p62-ERK1 轴在能量平衡和脂肪生成控制中的功能作用。
A functional role for the p62-ERK1 axis in the control of energy homeostasis and adipogenesis.
机构信息
Department of Cancer and Cell Biology, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
出版信息
EMBO Rep. 2010 Mar;11(3):226-32. doi: 10.1038/embor.2010.7. Epub 2010 Feb 12.
Abstract
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.
摘要
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。
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