Supplementary Material for: Weight Change Alters the Small RNA Profile of Urinary Extracellular Vesicles in Obesity

Introduction: Various kidney diseases reportedly show different urinary extracellular vesicles (EVs) RNA profiles. Although obesity is one of the main causes of chronic kidney disease, the expression pattern of urinary EVs RNA in obesity is uncertain. Our aim was to sequence the small RNA profiles of urinary EVs in obese patients before and after weight reduction and compared them to those of healthy volunteers (HVs). Methods: We recruited age-sex matched obese patients and HVs. The small RNA profiles of urinary EVs were analyzed using RNA sequencing. To evaluate the effect of weight reduction, small RNA profiles of urinary EVs 6 months after bariatric surgery were also analyzed. Results: The proportion of urinary EVs transfer RNA and microRNA of obese patients differed from that of HVs. Obese patients showed differential expression of 1343 small RNAs in urinary EVs compared to HVs (|fold change| ≥ 2 and p value < 0.05). Among those, 61 small RNAs were upregulated in obese patients and downregulated after weight reduction, whereas 167 small RNAs were downregulated in obese patients and upregulated after weight reduction. RNA sequencing revealed the correlation between the specific urinary EVs small RNAs and clinical parameters including body weight, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, serum glucose, estimated glomerular filtration rate, and albuminuria. Conclusion: Obese patients showed distinct urinary EVs small RNA profiles compared to HVs. Weight reduction altered urinary EVs small RNA profiles in obese patients.

引言：已有研究证实，多种肾脏疾病患者的尿液细胞外囊泡（extracellular vesicles, EVs）RNA谱存在显著差异。尽管肥胖是慢性肾脏病的主要诱因之一，但肥胖人群尿液细胞外囊泡RNA的表达模式仍未明确。本研究旨在对肥胖患者减重前后的尿液细胞外囊泡小RNA谱进行测序，并将其与健康志愿者（healthy volunteers, HVs）的对应谱图进行对比。
方法：本研究招募了年龄与性别匹配的肥胖患者及健康志愿者。采用RNA测序技术分析尿液细胞外囊泡的小RNA谱。为评估减重干预的效果，本研究同时检测了肥胖患者接受减重手术后6个月的尿液细胞外囊泡小RNA谱。
结果：相较于健康志愿者，肥胖患者尿液细胞外囊泡中转运RNA（transfer RNA, tRNA）与微小RNA（microRNA, miRNA）的占比存在显著差异。肥胖患者尿液细胞外囊泡中共1343个小RNA呈现差异表达（|折叠变化|≥2且p值<0.05）。其中，61个小RNA在肥胖患者中呈高表达，且在减重后表达下调；另有167个小RNA在肥胖患者中呈低表达，且在减重后表达上调。RNA测序结果显示，特定尿液细胞外囊泡小RNA与多项临床指标存在相关性，包括体重、低密度脂蛋白胆固醇、甘油三酯、高密度脂蛋白胆固醇、血清葡萄糖、估算肾小球滤过率（estimated glomerular filtration rate, eGFR）及白蛋白尿。
结论：与健康志愿者相比，肥胖患者的尿液细胞外囊泡小RNA谱存在显著差异。减重干预可改变肥胖患者的尿液细胞外囊泡小RNA谱。