Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation

Study Overview
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Brief Summary
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A goal of this study is to use a novel methodology to determine whether insulin resistance in women with polycystic ovary syndrome (PCOS) is related to the accumulation of proteins with modifications. This could lead to future research to determine if these modifications interfere with their proper function. Additionally, the investigators will determine how protein quality is affected by exercise training. Aerobic exercise enhances the endogenous oxidant buffering systems which may minimize oxidative damage to proteins. The investigators propose that aerobic exercise minimizes the accrual of modified proteins by increasing the synthesis of new proteins, but also by increasing the degradation and removal of old and damaged proteins. Based on our previous studies the investigators observed that insulin affects plasma protein synthesis and aerobic exercise improves insulin sensitivity not only in muscle but also in liver. The investigators therefore propose that aerobic exercise and related increase in insulin sensitivity (and decline in insulin levels) will reduce accumulation of old and modified skeletal muscle and plasma proteins leading to improved function.

Official Title
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Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation

Conditions
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Polycystic Ovarian Syndrome (PCOS), Insulin Resistance, Overweight, Obese

Intervention / Treatment
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* Behavioral: Aerobic Exercise Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 25 kg/m2 and 40 kg/m2 Fasting blood glucose < 126 mg/dL Diagnosed with PCOS as outlined by the Rotterdam criteria Insulin resistant as determined by a 3 hour oral glucose tolerance test Exclusion Criteria: Serum creatinine ≥1.5 mg/ dL. Serum transaminase elevation ≥ 3 times the upper limit of normal range Use of systemic glucocorticoids Use of oral anticoagulation Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Sedentary Control<br>Participants will be randomized to an exercise training program or sedentary control group. The sedentary will not perform any structured physical activity or exercise. Participants will be encouraged to maintain their sedentary lifestyle and will be monitored by an accelerometer to track physical activity. | |
| Experimental: Aerobic Exercise Training<br>Participants will perform 12-weeks of aerobic exercise training | Behavioral: Aerobic Exercise Training<br>* A progressive increase in duration, frequency and intensity so the last 8 weeks of exercise are performed for 60 min, 5 days per week and at 80% of aerobic capacity. The duration includes a 5 minute warm up and 5 minute cool down. All exercise will be performed on a stationary bicycle (i.e., cycle ergometer).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin sensitivity | To determine the effect of 12 weeks of aerobic exercise training or sedentary behavior on insulin sensitivity measured by a 3 hour hyperinsulinemic-euglycemic clamp and response to a mixed-meal. | Measured before and after 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protein modifications and accumulation | Alterations in protein modifications and accumulation will be measured by a novel methodology developed within our laboratory. Infusion of stable amino acid isotopes will be used to measure the accumulation of proteins before and after 12 weeks of aerobic exercise training or sedentary behavior. Plasma and muscle will be resolved using a two dimensional gel electrophoresis which will allow the identification of protein modifications and age. | Before and after 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovarian Syndrome (PCOS), Insulin Resistance, Overweight, Obese Women, Protein Metabolism, Post Translational Modifications