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<p>NAD<sup>+</sup> is a crucial metabolic cofactor whose intracellular levels can influence the progression of multiple metabolic and age-related complications. There is therefore a strong interest in using NAD<sup>+</sup> precursors (vitamin B3s) as therapeutic tools, but most current precursors exhibit either poor bioavailability or adverse effects. This study examines the metabolic impact of chronic dietary supplementation with a newly described NAD<sup>+</sup> precursor, dihydronicotinamide riboside (NRH), in mice using a comprehensive approach including phenotyping tests, RNA sequencing in different tissues and microbiome analyses. We show that chronic NRH administration at 100 mg/(kg*day) is well tolerated, yet has minimal metabolic effects in mice on a regular diet. However, NRH mitigates high-fat diet-induced metabolic complications when used as a preventive or as a treatment strategy, including improvements in glucose tolerance, increased hepatic expression of lipid catabolism genes and fat redistribution. These results highlight the potential of NRH as a therapeutic agent, although further studies are needed to optimize its use, as higher doses reveal signs of toxicity.</p>

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Therapeutic potential of dihydronicotinamide riboside (NRH) on obesity and glucose intolerance in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月25日

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  • Marie Rumpler,
  • Guido van Mierlo,
  • Kasper T. Vinten,
  • Maria Pilar Giner,
  • Stefan Christen,
  • Faisal Hayat,
  • Mikhail V. Makarov,
  • Vincent Gardeux,
  • Julie Russeil,
  • Bauke V. Schomakers,
  • Laurine van Gijn,
  • Horia Hashimi,
  • Clémence Steiner,
  • Judith Giroud-Gerbetant,
  • Magali Joffraud,
  • Jose Luis Sanchez Garcia,
  • Sofia Moco,
  • Marie E. Migaud,
  • Riekelt H. Houtkooper,
  • Bart Deplancke,
  • Carles Canto

摘要

NAD+ is a crucial metabolic cofactor whose intracellular levels can influence the progression of multiple metabolic and age-related complications. There is therefore a strong interest in using NAD+ precursors (vitamin B3s) as therapeutic tools, but most current precursors exhibit either poor bioavailability or adverse effects. This study examines the metabolic impact of chronic dietary supplementation with a newly described NAD+ precursor, dihydronicotinamide riboside (NRH), in mice using a comprehensive approach including phenotyping tests, RNA sequencing in different tissues and microbiome analyses. We show that chronic NRH administration at 100 mg/(kg*day) is well tolerated, yet has minimal metabolic effects in mice on a regular diet. However, NRH mitigates high-fat diet-induced metabolic complications when used as a preventive or as a treatment strategy, including improvements in glucose tolerance, increased hepatic expression of lipid catabolism genes and fat redistribution. These results highlight the potential of NRH as a therapeutic agent, although further studies are needed to optimize its use, as higher doses reveal signs of toxicity.