Pathways affected by 3,5-diiodo- l -thyronine in liver of high fat-fed rats: Evidence from two-dimensional electrophoresis, blue-native PAGE, and mass spectrometry
Abstract
3,5-Diiodo-l-thyronine (T2) powerfully reduces adiposity in rats fed a high-fat diet (HFD), stimulating (in the liver) fatty acid oxidation and mitochondrial uncoupling, and strongly counteracting steatosis, a condition commonly associated with diet-induced obesity. Proteomics offer unique possibilities for the investigation of changes in the levels and modifications of proteins. Here, combining 2D-E, mass spectrometry, and blue native (BN) PAGE, we studied how the subcellular hepatic phenotype responds to HFD and T2-treatment. By identifying differentially expressed proteins and analyzing their interrelation [using the Ingenuity Pathway Analysis (IPA) platform], we obtained an integrated view of the phenotypic/metabolic adaptations occurring in the liver proteome during HFD with or without T2-treatment. Interestingly, T2 counteracted several HFD-induced changes, mostly in mitochondria. BN-PAGE and subsequent in-gel activity analysis of OXPHOS complexes revealed a modified profile of individual complexes in HFDmitochondriavs. normal ones. This pattern was re-normalized in mitochondria from T2-treated HFD animals. These data indicate that in HFD rats, the effects of T2 on the liver proteome cause it to resemble that associated with a non-steatotic condition. The identified metabolic pathways (mainly at the mitochondrial level) may be responsible for the beneficial effects of T2 on liver adiposity and metabolism.
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Administration of 3,5-T2 to rats fed a high-fat diet leads to a liver proteome profile similar to that found in non-steatotic livers.
“More recently, it has been shown that the administration of 3,5-T2 to rats fed on a high-fat diet leads to a liver proteome profile similar to that found in non-steatotic livers, which is likely due to the hypolipidemic effect of this thyroid hormone metabolite (Silvestri et al. 2010).”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Silvestri et al. 2010
3,5-T2 exerts short-term beneficial metabolic effects on rats subjected to a high-fat diet.
“In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Silvestri et al. 2010
3,5-T2 prevents liver steatosis in animals fed a high-fat diet.
“Recent data have demonstrated the beneficial effects of 3,5-T2 in preventing liver steatosis in animals fed on a high-fat diet (Silvestri et al. 2010), and these authors claimed that 3,5-T2 exerts non-genomic effects.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Silvestri et al. 2010
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Padron, A. S., Neto, R. A. L., Pantaleão, T. U., de Souza dos Santos, M. C., Araujo, R. L., de Andrade, B. M., da Silva Leandro, M., de Castro, J. P. S. W., Ferreira, A. C. F., & de Carvalho, D. P. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0502 · Cited by 69 · see citing works
- Authors
- Silvestri, E., Cioffi, F., Glinni, D., Ceccarelli, M., Lombardi, A., de Lange, P., Chambery, A., Severino, V., Lanni, A., Goglia, F., & Moreno, M.
- Affiliations
- University of Sannio (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- University of Naples Federico II (IT)
- Dipartimento di Scienze della Vita, Seconda Università di Napoli b , Via Vivaldi 43, 81100 Caserta Italy
- Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio a , Via Port'Arsa 11, 82100 Benevento Italy moreno@unisannio.it +39 0824 23013 +39 0824 305124
- ORCID
- Venue
- Molecular BioSystems
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-09-16
- Volume
- 6
- Issue
- 11
- Pages
- 2256-2271
- ISSN
- 1742-2051 (ISSN-L)
- 1742-206X
- OpenAlex
- W2143705805
- Cited by
- 34
- References
- 5
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 3 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 7 · 2013: 2 · 2012: 1
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular BioSystems (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- 3,5-diiodo-L-thyronine, high-fat diet, liver proteome, hepatic steatosis, mitochondrial uncoupling, fatty acid oxidation, OXPHOS complexes, mitochondrial function, diet-induced obesity, metabolic pathways
- MeSH terms
- Animals, Cytoplasm, Dietary Fats, Diiodothyronines, Feeding Behavior, Liver, Mitochondria, Liver, Nuclear Proteins, Staining and Labeling, Triglycerides, Electrophoresis, Gel, Two-Dimensional, Signal Transduction, Rats, Wistar, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Computational Biology, Mitochondrial Proteins, Proteomics, Lipid Metabolism, Rats
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