The effect of hepatokine LECT2 on the pathphysiology of NASH

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19533
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kanazawa University
• Principal Investigator: Kosuke Shima 金沢大学, 医学系, 協力研究員 (20770613)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 非アルコール性脂肪肝 / LECT2 / ヘパトカイン

Outline of Final Research Achievements

As in the planed study design, a steatohepatitis model was created by administering CDAHFD (choline deficiency, methionine loss, containing 30% fat) to LECT2 deficient (KO) mice and LECT2 overexpressing (Tg) mice and compared with wild-type mice. Induction of steatohepatitis in LECT2 Tg mice significantly increased IL-6 expression in the liver compared to wild type, but did not significantly differ in TNF-a, MCP-1, F4 / 80, TGFb1. Hydroxyproline levels, which reflect liver fibrosis, were also elevated in Lect2 Tg mice, however there was no statistically significant difference. In Lect2 mice, there was no significant change in fibrotic inflammation-related genes, and contrary to the hypothesis, hepatic triglyceride was significantly elevated.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

本検討では、当初の仮説と異なり、肥満で誘導されるヘパトカインであるLect2は肝臓自身には強く作用せず、脂肪肝の病態に影響を及ぼすものではなかった。非アルコール性脂肪肝炎が形成される病態は複雑であり、多数の因子が関与していると考えられる。Lect2以外のヘパトカインがオートクラインパラクライン的に肝臓に作用する可能性もあり、今後の検討が待たれる。