Type I fiber decrease and ectopic fat accumulation in skeletal muscle from women with PCOS

E Stener-Victorin
G Eriksson
M Mohan Shrestha
V Rodriguez Paris
H Lu
J Banks
M Samad
C Perian
B Jude
V Engman
R Boi
E Nilsson
C Ling
J Nyström
I Wernstedt Asterholm
N Turner
J T Lanner
A Benrick author has email address

Department of Physiology and Pharmacology, Karolinska Institute, 17177 Stockholm, Sweden
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, NSW 2010, Australia
Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden
School of Health Sciences, University of Skövde, 54128 Skövde, Sweden

https://doi.org/10.7554/eLife.87592.2

Open access
Copyright information

Figures and data

Anthropometric and biochemical analyses in study participants.

A) Muscle and fat biopsies collected from 10 controls and 10 women with PCOS at baseline and after treatment with electrical stimulations. Electrical stimulations were given 3 times/week for 5 weeks. B) The electrical stimulation protocol alternating between protocol 1 in red dots and protocol 2 in blue dots. Acupuncture points not connected to the stimulator were stimulated manually. C) A PCOS-like mouse model treated with the androgen receptor blocker flutamide or lacking androgen receptors in skeletal muscle (SkMARKO). Created with BioRender.com

A) Volcano plot showing the mean protein log2 fold change in skeletal muscle (PCOS vs controls) plotted against the −log10 p value highlighting significantly regulated proteins in black (p<0.05, log2 fold change +/− 0.5), n=10/group. B) Increased protein expression of apolipoproteins C1 and C2, aldo-keto reductase (AKR) family 1 C1 and C3, and perilipin-1 in those with PCOS, C) staining of perilipin-1 and DAPI in skeletal muscle, D) quantification of perilipin-1 staining in skeletal muscle cells from control and PCOS groups.

A) Protein network on proteins with a lower expression in PCOS skeletal muscle vs. controls. Lines indicate protein-protein associations. B) Decreased expression of the slow type I skeletal muscle fibers myosin hevy chain beta (MYH7) in those with PCOS. C) Lower expression of proteins in slow-twitch type I muscle fibers in PCOS vs controls (p<0.05, log2 fold change <-0.5). D, E) lmmunoflourescent staining of type I muscle fibers with myosin heavy chain beta, and E) the cell membrane with WGA. F) Quantification of fiber cross-sectional area (CSA) in E). G) Differently phosphorylated sites in proteins expressed in muscle filaments (p<0.05, log2 fold change +/− 0.5).

A) Decreased expression of the slow type I skeletal muscle fibers myosin heavy chain beta (MYH7) in dihydrotestosterone (DHT) exposed PCOS-like mice. This effect was partly blocked by the androgen receptor antagonist flutamide (n=5-6/group). B) Decreased expression of slow type I skeletal muscle fibers (MYH7) in skeletal muscle-specific androgen receptor knockout mice (SkMARKO) compared to wild type (wt) (p=0.033). DHT exposure did not alter the number of type I fibers in SkMARKO (n=6-8/group) C) Representative expression of myosin heavy chain beta. Differences in A) are based on one-way ANOVA and B) on two-way ANOVA, and presented as mean ± SEM.

A) Volcano plot showing the mean protein log2 fold change in adipose tissue (PCOS vs controls) plotted against the −log10 p value highlighting significantly regulated proteins (black; p<0.05, log2 fold change +/− 0.5). n=10/group. B) All differentially expressed proteins in adipose tissue from women with PCOS. C) Picrosirius red staining of s.c. adipose tissue. Difference between women with PCOS and controls was based on Mann Whitney U test and is presented as mean± SD.

A) Volcano plot showing the mean protein log2 fold change in skeletal muscle (treatment vs baseline in PCOS) plotted against the −log10 p value highlighting significantly regulated proteins (black; p<0.05, log2 fold change +/− 0.5). n=10/group. B) GO terms for biological function of the changed proteins. C) Representative pictures and quantification of picrosirius red staining of skeletal muscle before and after treatment with electrical stimulation in the same individual. Changes between baseline and after treatment was based on Wilcoxon signed-rank test.

A) Volcano plot showing the mean protein log2 fold change in adipose tissue (treatment vs baseline in PCOS) plotted against the −log10 p value highlighting significantly regulated proteins (black; p<0.05, log2 fold change +/− 0.5). n=10/group. B) Representative pictures and quantification of picrosirius red staining of adipose tissue before and after treatment with electrical stimulation. Changes between baseline and after treatment was based on Wilcoxon signed-rank test.

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