RT Journal Article
SR Electronic
T1 NAD<sup>+</sup> repletion with niacin counteracts cancer cachexia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.06.499010
DO 10.1101/2022.07.06.499010
A1 Marc Beltrà
A1 Noora Pöllänen
A1 Claudia Fornelli
A1 Kialiina Tonttila
A1 Myriam Y. Hsu
A1 Sandra Zampieri
A1 Lucia Moletta
A1 Paolo E. Porporato
A1 Riikka Kivelä
A1 Marco Sandri
A1 Juha J. Hulmi
A1 Roberta Sartori
A1 Eija Pirinen
A1 Fabio Penna
YR 2022
UL http://biorxiv.org/content/early/2022/07/06/2022.07.06.499010.abstract
AB 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 confirmed that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of different mouse models and cachectic cancer patients. Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia. To examine NAD+ metabolism in a clinical setting, we showed that the low expression of NRK2 in cancer patients correlated with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose a novel therapy target, NAD+ metabolism, for cachectic cancer patients.Competing Interest StatementThe authors have declared no competing interest.