
- 3312-3324
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2124771971
- Cited by
- 71
- References
- 49
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 8 · 2018: 10 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 5 · 2012: 5
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Funders
- Regione Campania
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- 3,5-diiodo-L-thyronine, insulin resistance, high-fat diet, skeletal muscle, type 2 diabetes, obesity, thyroid hormone analogs, fatty acid translocase, glucose transporter 4, Akt phosphorylation, muscle fiber composition, glycolytic metabolism, phosphofructokinase, insulin signaling, gastrocnemius, adipogenesis
- MeSH terms
- Perilipin-2, Animals, Dietary Fats, Diiodothyronines, Gene Expression Regulation, Insulin, Insulin Resistance, Lipids, Male, Membrane Proteins, Sarcolemma, Triglycerides, Signal Transduction, Rats, Wistar, Muscle, Skeletal, Muscle Fibers, Skeletal, CD36 Antigens, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 4, Rats
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