Association of fibrotic steatohepatitis rat fed high-fat-cholesterol diet with hypertension via bile acid synthesis enzyme CYP7A1

2024 Fiscal Year Final Research Report

• Project/Area Number: 21K10406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: Kinjo Gakuin University
• Principal Investigator: Naito Hisao 金城学院大学, 生活環境学部, 教授 (90547556)
• Project Period (FY): 2021-04-01 – 2025-03-31
• Keywords: 非アルコール性脂肪性肝炎 / 線維化 / 高血圧 / プロテオミクス / DNAメチル化 / CYP7A1 / ヒドララジン / 胆汁酸

Outline of Final Research Achievements

Hypertensive spontaneously hypertensive rats (SHRs) fed a high-fat-cholesterol diet (HFC) developed fibrotic steatohepatitis. Hydralazine, an antihypertensive agent, was administered to these rats, and proteomic analysis of the liver was performed. The results confirmed that the antihypertensive agent suppressed fibrotic steatohepatitis.
Previous studies have shown a positive correlation between hypertension and the bile acid synthesis enzyme CYP7A1 protein expression, with no changes in Cyp7a1 mRNA expression but an increase in DNA methylation frequencies in Cyp7a1 promoter region. Therefore, we measured the DNA methylation frequencies and the mRNA expression levels in the livers of SHRs administrated with the antihypertensive agent. The results showed that the antihypertensive agent reduced the frequencies of the DNA methylation and increased the mRNA expression.

Free Research Field

衛生学

Academic Significance and Societal Importance of the Research Achievements

高血圧がNASHの原因の１つとして報告されているが、詳細なメカニズムは不明である。今回の研究結果から、血圧の抑制はNASH進展に対して抑制効果があることが確認され、より強固な証拠となった。以上のことから、高血圧予防はNASH予防につながる重要なポイントとして保健指導などに有用な知見が得られた。