| First Author | Beltrà M | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 1849 |
| PubMed ID | 37012289 | Mgi Jnum | J:335051 |
| Mgi Id | MGI:7460737 | Doi | 10.1038/s41467-023-37595-6 |
| Citation | Beltra M, et al. (2023) NAD(+) repletion with niacin counteracts cancer cachexia. Nat Commun 14(1):1849 |
| abstractText | 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. |
