Nicotinamide riboside supplementation confers marginal metabolic benefits in obese mice without remodeling the muscle acetyl-proteome

Ashley S Williams; Timothy R Koves; Yasminye D Pettway; James A Draper; Dorothy H Slentz; Paul A Grimsrud; Olga R Ilkayeva; Deborah M Muoio

doi:10.1016/j.isci.2021.103635

Nicotinamide riboside supplementation confers marginal metabolic benefits in obese mice without remodeling the muscle acetyl-proteome

iScience. 2021 Dec 16;25(1):103635. doi: 10.1016/j.isci.2021.103635. eCollection 2022 Jan 21.

Authors

Ashley S Williams¹, Timothy R Koves^{1

2}, Yasminye D Pettway¹, James A Draper¹, Dorothy H Slentz¹, Paul A Grimsrud^{1

3}, Olga R Ilkayeva^{1

3}, Deborah M Muoio^{1

3

4}

Affiliations

¹ Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27701, USA.
² Divison of Geriatrics, Duke University Medical Center, Durham, NC 27710, USA.
³ Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC 27710, USA.
⁴ Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

Nicotinamide riboside supplements (NRS) have been touted as a nutraceutical that promotes cardiometabolic and musculoskeletal health by enhancing nicotinamide adenine dinucleotide (NAD⁺) biosynthesis, mitochondrial function, and/or the activities of NAD-dependent sirtuin deacetylase enzymes. This investigation examined the impact of NRS on whole body energy homeostasis, skeletal muscle mitochondrial function, and corresponding shifts in the acetyl-lysine proteome, in the context of diet-induced obesity using C57BL/6NJ mice. The study also included a genetically modified mouse model that imposes greater demand on sirtuin flux and associated NAD⁺ consumption, specifically within muscle tissues. In general, whole body glucose control was marginally improved by NRS when administered at the midpoint of a chronic high-fat diet, but not when given as a preventative therapy upon initiation of the diet. Contrary to anticipated outcomes, the study produced little evidence that NRS increases tissue NAD⁺ levels, augments mitochondrial function, and/or mitigates diet-induced hyperacetylation of the skeletal muscle proteome.

Keywords: Nutrition; Physiology; Proteomics.

Abstract

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