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      The emergence of the nicotinamide riboside kinases in the regulation of NAD + metabolism

      review-article
      Author(s): ,
      Publication date (Electronic):
      Journal: Journal of Molecular Endocrinology
      Publisher: Bioscientifica Ltd
      Keywords: NAD+, metabolism, nicotinamide riboside, energy

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          Abstract

          The concept of replenishing or elevating NAD + availability to combat metabolic disease and ageing is an area of intense research. This has led to a need to define the endogenous regulatory pathways and mechanisms cells and tissues utilise to maximise NAD + availability such that strategies to intervene in the clinical setting are able to be fully realised. This review discusses the importance of different salvage pathways involved in metabolising the vitamin B3 class of NAD + precursor molecules, with a particular focus on the recently identified nicotinamide riboside kinase pathway at both a tissue-specific and systemic level.

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          Visfatin: a protein secreted by visceral fat that mimics the effects of insulin.

          Atsunori Fukuhara, Morihiro Matsuda, Masako Nishizawa … (2005)
          Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.
          Article 0 comments Cited 384 times – based on 0 reviews     Review now
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            CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.

            Juliana Camacho-Pereira, Mariana G Tarragó, Claudia Chini … (2016)
            Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases.
            Article 0 comments Cited 380 times – based on 0 reviews     Review now
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              Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

              Luis Rajman, David A Sinclair, Karolina Chwalek (2018)
              Nicotinamide adenine dinucleotide (NAD), the cell’s hydrogen carrier for redox enzymes, is well known for its role in redox reactions. More recently, it has emerged as a signaling molecule. By modulating NAD + sensing enzymes, it controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise and the time of day. NAD + levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility. Restoration of NAD + levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules. Such molecules hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan. Nicotinamide adenine nucleotide (NAD+) has emerged as a key regulator of cellular processes that control the body’s response to stress. Rajman et al. discuss NAD boosters, small molecules that raise NAD+ levels, which are now considered to be highly promising for the treatment of multiple diseases and the potential extension of human lifespan.
              Article 0 comments Cited 367 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Mol Endocrinol
                Journal ID (iso-abbrev): J. Mol. Endocrinol
                Journal ID (hwp): JME
                Title: Journal of Molecular Endocrinology
                Publisher: Bioscientifica Ltd (Bristol )
                ISSN (Print): 0952-5041
                ISSN (Electronic): 1479-6813
                Publication date Collection: October 2018
                Publication date (Electronic): 30 May 2018
                Volume: 61
                Issue: 3
                Pages: R107-R121
                Affiliations
                [1]Institute of Metabolism and Systems Research University of Birmingham, Birmingham, UK
                Author notes
                Correspondence should be addressed to G G Lavery: g.g.lavery@ 123456bham.ac.uk
                Article
                Publisher ID: JME180085
                DOI: 10.1530/JME-18-0085
                PMC ID: 6145238
                PubMed ID: 29848626
                SO-VID: 6f275934-6f96-4d9b-90e6-bcab1f6fc47b
                Copyright © © 2018 The authors
                License:

                This work is licensed under a Creative Commons Attribution 4.0 Unported License.

                History
                Date received : 21 May 2018
                Date accepted : 30 May 2018
                Categories
                Subject: Review

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: nad+,metabolism,nicotinamide riboside,energy
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: nad+, metabolism, nicotinamide riboside, energy

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