Study of NASH using human hepatocyte chimeric mouse and biopsy specimen

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H04817
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Chayama Kazuaki 広島大学, 医系科学研究科(医), 共同研究講座教授 (00211376)
• Co-Investigator(Kenkyū-buntansha): 茶山 弘美 広島大学, 医系科学研究科(医), 准教授 (70572329) ; 三木 大樹 広島大学, 医系科学研究科(医), 講師 (10584592) ; Hayes C.Nelson 広島大学, 医系科学研究科(医), 准教授 (50572327)
• Project Period (FY): 2021-04-05 – 2024-03-31
• Keywords: 脂肪化 / ヒト肝細胞 / 成長ホルモン / 線維化 / 治療

Outline of Final Research Achievements

Non-alcoholic fatty liver disease (NAFLD) is an inflammatory condition that can progress to cirrhosis and hepatocellular carcinoma. The global incidence of NAFLD is rapidly increasing in parallel with rising obesity rates. In this study, a fatty liver mouse model was generated using human hepatocyte chimeric mice. Six mice were fed a high-fat diet, six were fed a normal diet, and three mice from each group received growth hormone (GH), resulting in four distinct groups. After being fed their respective diets for eight weeks, the mice were sacrificed, and human hepatocytes were extracted for RNA-Seq, proteomics, and metabolomics analysis. A multi-omics approach was employed to investigate the metabolic status within each group. This approach offers a powerful model for the future development of therapeutic agents for NAFLD.

Free Research Field

肝疾患

Academic Significance and Societal Importance of the Research Achievements

ヒトの肝細胞の代謝が観察できるモデルはなく、これまで薬剤の開発の妨げとなっていた。本研究で開発したモデルはヒト肝細胞の代謝そのものの変化を観察できるうえに、繊維化などのメカニズムの解明、発達防止の治療開発などに有用であり、今後の応用研究が期待される。