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NAD+ repletion with niacin counteracts cancer cachexia

Author

Listed:
  • Marc Beltrà

    (University of Torino)

  • Noora Pöllänen

    (University of Helsinki)

  • Claudia Fornelli

    (University of Torino)

  • Kialiina Tonttila

    (University of Helsinki
    University of Jyväskylä)

  • Myriam Y. Hsu

    (University of Torino)

  • Sandra Zampieri

    (University of Padova
    University of Padova
    University of Padova)

  • Lucia Moletta

    (University of Padova)

  • Samantha Corrà

    (Veneto Institute of Molecular Medicine)

  • Paolo E. Porporato

    (University of Torino)

  • Riikka Kivelä

    (University of Helsinki
    University of Jyväskylä
    Wihuri Research Institute)

  • Carlo Viscomi

    (University of Padova
    University of Padova (CESNE))

  • Marco Sandri

    (University of Padova
    Veneto Institute of Molecular Medicine)

  • Juha J. Hulmi

    (University of Jyväskylä)

  • Roberta Sartori

    (University of Padova
    Veneto Institute of Molecular Medicine)

  • Eija Pirinen

    (University of Helsinki
    University of Oulu
    Oulu University Hospital and University of Oulu)

  • Fabio Penna

    (University of Torino)

Abstract

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients.

Suggested Citation

  • Marc Beltrà & Noora Pöllänen & Claudia Fornelli & Kialiina Tonttila & Myriam Y. Hsu & Sandra Zampieri & Lucia Moletta & Samantha Corrà & Paolo E. Porporato & Riikka Kivelä & Carlo Viscomi & Marco Sand, 2023. "NAD+ repletion with niacin counteracts cancer cachexia," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37595-6
    DOI: 10.1038/s41467-023-37595-6
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    References listed on IDEAS

    as
    1. Eugenia Migliavacca & Stacey K. H. Tay & Harnish P. Patel & Tanja Sonntag & Gabriele Civiletto & Craig McFarlane & Terence Forrester & Sheila J. Barton & Melvin K. Leow & Elie Antoun & Aline Charpagne, 2019. "Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
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