Polycystic Ovary Syndrome and Insulin Physiology: An Observational Quantitative Serum Proteomics Study in Adolescent, Normal‐Weight Females

Abstract

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance, even in the absence of overweight/obesity. The aim of the present study is to examine the global serum proteomic profile of adolescent, normal‐weight females with PCOS in order to gain novel insight in the association of this endocrine disorder with insulin physiology and to identify novel circulating markers that can guide intervention protocols. Methods Non‐depleted serum from normal‐weight (BMI: 18–23 kg m−2), adolescent females (13–21 years old) with PCOS (n = 20) is compared to BMI‐ and age‐matched healthy controls (n = 20) using our 3D quantitative proteomics methodology. Serum samples from study participants are randomly pooled to form four biological replicates of females with PCOS and four of healthy controls (n = 5 per sample pool). Results One‐hundred and twenty‐six proteins are differentially expressed in females with PCOS compared to controls. Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism and insulin‐like growth factor receptor signaling pathway. Circulating levels of IGF‐1 and ‐2 and IGFBP‐2, ‐3, and ‐4 are found to be lower in females with PCOS compared to healthy controls. Conclusions The present serum proteomics study provides insight into the pro‐inflammatory status and insulin dysregulation in young females with PCOS and identifies potential serological markers that can guide early intervention protocols.

TMT Based Proteomic Analysis of Human Follicular Fluid From Overweight/Obese and Normal-Weight Patients With Polycystic Ovary Syndrome

“…However, non-obese PCOS women still have increased incidence of metabolic disturbances and long-term metabolic complications as reported according to a recent systematic review and metaanalysis (47). A serum proteomics study of normal-weight PCOS adolescents showed the enrichment of inflammatory and immune responses, metabolism, and insulin-like growth factor receptor signaling pathway (48). Our findings suggest that the metabolic disturbance might not only be a consequent of obesity, but also an intrinsic etiologic basis for PCOS.…”

Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

“…Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism, and IGF-receptor signaling pathway. Circulating levels of IGF-1 and -2 and IGF binding protein-2, -3, and -4 are found to be lower in females with PCOS compared to healthy controls [117]. This is also confirmed in a study performed in follicular fluid, showing intrinsic abnormalities in PCOS patients, which were amplified by obesity [35].…”

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

“…Plasma is a complex matrix to analyze, and high-abundance protein depletion is the most common strategy to address this complexity ( 5 , 27 – 29 , 45 , 46 ). However, depletion may inadvertently coremove important analytes noncovalently bound to high-abundance proteins ( 26 ).…”