Nontargeted metabolomic analysis of skeletal muscle in a dehydroepiandrosterone‐induced mouse model of polycystic ovary syndrome

2019 ◽  
Vol 86 (4) ◽  
pp. 370-378 ◽  
Author(s):  
Qiyang Shen ◽  
Hai Bi ◽  
Fuhai Yu ◽  
Liting Fan ◽  
Menliang Zhu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Polycystic Ovary ◽  
Metabolomic Analysis ◽  
Ovary Syndrome

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

Myo‐inositol and D‐chiro‐inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model

2018 ◽  
Vol 234 (6) ◽  
pp. 9387-9398 ◽  
Author(s):  
Arturo Bevilacqua ◽  
Jessica Dragotto ◽  
Alessandro Giuliani ◽  
Mariano Bizzarri
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Functional Features

Evidence of an Inflammatory State in a Mouse Model of Polycystic Ovary Syndrome

2011 ◽  
pp. P3-387-P3-387
Author(s):  
Joseph S Marino ◽  
Abigail R Dowling ◽  
Xiaoliang Qiu ◽  
Laura Nedorezov ◽  
Laura FC Mueller ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Inflammatory State

scholarly journals Mechanisms underlying absent training-induced improvement in insulin action in lean, hyperandrogenic women with polycystic ovary syndrome (PCOS)

2020 ◽  
Author(s):  
Ada Admin ◽  
Solvejg L. Hansen ◽  
Kirstine N. Bojsen-Møller ◽  
Anne-Marie Lundsgaard ◽  
Frederikke L. Hendrich ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Ovary Syndrome ◽  
Leg Blood Flow

Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle improving glucose uptake and metabolism in both healthy and type 2 diabetic individuals. In the present study, lean, hyperandrogenic women with PCOS (n=9) and healthy controls (CON, n=9) completed 14 weeks of controlled and supervised exercise training. In CON, the training intervention increased whole body insulin action by 26% and insulin-stimulated leg glucose uptake by 53%, together with increased insulin-stimulated leg blood flow and a more oxidative muscle fiber type distribution. In PCOS, no such changes were found, despite similar training intensity and improvements in maximal oxygen uptake. In skeletal muscle of CON, but not PCOS, training increased GLUT4 and HKII mRNA and protein expressions. These data suggest that the impaired increase in whole body insulin action in women with PCOS with training is caused by an impaired ability to upregulate key glucose handling proteins for insulin-stimulated glucose uptake in skeletal muscle, and insulin-stimulated leg blood flow. Still, other important benefits of exercise training appeared in women with PCOS, including an improvement of the hyperandrogenic state.

Endothelial dysfunction in hyperandrogenic polycystic ovary syndrome is not explained by either obesity or ectopic fat deposition

2013 ◽  
Vol 126 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Victoria S. Sprung ◽  
Helen Jones ◽  
Christopher J. A. Pugh ◽  
Nabil F. Aziz ◽  
Christina Daousi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Disease Risk ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Alcoholic Fatty Liver

PCOS (polycystic ovary syndrome) is associated with IR (insulin resistance), increased visceral fat and NAFLD (non-alcoholic fatty liver disease) all of which may contribute to endothelial dysfunction, an early marker of CVD (cardiovascular disease) risk. Our objective was to examine the relationships between endothelial dysfunction in PCOS, the volume of AT (adipose tissue) compartments and the size of intracellular TAG (triacylglycerol) pools in liver and skeletal muscle. A total of 19 women with PCOS (means±S.D.; 26±6 years, 36±5 kg/m2) and 16 control women (31±8 years, 30±6 kg/m2) were recruited. Endothelial function was assessed in the brachial artery using FMD (flow-mediated dilation). VAT (visceral AT) and abdominal SAT (subcutaneous AT) volume were determined by whole body MRI, and liver and skeletal muscle TAG by 1H-MRS (proton magnetic resonance spectroscopy). Cardiorespiratory fitness and HOMA-IR (homoeostasis model assessment of IR) were also determined. Differences between groups were analysed using independent Student's t tests and ANCOVA (analysis of co-variance). FMD was impaired in PCOS by 4.6% [95% CI (confidence interval), 3.0–7.7; P<0.001], and this difference decreased only slightly to 4.2% (95% CI, 2.4–6.1; P<0.001) when FMD was adjusted for individual differences in visceral and SAT and HOMA-IR. This magnitude of impairment was also similar in lean and obese PCOS women. The results suggest that endothelial dysfunction in PCOS is not explained by body fat distribution or volume. FMD might be a useful independent prognostic tool to assess CVD risk in this population.

scholarly journals A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome

10.3791/58379 ◽  
2018 ◽  
Author(s):  
Ping Xue ◽  
Zhiqiang Wang ◽  
Xiaomin Fu ◽  
Junjiang Wang ◽  
Gopika Punchhi ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Polycystic Ovary ◽  
Ovary Syndrome

scholarly journals SAT-018 Androgen Actions in Adipose Tissue and the Brain Are Key Mediators in the Development of Polycystic Ovary Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Madeleine J Cox ◽  
Melissa C Edwards ◽  
Ali Aflatounian ◽  
Valentina Rodriguez Paris ◽  
William L Ledger ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Hepatic Steatosis ◽  
Polycystic Ovary ◽  
Reproductive Traits ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Adipocyte Hypertrophy ◽  
The Brain

Abstract Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanisms involved in the pathogenesis of PCOS would pave the way for the development of new interventions for PCOS. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signalling and adipose tissue function have been proposed as playing a pathogenic role in the development of experimental PCOS. To investigate the role of adipose tissue and the brain as potential key sites for androgen receptor (AR)-mediated development of PCOS, we combined an adipocyte and brain-specific ARKO knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. Wildtype (WT) and AdBARKO prepubertal mice were implanted with a blank or DHT implant and examined after 12 weeks. In WT control females, DHT exposure induced the PCOS reproductive traits of cycle irregularity, ovulatory dysfunction and reduced follicle health. In contrast, these reproductive features of PCOS were absent in DHT-treated AdBARKO females. The PCOS metabolic characteristics of increased adiposity, adipocyte hypertrophy and hepatic steatosis were induced by DHT in WT females. Despite DHT treatment, AdBARKO females displayed normal white adipose tissue weight, and adipocyte hypertrophy and hepatic steatosis were not evident. However, as with WT mice, DHT treatment induced increased fasting glucose levels in AdBARKO females. These results demonstrate that adipose tissue and the brain are key loci for androgen-mediated actions involved in the developmental origins of PCOS. These findings support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.

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