Enzymatic and metabolic adaptation to chronic alcohol consumption mediated by alcohol dehydrogenase 1 and 3 in mice.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09223
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Nippon Medical School
• Principal Investigator: Ohno Youkichi 日本医科大学, 大学院医学研究科, 大学院教授 (70152220)
• Co-Investigator(Kenkyū-buntansha): 五十嵐 勉 日本医科大学, 医学部, 准教授 (10421190) ; 奥田 貴久 日本医科大学, 医学部, 准教授 (20620305)
• Research Collaborator: HASEBA takeshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アルコール脱水素酵素 / アルコール代謝

Outline of Final Research Achievements

We investigated the effects of ADH1 and ADH3 on alcoholic liver disease during chronic alcohol consumption (CAC) to clarify their involvement in ADH pathogenesis. Nine-week-old male mice of different ADH genotypes (WT, Adh1-/-, and Adh3-/-) were administered 10% ethanol solution for 1 month, followed by acute ethanol administration (4.0 g/kg). Blood alcohol concentration (BAC) was measured, and the alcohol elimination rate (AER) was calculated. The liver content was evaluated by ELISA. CAC increased AER in all ADH genotypes, indicating that the mice acquired metabolic tolerance to ethanol in the early period of CAC. The increased ADH1 content was correlated with AER in WT mice. Similarly, the increased ADH3 content was also correlated with AER in both WT and Adh1-/- mice. We conclude that ADH1 contributes to metabolic pharmacokinetics of CAC with increased AER by increasing the enzyme content3. ADH3 also contributes to increased AER by an adaptive increase in the enzyme content.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

肝アルコール脱水素酵素では、ADH1・ADH3ともに代謝適応があり、慢性飲酒の初期には酵素量を増加させてアルコール代謝の亢進に寄与していることが示唆された。ADHを介したアルコール代謝では、ADH1のみならずADH3も慢性飲酒においても代謝耐性を獲得し、全身諸臓器でアルコール代謝に強く関与していると考えられた。