Polycystic ovary syndromes (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders in women. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead to changes in protein levels and biological function. To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation. Perilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differential protein activity. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue. Our results suggest that hyperandrogenic women with PCOS have higher levels of extramyocellular lipids, fewer oxidative and insulin-sensitive type I muscle fibers. These could be key factors leading insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective.

The authors have declared no competing interest.

Clinical trial ID NCT01457209

A.B. holds funding from the Swedish Research Council (2020-02485), E.SV. holds funding from the Swedish Research Council (2022-00550), the Novo Nordisk Foundation (NNF22OC0072904), and I.W.A. holds funding from the Swedish Research Council (2020-01463), Mary von Sydow Foundation and Diabetes Wellness Sverige, and JN holds funding from IngaBritt and Arne Lundberg Research Foundation. The funding bodies did not have a role in study design and have no role in the implementation of the study.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted at the Sahlgrenska University Hospital and at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, in accordance with the standards set by the Declaration of Helsinki. Procedures have been approved by the Regional Ethical Review Board of the University of Gothenburg (approval number 520-11) and the study was registered at ClinicalTrials.gov (NCT01457209). All women provided oral and written informed consent prior to participation in the study.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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The proteomics data have been deposited to the ProteomeXchange Consortium via the Proteomics Identifications (PRIDE) (RRID:SCR_003411) partner repository with the dataset identifier PXD025358 and will be made available when the manuscript is accepted for publication. The rest of the data that support the findings of this study are available from the corresponding author upon reasonable request.