Physiological and pathophysiological roles of NAMPT and NAD metabolism

Key Points

  • Nicotinamide phosphoribosyltransferase (NAMPT) is a regulator of the intracellular nicotinamide adenine dinucleotide (NAD) pool and, thus, regulates the activity of NAD-dependent enzymes

  • NAMPT is able to modulate processes involved in the pathogenesis of obesity and related disorders by influencing the oxidative stress response, apoptosis, lipid and glucose metabolism, inflammation and insulin resistance

  • Levels of extracellular NAMPT are associated with various metabolic disorders

  • NAMPT, which has a crucial role in cancer cell metabolism, is often overexpressed in tumour tissues and is an experimental target for antitumour therapies

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.

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Figure 1: Mammalian NAD metabolism.
Figure 2: Physiological actions of NAMPT.

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Acknowledgements

The authors thank colleagues from the Kiess laboratory for valuable discussions and acknowledge support from the German Diabetes Society, the German Competence Network Obesity, the Federal Ministry of Education and Research (grant 01GI1330 to A.G.), the Mitteldeutsche Kinderkrebsstiftung, the University of Chieti, Italy (for a scholarship to T.d.G.) and LIFE (Leipzig Research Centre for Civilization Diseases, University of Leipzig, Germany). LIFE is funded by the European Union, the European Regional Development Fund (ERDF; grant number: 4-7,531.70/5/4) and the Free State of Saxony within the framework of the excellence initiative.

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S.S., M.P., T.G. and T.d.G. researched data for the article. A.G., S.S., M.P., T.G., T.d.G. and W.K. provided substantial contributions to discussions of the content. A.G., S.S., M.P., T.G. and T.d.G. wrote the article. A.G., S.S. and W.K. reviewed and/or edited the manuscript before submission.

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Correspondence to Wieland Kiess.

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Garten, A., Schuster, S., Penke, M. et al. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 11, 535–546 (2015). https://doi.org/10.1038/nrendo.2015.117

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