Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway.
Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway.
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DOI：
10.1016/j.redox.2018.04.006
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发表时间：
2018-07
期刊：
影响因子：
11.4
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Wang S;Wan T;Ye M;Qiu Y;Pei L;Jiang R;Pang N;Huang Y;Liang B;Ling W;Lin X;Zhang Z;Yang L
烟酰胺核苷 (NR) 是一种烟酰胺腺嘌呤二核苷酸 (NAD+) 前体，存在于牛奶和啤酒等食品中。据报道，NR可以预防肥胖、延长寿命、促进肝再生。然而，NR 是否可以预防乙醇引起的肝损伤尚不清楚。本研究旨在探讨NR对乙醇所致肝损伤的影响及其潜在机制。我们用含有或不含400mg/kg·bw NR的Lieber-DeCarli乙醇液体饲料喂养C57BL/6J小鼠16天。分析肝损伤和 SirT1-PGC-1α-线粒体功能。体外实验中，HepG2细胞（CYP2E1过表达细胞）与乙醇±0.5mmol/L NR一起孵育。比较脂质积累和线粒体功能。进一步应用HepG2细胞中的SirT1敲低来证实SirT1在保护NR对脂质积累的作用中的作用。我们发现乙醇显着降低小鼠肝脏SirT1的表达和活性，并诱导脂质代谢酶的异常表达。体内和体外实验均表明，NR 通过增加 NAD+ 水平、减少氧化应激、增加 PGC-1α 的脱乙酰化和线粒体功能来激活 SirT1。在 SirT1 敲除的 HepG2 细胞中，NR 失去了增强线粒体功能的能力，以及对乙醇诱导的脂质积累的保护作用。 NR 可以通过补充 NAD+、减少氧化应激和激活 SirT1-PGC-1α-线粒体生物合成来防止乙醇引起的肝损伤。我们的数据表明，SirT1 在保护 NR 免受乙醇诱导的脂质积累和线粒体功能障碍方面发挥着重要作用。 NR可以逆转乙醇引起的肝脂肪变性和氧化应激。增强 NAD+、NR 通过调节 SirT1/PGC-1α 增强线粒体功能。 SirT1 在 NR 预防酒精性肝损伤中发挥着重要作用。
Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor which is present in foods such as milk and beer. It was reported that NR can prevent obesity, increase longevity, and promote liver regeneration. However, whether NR can prevent ethanol-induced liver injuries is not known. This study aimed to explore the effect of NR on ethanol induced liver injuries and the underlying mechanisms. We fed C57BL/6 J mice with Lieber-DeCarli ethanol liquid diet with or without 400 mg/kg·bw NR for 16 days. Liver injuries and SirT1-PGC-1α-mitochondrial function were analyzed. In in vitro experiments, HepG2 cells (CYP2E1 over-expressing cells) were incubated with ethanol ± 0.5 mmol/L NR. Lipid accumulation and mitochondrial function were compared. SirT1 knockdown in HepG2 cells were further applied to confirm the role of SirT1 in the protection of NR on lipid accumulation. We found that ethanol significantly decreased the expression and activity of hepatic SirT1 and induced abnormal expression of enzymes of lipid metabolism in mice. Both in vivo and in vitro experiments showed that NR activated SirT1 through increasing NAD+ levels, decreased oxidative stress, increased deacetylation of PGC-1α and mitochondrial function. In SirT1 knockdown HepG2 cells, NR lost its ability in enhancing mitochondrial function, and its protection against lipid accumulation induced by ethanol. NR can protect against ethanol induced liver injuries via replenishing NAD+, reducing oxidative stress, and activating SirT1-PGC-1α-mitochondrial biosynthesis. Our data indicate that SirT1 plays an important role in the protection of NR against lipid accumulation and mitochondrial dysfunctions induced by ethanol. NR could reverse ethanol induced hepatic steatosis and oxidative stress. Boosting NAD+, NR enhanced mitochondrial functions by regulating SirT1/ PGC-1α. SirT1 played an important role in NR's protection against alcohol liver injuries.
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影响因子：
25.7
作者：
Derdak, Zoltan;Villegas, Kristine A.;Harb, Ragheb;Wu, Annie M.;Sousa, Aryanna;Wands, Jack R.
通讯作者：
Wands, Jack R.
DOI：
10.1152/ajpgi.00456.2009
发表时间：
2010-03-01
影响因子：
4.5
作者：
Shen, Zheng;Liang, Xiaomei;You, Min
通讯作者：
You, Min
DOI：
10.1073/pnas.0702509104
发表时间：
2007-07-31
影响因子：
11.1
作者：
Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
4.8
作者：
Ponugoti, Bhaskar;Kim, Dong-Hyun;Kemper, Jongsook Kim
通讯作者：
Kemper, Jongsook Kim
DOI：
10.1152/ajpgi.90358.2008
发表时间：
2008-10-01
影响因子：
4.5
作者：
Ajmo, Joanne M.;Liang, Xiaomei;You, Min
通讯作者：
You, Min