The Efficacy Of Exercise Based On Metabolomics For Obese Adolescents With Fatty Liver Disease

Background:Obesity is the primary risk factor for fatty liver disease in adults.Obesity during adolescence can further increase the development of non-alcoholic fatty liver disease(NAFLD)in adulthood.Exercise intervention is one of the safest ways to treat NAFLD because of its effects with no side,no dependence,and no invasiveness.As a high-throughput technique for the discovery of biomarkers,metabolomics is used to detect thousands of metabolites and provides possible changes in metabolism and signaling pathways.Currently,metabolomics has been successfully applied to studies about exercise and NAFLD related to metabolic pathways in adults.However,the plasma metabolic profiles of the exercise-improved fatty liver based on metabolomics in obese children and adolescents have not been revealed.Objective:The aim of this study is to use liquid chromatography-mass spectrometry(LC-MS)to analyze the characteristics of plasma metabolites in obese children and adolescents before and after exercise.The principal component analysis and correlation analysis are used to find the metabolites responding to exercise and significantly related to the improvement of the fatty liver.Thus,new ideas for exercise prevention and treatment of fatty liver will be provided.Methods:This study included 27 obese children and adolescents(12.96±1.81 years old),including 18 boys and 9 girls,with a certain degree of controlled attenuation parameter(CAP)and liver stiffness measurement(LSM).All subjects performed a moderate-to-high-intensity exercise program with aerobic exercise and resistance exercise 6 days per week,4 weeks in total.The intervention lasted for 4 weeks,with 6days a week,2-3 times a day,2 hours each time.The indicators including baseline and post-intervention remained the same.Physical fitness,blood indicators,and plasma metabolomics are all included.Targeted metabolomics is used to analyze the changes of plasma metabolites caused by exercise.The principal component analysis is used to reveal the differences of plasma metabolites before and after exercise.KEGG pathway enrichment is used to analyze the metabolic pathways involved in differential metabolites,and correlation analysis is used to find out the relationship between the significant metabolites and the improvement of fatty liver.Results:After moderate-to-high-intensity exercise for 4 weeks,body weight,BMI,and body composition of obese adolescents significantly decreased(p<0.001),and blood pressure significantly decreased(p<0.01).The indicators reflecting glucose,such as fasting insulin,homeostasis model assessment of insulin resistance(HOMA-IR),and glycated hemoglobin significantly decreased(p<0.05).The indicators reflecting lipids,such as triglyceride,total cholesterol,high-density lipoprotein(HDL),low-density lipoprotein(LDL)significantly decreased(p<0.05),but the ratio of HDL and total cholesterol significantly increased(p<0.001).The indicators reflecting liver damage,such as alanine aminotransferase(ALT),aspartate aminotransferase(AST),andγ-glutamyltransferase(GGT)significantly reduced,while ALT/AST significantly increased(p<0.05).In addition,exercise can effectively improve liver CAP(p<0.001)and LSM(p<0.05)in obese children and adolescents.Plasma metabolomics showed that 51 metabolites were significantly changed after exercise.Meanwhile,10 metabolic pathways were enriched,such as valine,leucine,and isoleucine biosynthesis and D-Glutamine and D-glutamate metabolism are probably related to the improvement of fatty liver caused by exercise.Spearman correlation analysis showed that the improvement of CAP was positively correlated with Kynurenine.The improvement of LSM was negatively correlated with tyrosine,and significantly negatively correlated with glutamate,glutamine,and serine(p<0.05).Conclusion:Moderate-to-high-intensity exercise for four weeks can effectively reduce body weight and improve fatty liver disease in obese adolescents.The possible mechanism of exercise treatment of fatty liver in children and adolescents is related to the changes of kynurenine,tyrosine,glutamate,glutamine and serine,and is enriched in valine,leucine,and isoleucine biosynthesis,glutamine and glutamate metabolism pathway.