TYK2 和 STAT3 调控棕色脂肪组织分化和肥胖。
Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity.
机构信息
Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
出版信息
Cell Metab. 2012 Dec 5;16(6):814-24. doi: 10.1016/j.cmet.2012.11.005.
Abstract
Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high-fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2(-/-) brown preadipocytes. Furthermore, Tyk2(-/-) mice expressing CAStat3 transgene in BAT also show improved BAT development, normal levels of insulin, and significantly lower body weights. Stat3 binds to PRDM16, a master regulator of BAT differentiation, and enhances the stability of PRDM16 protein. These results define Tyk2 and Stat3 as critical determinants of brown fat lineage and suggest that altered levels of Tyk2 are associated with obesity in both rodents and humans.
摘要
由于 Myf5+棕色脂肪组织 (BAT) 的异常发育，缺乏 Jak 酪氨酸激酶成员 Tyk2 的小鼠会逐渐肥胖。高脂肪饮食和肥胖人群中，BAT 和与 BAT 具有共同前体的骨骼肌中的 Tyk2 RNA 水平显著降低。在 Tyk2(-/-)棕色前脂肪细胞中表达 Tyk2 或转录因子 Stat3 的组成型激活形式 (CAStat3) 可恢复分化。此外，在 BAT 中表达 CAStat3 转基因的 Tyk2(-/-)小鼠也表现出 BAT 发育改善、胰岛素水平正常和体重显著降低。Stat3 与 PRDM16 结合，后者是 BAT 分化的主调节因子，并增强 PRDM16 蛋白的稳定性。这些结果将 Tyk2 和 Stat3 定义为棕色脂肪谱系的关键决定因素，并表明 Tyk2 水平的改变与啮齿动物和人类的肥胖有关。
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2
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3
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6
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9
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Biochim Biophys Acta. 2010 Aug;1797(8):1470-6. doi: 10.1016/j.bbabio.2010.04.008. Epub 2010 Apr 21.
10
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