Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.
Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.
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DOI：
10.1016/j.cmet.2018.02.001
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发表时间：
2018-03-06
期刊：
影响因子：
29
通讯作者：
de Cabo R
中科院分区：
文献类型：
--
作者：
Mitchell SJ;Bernier M;Aon MA;Cortassa S;Kim EY;Fang EF;Palacios HH;Ali A;Navas-Enamorado I;Di Francesco A;Kaiser TA;Waltz TB;Zhang N;Ellis JL;Elliott PJ;Frederick DW;Bohr VA;Schmidt MS;Brenner C;Sinclair DA;Sauve AA;Baur JA;de Cabo R
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 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. Though neither hepatic NAD+ nor NADP+ were 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. Interventions that increase NAD+ bioavailability are of therapeutic interest for the improvement of healthspan and lifespan. Mitchell, Bernier et al. show that chronic treatment with nicotinamide, a NAD+ precursor, is associated with health improvements and lower inflammation in the absence of lifespan extension in high-fat diet-fed mice.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
82.9
作者：
Hong S;Moreno-Navarrete JM;Wei X;Kikukawa Y;Tzameli I;Prasad D;Lee Y;Asara JM;Fernandez-Real JM;Maratos-Flier E;Pissios P
通讯作者：
Pissios P
影响因子：
29
作者：
Camacho-Pereira J;Tarragó MG;Chini CCS;Nin V;Escande C;Warner GM;Puranik AS;Schoon RA;Reid JM;Galina A;Chini EN
通讯作者：
Chini EN
影响因子：
4.8
作者：
Bitterman, KJ;Anderson, RM;Sinclair, DA
通讯作者：
Sinclair, DA
影响因子：
11.1
作者：
Khan, Nahid A.;Auranen, Mari;Paetau, Ilse;Pirinen, Eija;Euro, Liliya;Forsstrom, Saara;Pasila, Lotta;Velagapudi, Vidya;Carroll, Christopher J.;Auwerx, Johan;Suomalainen, Anu
通讯作者：
Suomalainen, Anu