Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
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DOI：
10.7717/peerj.7568
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发表时间：
2019-08-28
期刊：
影响因子：
2.7
通讯作者：
Shi, Qiaojuan
中科院分区：
文献类型：
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作者：
Han, Xue;Bao, Xiaogang;Shi, Qiaojuan
背景和目标。衰老是非酒精性脂肪肝（NAFLD）的危险因素之一。然而，与衰老相关的 NAFLD 样综合征的潜在机制尚不完全清楚。烟酰胺腺嘌呤二核苷酸（NAD）是一种普遍存在的辅酶，具有抗衰老的保护作用。在这里，我们研究了 NAD 前体烟酰胺核苷 (NR) 对衰老引起的 NAFLD 发展的作用。方法。给老年小鼠喂食NR补充食品（2.5克/千克食物）三个月，而其他组则喂食正常食物。测量体重、食物摄入量、肝脏重量和脂肪质量。通过生化测定测定脂质含量、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和NAD的血清浓度。采用肝组织病理学评估和免疫组化分析评价NR对NAFLD发展和炎症浸润的影响。结果。补充NR显着减少了老年小鼠的脂肪质量，但没有改变体重、食物摄入量和肝脏重量。补充 NR 可以显着挽救老年小鼠 NAD 的减少。补充 NR 可以降低老年小鼠的总胆固醇和甘油三酯水平。老年组补充NR后，AST水平也显着降低，而ALT水平降低，但无显着性。值得注意的是，中度 NAFLD 表型，包括脂肪变性和肝纤维化，可以通过 NR 补充得到显着纠正。此外，老年小鼠中NR的补充也可以显着逆转库普弗细胞的积累和炎症浸润。结论。小鼠的衰老与 NAFLD 样表型相关，这种表型可以通过口服 NR 补充来逆转。因此，口服 NR 摄取可能是阻止 NAFLD 进展的一种有前途的策略。
Background & Aims. Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD.Methods. NR supplemented food (2.5 g/kg food) was applied to aged mice for three months while normal chow to the other groups. Body weight, food intake, liver 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 inflammatory infiltration.Results. NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice. The AST level was also significantly reduced by NR repletion in aged group, while the ALT level lowered but without significance. Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice.Conclusion. Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.