Aerobic Exercise Improves Hypercholesterolemia By Regulating The MiR-29a-mediated SREBP1c/PCSK9/LDLR Pathway

Purpose: Hypercholesterolemia is the most important risk factor for atherosclerosis;there have been relevant studies showing that aerobic exercise has the function of accelerating cholesterol metabolism;and mi RNAs are also closely related to the treatment of hypercholesterolemia.In the preliminary experiment of aerobic exercise in our laboratory to improve hypercholesterolemia,it was found that there are significant differences in mir-29 a,and LDLR is the main treatment marker for hypercholesterolemia.This experiment will be designed to verify how aerobic exercise regulates mir-29 a and affects LDLR levelsexpression.Methods: Thirty-six eight-week-old male C57BL/6J mice were divided into: ND group(normal diet group,n=12),HD group(continuous high-fat/high-cholesterol diet,n=12)and HS group(continuous high-fat diet,n=12)Fat/high cholesterol diet + eight weeks of aerobic exercise,n=12);Exercise program: 18m/min×45min,6% slope,6 days/week;Measure body length and weight at the end of the last training session each week;after the exercise program,all mice will be fasted for 24 hours,take blood and liver for follow-up experiments to detect blood lipid levels,liver morphology and degree of degeneration,at the same time,qPCR was used to detect mir-29 a,and qPCR and Western were used to detect the gene expression and protein levels of SREBP1c,HMGCR,LPL,SCD,PCSK9 and LDLR;Twenty mice of the same batch were kept on a high-fat/high-cholesterol diet,after reaching the age of twelve weeks,they were randomly divided into Blank control group and Mir-29 a adenovirus group(injected with mir-29 a adenovirus activator),the expression of SREBP1c,PCSK9 and LDLR in the downstream pathways guided by mir-29 a was tested again in vivo.Results: 1.Under the condition of high-fat/high-cholesterol diet,the HD group mice's weight gain was significantly faster than the ND group,while the HS group's weight gain slowed and was the same as the ND group's growth rate;after the eight-week aerobic exercise program,the weight of the HD group was significantly higher than that of the ND group(P<0.05);while the weight of the HS group was significantly lower than the HD group(P<0.01);compared with the ND group,TC was observed to be significantly increased in the HD group,while TG and LDL-C also significantly increased(P<0.01);compared to the HS group,the exercise program was significantly increased Improve the levels of TG,TC and LDL-C;2.Compared with the ND group,it was observed that the liver of the HD group was yellowish brown,lacking luster,and the edges were dull,and also observed that there were obvious black spots and inflammatory changes.;the liver in the HS group had complete morphology,smoother color,no obvious color changes,and more complete tissue morphology;Compared with the ND group,the HD group had severe liver damage,while the HS group had no significant pathological changes.According to the results of HE staining,compared with the ND group,the HD group had poorer liver cell morphology,enlarged nuclei,and damaged liver lobules;3.Compared with the ND group,mir-29 a was significantly reduced in the HD group,while the mir-29 a target genes SREBP1c,HMGCR,SCD and LPL were significantly increased(P<0.01).In the HS group,aerobic exercise activated mir-29 a expression,while achieved a significant inhibitory effect on its target genes;compared with the control group,the expression of mir-29 a was activated after adenovirus injection,and the target genes SREBP1c,HMGCR,SCD and LPL were significantly reduced;4.Compared with the ND group,the expressions of SREBP1c and PCSK9 in the HD group were significantly increased.At the same time,it was observed that the expression of LDLR was suppressed(P<0.01);In the HS group after the exercise program intervention was implemented,the expression of SREBP1c and PCSK9 was inhibited,and the number of LDLR increased in the body;Compared with the blank control group,SREBP1c and PCSK9 in the mir-29 a adenovirus injection group were significantly reduced,while the number of LDLR increased.Conclusion: 1.Aerobic exercise can slow down rapid weight gain and abnormal changes in blood lipid levels under hypercholesterolemia,as well as improve liver morphology and pathological changes;2.After aerobic exercise improves hypercholesterolemia,cholesterol levels are reduced.At the same time,it is found that mir-29 a and LDLR are significantly increased,and the expression of SREBP1c and PCSK9 is reduced;3.Aerobic exercise improve hypercholesterolemia through the SREBP1c/PCSK9/LDLR signaling pathway guided by mir-29 a.