title: Physiological and pathophysiological roles of NAMPT and NAD metabolism.
abstract: Nicotinamide phosphoribosyltransferase (NAMPT) is a regulator of the intracellular nicotinamide adenine dinucleotide (NAD) pool. NAD is an essential coenzyme involved in cellular redox reactions and is a substrate for NAD-dependent enzymes. In various metabolic disorders and during ageing, levels of NAD are decreased. Through its NAD-biosynthetic activity, NAMPT influences the activity of NAD-dependent enzymes, thereby regulating cellular metabolism. In addition to its enzymatic function, extracellular NAMPT (eNAMPT) has cytokine-like activity. Abnormal levels of eNAMPT are associated with various metabolic disorders. NAMPT is able to modulate processes involved in the pathogenesis of obesity and related disorders such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) by influencing the oxidative stress response, apoptosis, lipid and glucose metabolism, inflammation and insulin resistance. NAMPT also has a crucial role in cancer cell metabolism, is often overexpressed in tumour tissues and is an experimental target for antitumour therapies. In this Review, we discuss current understanding of the functions of NAMPT and highlight progress made in identifying the physiological role of NAMPT and its relevance in various human diseases and conditions, such as obesity, NAFLD, T2DM, cancer and ageing.
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 21, 04103 Leipzig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Garten
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 21, 04103 Leipzig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schuster
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 21, 04103 Leipzig, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Penke
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 21, 04103 Leipzig, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Gorski
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 21, 04103 Leipzig, Germany.
authors.forename: Tommaso
authors.initials: T
authors.lastname: de Giorgis
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 21, 04103 Leipzig, Germany.
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D009243:NAD / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics* / Q000502:physiology*; D009765:Obesity / Q000201:enzymology / Q000235:genetics
chemical_list: D016207:Cytokines; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human