NAMPT overexpression alleviates alcohol-induced hepatic steatosis in mice

PloS One
Xiwen XiongXinlai Qian

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.

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Citations

Feb 1, 2021·Biochemical and Biophysical Research Communications·Yue XinXiwen Xiong
Feb 26, 2020·Experimental Gerontology·Melanie R McReynoldsJoseph A Baur
Nov 25, 2021·Circulation·Daniel H KatzUNKNOWN National Heart, Lung, and Blood Institute TOPMed (Trans-Omics for Precision Medicine) Consortium†

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Methods Mentioned

BETA
PCR
ELISA
acetylation

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