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      Target identification of the novel antiobesity agent tungstate in adipose tissue from obese rats.

      Proteomics
      Adipose Tissue, drug effects, Animals, Anti-Obesity Agents, pharmacology, Down-Regulation, Electrophoresis, Gel, Two-Dimensional, Lipid Metabolism, Male, Obesity, physiopathology, Proteome, analysis, Rats, Rats, Wistar, Signal Transduction, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tungsten Compounds, Up-Regulation, Weight Gain, physiology

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          Abstract

          Adipose tissue plays an active role in the development of obesity, and thus characterization of the molecular changes related to obesity in this tissue is a priority. Recently, we identified tungstate as a potent body weight reducing agent in obese animals, adipose tissue being one of the targets of its action. In this study a proteomics approach combining 2-DE and MS was used to identify proteins associated with obesity and targets of tungstate in white adipose tissue. Twenty-nine proteins were found differentially expressed between lean and diet-induced obese rats. Expression changes in transferrin, vimentin, vinculin, peroxiredoxins, Rho-GTP dissociation inhibitor, grifin, guanine deaminase and 3-phosphoglycerate dehydrogenase were associated here for the first time with obesity. Furthermore, tungstate treatment of obese rats reverted expression changes of 70% of the proteins modulated by obesity and another ten proteins were regulated by tungstate independently of the body weight reduction. The results suggest that the tungstate antiobesity effect can be mediated by the modulation of cellular structure, metabolism, redox state and signalling processes in adipose tissue. These findings open new avenues for the study of the aetiology of obesity and its treatment.

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