Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affects circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDL were isolated from patients with severe obesity (n=53) before, 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDL were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222 and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222 and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222 and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase (PON1) activity were increased and intracellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with increase in cholesterol efflux capacity (r=0.326, P=0.027 and r=0.349, P=0.017 respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction, and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.

中文翻译：

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Roux-en-Y 胃绕道手术治疗严重肥胖后，高密度脂蛋白相关 miRNA 增加。

Roux-en-Y 胃旁路术 (RYGB) 是最常见的减肥手术之一，但严重肥胖和 RYGB 如何影响循环 HDL 相关 microRNAs (miRNAs) 仍不清楚。在这里，我们旨在研究 HDL 相关的 miRNAs 在严重肥胖中是如何被调节的，以及 RYGB 手术后体重减轻如何影响 HDL-miRNAs。通过使用山羊抗人 apoA-I 微珠进行免疫沉淀，在 RYGB 之前、6 和 12 个月从患有严重肥胖症的患者 (n = 53) 中分离血浆 HDL。HDL 也从 18 名健康参与者中分离出来。从分离的 HDL 中提取 miRNA，并通过 TaqMan miRNA 测定法测定 miR-24、miR-126、miR-222 和 miR-223 的水平。我们发现 HDL 相关的 miR-126、miR-222 和 miR-223 水平，但不是 miR-24 水平，与健康对照组相比，重度肥胖患者显着升高。在 RYGB 后 12 个月，HDL 相关的 miR-24、miR-222 和 miR-223 显着增加。此外，胆固醇流出能力和对氧磷酶 (PON1) 活性增加，细胞内粘附分子 1 (ICAM-1) 水平降低。HDL 相关 miR-24 和 miR-223 的增加与胆固醇流出能力的增加呈正相关（分别为 r=0.326，P=0.027 和 r=0.349，P=0.017）。在基线时观察到与 HDL 相关的 miR-223 和 ICAM-1 之间存在负相关。总之，这些研究结果表明，HDL 相关 miRNA 在健康和严重肥胖患者中受到不同的调节，并且在 RYGB 后发生改变。