Circulating and Adipose Tissue miRNAs in Women With Polycystic Ovary Syndrome and Responses to High-Intensity Interval Training

Sofie Lionett; Ida A Kiel; Donny M Camera; Eszter Vanky; Evelyn B Parr; Stian Lydersen; John A Hawley; Trine Moholdt

doi:10.3389/fphys.2020.00904

Circulating and Adipose Tissue miRNAs in Women With Polycystic Ovary Syndrome and Responses to High-Intensity Interval Training

Front Physiol. 2020 Jul 30:11:904. doi: 10.3389/fphys.2020.00904. eCollection 2020.

Authors

Sofie Lionett^{1

2

3}, Ida A Kiel^{1

2}, Donny M Camera⁴, Eszter Vanky², Evelyn B Parr³, Stian Lydersen⁵, John A Hawley³, Trine Moholdt^{1

2}

Affiliations

¹ Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
² Department of Obstetrics and Gynecology, St. Olav's Hospital, Trondheim, Norway.
³ Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC, Australia.
⁴ Department of Health and Medical Sciences, Swinburne University of Technology, Melbourne, VIC, Australia.
⁵ Regional Centre for Child and Youth Mental Health and Child Welfare, Norwegian University of Science and Technology, Trondheim, Norway.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. In women with polycystic ovary syndrome (PCOS), several miRNAs are differentially expressed compared to women without PCOS, suggesting a role for miRNAs in PCOS pathophysiology. Exercise training modulates miRNA abundance and is primary lifestyle intervention for women with PCOS. Accordingly, we measured the expression of eight circulating miRNAs selected a priori along with miRNA expression from gluteal and abdominal adipose tissue (AT) in 12 women with PCOS and 12 women matched for age and body mass index without PCOS. We also determined the miRNA expression "signatures" before and after high-intensity interval training (HIT) in 42 women with PCOS randomized to either: (1) low-volume HIT (LV-HIT, 10 × 1 min work bouts at maximal, sustainable intensity, n = 13); (2) high-volume HIT (HV-HIT, 4 × 4 min work bouts reaching 90-95% of maximal heart rate, n = 14); or (3) non-exercise control (Non-Ex, n = 15). Both HIT groups trained three times/week for 16 weeks. miRNAs were extracted from plasma, gluteal and abdominal AT, and quantified via a customized plate array containing eight miRNAs associated with PCOS and/or exercise training responses. Basal expression of circulating miRNA-27b (c-miR-27b), implicated in fatty acid metabolism, adipocyte differentiation and inflammation, was 1.8-fold higher in women with compared to without PCOS (P = 0.006) despite no difference in gluteal or abdominal AT miR-27b expression. Only the HV-HIT protocol increased peak oxygen uptake (VO₂peak L/min; 9%, P = 0.008). There were no changes in body composition. In LV-HIT, but not HV-HIT, the expression of c-miR-27b decreased (0.5-fold, P = 0.007). None of the remaining seven circulating miRNAs changed in LV-HIT, nor was the expression of gluteal or abdominal AT miRNAs altered. Despite increased cardiorespiratory fitness, HV-HIT did not alter the expression of any circulating, gluteal or abdominal AT miRNAs. We conclude that women with PCOS have a higher basal expression of c-miR-27b compared to women without PCOS and that 16 weeks of LV-HIT reduces the expression of this miRNA in women with PCOS. Intense exercise training had little effect on the abundance of the selected miRNAs within subcutaneous AT depots in women with PCOS.

Keywords: cardiorespiratory fitness; epigenetic modifications; exercise; female; insulin resistance; miRNA-27b.