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Obesity-Induced P53 Activation in Insulin-Dependent and Independent Tissues Is Inhibited by Beta-Adrenergic Agonist in Diet-Induced Obese Rats Publisher Pubmed



Zand H1 ; Homayounfar R2 ; Cheraghpour M1 ; Jedditehrani M3 ; Ghorbani A4 ; Pourvali K1 ; Soltani SR5
Authors
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Authors Affiliations
  1. 1. Department of Cellular and Molecular Nutrition, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, P.O. Box 19395-4741, Tehran, Iran
  2. 2. Department of Biochemistry, Fasa University of Medical Sciences, Fasa, Iran
  3. 3. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
  4. 4. Faculty of Nutrition and Diet Therapy, Department of Cellular and Molecular Nutrition, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran

Source: Life Sciences Published:2016


Abstract

Aims The purpose of this study was to assay the role of beta-adrenergic receptor signaling in the regulation of obesity-induced p53 in high fat feeding obese rats. Main methods The role of beta-adrenergic receptor/cyclic AMP in the regulation of p53 and its downstream mediators was evaluated by western blot and real-time quantitative RT-PCR among diet induced rats. Key findings Beta-adrenergic receptor agonist, isoproterenol, and an adenylate cyclase activator, forskolin, at a single dose significantly reduced insulin resistance consistent with a decrease in total and phospho-p53 levels in insulin and non-insulin metabolic target tissues. The decrease of p53 signaling was consistent with the elevation of AKT and subsequent activation. Obese rats exposed to fasting also exhibited improvement in insulin action despite a slight effect on p53 level. Significance Results of the present study obviously showed that beta-adrenergic receptor agonist/cAMP prevented obesity-induced p53 activation. Although this effect in metabolic insulin target tissues tempted us to consider them as insulin sensitizers in obesity-related diabetes, p53 inhibition in non-insulin target tissues warned about the impairment of anti-cancer mechanisms in obese subjects. © 2016 Elsevier Inc. All rights reserved.