Comparison Of Glycolipid Metabolism And MRNA-LncRNA Expression Profile Of Obesity/overweight Three TCM Constitution Types

Objectives:(1)To explore differences in glucose and lipid metabolism and differences in vascular endothelial function among obese/overweight and different types of body constitution in order to find the characteristics of lipid metabolism in each type of obese/overweight and compare the metabolic risk of the three groups in order to provide microscopic classification basis for TCM constitution identification among obese/overweight populations,which lays the foundation for the further exploration of the intrinsic mechanisms that contribute to each obese/overweight type of glucose and lipid metabolism and differences in endothelial function.(2)To compare the expression levels of mRNA and lncRNA in peripheral blood mononuclear cells of phlegm-dampness constitution,qi-deficiency constitution,and balance constitution within the whole genome.(3)To screen the differently expressed mRNA and lncRNAs for phlegm-dampness constitution,qi-deficiency constitution and balance constitution in order to provide molecular biological basis for TCM constitution classification in obese/overweight populations,to discuss the role that the differently expressed mRNA and the corresponding lncRNAs play in body constitution characteristics and its susceptibility to diseases among obese/overweight populations of different body constitution and to explore the potential mechanism.Methods:(1)Collect 40 cases of obese/overweight phlegm-dampness constitution group(OP),42 cases of qi-deficiency constitution group(OQ),39 cases of balance constitution group(OB)(control group).6 ml of venous blood was collected and blood glucose,triglyceride,cholesterol,high-density lipoprotein,low-density lipoprotein,insulin,and other glucose and lipid metabolism indexes were detected.Ultrasound was used to detect brachial artery blood flow in the three groups.Results:(1)①Waist circumference in the OP group was significantly different from the OQ group and the OB group.The difference was statistically significant(p<0.05).There was no significant difference between the OQ group and the OB group.The difference in hip circumference among the three groups was not statistically significant(p>0.05);the fasting blood glucose and glycosylated hemoglobin in the OP group were significantly different from the OQ group and the OB group(p<0.05).There was no significant difference between the OQ group and the OB group(p>0.05).There was no significant difference between the Qi group and the Qi group.The total cholesterol in the OP group was significantly different from the OQ group and the OB group and the difference was statistically significant(p<0.05).There was no statistically significant difference between the OQ group and the OB group;the apolipoprotein B in the OP group was different from the OQ group and the OB group(p<0.05).There was no statistical difference between the OQ group and the OB group(p>0.05).The distribution of hip circumference,triglyceride,apolipoprotein A1,serum lipoprotein a,fasting insulin,and high-sensitivity C-reactive protein did not differ among groups(p>0.05).The degree of insulin resistance among the 3 groups were all significantly different from each other(p<0.05).② The degree of insulin resistance was significantly different in the two groups of phlegm,Qi deficiency and Pinghe groups.The OP group was most susceptible to insulin resistance,and the degree of insulin resistance was the heaviest.The difference was statistically significant(p<0.05).③The distribution difference of FMD among the 3 groups was statistically significant(p<0.05).Obese/overweight phlegm-dampness constitution had the highest risk of suffering from endothelial dysfunction.(2)①There were 5177 differentially expressed mRNAs in the OP group compared with the OB group.Among them,2730 differentially expressed mRNAs were up-regulated and 2447 differentially expressed mRNAs were down-regulated;There were 520 differentially expressed lncRNAs in the OP group compared with the OB group,upregulated 269 differentially expressed lncRNAs and downregulated 251 differentially expressed lncRNAs.②There were 323 differentially expressed mRNAs in the OQ group compared with the OB group.Among them,199 differentially expressed mRNAs were up-regulated and 124 differentially expressed mRNAs were down-regulated;There were 26 differentially expressed lncRNAs in the OQ group compared with the OB group.17 differentially expressed lncRNAs were up-regulated,9 differentially expressed lncRNAs were down-regulated.③There were 2339 differentially expressed mRNAs in the OP group compared with the OQ group,in which 1429 differentially expressed mRNAs were upregulated,910 differentially expressed mRNAs were downregulated.There were 253 differentially expressed lncRNAs in the OP group compared with the OQ group.140 differentially expressed lncRNAs were up-regulated and 113 differentially expressed lncRNAs were down-regulated.