Impact of chronic nicotinamide supplementation on health and survival in mice

ABSTRACT: Interventions that increase NAD+ bioavailability activate sirtuins and prolong lifespan in mice. Whether nicotinamide (NAM) supplementation is beneficial to health is not known and difficult to predict. While NAM is a precursor to NAD+ it is also an inhibitor of sirtuins. We report that NAM supplementation in mice raises NAD+ levels and improves a variety of health parameters in high-fat diet (HFD)-fed mice, including reduced hepatosteatosis and protein carbonylation, improved glucose homeostasis and locomotor activity, and lower anxiety. Functional shifts in glucose, branched-chain amino acids and urea metabolism were apparent in HFD-fed mice but not SD mice. In contrast, no increase in lifespan was seen on either a standard or HFD, coincident with increased acetylation of Sirt1 target proteins. Together, these data indicate that NAM supplementation, while leading to increases in NAD+ and improving health under HFD, fails to provide any longevity benefits, perhaps through NAM’s inhibitory effects on sirtuins. Overall design: Microarray analysis was performed on 32 animals, with no nicotinamide (NAM) supplementation (N=6) for standard (SD) or High fat diet (HFD), and SD group with low NAM (L, 0.5g NAM/kg chow); N=4 for HFD group with low NAM; N=5 for SD and HFD groups with high NAM (H, 1.0 g NAM/kg chow).

INSTRUMENT(S): Illumina MouseRef-8 v2.0 expression beadchip

ORGANISM(S): Mus Musculus

SUBMITTER: Kevin G Becker  

PROVIDER: GSE92499 | GEO |

SECONDARY ACCESSION(S): PRJNA357721

REPOSITORIES: GEO