Improved physiology and metabolic flux after Roux-en-Y gastric bypass is associated with temporal changes in the circulating microRNAome: A longitudinal study in humans

Background: The global pandemic of obesity and the metabolic syndrome are leading causes of mortality and morbidity. Bariatric surgery leads to sustained weight loss and improves obesity-associated morbidity including remission of type 2 diabetes. MicroRNAs are small, endogenous RNAs that regulate gene expression post-transcriptionally, controlling most of the human transcriptome and contributing to the regulation of systemic metabolism. This preliminary, longitudinal, repeat sampling study, in which subjects acted as their own control, aimed to assess the temporal effect of bariatric surgery on circulating microRNA expression profiles. Methods: We used Exiqon's optimized circulating microRNA panel (comprising 179 validated miRNAs) and miRCURY locked nucleic acid plasma/serum Polymerase Chain Reaction (PCR) to assess circulating microRNA expression. The microRNAome was determined for Roux-en-Y gastric bypass (RYGB) patients examined preoperatively and at 1 month, 3 months, 6 months, 9 months and 12 months postoperatively. Data was analysed using multivariate and univariate statistics. Results: Compared to the preoperative circulating microRNA expression profile, RYGB altered the circulating microRNAome in a time dependent manner and the expression of 48 circulating microRNAs were significantly different. Importantly, these latter microRNAs are associated with pathways involved in regulation and rescue from metabolic dysfunction and correlated with BMI, the percentage of excess weight loss and fasting blood glucose levels. Conclusions: The results of this pilot study show that RYGB fundamentally alters microRNA expression in circulation with a time-dependent progressive departure in profile from the preoperative baseline and indicate that microRNAs are potentially novel biomarkers for the benefits of bariatric surgery.