A Functional Leptin System Is Essential for Sodium Tungstate Antiobesity Action

Abstract

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.

Comparison of urine toxic metals concentrations in athletes and in sedentary subjects living in the same area of Extremadura (Spain)

“…The major sources of Cd exposure are food (up to several hundred g/ day) for the non-smoking general population, and tobacco for smokers. Tungsten (W), is a transition metal used extensively for Wlaments for electric lamps, and television tubes with no recognized physiologic role and very limited available information of its toxicological eVects (Goldoni et al 2004;Koutsospyros et al 2006;Strigul et al 2010), although, in recent years W compounds have been proposed as anti-diabetic and anti-obesity agents (BarceloBatllori et al 2005;Canals et al 2009). Tellurium (Te) is used in semiconductor device fabrication (Schiar et al 2009), and can inhibit the activity of selenium dependent glutathione peroxidase, which can lead to an exacerbation of intracellular oxidative stress (Garberg et al 1999).…”

Anti-Obesity Sodium Tungstate Treatment Triggers Axonal and Glial Plasticity in Hypothalamic Feeding Centers

“…1C). The effects of sodium tungstate observed here have been widely described in different models of obesity [14], [15], [19], [27].…”

“…We have previously demonstrated that sodium tungstate regulated neuropeptide gene expression in the hypothalamus and neural cells [14], [28]. Therefore, protein expression levels would also be modified using this treatment.…”

“…In aqueous solution it acts as a phosphatase inhibitor, changing the catalytic activity of these enzymes [12], [13]. Several animal studies have highlighted the possible role of sodium tungstate in regulating different aspects of energy homeostasis in rodents [14], [15]. We have demonstrated that sodium tungstate also plays an important role in the hypothalamus, activating leptin’s pathway [16] and regulating the gene expression of the main neuropeptides involved in the control of food intake: neuropeptide Y (NPY), agouti related peptide (AgRP) and proopiomelanocortin (POMC) [14].…”

“…Several animal studies have highlighted the possible role of sodium tungstate in regulating different aspects of energy homeostasis in rodents [14], [15]. We have demonstrated that sodium tungstate also plays an important role in the hypothalamus, activating leptin’s pathway [16] and regulating the gene expression of the main neuropeptides involved in the control of food intake: neuropeptide Y (NPY), agouti related peptide (AgRP) and proopiomelanocortin (POMC) [14]. Furthermore, it has been described that sodium tungstate can inactivate glycogen synthase-3β (GSK3β) (a kinase that hyperphosphorylates tau in Alzheimer’s disease) in neuroblastoma cells and in the rat cerebral cortex [17], showing its involvement in other neurological areas.…”