人前体脂肪细胞分化过程及肥胖人群脂肪组织中hsa_circ_0017650高表达

High expression of hsa_circ_0017650 in human adipocyte differentiation process and adipose tissue of obese people

目的探讨hsa_circ_0017650在人前体脂肪细胞分化过程以及肥胖人群脂肪组织中的表达变化。方法RT-qPCR测定人前体脂肪细胞分化第0/1/3/5/7/9/12天hsa_circ_0017650的水平变化;油红O染色观察人前体脂肪细胞分化第0/6/12天脂滴形成;RT-qPCR测定人前体脂肪细胞中CCAAT增强子结合蛋白α(C/EBPα)、脂肪酸结合蛋白4(FABP4/ap2)和脂蛋白脂酶(LPL)mRNA水平;根据体质指数(BMI)将125例患者分为肥胖组和对照组,比较2组腹膜后白色脂肪组织hsa_circ_0017650表达差异;Pearson相关性分析hsa_circ_0017650表达水平与肥胖组患者BMI、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)相关性。结果培养第12天时人前体脂肪细胞中C/EBPα、FABP4/ap2和LPL水平均高于第0天(P<0.001);Hsa_circ_0017650表达呈时间依赖性,其中第3天达到峰值(P<0.001)。与对照组相比,肥胖组白色脂肪组织中hsa_circ_0017650水平及BMI、腰臀比、TC、TG、LDL-C水平以及升高(P<0.001);Hsa_circ_0017650与BMI、TG、LDL-C呈正相关(r=0.554、0.569、0.618,P<0.001)。结论Hsa_circ_0017650在人前体脂肪细胞分化过程以及肥胖人群白色脂肪组织中高表达,与患者肥胖密切相关,为肥胖患者的治疗提供靶点。

Objective To investigate the expression changes of hsa_circ_0017650 in the human adipocyte differentiation process and adipose tissue of obese people.Methods The changes of hsa_circ_0017650 on the 0th,1st,3rd,5th,7th,9th and 12th days of human preadipocyte differentiation were determined by RT-qPCR;Oil Red O staining was performed to observe the formation of lipid droplets on 0th,6th,and 12th days of human preadipocyte differentiation.The mRNA levels of CCAAT enhancer-binding proteinα(C/EBPα),fatty acid-binding protein 4(FABP4/ap2),and lipoprotein lipase(LPL)in human preadipocytes were determined by RT-qPCR to identify the differentiation of human preadipocytes.A total of 125 patients who underwent appendectomy in our hospital were selected as research subjects,and were divided into obesity group(53 cases)and control group(72 cases)according to body mass index(BMI).The expression differences of hsa_circ_0017650 in retroperitoneal white adipose tissue of the two groups were compared.The Pearson's correlation coefficient between the expression level of hsa_circ_0017650 and BMI,triacylglycerol(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)in obesity group was analyzed.Results Human preadipocytes gradually changed from spindle to oval or round,with a gradual increase in volume and an increase in fat droplets.On the 12th day of culture the levels of C/EBPα,FABP4/ap2 and LPL in human precursor adipocytes were higher than those on day 0(P<0.001).Compared with baseline of day zero(1.02±0.13),the expression of hsa_circ_0017650 increased on the 1st(2.47±0.30),3rd(27.38±3.42),5th(15.62±1.95),7th(16.24±2.03),9th(18.37±2.29)and 12th(16.24±2.21),and reached the peak on the 3rd day(P<0.001).Compared with the control group,the levels of BMI,waist-to-hip ratio,TC,TG,LDL-C and of hsa_circ_0017650 in white adipose tissue increased in the obesity group(P<0.001);Hsa_circ_0017650 was positively correlated with BMI,TG,and LDL-C(r=0.554,0.569,0.618,P<0.001).Conclusions Hsa_circ_0017650 is highly expressed during human adipocyte differentiation and mainly in white adipose tissue of obese individual.It is closely related to obesity and is potential for the treatment of obese patients.