Department of Cancer and Cell Biology, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
EMBO Rep. 2010 Mar;11(3):226-32. doi: 10.1038/embor.2010.7. Epub 2010 Feb 12.
In vivo genetic inactivation of the signalling adapter p62 leads to mature-onset obesity and insulin resistance, which correlate with reduced energy expenditure (EE) and increased adipogenesis, without alterations in feeding or locomotor functions. Enhanced extracellular signal-regulated kinase (ERK) activity in adipose tissue from p62-knockout (p62(-/-)) mice, and differentiating fibroblasts, suggested an important role for this kinase in the metabolic alterations of p62(-/-) mice. Here, we show that genetic inactivation of ERK1 in p62(-/-) mice reverses their increased adiposity and adipogenesis, lower EE and insulin resistance. These results establish genetically that p62 is a crucial regulator of ERK1 in metabolism.
体内遗传敲除信号接头蛋白 p62 会导致成年肥胖和胰岛素抵抗，这与能量消耗减少和脂肪生成增加相关，而摄食和运动功能没有改变。p62 敲除（p62(-/-)）小鼠和分化的成纤维细胞的脂肪组织中细胞外信号调节激酶（ERK）活性增强，提示该激酶在 p62(-/-) 小鼠的代谢改变中起着重要作用。在这里，我们表明在 p62(-/-) 小鼠中遗传敲除 ERK1 可逆转其肥胖和脂肪生成增加、降低能量消耗和胰岛素抵抗。这些结果从遗传学上证实了 p62 是代谢中 ERK1 的关键调节因子。
