Metabolomics Analysis In Overweight/Obese People With Weight Loss After Diet Interventions

ObjectiveWith the rise of metabolomic research in overweight/obese,the identification of obesity-related metabolites and the exploration of dietary weight loss mechanisms have gradually opened new perspectives.Using different diet interventions to get weightloss and analyzing the metabolic profile between them,this study aims to find the similarities and differences of changes in serum metabolites caused by different weight loss diets in overweight/obese participants,and identify obesity-related metabolites and observe their association with clinical characteristics.MethodsAmong 257 overweight/obese subjects with 12 weeks of dietary interventions(Group A:Control group,Group B:a low-carbohydrate diet,Group C:a calorierestricted diet,Group D:a combination of low-carbohydrate and calorie-restricted Diet),5 representative subjects in each group(20 cases in total)were selected.LC-MSbased Targeted Metabolomics were performed in these 20 patients and data were analyzed by PCA,PLS-DA,OPLS-DA,Metabolic Pathway Enrichment Analysis.Also variance analysis and correlation analysis were applied to distinguish changing metabolites after different diet interventions and to find obesity-related metabolites and their correlation with changes in clinical characteristics.ResultsCompared to control group,the level of tyrosine decreased after weight loss in all the intervention groups(group A 95.15umol/L,group B 67.01umol/L,group C 62.97umol/L,group D 72.74umol/L,p<0.05).The concentration of tryptophan reduced in groups containing calorie restriction(group A 87.40umol/L,group C 51.81umol/L,group D 61.34umol/L,p<0.05).Even without statistically significant,tryptophan levels in group B also showed a downward trend(group A 87.40umol/L,group B 62.47umol/L,p=0.22).While the increased level of α-aminobutyric acid was found in the intervention groups with low-carbohydrate diet(group A 5.08umol/L,group B 8.08umol/L,group D 8.86umol/L,p<0.05).By head-to-head comparison between group B and group C,we found the difference in 3-hydroxyisovalerylcarnitine and glutarylcamitine between these two groups was statistically significant(3hydroxyisovalerylcarnitine:group B 0.28umol vs group C 0.19umol/L,p=0.00;glutarylcarnitine:group B 0.33umol/L vs group C 0.27umol/L,p=0.03).Correlation analysis results showed that itaconic acid,citrulline and creatine were related to a variety of physical indicators,but improvement in physical indicators was more closely related to changes in acylcarnitine,like change of BMI was negatively correlated with change of propionylcarnitine(r=-0.4866,p=0.030)and weight-loss was also negatively correlated with change in hexanoylcarnitine(r=-0.4511,p=0.047).Meanwhile,hexanoylcarnitine also correlated with other clinical characteristics like Muscle Rate(r=-0.5924,p=0.006),Body Fat Rate(r=-0.5120,p=0.021)and Basal Metabolic Rate(r=-0.4511,p=0.047).In addition,the changes of alanine(r=-0.4449,p=0.049)and guanidine acetate(r=0.4923,p=0.027)were correlated with Visceral Fat Area.ConclusionAromatic Amino was the common changing metabolites by weight loss independent of diet patterns.While acyl carnitines were the main variant metabolites between two different diets,low-carbohydrate diet and calorie-restricted diet,and closely related to the improvement of various clinical characteristics.In addition,itaconic acid,creatine and citrulline were three newly discovered obesity-related metabolites,while α-aminobutyric acid may be a potential metabolism regulator during weight loss caused by low-carbohydrate diet.Changes in two amino acids,guanidine acetate and alanine,were found associated with improvement in Visceral Fat Area,supplementing the amino acid profile associated with change in Visceral Fat Area.