Reduction of fatty liver in rats by nicotinamide via the regeneration of the methionine cycle and the inhibition of aldehyde oxidase

Chie Yokouchi, Yukari Nishimura, Hirohiko Goto, Makoto Sato, Yuya Hidoh, Kenji Takeuchi, Yuji Ishii

Research output: Contribution to journalArticlepeer-review

Abstract

— Nonalcoholic fatty liver disease, which has been rapidly increasing in the world in recent years, is roughly classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis. This study was based on our previous reports that stated that the combination treatment of N1-methylnicotina-mide (MNA) and hydralazine (HYD) improves fatty liver in NAFL model rats. This finding was attribut-ed to the MNA metabolism inhibition by HYD, which is a strong inhibitor of aldehyde oxidase (AO); this results in an increase in hepatic MNA and improved fatty liver. We hypothesized that orally administered nicotinamide (NAM), which is the precursor of MNA and is a form of niacin, would be efficiently metab-olized by nicotinamide N-methyltransferase in the presence of exogenous S-adenosylmethionine (SAM) in NAFL rats. To address this issue, NAFL model rats were orally administered with NAM, SAM, and/or HYD. As a result, liver triglyceride (TG) and lipid droplet levels were barely altered by the administration of NAM, SAM, NAM+SAM, or NAM+HYD. By contrast, the triple combination of NAM+SAM+HYD significantly reduced hepatic TG and lipid droplet levels and significantly increased hepatic MNA levels. These findings indicated that the combination of exogenous SAM with AO inhibitors, such as HYD, has beneficial effects for improving fatty liver with NAM.

Original languageEnglish
Pages (from-to)31-42
Number of pages12
JournalJournal of Toxicological Sciences
Volume46
Issue number1
DOIs
Publication statusPublished - 2021

All Science Journal Classification (ASJC) codes

  • Toxicology

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