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Integrative Biology

Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk

International Journal of Obesity volume 41, pages 1121–1130 (2017)Cite this article

Subjects

Abstract

Background/Objectives:

Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (SI) and β-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 (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in SI and cardiometabolic risk factors.

Subjects/Methods:

Ninety-four 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 surgery-induced 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.

Conclusions:

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.

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Acknowledgements

This study was supported by funding from the NIDDK (R01DK078192, R01DK078192-02S1, BHG), and the University of Pittsburgh Clinical Translational Research Center (M01RR00056) and Obesity and Nutrition Research Center (P30DK46204). We would like to thank for Florida hospital for making the funds available to AAS and BHG to conduct this study.

Author contributions

AAS contributed to the conception and design of the research design, analysis plan, supervision of the analysis, study implementation, data acquisition and interpretation, writing of the manuscript and critical revision and final approval of the manuscript. YONL performed the experiments, conducted the data and statistical analysis, contributed to the data interpretation, writing of the manuscript and critical revision of the manuscript. PMC and BHG contributed to the study design, study implementation, the data interpretation, writing of the manuscript and critical revision and final approval of the manuscript. AAS is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Author notes

  1. Y O Nunez Lopez and P M Coen: These authors contributed equally to this work.

Authors and Affiliations

  1. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA

    Y O Nunez Lopez, P M Coen, B H Goodpaster & A A Seyhan

  2. Sanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL, USA

    P M Coen, B H Goodpaster & A A Seyhan

  3. Chemical Engineering Department Cambridge, Massachusetts Institute of Technology, MA, USA

    A A Seyhan

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  1. Y O Nunez Lopez
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Correspondence to B H Goodpaster or A A Seyhan.

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Nunez Lopez, Y., Coen, P., Goodpaster, B. et al. Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk. Int J Obes 41, 1121–1130 (2017). https://doi.org/10.1038/ijo.2017.84

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