NAD + repletion with niacin counteracts cancer cachexia
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 mit...
Saved in:
Published in | Nature communications Vol. 14; no. 1; p. 1849 |
---|---|
Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Nature Publishing Group
03.04.2023
Nature Publishing Group UK Nature Portfolio |
Subjects | |
Online Access | Get full text |
Cover
Loading…
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 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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-023-37595-6 |