Alleviation of fatty liver in a rat model by enhancing N 1 -methylnicotinamide bioavailability through aldehyde oxidase inhibition

Kenji Takeuchi, Chie Yokouchi, Hirohiko Goto, Ken Umehara, Hideyuki Yamada, Yuji Ishii

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Nonalcoholic fatty liver disease (NAFLD) has increased worldwide in recent years. NAFLD is classified into two types, nonalcoholic fatty liver (NAFL), with few complications, and nonalcoholic steatohepatitis (NASH), which leads to liver cirrhosis or cancer. This study was based on previous reports that N 1 -methylnicotinamide (MNA) can stabilise sirtuin 1 protein, leading to decreased lipid levels in the liver. We hypothesised that fatty liver improvement by MNA would be further enhanced by suppressing its rapid metabolism by aldehyde oxidase in the liver. To test this, hydralazine (HYD), a potent aldehyde oxidase inhibitor, was administered orally to NAFL model rats. Liver triglyceride (TG) levels in the model were nearly unchanged by administration of MNA alone. In contrast, TG levels were marked decreased in NAFL rats treated with a combination of MNA and HYD. In addition, TG levels were decreased even in NAFL rats treated with only HYD. These findings supported our hypothesis that maintaining MNA concentrations in the liver, by suppressing MNA metabolism, would at least partially ameliorate fatty liver.

Original languageEnglish
Pages (from-to)203-210
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume507
Issue number1-4
DOIs
Publication statusPublished - Dec 9 2018

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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