Obesity-induced p53 activation in insulin-dependent and independent tissues is inhibited by beta-adrenergic agonist in diet-induced obese rats

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• 作者：Hamid Zand^a ; ¹ ; ^{hamid_zand@sbmu.ac.ir" class="auth_mail" title="E-mail the corresponding author} ; Reza Homayounfar^b ; ¹ ; Makan Cheraghpour^a ; Mahmood Jeddi-Tehrani^c ; Arman Ghorbani^d ; Katayoun Pourvali^a ; Sama Reza Soltani^e
• 关键词：Beta-adrenergic receptors ; Cyclic AMP ; p53 ; Insulin resistance ; Obesity- related cancer
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：147
• 期：Complete
• 页码：103-109
• 全文大小：739 K

文摘

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.

3">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.