title: Growth hormone is necessary for the p53-mediated, obesity-induced insulin resistance in male C57BL/6J x CBA mice.
abstract: Insulin resistance is a key marker of both obesity and GH excess. The purpose of the study was to assess the role of GH on p53-mediated insulin resistance of male mice with obesity due to a high-fat diet. C57BL/6J × CBA male mice fed on a high-fat diet (Obe) were studied; male mice fed a normal diet (Lean) or transgenic mice for bovine GH under the same genetic background (Acro) served as controls. The convergence of p53 and GH pathways was evaluated by Western blot. Obe mice had insulin resistance, which was sustained by a selective increased expression of p53 in adipose tissue. Normal insulin sensitivity was restored, and adipose p53 expression normalized when the GH pathway was blocked. Only the adipose p53 expression was sensitive to the GH blockage, which occurred through the p38 pathway. Adipose tissue of Obe mice had a coordinate overexpression of suppressors of cytokine signal 1-3 and signal transducers and activators of transcription-1, -3, and -5b, not different from that of Acro mice, suggesting an increased sensitivity of adipose tissue to GH. On the contrary, Lean mice were unaffected by changes of GH action. GH seems to be necessary for the increased adipose p53 expression and for insulin resistance of obese mice.
authors.affiliation: MD, PhD, Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124 Pisa, Italy. fbogazzi@hotmail.com; or fausto.bogazzi@med.unipi.it.
authors.forename: Fausto
authors.initials: F
authors.lastname: Bogazzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Raggi
authors.forename: Dania
authors.initials: D
authors.lastname: Russo
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
authors.forename: Chiara
authors.initials: C
authors.lastname: Sardella
authors.forename: Claudio
authors.initials: C
authors.lastname: Urbani
authors.forename: Martina
authors.initials: M
authors.lastname: Lombardi
authors.forename: Luca
authors.initials: L
authors.lastname: Manetti
authors.forename: Isabella
authors.initials: I
authors.lastname: Lupi
authors.forename: Jan
authors.initials: J
authors.lastname: Tornell
authors.forename: Enio
authors.initials: E
authors.lastname: Martino
mesh_terms: D000172:Acromegaly; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D013006:Growth Hormone