Lan Fei, Misu Hirofumi, Chikamoto Keita, Takayama Hiroaki, Kikuchi Akihiro, Mohri Kensuke, Takata Noboru, Hayashi Hiroto, Matsuzawa-Nagata Naoto, Takeshita Yumie, Noda Hiroyo, Matsumoto Yukako, Ota Tsuguhito, Nagano Toru, Nakagen Masatoshi, Miyamoto Ken-ichi, Takatsuki Kanako, Seo Toru, Iwayama Kaito, Tokuyama Kunpei, Matsugo Seiichi, Tang Hong, Saito Yoshiro, Yamagoe Satoshi, Kaneko Shuichi, Takamura Toshinari
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
Diabetes. 2014 May;63(5):1649-64. doi: 10.2337/db13-0728. Epub 2014 Jan 29.
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.
近期的文章报道了人类脂肪肝疾病与全身胰岛素抵抗之间的关联，但因果关系仍不明确。肝脏可能通过释放一种名为肝因子的分泌蛋白来导致肌肉胰岛素抵抗。在此，我们证明白细胞来源的趋化因子2（LECT2），一种能量感知肝因子，是肥胖与骨骼肌胰岛素抵抗之间的一个联系。循环中的LECT2与人类肥胖和胰岛素抵抗的严重程度呈正相关。在H4IIEC肝细胞中，LECT2的表达受到饥饿感应激酶单磷酸腺苷激活蛋白激酶的负调控。小鼠中LECT2的基因缺失增加了骨骼肌的胰岛素敏感性。用重组LECT2蛋白处理会通过C2C12肌细胞中Jun NH2末端激酶的磷酸化损害胰岛素信号传导。这些结果证明了LECT2参与葡萄糖代谢，并表明LECT2可能是肥胖相关胰岛素抵抗的一个治疗靶点。
