Growth Hormone Is Necessary for the p53-Mediated, Obesity-Induced Insulin Resistance in Male C57BL/6J x CBA Mice
Growth Hormone Is Necessary for the p53-Mediated, Obesity-Induced Insulin Resistance in Male C57BL/6J x CBA Mice
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DOI：
10.1210/en.2013-1220
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发表时间：
2013-11-01
期刊：
影响因子：
4.8
通讯作者：
Martino, Enio
中科院分区：
文献类型：
--
作者：
Bogazzi, Fausto;Raggi, Francesco;Martino, Enio
胰岛素抵抗是肥胖和GH过量的关键标志。本研究的目的是评估GH对高脂饮食导致肥胖的雄性小鼠p53介导的胰岛素抵抗的作用。研究了喂食高脂饮食（Obe）的C57 BL/6 J x CBA雄性小鼠;喂食正常饮食（Lean）的雄性小鼠或相同遗传背景下的牛GH转基因小鼠（Acro）作为对照。Western blot检测p53和GH信号通路的会聚性。Obe小鼠有胰岛素抵抗，这是通过选择性增加脂肪组织中p53的表达来维持的。正常的胰岛素敏感性恢复，脂肪p53表达正常时，GH通路被阻断。只有脂肪p53表达对GH阻断敏感，GH阻断通过p38途径发生。Obe小鼠的脂肪组织中细胞因子信号抑制因子1-3和信号转导因子和转录激活因子-1，3和-5b的协同过表达，与Acro小鼠没有差异，表明脂肪组织对GH的敏感性增加。相反，瘦小鼠不受GH作用变化的影响。生长激素似乎是必要的脂肪p53的表达增加和肥胖小鼠的胰岛素抵抗。
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 x 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.