NR对C57BL/6J小鼠糖耐量、胰岛素抵抗的影响及其机制  

The effects and underlying mechanism of NR on glucose tolerance and insulin resistance in C57BL/6J mice

作　　者：姜瑞 王素凡 丘云 裴蕾 杨丽丽[1] JIANG Rui;WANG Su-fan;QIU Yun;PEI Lei;YANG Li-li(Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China)

机构地区：[1]中山大学公共卫生学院营养与食品卫生学系,广东广州510080

出　　处：《热带医学杂志》2018年第4期435-439,共5页Journal of Tropical Medicine

基　　金：国家自然科学基金(81370528);国家自然科学基金(81573142);广东省特支计划青年拔尖人才项目基金(2016TQ03R517)

摘　　要：目的探索尼克酰胺核糖(NR)能否通过保护棕色脂肪(BAT)中线粒体,增加BAT代谢活性,改善高脂加酒精诱导的小鼠糖耐量和胰岛素抵抗。方法将C57BL/6J小鼠随机分为对照组、高脂酒精组(H+E组)、400 mg/(kg·d)NR干预组、800 mg/(kg·d)NR干预组和治疗组(T组),进行为期16周的动物干预实验。采用糖耐量实验(OGTT)、胰岛素抵抗实验(IPITT)观察小鼠糖耐量及胰岛素抵抗情况;小动物PET/CT显像技术检测棕色脂肪形态及活性改变;透射电镜观察棕色脂肪及白色脂肪(e WAT)中线粒体数目及形态改变。结果糖耐量实验中,120 min时800NR组、T组血糖变化比值较H+E组小鼠低(P<0.05)。800NR组血糖曲线下面积(AUC)对比H+E组显著降低,差异有统计学意义(P<0.05)。胰岛素抵抗试验中,对比H+E组,60 min时400NR组、800NR组、T组血糖变化比值均降低(P<0.05),30 min及90 min时,T组血糖变化比值降低(P<0.05)。PET/CT显示400NR组、800NR组、T组小鼠BAT较H+E组小鼠形态增大。透射电镜显示H+E组小鼠BAT线粒体数目减少,形态不完整,400NR组小鼠线粒体数目增多,线粒体嵴增加。结论 NR可通过增加线粒体数目,保护线粒体结构,增加BAT活性,改善高脂酒精诱导的小鼠葡萄糖不耐受和胰岛素抵抗。Objective This study investigated whether nicotinamide riboside（NR）could protect mitochondria in brown adipose tissu（BAT）,increase the BAT metabolic activity,and further ameliorate the glucose tolerance and insulin resistance in mice induced by a high fat diet plus ethanol stimulation. Methods C57BL/6J mice were divided randomly into 5 groups,which respectively were control group,high fat diet plus ethanol group（H＋E group）,400 mg/（kg·d）NRpreventive group,800 mg/（kg·d）NR preventive group and NR therapeutic group（T group）. The whole animal experiment proceeded for 16 weeks. Oral glucose tolerance test（OGTT）and intraperitoneal insulin resistance（IPITT）experiment were used for observing the glucose tolerance and insulin resistance in mice. PET/CT was used for observing the variations of morphologyand activity in BAT. Transmission electron microscope was used for exploring the variations of mitochondria inBAT and epididymal white adipose tissue（e WAT）. Results In the OGTT,the relative blood glucose ratio（blood glucose/blood glucose at 0 min）of 800 NR and T group were decreased comparing with H＋E group mice,after glucose treatment for 120 min（P〈0.05）. Area under the curve（AUC）of 800 NR group was decreased comparing with H＋E group（P〈0.05）. In the IPITT,comparing with H＋E group mice,the relative blood glucose ratio of 400 NR group,800 NR group and T group mice were decreased after insulin treatment for 60 min（P〈0.05）,and the relative blood glucose ratio of T group mice were decreased after insulin treatment for 30 min and 90 min（P〈0.05）. Result of PET/CT demonstrated that BAT of 400 NR group,800 NR group and T group mice were bigger than BAT of H＋E group mice in size. Result of transmission electron microscope showed that the mitochondria in H＋E group mice BAT were reduced and incomplete comparing with control group mice. Mitochondria and mitochondrial cristaes in 400 NR group mice BAT were increased. Conclusion NR could protect against the

关 键 词：尼克酰胺核糖 棕色脂肪 线粒体 糖耐量 

分 类 号：R587.1[医药卫生—内分泌]