Lee Hee Jae, Hong Young-Shick, Jun Woojin, Yang Soo Jin
1 Division of Food and Nutrition, Human Ecology Research Institute, Chonnam National University , Gwangju, Korea.
2 Department of Food and Nutrition, Seoul Women's University , Seoul, Korea.
J Med Food. 2015 Nov;18(11):1207-13. doi: 10.1089/jmf.2015.3439. Epub 2015 May 14.
Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome.
低度慢性炎症（代谢性炎症）是2型糖尿病、肥胖症和心血管疾病等代谢性疾病发生和发展的主要促成因素。存在于牛奶和啤酒中的烟酰胺核糖（NR）是一种对代谢调节具有有益作用的功能性维生素B3。然而，NR的抗炎能力尚不清楚。本研究评估了NR是否调节肝脏核苷酸结合寡聚化结构域样受体家族含pyrin结构域3（NLRP3）炎性小体。将8周龄雄性KK/HlJ小鼠分为对照组或NR组。通过渗透泵给予NR（100mg/kg/天）或载体（磷酸盐缓冲盐水），持续7天。分析血糖控制、血脂谱、NLRP3炎性小体和炎症标志物，并进行结构和组织学分析。NR治疗不影响体重增加、食物摄入量和肝功能。基于口服葡萄糖耐量试验的血糖控制以及血清胰岛素和脂联素水平通过NR治疗得到改善。在测试的血脂谱中，NR降低了肝脏中的总胆固醇浓度。分别通过苏木精和伊红染色以及透射电子显微镜进行的组织学和结构分析表明，NR挽救了肥胖和糖尿病KK小鼠肝脏中线粒体和细胞核受损的细胞完整性。此外，NR治疗显著改善了肝脏促炎标志物，包括肿瘤坏死因子-α、白细胞介素（IL）-6和IL-1。这些改善伴随着NLRP3炎性小体成分（NLRP3、ASC和半胱天冬酶1）的显著变化。这些结果表明，NR通过调节NLRP3炎性小体减轻肝脏代谢性炎症。
