Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice

Cells. 2023 Feb 10;12(4):568. doi: 10.3390/cells12040568.


Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Thus far, hepatic Nampt has not been extensively explored in terms of its effects on serum lipid stability and liver lipids metabolism. In this study, hepatocyte-specific Nampt knockout (HC-Nampt-/-) mice were generated by Cre/loxP system. Nampt mRNA expression was reduced in the liver, but not in other tissues, in HC-Nampt-/- mice compared with wild-type (WT) mice. Hepatic Nampt deficiency had no effect on body weight and fasting blood glucose, and it did not induce atherosclerosis in mice under both normal chow diet (NCD) and high fat diet (HFD). At baseline state under NCD, hepatic Nampt deficiency also did not affect liver weight, liver function index, including alanine aminotransferase, aspartate aminotransferase, albumin and alkaline phosphatase, and serum levels of lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA). However, under HFD, deficiency of hepatic Nampt resulted in increased liver weight, liver function index, and serum levels of TG, TC, HDL-C, and NEFA. Meanwhile, histopathological examination showed increased fat accumulation and fibrosis in the liver of HC-Nampt-/- mice compared with WT mice. Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver.

Keywords: Nampt; dyslipidemia; fatty liver; hepatocyte; hepatopathy; serum lipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol, HDL
  • Diet, High-Fat
  • Dyslipidemias*
  • Fatty Acids, Nonesterified
  • Fatty Liver* / metabolism
  • Mice
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Noncommunicable Diseases*
  • Triglycerides / metabolism


  • Nicotinamide Phosphoribosyltransferase
  • Fatty Acids, Nonesterified
  • Triglycerides
  • Cholesterol, HDL

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China Major Project (No.82030110 and No.81730098 to Chao-Yu Miao) and the National Natural Science Foundation of China Young Program (No.81903728 to Tian-Guang Zhang).