Identification of sucrose non-fermenting-related kinase (SNRK) as a suppressor of adipocyte inflammation.
Identification of sucrose non-fermenting-related kinase (SNRK) as a suppressor of adipocyte inflammation.
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作者：
Li Y;Nie Y;Helou Y;Ding G;Feng B;Xu G;Salomon A;Xu H
在这项研究中，蔗糖非发酵相关激酶（SNRK）在白色脂肪细胞生物学的作用进行了研究。SNRK在脂肪组织中大量表达，并且在肥胖小鼠中表达水平降低。在培养的脂肪细胞中，SNRK的表达被炎症信号抑制，但被胰岛素增敏剂增加。在体内，脂肪组织SNRK表达可以通过脂质注射降低，但通过巨噬细胞消融增强。在培养的脂肪细胞中敲低SNRK可激活JNK和IKKβ通路，并促进脂解。胰岛素刺激的Akt磷酸化和葡萄糖摄取在SNRK敲低脂肪细胞中受损。对SNRK敲除脂肪细胞的磷酸化蛋白质组学分析显示，49种蛋白质的磷酸化显著降低了25%或更多，这些蛋白质参与脂肪细胞功能的各个方面，明确表明mTORC 1信号转导减弱。43种蛋白质的磷酸化显著增加一倍或更高，其中几种蛋白质已知参与炎症途径。SNRK敲除脂肪细胞中的炎症反应可以部分归因于缺陷的mTORC 1信号传导，因为雷帕霉素处理激活IKKβ并诱导脂肪细胞中的脂解。总之，SNRK可以作为脂肪细胞炎症的抑制剂，并且其存在对于维持正常脂肪细胞功能是必要的。
In this study, the role of sucrose non-fermenting–related kinase (SNRK) in white adipocyte biology was investigated. SNRK is abundantly expressed in adipose tissue, and the expression level is decreased in obese mice. SNRK expression is repressed by inflammatory signals but increased by insulin sensitizer in cultured adipocytes. In vivo, adipose tissue SNRK expression can be decreased by lipid injection but enhanced by macrophage ablation. Knocking down SNRK in cultured adipocytes activates both JNK and IKKβ pathways as well as promotes lipolysis. Insulin-stimulated Akt phosphorylation and glucose uptake are impaired in SNRK knockdown adipocytes. Phosphoproteomic analysis with SNRK knockdown adipocytes revealed significantly decreased phosphorylation of 49 proteins by 25% or more, which are involved in various aspects of adipocyte function with a clear indication of attenuated mTORC1 signaling. Phosphorylation of 43 proteins is significantly increased by onefold or higher, among which several proteins are known to be involved in inflammatory pathways. The inflammatory responses in SNRK knockdown adipocytes can be partially attributable to defective mTORC1 signaling, since rapamycin treatment activates IKKβ and induces lipolysis in adipocytes. In summary, SNRK may act as a suppressor of adipocyte inflammation and its presence is necessary for maintaining normal adipocyte function.
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