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Role of Transcription Factor NFAT in Glucose and Insulin Homeostasis

机译:转录因子NFAT在葡萄糖和胰岛素稳态中的作用

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Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is induced upon adipogenesis and in obese mice. Mice with the Nfatc2?/? Nfatc4?/? compound disruption exhibit defects in fat accumulation and are lean. Nfatc2?/? Nfatc4?/? mice are also protected from diet-induced obesity. Ablation of NFATc2 and NFATc4 increases insulin sensitivity, in part, by sustained activation of the insulin signaling pathway. Nfatc2?/? Nfatc4?/? mice also exhibit an altered adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT is recruited to the transcription loci and regulates resistin gene expression upon insulin stimulation. Together, these results establish a role for NFAT in glucose/insulin homeostasis and expand the repertoire of NFAT function to metabolic pathogenesis and adipokine gene transcription.
机译:免疫调节受损会导致肥胖和代谢发病机制中的并发症。在这里,我们证明了转录因子的活化T细胞(NFAT)组的核因子有助于葡萄糖和胰岛素的体内稳态。 NFAT家族的两个成员(NFATc2和NFATc4)的表达在脂肪形成和肥胖小鼠中被诱导。 Nfatc2 ?/? Nfatc4 ?/? < / sup>化合物破坏表现出脂肪蓄积的缺陷,并且很瘦。 Nfatc2 ?/? Nfatc4 ?/? 还保护小鼠免于饮食引起的肥胖。 NFATc2和NFATc4的消融部分通过持续激活胰岛素信号通路来提高胰岛素敏感性。 Nfatc2 ?/? Nfatc4 ?/? 小鼠还显示出改变的脂肪因子分布,其中抵抗素和瘦素水平降低。从机制上讲,NFAT被募集到转录位点,并在胰岛素刺激后调节抵抗素基因的表达。在一起,这些结果建立了NFAT在葡萄糖/胰岛素稳态中的作用,并将NFAT功能范围扩展到代谢发病机理和脂肪因子基因转录。

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