LECT2 Functions as a Hepatokine That Links Obesity to Skeletal Muscle Insulin Resistance
LECT2 Functions as a Hepatokine That Links Obesity to Skeletal Muscle Insulin Resistance
复制标题
DOI：
10.2337/db13-0728
复制
发表时间：
2014-05-01
期刊：
影响因子：
7.7
通讯作者：
Takamura, Toshinari
中科院分区：
文献类型：
--
作者：
Lan, Fei;Misu, Hirofumi;Takamura, Toshinari
最近的文章报道了脂肪肝和人体全身胰岛素抵抗之间的联系，但因果关系仍不清楚。肝脏可能通过释放称为肝细胞因子的分泌性蛋白质而导致肌肉胰岛素抵抗。在这里，我们证明了白细胞来源的趋化因子2（LECT 2），一种能量敏感的肝细胞因子，是肥胖和骨骼肌胰岛素抵抗之间的联系。循环LECT 2与人类肥胖和胰岛素抵抗的严重程度呈正相关。H4 IIEC肝细胞中LECT 2的表达受饥饿敏感激酶一磷酸腺苷激活蛋白激酶的负调控。小鼠LECT 2基因缺失增加了骨骼肌的胰岛素敏感性。用重组LECT 2蛋白治疗通过C2 C12肌细胞中Jun NH 2-末端激酶的磷酸化损害胰岛素信号传导。这些结果表明LECT 2参与葡萄糖代谢，并表明LECT 2可能是肥胖相关胰岛素抵抗的治疗靶点。
Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance.