Nicotinamide riboside (NR),
vitamin B3, is a substrate for
nicotinamide adenine dinucleotide (
NAD+)-consuming
enzymes and is a
coenzyme for hydride-transfer
enzymes, including
adenosine diphosphate (
ADP)-ribose transferases,
poly (ADP-ribose) polymerases,
cADP-ribose synthases, and
sirtuins, which play a central role in the aging process, neurodegenerative processes, and
myopathy. Since
cancer cachexia is a disease condition presenting with
weight loss, skeletal muscle
atrophy, and loss of adipose tissue in patients with advanced
cancer, we hypothesized that NR intake could ameliorate
sarcopenia. In this study, we investigated whether preemptive administration of NR ameliorated C26
adenocarcinoma-induced
cancer cachexia and explored anti-cachexic mechanisms focused on the changes in
muscle atrophy, cachexic
inflammation, and catabolic catastrophe. Dietary intake of the NR-containing pellet diet significantly attenuated
cancer cachexia in a mouse model. Starting with significant inhibition of cachexic factors,
tumor necrosis factor alpha, and
interleukin-6, NR significantly inhibited muscle-specific
ubiquitin-
proteasome ligases, such as atrogin-1, muscle RING-finger protein-1 (MuRF-1), mitofusin-2, and
peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PCG-1α). Significant inhibition of epididymal fat lipolysis was noted with significant inhibition of adipose
triglyceride lipase (ATGL) gene. Furthermore, NR administration significantly increased the levels of crucial
enzymes involved in the biosynthesis of NAD+ and
nicotinamide phosphoribosyl
transferase and significantly inhibited the
NAD+-sensitive deacetylase
sirtuin 1 (
SIRT1). Preemptive intake of NR in patients vulnerable to
cachexia can be a preemptive option to ameliorate
cancer cachexia.