(3)① Compared with the OP group and the OB group,the most marked up-regulated expressed mRNA was VMAC,the most marked down-regulated expressed mRNA was CCL8;the most marked up-regulated expressed vncRNA was lnc-ECI2-2,the most marked down-regulated expressed lncRNA islnc-C2orf55-1.②Compared with the OQ group and the OB group,the most marked up-regulated expressed mRNA was LRRD1,the most marked down-regulated expressed mRNA was CCL13;the most marked up-regulated expressed lncRNA was lnc-TRA2A-1.the most marked down-regulated expressed lncRNA was MIR210HG.③ Compared with the OP group and the OQ group,the most marked up-regulated expressed mRNA was LGALS2,the most marked down-regulated expressed mRNA was MS4A1;the most marked up-regulated expressed lncRNA was LOC100507642,the most marked down-regulated expressed lncRNA was LINC00892.(4)Further GO and KEGG analysis of the above target gene functions revealed that the differential mRNA function was mainly enriched in glucose and lipid metabolism and vascular endothelial function compared with the OP group and the OB group.Differential mRNA function mainly enriched in iron ion homeostasis and regulation of muscle metabolism between the OQ group and the OB group,differential mRNA function was mainly enriched in endocytosis and immune response between the OP group and the OQ group.(5)According to the differential mRNA enrichment function to find the corresponding lncRNA,a joint analysis of mRNA and lncRNA was carried out.We found that:① compared the OP group with the OB group,the differential mRNA-lncRNAs that mainly regulated the above functions were ACSL4,MAPK13,LOC100132891,lnc-C2orf27B-3,etc.②Compared the OQ group with the OB group,the differential mRNA-lncRNAs that mainly regulated the above functions were SLC25A37,STEAP1;LINC01088,lnc-SARM1-2,etc.③Compared the OP group with the OQ group,the differential mRNA-lncRNAs that mainly regulated the above functions were RAB1A,NCR3,LOC100289473,and lnc-MRPL3-2.Conclusion:(1)Obese/overweight populations had the appearance of excessive BMI.However,with different body constitution subtypes,the risks of suffering from metabolic diseases and cardiovascular and cerebrovascular diseases were also different.The glycolipid metabolism and vascular endothelial function in the OP group were lower than those in the OQ and the OB group.There was also obvious insulin resistance,suggesting that the phlegm is an influential factor of metabolic syndrome that was independent of obese/overweight;Subjects in the OQ group and the OB group had relatively normal insulin sensitivity and glycolipid metabolism;Obese/overweight qi deficiency constitution tend to belong to the transition stage of the above two constitution subtypes,there are certain The risk of glucose and lipid metabolism and endothelial dysfunction cannot be ignored,and its underlying mechanism of action needs further exploration.(2)The 3 obese/overweight subjects with different TCM body constitution had mRNA and lncRNA expression differences in the whole genome,which had provided a genetic level for obese/overweight people in TCM constitution classification.(3)The role of mRNA and lncRNA in regulating the development process and clinical manifestations of different body types of obese/overweight was different,resulting in the difference in glucose and lipid metabolism,vascular function status,energy output,etc.①Compared the OP group with the OB group,the difference were mainly enriched in lipid metabolism and vascular status,which provided a genetic level for metabolic syndrome and vascular endothelial dysfunction in obese/overweight individuals;②Compared the OQ group with the OB group,the difference were mainly enriched in the body iron ion homeostasis and muscle regulation metabolism,the differential expressed genes played an important role in the mitochondrial iron consumption process and heme synthesis process which showed the important role that the differential expressed genes played in mitochondrial respiratory disorders and energy output.To a certain extent,this also explained the intrinsic mechanisms of fatigue and muscle relaxation among the obese/overweight populations with qi deficiency constitution;③ Compared the OP group with the OQ group,the difference were mainly enriched in endocytosis and immune response.The key gene RAB1A was involved in the process of autophagosome formation in autophagy,and autophagy was a hot topic in recent years involved in obesity metabolism,but the difference between the two types of obese/overweight in this area still needs further confirmation.The above findings have laid the foundation for the analysis of obese/overweight formation mechanism and the follow-up clinical intervention research based on the classification of different TCM constitutions.