Effects Of Hypoxia Training On Insulin Resistance And Hepatic CB1 In Obese Mice

Objective:Obesity induces insulin resistance in the body and increases the expression of CB1 in the liver.Hypoxic training can improve on insulin resistance.However,the effect of hypoxic training on liver CB1 expression and the role of liver CB1 in hypoxic training regulating insulin resistance are still unclear.The purpose of this study was to establish a high-fat mouse model of obesity insulin resistance through a high-fat diet to investigate the role of liver CB1 in hypoxia training in regulating insulin resistance in obese mice.Method:We selected 65 4-week-old C57BL/6J male mice.They were randomly divided into standard diet group(SD,n = 20,were fed normal diet)group and high fat diet-induced group(HFD,n = 45,feeding with high fat diet,D12492,60% of energy from fat),for 12 weeks.After 12 weeks of the high-fat diet,the body weight of the mice exceeded 20% of the average of the control mice were considered to be obese mice.Some obese mice were sacrificed for obesity and insulin resistance model validation.Then,the obese mice were randomly divided into obesity control group(DIO,n=9,high-fat diet,quiet),training group(T,n=9,running treadmill every night,running platform slope is 0 °,speed 14min/min,time 60 min,frequency: 6d/w),hypoxia exposure group(H,n=9,the mice were placed in the TSE Pheno Master system hypoxic chamber every day during the day,oxygen partial pressure: 110 mmHg,atmosphere Oxygen content 14.4%,time: 8h / d,frequency: 6d / w),hypoxic training group(HT,n=9,hypoxia combined with training).All groups were given a 4-week intervention.After 4 weeks of intervention,the mice were sacrificed and collected,serum,left and right epididymal fat,left and right perirenal fat,liver.The mice body weight changes and abdominal fat ratio were calculated;The fasting insulin(FINS)and insulin resistance index(HOMA-IR),insulin sensitivity index(ISI),and insulin tolerance,glucose tolerance test were comprehensively utilized to evaluate the establishment of animal models and experimental intervention effect.Liver CB1 expression was detected by RT-qPCR and Western blot(WB).Results: 1.Establishment of a mice model of obesity insulin resistance induced by high fat dietThe results showed that the body weight and abdominal fat ratio in the HFD group were significantly greater than those in the SD group after 12 weeks of high-fat diet(P<0.01,P<0.01).Compared with the SD group,the fasting blood glucose level in the HFD group increased(P<0.01),the fasting insulin level increased(P<0.05),the insulin resistance index increased(P<0.01),and insulin sensitivity decreased(P<0.01).And compared with the SD group,the glucose tolerance and insulin tolerance of the HFD group were severely impaired.2.Changes in liver CB1 expression in obese insulin resistant mice After 12 weeks of high-fat diet,the expression of CB1 gene and protein in liver of HFD group increased compared with SD group(P<0.05,P<0.05).3.Effects of hypoxic training on insulin resistance in obese miceAfter hypoxic training intervention,the body weight of the T group(P<0.01),H group(P<0.01),and HT group(P<0.01)decreased significantly,and the decrease of HT group was the most obvious,compared with the DIO group.The liposome ratio of group H(P<0.01)and HT group(P<0.01)was also significantly lower than group DIO.Compared with the DIO group,the fasting blood glucose levels of the H group(P<0.01)and the HT group(P<0.01)decreased significantly,and the fasting insulin levels of the HT(P<0.01)group decreased significantly;the H group(P<0.01)and HT Insulin resistance index decreased in group(P<0.01),and insulin sensitivity increased in group H(P<0.05)and group T(P<0.01).The glucose tolerance and insulin tolerance of the HT group were improved relative to the DIO group.4.Effects of hypoxic training on the expression of liver CB1 in obese insulin resistant mice After 4 weeks of hypoxic training,the expression of CB1 gene and protein in liver of HT group decreased compared with DIO group(P<0.05,P<0.05).5.The role of liver CB1 in hypoxia training to improve insulin resistance in obese mice After 4 weeks of intervention,compared with the DIO group,the fasting blood glucose level of the WIN+HT group(P<0.01)was significantly decreased,the fasting insulin level of the HT(P<0.01)group was significantly decreased,the insulin resistance index decreased,and glucose tolerance and Insulin tolerance is improved.Conclusions: 1.Hypoxia training can reduce weight and improve insulin resistance in obese mice,which is better than simple hypoxia or simple training.2.Obesity can cause insulin resistance in the body and cause overexpression of CB1 in the liver.Hypoxia can inhibit the overexpression of CB1.3.The effect of hypoxic training on insulin resistance in obese mice may be independent of the regulation of liver CB1 expression in mice.