肥胖代谢状态与内脏脂肪免疫细胞的关联分析

The correlation analysis between metabolic status in obesity and immune cells in visceral adipose tissue

目的:探究体重正常(lean)、肥胖代谢正常(metabolically healthy obesity,MHO)与肥胖代谢异常(metabolically unhealthy obesity,MUO)个体内脏脂肪组织(visceral adipose tissue,VAT)中免疫细胞占比差异。方法:内脏脂肪组织标本来源于南京医科大学第一附属医院因肥胖行代谢手术治疗的48例患者及体重和代谢指标正常但因其他非炎症性疾病(疝气、胆结石及肾囊肿等)行腹腔镜手术的11例患者。提取脂肪组织RNA,进行RNA-seq检测,根据RNA-seq结果统计分析3组间内脏脂肪免疫细胞构成比情况和差异基因表达情况,通过单因素方差分析及Pearson相关性分析等分析方法进行数据统计。结果:各组间调节性T细胞,激活的NK细胞及M0、M2型巨噬细胞占比存在差异,P值分别为0.031、0.002、0.004和0.024;与其他两组相比,MUO组M2型细胞占比下降(P=0.014);两组肥胖患者的内脏脂肪中SPP1、CHIT1、ITGAX、CD300LB、IL1RN及DCSTAMP等基因与M0、M1型巨噬细胞占比呈正相关关系,而与M2型巨噬细胞占比多呈负相关关系。C5a受体1(complement fragment 5a receptor 1,C5AR1)及G蛋白偶联受体183(G-protein coupled receptor 183,GPR183)基因在MHO组中表现为与M0及M1型巨噬细胞占比正相关,与M2型巨噬细胞占比负相关;在MUO组中则呈现相反的关联性。结论:与体重正常组相比较,肥胖组人群的内脏脂肪组织存在显著巨噬细胞浸润;肥胖两组间比较,代谢异常者巨噬细胞亚类中M1型巨噬细胞占比升高,提示机体内高炎症水平与代谢能力受损有关;C5AR1、GPR183可能作为预测肥胖患者代谢状态的生物学指标。

Objective:The study aims to investigate the different proportions of immune cells in visceral adipose tissue(VAT)among lean group,metabolically healthy obesity(MHO)group and metabolically unhealthy obesity(MUO)group.Methods:Samples of VAT came from 48 obese patients who received metabolic surgeries and 11 other patients who had non-inflammatory disease(such as hernia,cholecystolithiasis and renal cyst)and received laparoscopic surgery at the First Affiliated Hospital of Nanjing Medical University.After extracting RNA from VAT,we applied RNA-seq technology to count and analyze proportions of immune cells and differentially expressed genes in VAT among three groups.One-way ANOVA and Pearson correlation analysis were used for statistical analysis.Results:The proportion of regulatory T cells,natural killer cells,M0 macrophages,and M2 macrophages varied among three groups(P=0.031;P=0.002;P=0.004;P=0.024).In MUO group,the proportion of M2 macrophages decreased compared with other two groups(P=0.014).SPP1,CHIT1,ITGAX,CD300LB,IL1RN,DCSTAMP and some other genes had positive correlation with the proportion of M0and M1 macrophages in two obese groups,but had negative correlation with the proportion of M2 macrophages.C5AR1 and GPR183had positive correlation with the proportion of M0 and M1 macrophages in MHO group and had negative correlations with the proportion of M2 macrophages.However,the correlation between these two genes and macrophages is opposite in MUO group compared with MHO group.Conclusion:Compared with lean group,the infiltration status of immune cells in VAT is more severe in MHO and MUO group.Comparing between MHO and MUO group,the proportion of M1 macrophages in VAT lifted,indicating that higher level of inflammation in vivo connects with impaired metabolic ability.The differently expressed gene C5AR1 and GPR183between two obese groups may play a role in predicting alterations in metabolic ability.