eNOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity.
eNOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity.
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DOI：
10.1016/j.bbrc.2012.12.110
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发表时间：
2013-02-08
影响因子：
3.1
通讯作者：
Huang, Paul L.
中科院分区：
文献类型：
--
作者：
Kashiwagi, Satoshi;Atochin, Dmitriy N.;Li, Qian;Schleicher, Michael;Pong, Terrence;Sessa, William C.;Huang, Paul L.
内皮型一氧化氮合酶（eNOS）的磷酸化是其酶活性的重要调节因子。我们产生了敲入小鼠表达磷酸化模拟（SD）和非磷酸化（SA）eNOS突变S1176研究eNOS磷酸化的作用。单个氨基酸SA突变与高血压和血管反应性降低相关，而SD突变导致基础和刺激的内皮NO产生增加。除了这些血管效应外，S1176磷酸化位点的调节导致对代谢的非预期效应。eNOS SA突变导致胰岛素抵抗、高胰岛素血症、肥胖和高脂肪增加的体重增加。相比之下，eNOS SD突变与胰岛素水平降低和对高脂肪诱导的体重增加的抵抗有关。这些结果表明eNOS在调节胰岛素敏感性、能量代谢和体重调节中的重要性，并表明eNOS磷酸化作为治疗肥胖和胰岛素抵抗的新靶点。
Phosphorylation of endothelial nitric oxide synthase (eNOS) is an important regulator of its enzymatic activity. We generated knockin mice expressing phosphomimetic (SD) and unphosphorylatable (SA) eNOS mutations at S1176 to study the role of eNOS phosphorylation. The single amino acid SA mutation is associated with hypertension and decreased vascular reactivity, while the SD mutation results in increased basal and stimulated endothelial NO production. In addition to these vascular effects, modulation of the S1176 phosphorylation site resulted in unanticipated effects on metabolism. The eNOS SA mutation results in insulin resistance, hyperinsulinemia, adiposity, and increased weight gain on high fat. In contrast, the eNOS SD mutation is associated with decreased insulin levels and resistance to high fat-induced weight gain. These results demonstrate the importance of eNOS in regulation of insulin sensitivity, energy metabolism, and bodyweight regulation, and suggest eNOS phosphorylation as a novel target for the treatment of obesity and insulin resistance.
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影响因子：
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DOI：
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发表时间：
1996-02-15
影响因子：
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作者：
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