| Diabetes Mellitus(DM)has been a serious threat to human health.As an effective method to prevent and treat DM,exercise plays an important role in improving insulin sensitivity and increasing the utilization of glucose in skeletal muscle.However,we can't be so clear about function of the regulation mechanism of exercise intervention.That means it is slightly difficult to make clear about the pathophysiological mechanism of exercise intervention type 2 diabetes mellitus(T2DM)from the aspect of above mentioned.To make up for this inadequacy,we adopted metabolomics techniques in this study,where the serum metabolites of rats after 5 weeks of experimental intervention(aerobic exercise intervention and high-sugar high-fat diet feeding)were detected,and the metabolism of each group of rats after experimental intervention was delineated.After then,we continued contouring and searching for specific metabolic small molecule substances as well as elucidating the mechanism of action of high-sugar and high-fat diets in inducing T2 DM metabolic control network and exercise.Systematically revealing the reaction about whether exercise can advance metabolic process of T2 DM substances.Meanwhile,based on metabolite changes,we tried to identify the key point of exercise prevention T2 DM.Accordingly,we also conducted comprehensive intervention for potential new targets to achieve optimal intervention and precise prevention and treatment.Method:Eighteen 12-month-old male rats were fed with basal diet for 1 week.They were randomly divided into normal control group(C group),high-sugar high-fat group(H group)and high-sugar high-fat combined aerobic exercise.Group(HE group),6 in each group.Otherwise,experimental intervention of five weeks was adopted in this study.On the other hand,group C was fed with basal diet,group H with high-sugar high-fat diet,HE group with high-sugar and high-fat diet and aerobic exercise intervention.Adopted aerobic exercise programs: adaptive training for 2 weeks(speed from 0.3Km/h~0.8Km/h,increments every 2days,increments of 0.1Km/h each time),formal training for 3 weeks(speed 0.9Km/h,constant speed),each Training for 6 days a week,every 45 minutes,slope 5 °.After the end of the experimental intervention,fasting blood glucose was taken from the tail tip to test the fasting blood glucose in the rats.After anaesthetizing the heart to take blood,centrifuge and extract serum,gas chromatography-mass spectrometry(GC-MS)was used to detect serum metabolites in each group of rats.Finally,the resulting metabolomics data were processed with MetaboAnalyst3.0.The biochemical indicators of each group were processed with SPSS20.0 software.Result:(1)After 5 weeks of experimental intervention,there was a statistical difference between fasting blood glucose in each group(P<0.01).Fasting blood glucose in the C group was within the normal range,and the fasting blood glucose level in the H group was higher and it was in the early stage of diabetes.However,the fasting blood glucose level in the HE group was between the C group and the H group but failed to reach the T2 DM level.(2)Metabolomic analysis to evaluate rat models,principal component analysis(PCA)showed that the samples of group C,group H,and group HE were agglomerated,and the serum metabolic profile of each group was clearly separated.Partial Least Squares-Discriminant Analysis(PLS-DA)showed that there was a clear separation between the serum metabolic profile of each group,and the serum metabolic profile of the HE group was located between the C group and the H group.(3)One-way analysis of variance showed that compared with group C,the levels of succinic acid,glycerol,threonine,triglyceride,threonine,mannose,and ribose in group H were statistically significant(P<0.05);compared with group H,there were statistical differences between mannose,succinate,threonine,glycine,inositol,creatinine,mannose,serine,glucose,ribose,lactic acid and asparagine in the HE group(P<0.05).(4)The heatmap shows that the color difference of metabolites in group C,H and HE is large,but the model groups can be completely separated,and the HE group is located between C and H groups,indicating that the aerobic exercise pairs High-sugar high-fat induced T2 DM metabolites have a certain role in improving.Correlation analysis shows that there is a clear correlation between metabolites.(5)Analysis of metabolic pathways showed that there were 7 metabolic pathways most involved in experimental interventions: galactose metabolism;valine,leucine and isoleucine biosynthesis;arachidonic acid metabolism;glycine and serine And threonine metabolism;glycerol lipid metabolism;tryptophan metabolism;inositol phosphate metabolism.Conclusion:(1)5 weeks aerobic exercise made the fasting blood glucose of T2 DM rats induced by high glucose and high-fat diet decreased,delayed the occurrence of T2 DM,and achieved the preventive effect of T2 DM.(2)5 weeks of aerobic exercise intervention significantly improved the serum metabolic network of T2 DM rats induced by high glucose and high-fat diet,in which the improvement of glucose metabolic markers was the most significant.Aerobic exercise intervention can reverse the metabolic disorders of ribose,mannose and threonine to some extent.In addition,aerobic exercise has also been found to have significant effects on citric acid cycle metabolism,amino acid and lipid metabolism. |
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