title: Hepatic NAD salvage pathway is enhanced in mice on a high-fat diet.
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.
authors.affiliation: 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.
authors.forename: Melanie
authors.initials: M
authors.lastname: Penke
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Per S
authors.initials: PS
authors.lastname: Larsen
authors.affiliation: 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.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schuster
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Dall
authors.affiliation: Department of Biology, Laboratory for Genomics and Molecular Biomedicine, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Benjamin A H
authors.initials: BA
authors.lastname: Jensen
authors.affiliation: Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Gorski
authors.affiliation: 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.
authors.forename: Andrej
authors.initials: A
authors.lastname: Meusel
authors.affiliation: Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany.
authors.forename: Sandy
authors.initials: S
authors.lastname: Richter
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sara G
authors.initials: SG
authors.lastname: Vienberg
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Treebak
authors.affiliation: 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.
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.affiliation: Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Garten
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D015870:Gene Expression; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D008810:Mice, Inbred C57BL; D009243:NAD / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Fatty liver; High-fat diet; Mouse; NAD; NAMPT