Context: Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture but the mechanisms are largely unknown.

Objective: To identify the molecular mechanisms underlying electroacupuncture-induced glucose uptake in skeletal muscle in insulin-resistant overweight/obese women with and without polycystic ovary syndrome (PCOS).

Design/Participants: In a case-control study, skeletal muscle biopsies were collected from 15 women with PCOS and 14 controls before and after electroacupuncture. Gene expression and methylation was analyzed using Illumina BeadChips arrays.

Results: A single bout of electroacupuncture restores metabolic and transcriptional alterations and induces epigenetic changes in skeletal muscle. Transcriptomic analysis revealed 180 unique genes (q < 0.05) whose expression was changed by electroacupuncture, with 95% of the changes towards a healthier phenotype. We identified DNA methylation changes at 304 unique sites (q < 0.20), and these changes correlated with altered expression of 101 genes (p < 0.05). Among the 50 most upregulated genes in response to electroacupuncture, 38% were also upregulated in response to exercise. We identified a subset of genes that were selectively altered by electroacupuncture in women with PCOS. For example, MSX1 and SRNX1 were decreased in muscle tissue of women with PCOS and were increased by electroacupuncture and exercise. siRNA-mediated silencing of these two genes in cultured myotubes decreased glycogen synthesis, supporting a role for these genes in glucose homeostasis.

Conclusion: Our findings provide evidence that electroacupuncture normalizes gene expression in skeletal muscle in a manner similar to acute exercise. Electroacupuncture might therefore be a useful way of assisting those who have difficulties performing exercise.

The cohort consisted of 21 overweight or obese women (BMI = 25–35 kg/m²) with PCOS and 21 age, weight, and BMI-matched controls. Of these, we successfully collected skeletal muscle biopsies from 15 women with PCOS and from 14 controls. Therefore, baseline data are only given for those included in the gene expression and DNA methylation analyses. Inclusion criteria for the controls were 18–38 yr old, BMI .25 to ,35, regular menstrual cycles of 28 +/- 2 d, and normal ovarian morphology. Controls were excluded if they showed signs of hyperandrogenism (Ferriman- Gallwey score >4). Women with PCOS were diagnosed according to the Rotterdam criteria fulfilling 2 of 3 criteria: ultrasound-verified polycystic ovaries (>12 follicles of 2–9mmand/or ovarian volume >10 ml in 1 or both ovaries), oligomenorrhea (>35 d between, or ,<6 menstruations in the past year), amenorrhea (absence of menstrual bleedings in the past 90 d), or clinical signs of hyperandrogenism (acneor hirsutism, Ferriman-Gallwey score >8). The study was conducted in accordance with the Declaration of Helsinki at Sahlgrenska University Hospital and the Sahlgrenska Academy, University of Gothenburg, Sweden, and was approved by the Regional Ethical Review Board of the University of Gothenburg. All participants gave oral and written informed consent before inclusion. The study was registered at ClinicalTrials.gov (NCT01457209) and is reported according to the CONSORT and STRICTA guidelines.

Supplemental figures and tables for the article "Electroacupuncture mimics exercise-induced changes in skeletal muscle gene expression in women with polycystic ovary syndrome" (Journal of Clinical Endocrinology & Metabolism)