Ontology highlight
ABSTRACT: Background
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.Methods
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-1?-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.Results
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-1? 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.Conclusions
NR can protect against ethanol induced liver injuries via replenishing NAD+, reducing oxidative stress, and activating SirT1-PGC-1?-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.
SUBMITTER: Wang S
PROVIDER: S-EPMC6007172 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Wang Sufan S Wan Ting T Ye Mingtong M Qiu Yun Y Pei Lei L Jiang Rui R Pang Nengzhi N Huang Yuanling Y Liang Baoxia B Ling Wenhua W Lin Xiaojun X Zhang Zhenfeng Z Yang Lili L
Redox biology 20180405
<h4>Background</h4>Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD<sup>+</sup>) 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.<h4>Methods</h4>We fed C57BL/6 J mice with Lieber-DeCar ...[more]