Understanding the role of disorder of vagus function in lifestyle-related diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 18KT0020
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: Kanazawa University
• Principal Investigator: Inoue Hiroshi 金沢大学, 新学術創成研究機構, 教授 (50397832)
• Project Period (FY): 2018-07-18 – 2021-03-31
• Keywords: 生活習慣病 / 迷走神経 / 肝臓 / 臓器連関

Outline of Final Research Achievements

Nonalcoholic steatohepatitis (NASH), which occurs in association with insulin resistance and hepatic fat accumulation, confers high risk of liver fibrosis and chronic liver injury. In this study, using systemic α7 nicotinic acetylcholine receptor (A7nAchR) knockout mice (A7KO), we investigated the role of A7nAchR in NASH. Specifically, A7KO mice were fed an atherogenic high-fat diet (AD), which induce NASH. Hepatic triglyceride accumulation and elevated plasma transaminase levels were observed in AD mice, and we found the plasma transaminase level increase was higher in A7KO mice than in control mice. A7KO mice fed an AD showed significant upregulation of fibrosis-related genes and proinflammatory-cytokine genes in the liver. Histological analysis with Sirius red revealed that AD exacerbated liver fibrosis in A7KO mice. From these findings, it is clear that A7nAchR deficiency exacerbates hepatitis and fibrosis due to hepatic fat accumulation.

Free Research Field

食生活学、栄養代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究からα7型ニコチン受容体(A7nAchR)が、非アルコール性脂肪肝炎(NASH)の新規な予防・治療薬候補であることを見出した。しかし、A7nAchRは中枢神経作用に多く発現しており、A7nAchRアゴニストの中枢神経作用はNASH治療薬としての妨げとなる可能性がある。NASH予防・治療へのA7nAchR活性化の応用には、肝臓以外の臓器におけるA7nAchR作用の更なる解析と、アゴニストの肝臓特異的なドラッグデリバリー法の開発が必要であると考えられた。