一种Jak2抑制剂AG490可逆转肿瘤坏死因子-α（TNF-α）对3T3-L1脂肪细胞中脂联素-1的抑制作用。
A Jak2 inhibitor, AG490, reverses lipin-1 suppression by TNF-alpha in 3T3-L1 adipocytes.
作者信息
Tsuchiya Yoshihiro, Takahashi Nobuhiko, Yoshizaki Takayuki, Tanno Sachie, Ohhira Masumi, Motomura Wataru, Tanno Satoshi, Takakusaki Kaoru, Kohgo Yutaka, Okumura Toshikatsu
机构信息
Department of General Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
出版信息
Biochem Biophys Res Commun. 2009 May 1;382(2):348-52. doi: 10.1016/j.bbrc.2009.03.021. Epub 2009 Mar 10.
Lipin-1 is a multifunctional metabolic regulator, involving in triacylglycerol and bioactive glycerolipids synthesis as an enzyme, transcriptional regulation as a coactivator, and adipogenesis. In obesity, adipose lipin-1 expression is decreased. Although lipin-1 is implicated in the pathogenesis of obesity, the mechanism is still not clear. Since TNF-alpha is deeply involved in the pathogenesis of obesity, insulin resistance, and diabetes, here we investigated the role of TNF-alpha on lipin-1 expression in adipocytes. Quantitative PCR studies showed that TNF-alpha suppressed both lipin-1A and -1B isoform expression in time- and dose-dependent manners in mature 3T3-L1 adpocytes. A Jak2 inhibitor, AG490, reversed the suppressive effect of TNF-alpha on both lipin-1A and -1B. In contrast, NF-kappaB, MAPKs, ceramide, and beta-catenin pathway tested were not involved in the mechanism. These results suggest that TNF-alpha could be involved in obesity-induced lipin-1 suppression in adipocytes and Jak2 may play an important role in the mechanism.
脂联素-1是一种多功能代谢调节因子，作为一种酶参与三酰甘油和生物活性甘油脂的合成，作为辅激活因子参与转录调控以及脂肪生成。在肥胖状态下，脂肪组织中脂联素-1的表达会降低。尽管脂联素-1与肥胖的发病机制有关，但其机制仍不清楚。由于肿瘤坏死因子-α（TNF-α）与肥胖、胰岛素抵抗和糖尿病的发病机制密切相关，因此我们在此研究了TNF-α对脂肪细胞中脂联素-1表达的作用。定量PCR研究表明，在成熟的3T3-L1脂肪细胞中，TNF-α以时间和剂量依赖性方式抑制脂联素-1A和-1B亚型的表达。一种Jak2抑制剂AG490可逆转TNF-α对脂联素-1A和-1B的抑制作用。相比之下，所检测的核因子-κB（NF-κB）、丝裂原活化蛋白激酶（MAPKs）、神经酰胺和β-连环蛋白途径均不参与该机制。这些结果表明，TNF-α可能参与了肥胖诱导的脂肪细胞中脂联素-1的抑制，且Jak2可能在该机制中起重要作用。
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