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A Functional Leptin System Is Essential for Sodium Tungstate Antiobesity Action

Diabetes and Obesity Laboratory (I.C., M.C.C., M.A., A.Ba., R.G.), Endocrinology and Nutrition Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic de Barcelona, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (M.A., R.G.), and Department of Neurochemistry and Neuropharmacology (A.Bo.), Institut d’Investigacions Biomèdiques de Barcelona (Consejo Superior de Investigacíones Científicas), Institut d’Investigacions Biomèdiques August Pi i Sunyer, E-08036 Barcelona, Spain

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

Sodium tungstate is a novel agent in the treatment of obesity. In diet-induced obese rats, it is able to reduce body weight gain by increasing energy expenditure. This study evaluated the role of leptin, a key regulator of energy homeostasis, in the tungstate antiobesity effect. Leptin receptor-deficient Zucker fa/fa rats and leptin-deficient ob/ob mice were treated with tungstate. In lean animals, tungstate administration reduced body weight gain and food intake and increased energy expenditure. However, in animals with deficiencies in the leptin system, treatment did not modify these parameters. In ob/ob mice in which leptin deficiency was restored through adipose tissue transplantation, treatment restored the tungstate-induced body weight gain and food intake reduction as well as energy expenditure increase. Furthermore, in animals in which tungstate administration increased energy expenditure, changes in the expression of key genes involved in brown adipose tissue thermogenesis were detected. Finally, the gene expression of the hypothalamic neuropeptides, Npy, Agrp, and Cart, involved in the leptin regulation of energy homeostasis, was also modified by tungstate in a leptin-dependent manner. In summary, the results indicate that the effectiveness of tungstate in reducing body weight gain is completely dependent on a functional leptin system.