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Statement of the Problem: Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (SI) and �²-cell function in obese
non-diabetic subjects. Exercise also improves SI and may be an effective adjunct therapy to RYGB surgery. However, the mechanisms
by which exercise or weight loss improve peripheral SI after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs)
mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma
miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (NCT00692367), to assess whether
miRNA levels track with improvements in SI and cardiometabolic risk factors.
Methodology & Theoretical Orientation: Ninety-four (94) miRNAs implicated in metabolism were profiled in plasma samples
from 22 severely obese subjects who were recruited 1-3 months after RYGB surgery and followed for 6 months of RYGB surgeryinduced
weight loss with (exercise program (EX), N=11) or without (CON, N=11) an exercise training intervention. The subjects
were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for
repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis.
Results: Mirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic
risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and
miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and
miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, SI and other cardiometabolic
risk factors.
Conclusion & Significance: These findings present novel insights into the RYGB surgery-induced molecular changes and the effects of
mild exercise to facilitate and/or maintain the benefits of a comprehensive weight-loss intervention with concomitant improvements
in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.