SUMMARY
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 Statement
The authors have declared no competing interest.
Footnotes
↵13 These authors jointly supervised this work: Roberta Sartori, Eija Pirinen, Fabio Penna. e-mail: roberta.sartori{at}unipd.it; eija.pirinen{at}helsinki.fi; fabio.penna{at}unito.it.