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

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.

Copyright © 2020 Lionett, Kiel, Camera, Vanky, Parr, Lydersen, Hawley and Moholdt.

Figures

FIGURE 1
FIGURE 1
Study protocol. The testing days included: VO2peak, body fat percentage, waist and hip circumference measurements as well as blood and adipose tissue sampling. Non-PCOS (n = 12) women were only tested at baseline, whereas all women with PCOS (n = 42) were tested at baseline and after the 16 weeks exercise intervention. The 12 PCOS women in the case-control comparison also took part in the exercise intervention. Non-PCOS were age- and BMI-matched to these 12 women with PCOS.
FIGURE 2
FIGURE 2
Circulatory microRNA expression patterns. (A) c-miR-21-5p, (B) c-miR-27b-5p, (C) c-miR-93-5p, (D) c-miR-103a-3p, (E) c-miR-146a-5p, (F) c-miR-155-5p, (G) c-miR-222-3p, (H) c-miR-223-3p abundance in women with (PCOS; open, red circles) and without PCOS (Non-PCOS; blue squares). Values are arbitrary units expressed relative to the geometric mean of UniSp3, UniSp6 and RNU1A1. Individual data with group means and SD are displayed. PCOS, polycystic ovary syndrome; c, circulating; miR, microRNA; AU, arbitrary units.
FIGURE 3
FIGURE 3
Gluteal adipose tissue (ATG) microRNA expression patterns. (A) ATG-miR-21-5p, (B) ATG-miR-27b-5p, (C) ATG-miR-93-5p, (D) ATG-miR-103a-3p, (E) ATG-miR-146a-5p, (F) ATG-miR-155-5p, (G) ATG-miR-222-3p, (H) ATG-miR-223-3p abundance in women with (PCOS; open, red circles) and without PCOS (Non-PCOS; blue squares). Values are arbitrary units expressed relative to the geometric mean of SNORD44, UniSp3, UniSp6, and RNU1A1. Individual data with group means and SD are displayed. PCOS, polycystic ovary syndrome; ATG, gluteal adipose tissue; miR, microRNA; AU, arbitrary units.
FIGURE 4
FIGURE 4
Abdominal adipose tissue (ATA) microRNA expression patterns. (A) ATA-miR-21-5p, (B) ATA-miR-27b-5p, (C) ATA-miR-93-5p, (D) ATA-miR-103a-3p, (E) ATA-miR-146a-5p, (F) ATA-miR-155-5p, (G) ATA-miR-222-3p, (H) ATA-miR-223-3p abundance in women with (PCOS; open, red circles) and without PCOS (Non-PCOS; blue squares). Values are arbitrary units expressed relative to the geometric mean of SNORD44, UniSp3, UniSp6, and RNU1A1. Individual data with group means and SD are displayed. PCOS, polycystic ovary syndrome; ATA, abdominal adipose tissue; miR, microRNA; AU, arbitrary units.

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