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Tungstate Decreases Weight Gain and Adiposity in Obese Rats through Increased Thermogenesis and Lipid Oxidation

Endocrinology and Nutrition Unit (M.C., H.C., I.C., S.B.-B., R.G.), Hospital Clínic Universitari, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Faculty of Medicine, and Institut de Recerca Biomèdica de Barcelona (J.J.G.), Parc Científic de Barcelona, University of Barcelona; and Pharmacology and Toxicology Department (J.S.), Institut d’Investigacions Biomèdiques de Barcelona, 08036 Barcelona, Spain

Address all correspondence and requests for reprints to: Ramon Gomis, Endocrinology and Nutrition Unit, Hospital Clínic Universitari, Villarroel 170, 08036 Barcelona, Spain. E-mail: rgomis{at}clinic.ub.es.

The increasing worldwide incidence of obesity and the limitations of current treatments raise the need for finding novel therapeutic approaches to treat this disease. The purpose of the current study was first to investigate the effects of tungstate on body weight and insulin sensitivity in a rat model of diet-induced obesity. Second, we aimed to gain insight into the molecular mechanisms underlying its action. Oral administration of tungstate significantly decreased body weight gain and adiposity without modifying caloric intake, intestinal fat absorption, or growth rate in obese rats. Moreover, the treatment ameliorated dislipemia and insulin resistance of obese rats. These effects were mediated by an increase in whole-body energy dissipation and by changes in the expression of genes involved in the oxidation of fatty acids and mitochondrial uncoupling in adipose tissue. Furthermore, treatment increased the number of small adipocytes with a concomitant induction of apoptosis. Our results indicate that tungstate treatment may provide the basis for a promising novel therapy for obesity.

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