A functional role for the p62-ERK1 axis in the control of energy homeostasis and adipogenesis
A functional role for the p62-ERK1 axis in the control of energy homeostasis and adipogenesis
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DOI：
10.1038/embor.2010.7
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发表时间：
2010-03-01
期刊：
影响因子：
7.7
通讯作者：
Moscat, Jorge
中科院分区：
文献类型：
--
作者：
Lee, Sang Jun;Pfluger, Paul T.;Moscat, Jorge
在体内遗传失活的信号转导衔接子p62导致成熟型肥胖症和胰岛素抵抗，这与减少能量消耗（EE）和增加脂肪生成，没有改变进食或运动功能。p62基因敲除（p62（-/-））小鼠脂肪组织中细胞外信号调节激酶（ERK）活性增强，以及成纤维细胞分化，表明这种激酶在p62（-/-）小鼠的代谢改变中起重要作用。在这里，我们表明，在p62（-/-）小鼠中，ERK 1的遗传失活逆转了他们增加的肥胖和脂肪形成，降低EE和胰岛素抵抗。这些结果从遗传学上证实了p62是ERK 1在代谢中的重要调节因子。
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.