Effect And Mechanism Of Combining Exercise With Diet Restriction On Vascular Function In Obese Adults

Research objectives:Obesity is a growing problem worldwide,and vascular dysfunction caused by obesity is an important cause of cardiovascular disease(CVD).Exercise and diet restriction have been shown to be effective in reducing risk factors for CVD and improving vascular endothelial function.However,the effect and mechanism of exercise combined with diet restriction on the improvement of endothelial function in obese adults remains unclear.In recent years,studies have found that miRNA(micro RNA)is widely involved in the regulation of vascular function,and exercise can induce differential expression of miRNA in the body.But there are few studies on the effect of exercise on miRNA expression and vascular function in obese people.In order to understand the effects of exercise training combined with diet restriction on body morphological indices,blood biochemical markers and indicators of vascular function of obese adults in a Gated-Weight Loss Camp,here we study the relationship between cardiac autonomic nerve and arteriosclerosis.Moreover,we investigate the potential mechanism of improving the function of vascular endothelial progenitor cells(EPC),and the protective effect of miRNA related to endothelial function,so as to provide targets for the prevention and treatment of CVD in obese people with lifestyle changes and promote the health of the whole population.Research methods:Part 1 Effects of exercise training combined with diet restriction on vascular function in obese adults1.A total of 35 obese adults in the camp of Shen Zhen were enrolled in this experiment,including 17 in the obesity experimental group(EXD)and 18 in the obesity control group(CON).EXD group underwent 8 weeks of fully enclosed exercise training and diet restriction.2.Obese subjects were tested and data were collected before and after the exercise training intervention.The indicators of obese subjects included body composition(height,weight,body fat rate),biochemical markers(FBG,FINS,TG,TC,HDL-c,LDL-c,e NOS,VEGF and miR-214),hemodynamic indexes(peripheral and central arterial pressure),vascular stiffness indexes(PWV),cardiac autonomic nervous function indexes(HRV),vascular endothelial function indexes(FMD,EPC).Part 2 Regulation and function of miR-214 in EPC function and its possible mechanism1.First,the overexpression of miR-214 experiment was performed on EPC,and the changes of EPC proliferation ability were investigated by CCK8 assay,and the changes of EPC migration ability were investigated by cell scratch assay.2.RNA sequencing was performed after the transfection of EPC.Related pathways and differentially expressed genes were screened to further understand the possible pathways and mechanisms of miR-214 affecting EPC function.3.Differential expression gene COL1A2 and PI3K-Akt signaling pathway were screened to overexpress miR-214 and silence COL1A2 gene in EPCs.PI3K-AKTt signaling pathway was blocked by inhibitors LY294002 to verify the role of COL1A2 and PI3K-Akt signaling pathway in miR-214 regulation of EPC function.Research results:Part 1 Effects of exercise training combined with diet restriction on vascular function in obese adultsAfter 8 weeks of exercise training and diet restriction,the indicators of obese subjects were as follows:1.Body composition: Compared with CON group,body weight,BMI and body fat percentage in EXD group were significantly changed(P<0.001).2.Blood biochemical markers: Insulin resistance was measured by HOMA-IR method,and the experimental results showed that insulin resistance in EXD group decreased significantly after intervention(P<0.01).Serum lipid levels: TC,TG,LDL-C decreased significantly(P<0.05).3.Cardiovascular function indicators: Compared with CON group,SDNN(P<0.001),RMSSD(P<0.05),LF/HF were significantly improved(P<0.05).Ba PWV(P<0.05)and cf PWV(P<0.05)were decreased significantly.In addition,EXD group b PP(P<0.05),c SBP(P<0.001),c SDP(P<0.05)and AIx75(P<0.001)were significantly reduced.4.Endothelial function index: FMD,a flow-mediated vasodilation function,was significantly increased in the EXD group than in the CON group(P<0.05).VEGF(P<0.001)and e NOS(P<0.01).In addition,the number of peripheral blood EPCs in EXD group increased significantly(P<0.01),EPC migration ability(P<0.001)and adhesion(P<0.05)significantly improved.Endothelial function-related miR-214(P<0.05)were significantly increased.5.Correlation of changes in various indicators:After 8 weeks of exercise training and dietary intervention,the change of LDL-c was positively correlated with the change of body weight and the change of TC was positively correlated with the change of body fat.The changes of circulating VEGF were correlated with the changes of HDL-c.The changes of miR-214 were positively correlated with EPG and EPCs.Part 2 Regulation and function of miR-214 in EPCs function and its possible mechanism1.After miR-214 overexpression of EPCs,EPCs survival were significantly increased in the miR-214 mimics group compared with the mimics NC group and miR-214 inhibitor group.In the scratch experiment,the migration ability of EPCs in miR-214 mimics group was improved,indicating that overexpression of miR-214 could significantly improve the function of EPCs.2.KEGG enrichment analysis of EPCs transcriptional group showed that 52 differentially expressed genes in miR-214 mimics group and mimics NC group increased while 49 differentially expressed genes decreased.Differentially expressed genes are mainly involved in PI3K-Akt signaling pathway,JAK-Stat signaling pathway,Hippo signaling pathway and Wnt signaling pathway,what’s more,the expression of PI3K-Akt pathway related gene COL1A2 expression was increased.3.Using inhibitors LY294002 to block the PI3K-Akt signaling pathway,we found that miR-214 induced positive effect on EPC function was inhibited.After COL1A2 gene silencing,the improvement of EPCs function by Mir-214 was inhibited.Research conclusion:1.8-week exercise training combined with diet restriction can reduce risk factors for cardiovascular disease in obese adults,as shown by loss of body weight and body fat,regulation of glucose and lipid metabolism,improvement of hemodynamic indicators and autonomic nerve function,and reduction of arterial stiffness of obese adults.Moreover,the level of endothelium-related factors can be improved and EPC function can be improved and circulating miR-214 is positively correlated with EPC.2.Mi R-214 can promote the function of EPC,and its potential mechanism may be that miR-214 upregulates COL1A2 expression and activates PI3K-Akt signaling pathway.