NAD+ repletion with niacin counteracts cancer cachexia
Beltrà, M., Pöllänen, N., Fornelli, C., Tonttila, K., Hsu, M. Y., Zampieri, S., Moletta, L., Corrà, S., Porporato, P. E., Kivelä, R., Viscomi, C., Sandri, M., Hulmi, J. J., Sartori, R., Pirinen, E., & Penna, F. (2023). NAD+ repletion with niacin counteracts cancer cachexia. Nature Communications, 14, Article 1849. https://doi.org/10.1038/s41467-023-37595-6
Julkaistu sarjassa
Nature CommunicationsTekijät
Päivämäärä
2023Tekijänoikeudet
© The Author(s) 2023
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.
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Nature Publishing GroupISSN Hae Julkaisufoorumista
2041-1723Asiasanat
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https://converis.jyu.fi/converis/portal/detail/Publication/182673048
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We are grateful to Dr. Gareth G Lavery (Department of Biosciences, Nottingham Trent University) who kindly donated the antibody against the NRK2 protein. Also, we thank Valentina Audrito (DISIT, University of Piemonte Orientale) for reviewing and advising on the first draft of the paper. This work was supported by Fondazione AIRC (IG 2018—ID. 21963 project, PI: F.P.), the Finnish Cancer Foundation, Finnish Cancer Center FICAN South (PIs: E.P. and Dr. Tommi Järvinen, respectively), the Academy of Finland (profi6 336449 to E.P.), The Finnish Medical Foundation (doctoral research grant to N.P.), and by two post-doctoral Fellowships from Fondazione Umberto Veronesi (ID2496 and ID3519 to R.S). Figures 3a, j and 6 were created with BioRender.com. ...Lisenssi
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Activin Receptor Ligand Blocking and Cancer Have Distinct Effects on Protein and Redox Homeostasis in Skeletal Muscle and Liver
Hentilä, Jaakko; Nissinen, Tuuli; Korkmaz, Ayhan; Lensu, Sanna; Silvennoinen, Mika; Pasternack, Arja; Ritvos, Olli; Atalay, Mustafa; Hulmi, Juha (Frontiers Research Foundation, 2019)Muscle wasting in cancer cachexia can be alleviated by blocking activin receptor type 2 (ACVR2) ligands through changes in protein synthesis/degradation. These changes in cellular and protein metabolism may alter protein ...
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