High density lipoprotein-associated miRNA is increased following Roux-en-Y gastric bypass surgery for severe obesity.

ABSTRACT

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affect 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 HDLs were isolated from patients with severe obesity (n = 53) before and 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDLs 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 activity were increased and intercellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with an 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 participants 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.