NAMPT overexpression alleviates alcohol-induced hepatic steatosis in mice

Xiwen Xiong, Jiahui Yu, Rui Fan, Cuicui Zhang, Lin Xu, Xupeng Sun, Yanmei Huang, Qingzhi Wang, Hai Bin Ruan, Xinlai Qian

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD) + biosynthesis. Through its NAD + -biosynthetic activity, NAMPT influences the activity of NAD + -dependent enzymes, such as sirtuins. NAMPT is able to modulate processes involved in the pathogenesis of non-alcohol induced fatty liver disease (NAFLD), but the roles NAMPT plays in development of alcoholic liver disease (ALD) still remain unknown. Here, we show that ethanol treatment suppresses the expression of Nampt in hepatocytes. Consistently, chronic ethanol administration also reduces Nampt expression in the mouse liver. We next demonstrate that hepatocytes infected with Ad-NAMPT adenovirus exhibit significantly elevated intracellular NAD + levels and decreased ethanol-induced triglyceride (TG) accumulation. Similarly, adenovirus-mediated overexpression of NAMPT in mice ameliorates ethanol induced hepatic steatosis. Moreover, we demonstrate that SIRT1 is required to mediate the effects of NAMPT on reduction of hepatic TG accumulation and serum ALT, AST levels in ethanol-fed mice. Our results provide important insights in targeting NAMPT for treating alcoholic fatty liver disease.

Original languageEnglish (US)
Article numbere0212523
JournalPloS one
Volume14
Issue number2
DOIs
StatePublished - Feb 2019

Bibliographical note

Funding Information:
The present work was supported by grants from the Key Science and Technology Project of Xinxiang (CXGG17007, to X.X), National Natural and Science Foundation of China (81670526, to X.X), the Key Science and Technology Project of Henan (182102310107, to X.X), and the Key Scientific Research Project of Universities in Henan (19A180005, to X.X). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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