Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell Metab. 2009 Dec;10(6):491-8. doi: 10.1016/j.cmet.2009.09.007.
Nonalcoholic steatosis (fatty liver) is a major cause of liver dysfunction that is associated with insulin resistance and metabolic syndrome. The cJun NH(2)-terminal kinase 1 (JNK1) signaling pathway is implicated in the pathogenesis of hepatic steatosis and drugs that target JNK1 may be useful for treatment of this disease. Indeed, mice with defects in JNK1 expression in adipose tissue are protected against hepatic steatosis. Here we report that mice with specific ablation of Jnk1 in hepatocytes exhibit glucose intolerance, insulin resistance, and hepatic steatosis. JNK1 therefore serves opposing actions in liver and adipose tissue to both promote and prevent hepatic steatosis. This finding has potential implications for the design of JNK1-selective drugs for the treatment of metabolic syndrome.
非酒精性脂肪性肝病（脂肪肝）是一种主要的肝功能障碍病因，与胰岛素抵抗和代谢综合征有关。cJun NH（2）-末端激酶 1（JNK1）信号通路与肝脂肪变性的发病机制有关，靶向 JNK1 的药物可能对这种疾病的治疗有用。事实上，脂肪组织中 JNK1 表达缺陷的小鼠可预防肝脂肪变性。在这里，我们报告说，肝细胞中 Jnk1 特异性缺失的小鼠表现出葡萄糖不耐受、胰岛素抵抗和肝脂肪变性。因此，JNK1 在肝脏和脂肪组织中发挥相反的作用，既能促进又能预防肝脂肪变性。这一发现可能对设计用于治疗代谢综合征的 JNK1 选择性药物具有重要意义。
