A reduced form of nicotinamide riboside defines a new path for NAD + biosynthesis and acts as an orally bioavailable NAD + precursor.

Autor:	Giroud-Gerbetant J; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland., Joffraud M; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland., Giner MP; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland., Cercillieux A; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland; School of Life Sciences, EPFL, Lausanne, 1015, Switzerland., Bartova S; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland., Makarov MV; Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, 36604, Alabama, USA., Zapata-Pérez R; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands., Sánchez-García JL; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland., Houtkooper RH; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands., Migaud ME; Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, 36604, Alabama, USA., Moco S; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland., Canto C; Nestlé Institute of Health Sciences, Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland; School of Life Sciences, EPFL, Lausanne, 1015, Switzerland. Electronic address: carlos.cantoalvarez@rd.nestle.com.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2019 Dec; Vol. 30, pp. 192-202. Date of Electronic Publication: 2019 Oct 03.
DOI:	10.1016/j.molmet.2019.09.013
Abstrakt:	Objective: A decay in intracellular NAD + levels is one of the hallmarks of physiological decline in normal tissue functions. Accordingly, dietary supplementation with NAD + precursors can prevent, alleviate, or even reverse multiple metabolic complications and age-related disorders in diverse model organisms. Within the constellation of NAD + precursors, nicotinamide riboside (NR) has gained attention due to its potent NAD + biosynthetic effects in vivo while lacking adverse clinical effects. Nevertheless, NR is not stable in circulation, and its utilization is rate-limited by the expression of nicotinamide riboside kinases (NRKs). Therefore, there is a strong interest in identifying new effective NAD + precursors that can overcome these limitations. Methods: Through a combination of metabolomics and pharmacological approaches, we describe how NRH, a reduced form of NR, serves as a potent NAD + precursor in mammalian cells and mice. Results: NRH acts as a more potent and faster NAD + precursor than NR in mammalian cells and tissues. Despite the minor structural difference, we found that NRH uses different steps and enzymes to synthesize NAD + , thus revealing a new NRK1-independent pathway for NAD + synthesis. Finally, we provide evidence that NRH is orally bioavailable in mice and prevents cisplatin-induced acute kidney injury. Conclusions: Our data identify a new pathway for NAD + synthesis and classify NRH as a promising new therapeutic strategy to enhance NAD + levels. (Copyright © 2019 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
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