Dual effects of sodium tungstate on adipocyte biology: inhibition of adipogenesis and stimulation of cellular oxygen consumption

Objective: 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. Methods: 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. Results: 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 (PPAR gamma)) was reduced by sodium tungstate, whereas C/EBP beta isoform LIP expression level was increased. TG accumulation and changes in C/EBP beta 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. Conclusions: 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. International Journal of Obesity (2009) 33, 534-540; doi:10.1038/ijo.2009.34; published online 3 March 2009