Effects Of Hypoxic Training On Endocannabinoid System And Expression Of Lipid Metabolism Genes In Adipose Tissue Of Obese Mice

Objective Hypoxic training plays a positive role in reducing body weight and improving lipid metabolism,but the mechanism involved is still unclear.Excessive activation of endogenous cannabinoid system dominated by CB1 in obese individuals.The inhibition of CB1 signaling obesity is reversed,and lipid metabolism disorders are corrected.The aim of this study is to investigate whether hypoxia training can improve the adipose tissue lipid metabolism disorder in obese mice and to inhibit the excessive activation of endocannabinoid system,and provide more theoretical basis for hypoxia training to reduce weight.Methods 4-week-old SPF-class C57BL/6J male mice were randomly divided into the normal diet group(SD,n=18)and the high-fat diet induction group(HFD,n=60)after1 week of adaptive feeding.After 12 weeks of feeding,the mice in the HFD group weighed 20% of the average body weight of the SD group as obese mice.Part of the mice were taken to verify obesity.After the obese model was established,obese mice were randomly divided into an diet-induced obese group(DIO,n=9,high-fat diet,no intervention),training group(T,n=9,running platform slope 0%,speed: 14 m/min,Time: 60 min/d,frequency: 6d/w),hypoxic exposure group(H,n=9,hypoxia exposure during the day: mice were exposed to 14.4% oxygen at 1 atmosphere absolute for 8h/d,6d/w;training at night:14m/min,60min/d,6d/w),hypoxic training group(HT,n=9,hypoxic exposure combined with training intervention program),at the same time seting up a control group(CON,n = 9,normal diet,no intervention).The body weight of each group of mice was recorded at a fixed time per week for a four-week intervention.The rats were harvested within 24 hours after the intervention,and the perirenal and epididymal fat tissues of the mice were collected.Calculate the amount of abdominal fat and abdominal fat ratio in mice.HE staining for observation of adipose tissue morphological changes in mice.RT-qPCR was used to compare the expression of endocannabinoid gene and lipid metabolism gene mRNA in adipose tissue after mouse intervention.Results 1.After 12-week highfat diet,the abdominal fat ratio of mice in HFD group was significantly higher than that in SD group(P<0.01).HE staining showed that the volume of adipocytes in the HFD group was significantly increased.FBG(P<0.01)and serum LDL-C(P<0.01)were significantly higher than SD group.Serum cannabinoid 2-AG(P<0.05)and AEA(P<0.01)levels in HFD group were significantly higher than SD group.2.After 4 weeks of intervention,compared with the DIO group,the abdominal fat mass of the mice in the H group(P<0.05)and the HT group(P<0.01)was significantly lower.There was also a significant decrease in abdominal fat ratio in H group(P<0.05)and HT group(P<0.01).HE staining showed that the volume of adipocytes in the HT group was significantly reduced compared with the DIO group,but there was no significant change in the T group and the H group.3.After 4 weeks of intervention,compared with DIO group,the expression of ATGL mRNA in adipose tissue of HT group was significantly increased(P<0.05).Three intervention methods can significantly reduce the expression of SREBP-1c mRNA in adipose tissue(P<0.01).Compared with the DIO group,there was no significant difference in the expression of ACC1 mRNA in the adipose tissue of the T group,H group and HT group;In addition,compared with the DIO group,the expression levels of FAS mRNA in the H group(P<0.05)and the HT group(P<0.01)decreased significantly;4.Under hypoxic training,the expression of SREBP-1c mRNA in adipose tissue was significantly positively correlated with CB1(P<0.01)and NAPE-PLD(P<0.01)mRNA expression.At the same time,the expression of FAS mRNA in adipose tissue was also positively correlated with CB1(P<0.01)and NAPE-PLD(P<0.01)mRNA expression.5.After hypoxic training,compared with the DIO group,the CB1 mRNA in the adipose tissue of the HT group was significantly decreased(P<0.01),and the expression of NAPE-PLD mRNA was significantly decreased(P<0.05).There was no statistical difference in DAGL?.Compared with the DIO group,the expression levels of MAGL mRNA(P<0.05)and FAAH mRNA(P<0.05)in the HT group were significantly increased.Conclusions 1.4 weeks of hypoxic training effectively reduced the body fat content and abdominal fat ratio in obese mice,down-regulated the expression of key genes SREBP-1c and FAS mRNA in adipose tissue fat synthesis,and increased the expression of ATGL mRNA,a key enzyme in lipolysis.,and the effect of hypoxic training was better than that of hypoxia or aerobic training alone.2.The improvement of lipid metabolism in adipose tissue by hypoxic training may be related to the decrease of CB1 expression,the decrease of cannabinoid synthase NAPE-PLD,and the increase of degrading enzymes MAGL and FAAH in adipose tissue.