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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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

Fingerprint

Thyronines
Native Polyacrylamide Gel Electrophoresis
High Fat Diet
Electrophoresis
Mass Spectrometry
Fats
Liver
Mitochondria
Adiposity
Proteome
Metabolic Networks and Pathways
Proteomics
Proteins
Fatty Acids
Obesity
Gels
Diet
Phenotype

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

Cite this

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

In: Molecular BioSystems, Vol. 6, No. 11, 01.11.2010, p. 2256-2271.

Research output: Contribution to journalArticle

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, vol. 6, no. 11, pp. 2256-2271. https://doi.org/10.1039/c0mb00040j
Silvestri, Elena ; Cioffi, Federica ; Glinni, Daniela ; Ceccarelli, Michele ; Lombardi, Assunta ; De Lange, Pieter ; Chambery, Angela ; Severino, Valeria ; Lanni, Antonia ; Goglia, Fernando ; Moreno, Maria. / 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. In: Molecular BioSystems. 2010 ; Vol. 6, No. 11. pp. 2256-2271.
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