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

doi:10.1039/C0MB00040J

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,^a Federica Cioffi,^b Daniela Glinni,^a Michele Ceccarelli,^ac Assunta Lombardi,^d Pieter de Lange,^b Angela Chambery,^b Valeria Severino,^b Antonia Lanni,^b Fernando Goglia^a and Maria Moreno*^a

Author affiliations

* Corresponding authors

^a Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy
E-mail: moreno@unisannio.it
Fax: +39 0824 23013
Tel: +39 0824 305124

^b Dipartimento di Scienze della Vita, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy

^c Bioinformatics Lab, IRGS Istituto di Ricerche Genetiche G. Salvatore, c/o BioGeM s.c.a r.l., Ariano Irpino (AV), Italy

^d Dipartimento delle Scienze Biologiche, Sezione Fisiologia, Università degli Studi di Napoli “Federico II”, Via Mezzocannone 8, 80134 Napoli, Italy

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.

Molecular BioSystems

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

Supplementary files

Article information

Download Citation

Permissions

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

Search articles by author

Spotlight

Advertisements