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Background: Polycystic ovary syndrome (PCOS) and metabolic inflexibility are linked to insulin resistance, and women with PCOS appear to be metabolic inflexible in the rested, insulin-stimulated state. Exercise training is a primary lifestyle intervention in PCOS. Exercise training improves whole-body fat oxidation during submaximal exercise in healthy women, yet little is known about the effect on this outcome in women with PCOS.Methods: We measured whole-body fat oxidation rates during sub maximal exercise before and after 16 weeks of high-intensity interval training (HIT) in women with PCOS randomly allocated to either: low- or high-volume HIT (n = 41; low-volume HIT, 10 × 1 min work bouts at maximal, sustainable intensity and high-volume HIT, 4 × 4 min work bouts at 90–95% of maximal heart rate) or non-exercise control (n = 23), and in women without PCOS (Non-PCOS) allocated to low- or high volume HIT (n = 15). HIT was undertaken three times weekly. In a subset of women with and without PCOS, we measured mitochondrial respiration in abdominal and gluteal subcutaneous adipose tissue using high-resolution respirometry, as well as fat cell sizes in these tissues.Results: At baseline, women with PCOS had lower whole-body fat oxidation and mitochondrial respiration rates in abdominal adipose tissue compared to Non-PCOS. Peak oxygen uptake (mL/min/kg) increased in women with PCOS (~4%, p = 0.006) and Non-PCOS (~6%, p = 0.003) after 16 weeks of HIT. Whole-body fat oxidation only improved in Non-PCOS after HIT. No changes were observed in mitochondrial respiration and cell size in abdominal and gluteal adipose tissue after HIT in either group of women.Conclusion: We observed exercise-induced improvements in whole-body fat oxidation during submaximal exercise in Non-PCOS, but not in women with PCOS, after 16 weeks of HIT, suggesting metabolic inflexibility in women with PCOS.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT02419482 and NCT02943291.

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.