Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA; Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Cell Metab. 2018 Mar 6;27(3):667-676.e4. doi: 10.1016/j.cmet.2018.02.001.
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.
烟酰胺（NAM）是 NAD 的生理前体，其在长寿和健康寿命中的作用尚不清楚。在这里，我们报告称，慢性 NAM 补充可改善高脂肪饮食（HFD）小鼠的健康寿命衡量标准，而不会延长其寿命。对肝脏的非靶向代谢物分析和源自肝脏的细胞的代谢通量分析显示，NAM 可改善 HFD 小鼠的葡萄糖稳态，这与肝脂肪变性和炎症减少以及糖原沉积和戊糖磷酸和糖酵解途径通量增加相关。对肝脏的靶向 NAD 代谢组分析显示，NAM 处理的小鼠中 NAM 回收的表达降低，而新的 NAD 生物合成酶的表达增加则抵消了这种作用。尽管 NAM 并未增加肝 NAD 或 NADP，但 NAM 补充可在饮食和 NAM 剂量依赖性的方式下增强某些 SIRT1 靶标的乙酰化。总的来说，我们的结果表明，在没有生存效应的情况下，补充 NAM 的 HFD 喂养的小鼠的健康状况得到了改善。
