NAD⁺ repletion with niacin counteracts cancer cachexia
Beltrà, Marc; Pöllänen, Noora; Fornelli, Claudia; Tonttila, Kialiina; Hsu, Myriam Y.; Zampieri, Sandra; Moletta, Lucia; Corrà, Samantha; Porporato, Paolo E.; Kivelä, Riikka; Viscomi, Carlo; Sandri, Marco; Hulmi, Juha J.; Sartori, Roberta; Pirinen, Eija; Penna, Fabio (2023-04-03)
Beltrà, M., Pöllänen, N., Fornelli, C. et al. NAD⁺ repletion with niacin counteracts cancer cachexia. Nat Commun 14, 1849 (2023). https://doi.org/10.1038/s41467-023-37595-6
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https://urn.fi/URN:NBN:fi-fe20230921134573
Tiivistelmä
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.
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