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

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

Author information

1
Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany; LIFE Leipzig Research Centre for Civilization Diseases, University of Leipzig, Philipp-Rosenthalstr. 27, D-04103 Leipzig, Germany. Electronic address: melanie.penke@medizin.uni-leipzig.de.
2
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
3
Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany; LIFE Leipzig Research Centre for Civilization Diseases, University of Leipzig, Philipp-Rosenthalstr. 27, D-04103 Leipzig, Germany.
4
Department of Biology, Laboratory for Genomics and Molecular Biomedicine, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
5
Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany.
6
Department of Biology, Laboratory for Genomics and Molecular Biomedicine, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; Institut für Medizinische Physik und Biophysik, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany.

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

PMID:
26033245
DOI:
10.1016/j.mce.2015.05.028
[Indexed for MEDLINE]

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