title: Obesity-induced p53 activation in insulin-dependent and independent tissues is inhibited by beta-adrenergic agonist in diet-induced obese rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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, Tehran, Iran. Electronic address: hamid_zand@sbmu.ac.ir.
authors.forename: Hamid
authors.initials: H
authors.lastname: Zand
authors.affiliation: Department of Biochemistry, Fasa University of Medical Sciences, Fasa, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Homayounfar
authors.affiliation: 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, Tehran, Iran.
authors.forename: Makan
authors.initials: M
authors.lastname: Cheraghpour
authors.affiliation: Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.affiliation: Faculty of Nutrition and Diet Therapy, Department of Cellular and Molecular Nutrition, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arman
authors.initials: A
authors.lastname: Ghorbani
authors.affiliation: 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, Tehran, Iran.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Pourvali
authors.affiliation: Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Sama Reza
authors.initials: SR
authors.lastname: Soltani
mesh_terms: D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D016159:Tumor Suppressor Protein p53; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol
keywords: Beta-adrenergic receptors; Cyclic AMP; Insulin resistance; Obesity- related cancer; p53