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

Elena Silvestri, Federica Cioffi, Daniela Glinni, Michele Ceccarelli, Assunta Lombardi, Pieter De Lange, Angela Chambery, Valeria Severino, Antonia Lanni, Fernando Goglia, Maria Moreno

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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 HFD mitochondria vs. 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.

Original languageEnglish
Pages (from-to)2256-2271
Number of pages16
JournalMolecular BioSystems
Volume6
Issue number11
DOIs
Publication statusPublished - 1 Nov 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

Cite this

Silvestri, E., Cioffi, F., Glinni, D., Ceccarelli, M., Lombardi, A., De Lange, P., Chambery, A., Severino, V., Lanni, A., Goglia, F., & Moreno, M. (2010). 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. Molecular BioSystems, 6(11), 2256-2271. https://doi.org/10.1039/c0mb00040j