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Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice

2018; Cell Press; Volume: 27; Issue: 3 Linguagem: Inglês

10.1016/j.cmet.2018.02.001

1932-7420

Sarah J. Mitchell, Michel Bernier, Miguel A. Aon, Sonia Cortassa, Eun Young Kim, Evandro Fei Fang, Hector H. Palacios, Ahmed Ali, Ignacio Navas‐Enamorado, Andrea Di Francesco, Tamzin Kaiser, Tyler B. Waltz, Ning Zhang, James L. Ellis, Peter J. Elliott, David W. Frederick, Vilhelm A. Bohr, Mark S. Schmidt, Charles Brenner, David Sinclair, Anthony A. Sauve, Joseph A. Baur, Rafael de Cabo,

Adipose Tissue and Metabolism

The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+, is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD+ nor NADP+ was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects.