Nicotinamide riboside induces a thermogenic response in lean mice
Nicotinamide riboside induces a thermogenic response in lean mice
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DOI：
10.1016/j.lfs.2018.09.015
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发表时间：
2018-10-15
期刊：
影响因子：
6.1
通讯作者：
Ropelle, Eduardo R.
中科院分区：
文献类型：
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作者：
Crisol, Barbara M.;Veiga, Camilla B.;Ropelle, Eduardo R.
目的：烟酰胺核苷(NR)是一种NAD(+)促进剂，具有广泛的生理作用，包括改善糖脂平衡，延长哺乳动物的预期寿命。然而，天然产物对新陈代谢的影响还只有一部分人知道。在这里，我们评估了NR对发热反应的影响，突出了瘦小鼠的棕色脂肪组织(BAT)。主要方法：雄性C57BL/67小鼠连续5周补充NR(400 mg/kg/d)。利用实验室动物综合监测系统(CLAMS)和热像仪对NR处理的生理效应进行了评价。提取蝙蝠，用Western blotting和qPCR进行分析。此外，生物信息学分析建立了蝙蝠NAD(+)合成途径与几个BXD小鼠等基因品系的发热反应之间的联系。关键发现：转录分析表明蝙蝠中参与NAD(+)合成的基因(NAMPT和Nmnat1)与体重和脂肪质量呈负相关。热图显示BAT中NAMPT和Ucp1基因的表达与几个品系BXD瘦小鼠的体温呈显著正相关。实验方法表明，口服NR减少了C57BL/6J小鼠的腹部内脏脂肪储备，并对耗氧量产生了离散的影响。有趣的是，NR显著提高了小鼠的体温，并伴随着BAT中UCP1蛋白和PGC1αmRNA的高水平表达。意义：本研究证明，口服NR足以诱导瘦小鼠的生热反应，改变BAT的代谢。
Aims: Nicotinamide Riboside (NR) is a NAD(+) booster with wide physiological repercussion including the improvement on glucose and lipid homeostasis, increasing the life expectancy in mammals. However, the effects of NR on metabolism are only partially known. Here, we evaluated the effects of NR on the thermogenic response, highlighting the brown adipose tissue (BAT) in lean mice.Main methods: Male C57BL/67 mice were supplement with NR (400 mg/Kg/day) during 5 weeks. The Comprehensive Lab Animal Monitoring System (CLAMS) and thermographic images were used to evaluated the physiological effects of NR treatment. The BAT were extracted and analyzed by Western Blotting and qPCR. Also, bioinformatics analyses were performed to establish the connection between the NAD(+) synthesis pathway in BAT and thermogenic response in several isogenic strains of BXD mice.Key findings: Transcriptomic analysis revealed that genes involved in NAD(+) synthesis (Nampt and Nmnat1) in the BAT were negatively correlated with body weight and fat mass. The heat map showed a strong positive correlation between Nampt and Ucp1 mRNA in BAT and body temperature in several strains of BXD lean mice. The experimental approaches demonstrated that oral NR supplementation reduced the abdominal visceral fat depots, with discrete impact on oxygen consumption in C57BL/6J mice. Interestingly, NR significantly increased the body temperature, and this phenomenon was accompanied by high levels of UCP1 protein content and Pgc1 alpha mRNA in BAT.Significance: This study demonstrated the oral NR supplementation was sufficient to induce the thermogenic response in lean mice changing the BAT metabolism.