Hepatic NAD salvage pathway is enhanced in mice on a high-fat diet

Mol Cell Endocrinol. 2015 Sep 5:412:65-72. doi: 10.1016/j.mce.2015.05.028. Epub 2015 May 29.

Abstract

Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme for NAD salvage and the abundance of Nampt has been shown to be altered in non-alcoholic fatty liver disease. It is, however, unknown how hepatic Nampt is regulated in response to accumulation of lipids in the liver of mice fed a high-fat diet (HFD). HFD mice gained more weight, stored more hepatic lipids and had an impaired glucose tolerance compared with control mice. NAD levels as well as Nampt mRNA expression, protein abundance and activity were significantly increased in HFD mice. Enhanced NAD levels were associated with deacetylation of p53 and Nfκb indicating increased activation of Sirt1. Despite impaired glucose tolerance and increased hepatic lipid levels in HFD mice, NAD metabolism was significantly enhanced. Thus, improved NAD metabolism may be a compensatory mechanism to protect against negative impact of hepatic lipid accumulation.

Keywords: Fatty liver; High-fat diet; Mouse; NAD; NAMPT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Apoptosis
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects*
  • Gene Expression
  • Lipid Metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Metabolic Networks and Pathways
  • Mice, Inbred C57BL
  • NAD / metabolism*
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Protein Processing, Post-Translational
  • Sirtuin 1 / metabolism

Substances

  • Cytokines
  • NAD
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, mouse
  • Sirt1 protein, mouse
  • Sirtuin 1