The protective effect of nicotinamide riboside against age-induced hepatic disease in mice
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Abstract
Background & Aims. Aging is one of the key triggers of non-alcoholic fatty liver disease (NAFLD). Yet, the pathomechanism of the age-associated NAFLD is not fully understood. Nicotinamide adenine dinucleotide (NAD), an ubiquitous coenzyme, has beneficial effects on aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of age-induced NAFLD. Methods. NR supplied food (2.5g/kg food) was applied to aged mice for three months. Changes of body weight, food intake, hepar weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammation infiltrated. Results. NR significantly reduced fat pat mass, lipid content and AST in aged mice, but didn't modify in terms of body weight, food intake, hepar weight and ALT in aged mice. Given normal chow, aged mice displayed decline of NAD concentration. In aged mice model, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis (Masson's trichrome staining and TGF-β staining) were observed in liver. In addition, Kupffer cells accumulated and pro-inflammatory cytokines expression were more aggravated in hepatic tissues. Whereas, NR administration completely corrected these NAFLD phenotypes and inflammation infiltrated in liver. Conclusion. NR has benefits on age-associated lipid accumulation and hepatic steatosis, and the oral uptake of NR may be a promising strategy to prevent the progression of NAFLD.
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2019. The protective effect of nicotinamide riboside against age-induced hepatic disease in mice. PeerJ Preprints 7:e27705v1 https://doi.org/10.7287/peerj.preprints.27705v1note This preprint is not peer-reviewed. You may wish to reference the subsequent peer-reviewed version of this article.
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This is a submission to PeerJ for review.
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Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Xue Han conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
Xiaogang Bao performed the experiments.
Qi Lou performed the experiments, contributed reagents/materials/analysis tools.
Xian Xie analyzed the data, contributed reagents/materials/analysis tools.
Shasang Zhou performed the experiments.
Guojun Jiang conceived and designed the experiments, authored or reviewed drafts of the paper.
Animal Ethics
The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):
Institutional Animal Care and Use Committee of the Zhejiang Academy of Medical Sciences provided full approval for this research (DLSY.2017(80)).
Data Deposition
The following information was supplied regarding data availability:
The raw measurements are provided in the supplementary files1.
Funding
This study was supported by the Natural Science Foundation of Zhejiang (Grants LGJ18H310002, LQY19H090001, LY18H310009 and LQY18C040001) and the Shanghai Committee of Science and Technology, China (Grant No. 15411951000 and 2018QN13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
