Effect of nicotinamide riboside on insulin resistance in mice liver
Objective To explore whether nicotinamide ribose(NR)can improve hepatic insulin resistance.Methods C57BL/6J mice were randomly divided into control group(n=8),model group(n=8),and NR intervention group(NR group,n=7).The control group was fed with the standard control diet(XT 304)with double steam gavage daily;the model group and nicotinamide ribose intervention group were given high fructose and high fat diet(XT 310,40％carbohydrate,40％fat),the model group received distilled gavage daily and the NR group received 400 mg/(kg·BW daily)NR solution gavage intervention.The whole animal experiment proceeded for 11 weeks.Oral glucose tolerance test(OGTT)and fasting insulin test were used to evaluate the glucose regulation ability of mice.Liver hematoxylin and eosin staining sections were used to verify whether hepatic lipid accumulation could be alleviated by NR.HepG2 cells were intervened with 0.25 mmol/L palmitic acid(PA)for 24 h to establish an insulin resistance model,and 0.5 mmol/L NR was added for intervention.At the end of the intervention,100 nmol/L insulin was given to stimulate HepG2 cells for 30 minutes and then glucose uptake assay was performed.Mitotracker Red staining was used to preliminarily explore the mechanism of NR in preventing hepatic insulin resistance.Results At the termination of the experiment,the body weights of mice in each group were as follows:control group(28.60±0.72)g,model group(27.00±1.98)g,and NR group(23.44±1.89)g.Comparison of the body weights of the three groups of mice showed that there was a trend of lower body weight in the NR group,and the difference was statistically significant(F=33.540,P＜0.05).There was a significant difference in the area under the glucose tolerance curve among the three groups(F=7.003,P＜0.05),and the area under the glucose tolerance curve in the model group(1 579.25±313.21)was significantly higher(P＜0.05)compared with that in the control group(1 167.56±91.15).The area of the glucose tolerance curve was significantly lower in the NR group(1 334.25±102.00)compared to the model group(P＜0.05).The trends of insulin level and insulin resistance index in the three groups were consistent with the glucose tolerance experiment(P＜0.05).The liver lipid accumulation in NR group was reduced compared to model gorups.Cellular experiments demonstrated that NR ameliorated palmitic acid-induced diminished glucose uptake in HepG2 cells.Palmitic acid intervention led to decreased mitochondrial activity in hepatocytes,whereas NR ameliorated palmitic acid induced reduction of mitochondrial activity in hepatocytes(F=31.480,P＜0.05).Conclusions NR could ameliorate hepatic insulin resistance and the mechanism might be related to mitochondria.
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