Dual effects of sodium tungstate on adipocyte biology: inhibition of adipogenesis and stimulation of cellular oxygen consumption
- 3 March 2009
- journal article
- Published by Springer Science and Business Media LLC in International Journal of Obesity
- Vol. 33 (5), 534-540
- https://doi.org/10.1038/ijo.2009.34
Abstract
We have recently shown the in vivo anti-obesity effects of sodium tungstate. In this study, we investigate the in vitro effects of sodium tungstate on adipocyte differentiation and function. 3T3-F442A cells were allowed to differentiate in the presence of sodium tungstate, and were analyzed for triglyceride (TG) accumulation, adipocyte differentiation and mitochondrial oxygen consumption. Sodium tungstate treatment of adipose cells decreased TG accumulation and adipocyte differentiation. Expression of key genes for adipocyte function (aP2, ACC, fatty acid synthase (FAS) and lipoprotein lipase (LPL)) and differentiation (CCAAT enhancer-binding protein (C/EBP)alpha and peroxisome proliferator-activated receptor gamma (PPARgamma)) was reduced by sodium tungstate, whereas C/EBPbeta isoform LIP expression level was increased. TG accumulation and changes in C/EBPbeta expression were partially recovered by inactivating the erk1/2 pathway. Finally, tungstate treatment increased the oxygen consumption of adipose cells without changes in the expression of oxidative genes. Sodium tungstate inhibits adipocyte differentiation by promoting the translation of LIP, a master dominant-negative regulator of this process, and regulates the mitochondrial oxygen consumption of adipose cells. These effects contribute to the anti-obesity activity of sodium tungstate and confirm its potential as a powerful alternative for the treatment of obesity.Keywords
This publication has 41 references indexed in Scilit:
- Integration of DIGE and Bioinformatics Analyses Reveals a Role of the Antiobesity Agent Tungstate in Redox and Energy Homeostasis Pathways in Brown Adipose TissueMolecular & Cellular Proteomics, 2008
- Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cellsBiochemical and Biophysical Research Communications, 2007
- DocetaxelDrugs, 2007
- Transcriptional control of adipocyte formationCell Metabolism, 2006
- Molybdenum and tungsten enzymes: the xanthine oxidase familyCurrent Opinion in Chemical Biology, 2006
- Mitochondrial AKAP121 Links cAMP and src Signaling to Oxidative MetabolismMolecular Biology of the Cell, 2006
- Adipogenesis: cellular and molecular aspectsBest Practice & Research Clinical Endocrinology & Metabolism, 2005
- Mo and W bis-MGD enzymes: nitrate reductases and formate dehydrogenasesJBIC Journal of Biological Inorganic Chemistry, 2004
- Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3‐kinase activationJournal of Neurochemistry, 2003
- Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 DiabetesPublished by Elsevier BV ,2003