Improvement Of Hyperlipidemia By Aerobic Exercise In Mice Through A Regulatory Effect Of MiR-21a On Its Target Genes

Purpose: Aerobic exercise affecting miRNA levels is an important mechanism for regulating lipid metabolism.Studies have shown that miR-21 a is an important target for lipid homeostasis.Through biological information prediction analysis,FABP7,HMGCR,PPAR?,PTEN,ACAT1 and OLR1 are the target genes of miR-21 a and closely related to lipid metabolism.Therefore,experiments were designed to verify aerobic exercise regulates lipid metabolism through miR-21a-induced changes of target genes.Methods: SPF male mice were randomly divided into three groups: Normal control group(NC group),High fat/ High cholesterol diet group(HH group),and High fat/ High cholesterol plus aerobic exercise group(HHE group).The NC group was given a normal diet,while the HH group and HHE group were given a high fat/ high cholesterol diet.And the HHE group was given eight weeks of aerobic exercise intervention on the basis of highfat/high-cholesterol diet.The exercise intensity was: 18m/min�45min,6% slope,6 days/week.After the last exercise intervention,injected anaesthetic,taken 2 mL blood sample from the eye socket,and then collected liver tissue.Plasma was separated and blood lipid level was detected by a spectrophotometer;liver tissues were stained with HE to check the degree of liver steatosis;QPCR was used to detect the expression level of miR-21 a and its target genes.Results: 1.The body weight of mice in the high-fat / high-cholesterol diet group showed a rapid upward trend,which was remarkably higher than that in the normal control group(P <0.05).However,on the basis of a high-fat / highcholesterol diet,8 weeks of aerobic exercise intervention can significantly reduce the weight of mice(P <0.05).2.Compared with NC group,serum TG,TC,LDL-C,HDL-C in HH group were significantly elevated,fat and cholesterol accumulation were evident.After 8 weeks of aerobic intervention,the blood lipid concentration of the mice in the HHE group returned to normal levels.3.The liver of mice with high-fat / high-cholesterol diet had steatosis,lipid droplets increased,and inflammatory cell infiltration occurred.After aerobic exercise intervention,the livers of mice in the HHE group were observed with the naked eye or stained,and it was found that the liver tissue morphology was similar to that of normal mice,lipid droplets were reduced,and liver cells were arranged neatly.4.MiR-21 a expression was significantly reduced in HH group mice,and the expression levels of target genes FABP7,HMGCR,ACAT1 and OLR1 were significantly increased,while PPAR?,PTEN expressions decreased(P <0.05).After aerobic exercise intervention,miR-21 a elevated significantly in HHE group,the expression of FABP7,HMGCR,ACAT1,OLR1 decreased,whereas,PPAR? and PTEN mRNA levels were significantly increased(P <0.05).5.In miR-21 a KD mice,body weight and blood lipid levels increased.Liver FABP7,HMGCR,ACAT1,OLR1 expression levels were elevated(P <0.05).However,there was no significant change in PPAR? and PTEN.6.After 4 weeks of aerobic exercise in miR-21 a KD mice,the expression of miR-21 a significantly increased,and the target genes also changed accordingly,and blood lipids significantly diminished.Conclusion: 1.Aerobic exercise can regulate the balance of lipids,reduce weight and improve hyperlipidemia.2.miR-21 a can affect lipid metabolism by regulating the expression of target genes FABP7,HMGCR,ACAT1 and OLR1.3.Aerobic exercise can improve hyperlipidemia through mi R-21a-induced changes of target genes.