LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance

Fei Lan, Hirofumi Misu, Keita Chikamoto, Hiroaki Takayama, Akihiro Kikuchi, Kensuke Mohri, Noboru Takata, Hiroto Hayashi, Naoto Matsuzawa-Nagata, Yumie Takeshita, Hiroyo Noda, Yukako Matsumoto, Tsuguhito Ota, Toru Nagano, Masatoshi Nakagen, Ken Ichi Miyamoto, Kanako Takatsuki, Toru Seo, Kaito Iwayama, Kunpei TokuyamaSeiichi Matsugo, Hong Tang, Yoshiro Saito, Satoshi Yamagoe, Shuichi Kaneko, Toshinari Takamura

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1649-1664
Number of pages16
JournalDiabetes
Volume63
Issue number5
DOIs
Publication statusPublished - 2014 May
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Lan, F., Misu, H., Chikamoto, K., Takayama, H., Kikuchi, A., Mohri, K., Takata, N., Hayashi, H., Matsuzawa-Nagata, N., Takeshita, Y., Noda, H., Matsumoto, Y., Ota, T., Nagano, T., Nakagen, M., Miyamoto, K. I., Takatsuki, K., Seo, T., Iwayama, K., ... Takamura, T. (2014). LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance. Diabetes, 63(5), 1649-1664. https://doi.org/10.2337/db13-0728