Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway
Sufan Wang,
Ting Wan,
Mingtong Ye,
Yun Qiu,
Lei Pei,
Rui Jiang,
Nengzhi Pang,
Yuanling Huang,
Baoxia Liang,
Wenhua Ling,
Xiaojun Lin,
Zhenfeng Zhang,
Lili Yang
Affiliations
Sufan Wang
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China
Ting Wan
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China
Mingtong Ye
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China
Yun Qiu
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China
Lei Pei
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China
Rui Jiang
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China
Nengzhi Pang
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China
Yuanling Huang
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China
Baoxia Liang
Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China
Wenhua Ling
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China
Xiaojun Lin
Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China; Corresponding authors.
Zhenfeng Zhang
Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China; Corresponding authors.
Lili Yang
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, PR China; Corresponding author at: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
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-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. 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-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. Conclusions: 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. Keywords: Alcoholic liver disease, NAD+, Nicotinamide Riboside, SirT1, Oxidative stress, Mitochondrial biosynthesis