Evaluation of mitochondrial DNA copy number and function in hepatocyte of non-alcoholic steatohepatitis in mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16983
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Niigata University
• Principal Investigator: Arao Yoshihisa 新潟大学, 医歯学総合病院, 特任准教授 (40870142)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: MASH / ミトコンドリア / DNA copy number

Outline of Final Research Achievements

Mitophagy reporter mice were treated with normal diet, MCD, and HFD to evaluate fat and fibrosis, but no significant changes were observed. For observation of mCherry alone, which suggests mitophagy, quenching treatment was performed, but stable observation could not be established due to autofluorescence. q-PCR was used to evaluate BNIP3 and BNIP3L, and their expression was decreased in HFD and MCD. ATP assay was performed as a functional evaluation, showing a decreasing trend in HFD and MCD. Western blotting and immunofluorescence stained images were used to evaluate BNIP3 and other proteins, but no significant differences were observed. The study was terminated because it was deemed difficult to continue the study any further.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

メタボリック症候群や肥満の増加に伴って日本でも代謝機能不全に関連した脂肪肝炎（MASH：Metabolic dysfunction associated steatohepatitis）が増加している。脂肪肝炎から肝硬変への進展における肝細胞において、活性酸素による酸化ストレスは原因の一つであり、その影響を受けやすいミトコンドリアDNA（mtDNA）コピー数の変化は、病態のマーカー、重症度などとの関連が示唆されているが、未だ明らかとなっていない。mtDNAコピー数による効率的なMSAHの新規マーカーの有用性を見出そうとしたが、今回の研究では探索することが困難であった。