肥胖患者脂肪组织STAU1表达变化及其在脂肪间充质干细胞成脂分化中的作用

Expression of STAU1 in adipose tissues of obese patients and its role in adipogenesis of human adipose mesenchymal stem cells

目的探讨双链RNA结合蛋白STAU1在肥胖患者脂肪组织中的表达变化,及其在人脂肪间充质干细胞(h ADSCs)成脂分化中的作用。方法选择56例慢性胆囊结石及疝气择期手术患者,根据BMI分为肥胖组27例和非肥胖组29例;术中取患者网膜及皮下脂肪组织,采用RT-qPCR及Western blotting法检测脂肪组织中的STAU1基因和蛋白,分析肥胖组患者网膜组织中STAU1基因与腰围、臀围、BMI、血压、血糖、血脂等指标的相关性。经网膜脂肪组织获取h ADSCs,分别于成脂诱导液处理0、2、4、6、8 d,油红O染色法检测细胞中甘油三酯生成情况(OD值),同法检测细胞中STAU1、过氧化物酶体增殖剂激活受体(PPARγ)表达水平。将h ADSCs分为3组,干扰1、2组分别转染siRNA STAU1-homo-718、STAU1-homo-923,对照组不转染;转染2、4 d,同法检测甘油三酯生成情况及STAU1、PPARγ表达水平。结果肥胖组网膜脂肪组织中STAU1基因和蛋白表达水平高于非肥胖组(P均<0. 05),而皮下脂肪组织中STAU1基因表达差异无统计学意义;肥胖组网膜脂肪组织中STAU1基因表达水平与患者的腰围、臀围、低密度脂蛋白、高密度脂蛋白、空腹血糖无明显相关性,与BMI、甘油三酯呈正相关(r分别为0. 777、0. 795,P均<0. 01)。随着诱导分化天数增加,h ADSCs中甘油三酯生成增多,STAU1、PPARγ表达水平逐渐升高(P均<0. 05)。与对照组比较,干扰1、2组转染2、4 d时h ADSCs中STAU1表达降低,甘油三酯生成及PPARγ表达减少(P均<0. 05)。结论肥胖患者网膜脂肪组织中STAU1表达增加,且与BMI、甘油三酯呈正相关; STAU1可能通过上调PPARγ的表达,从而促进人网膜脂肪组织及h ADSCs成脂分化中甘油三酯的生成。

Objective To investigate the expression of double stranded RNA binding protein STAU1 in adipose tissues of obese patients and its role in adipogenesis of human adipose mesenchymal stem cells (hADSCs). Methods Fifty-six patients with chronic cholecystolithiasis and hernia were selected for elective surgery.According to BMI,they were divided into the obese group (27 cases) and non-obese group (29 cases).During the operation,retinal and subcutaneous adipose tissues of patients were taken,and the Staufen1 (STAU1) gene and protein in the adipose tissues were detected by RT-qPCR and Western blotting.The correlation between STAU1 gene and waist circumference,hip circumference,BMI,blood pressure,blood glucose,blood lipid,and other indicators in the retinal tissues of the patients in the obese group was analyzed.The hADSCs were obtained from retinal tissues and were treated with lipogenic induction solution on day 0,2,4,6,and 8,respectively.The production of triglycerides in cells (OD value) was detected by oil red O staining,and the expression levels of STAU1 and peroxisome proliferator-activated receptor γ(PPARγ) in cells were detected by the same method.The hADSCs were divided into three groups:the interference groups 1 and 2,and control group.The cells in the interference groups 1 and 2 were transfected with siRNA stau1-homo-718 and stau1-homo-923,respectively;the cells in the control group were not transfected.On the second and fourth days after transfection,triglyceride production and expression levels of double-stranded RNA binding protein STAU1 and PPARγ were detected by the same method. Results The expression levels of STAU1 gene and protein in the omental adipose tissues of the obese group were higher than those of the non-obese group (both P <0.05),while the difference in the STAU1 gene of subcutaneous adipose tissues was not statistically significant.The expression level of STAU1 gene in the retinal adipose tissues of the obese group was not significantly correlated with waist circumference,hip circumference,low-density lipoprotein,high-density lipoprotein or fasting blood glucose of the patients,but was positively correlated with BMI ( r =0.777) and triglyceride ( r =0.795)(all P <0.01).Over the time of induced differentiation,the generation of triglycerides in hADSCs increased,and the expression levels of STAU1 and PPARγ gradually increased (all P <0.05).Compared with the control group,STAU1 expression,triglyceride generation and PPARγ expression decreased in hADSCs at 2 and 4 d after transfection in the interference groups 1 and 2 (all P <0.05).Conclusion The expression of STAU1 in the retinal adipose tissues of obese patients increases and is positively correlated with BMI and triglyceride;STAU1 may promote the production of triglycerides in adipogenic differentiation of human retinal adipose tissues and hADSCs by up-regulating the expression of PPARγ.