Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD+ without impacting respiratory capacity or insulin sensitivity

Mads V. Damgaard, Thomas S. Nielsen, Astrid L. Basse, Sabina Chubanava, Kajetan Trost, Thomas Moritz, Ryan W. Dellinger, Steen Larsen, Jonas T. Treebak*

*Corresponding author for this work

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Abstract

In clinical trials, oral supplementation with nicotinamide riboside (NR) fails to increase muscle mitochondrial respiratory capacity and insulin sensitivity but also does not increase muscle NAD+ levels. This study tests the feasibility of chronically elevating skeletal muscle NAD+ in mice and investigates the putative effects on mitochondrial respiratory capacity, insulin sensitivity, and gene expression. Accordingly, to improve bioavailability to skeletal muscle, we developed an experimental model for administering NR repeatedly through a jugular vein catheter. Mice on a Western diet were treated with various combinations of NR, pterostilbene (PT), and voluntary wheel running, but the metabolic effects of NR and PT treatment were modest. We conclude that the chronic elevation of skeletal muscle NAD+ by the intravenous injection of NR is possible but does not affect muscle respiratory capacity or insulin sensitivity in either sedentary or physically active mice. Our data have implications for NAD+ precursor supplementation regimens.

Original languageEnglish
Article number103863
JournaliScience
Volume25
Issue number2
Number of pages21
ISSN2589-0042
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Keywords

  • Drugs
  • Molecular physiology
  • Transcriptomics

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