M C Carmona1, M Amigó, S Barceló-Batllori, M Julià, Y Esteban, S Moreno, R Gomis. 1. Laboratori de Diabetis i Obesitat, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic, Universitat de Barcelona, Villarroel 170, Barcelona, Spain. carmona@clinic.ub.es
Abstract
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 (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. 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.
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 (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. 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.
Authors: Marta Amigó-Correig; Sílvia Barceló-Batllori; Guadalupe Soria; Alice Krezymon; Alexandre Benani; Luc Pénicaud; Raúl Tudela; Anna Maria Planas; Eduardo Fernández; Maria del Carmen Carmona; Ramon Gomis Journal: PLoS One Date: 2012-07-03 Impact factor: 3.240