Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS): evidence of adipocyte hypertrophy and tissue-specific inflammation

• Published in: PloS one 2012-10, Vol.7 (10), p.e48643-e48643
• Main Authors: Marino, Joseph S, Iler, Jeffrey, Dowling, Abigail R, Chua, Streamson, Bruning, Jens C, Coppari, Roberto, Hill, Jennifer W
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Adipocytes - pathology; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Analysis; Animals; B cells; Biology; Blood Glucose - metabolism; Body composition; Body fat; Computed tomography; Cytokines; Diabetes mellitus; Diabetes therapy; Disease Models, Animal; Estrus cycle; Etiology; Female; Gene Expression; Glucose; Health risks; Humans; Hyperglycemia; Hypertrophy; Infiltration; Inflammation; Inflammation - genetics; Inflammation - metabolism; Insulin; Insulin receptors; Insulin resistance; Interleukin-1beta - blood; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - blood; Interleukin-6 - genetics; Interleukin-6 - metabolism; Leptin; Liver; Liver - metabolism; Liver - pathology; Macrophages; Magnetic Resonance Imaging; Male; Medicine; Melanocyte stimulating hormone; Mice; Mice, Knockout; Obesity; Ovary - metabolism; Ovary - pathology; Ovulation; Ovulation - genetics; Pathogenesis; Physiological aspects; Polycystic ovary syndrome; Polycystic Ovary Syndrome - blood; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Pregnancy; Proopiomelanocortin; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Receptors; Receptors, Leptin - genetics; Receptors, Leptin - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA; Systematic review; Therapeutic applications; Tomography, X-Ray Computed; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048643

Clinical research shows an association between polycystic ovary syndrome (PCOS) and chronic inflammation, a pathological state thought to contribute to insulin resistance. The underlying pathways, however, have not been defined. The purpose of this study was to characterize the inflammatory state of a novel mouse model of PCOS. Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. Tissue-specific macrophage infiltration and cytokine mRNA expression were measured, as well as circulating cytokine levels. Finally, glucose regulation during pregnancy was evaluated as a measure of risk for diabetes development. Forty-five percent of IR/LepR(POMC) mice showed reduced or absent ovulation. IR/LepR(POMC) mice also had increased fat mass and adipocyte hypertrophy. These traits accompanied elevations in macrophage accumulation and inflammatory cytokine production in perigonadal adipose tissue, liver, and ovary. These mice also exhibited gestational hyperglycemia as predicted. This report is the first to show the presence of inflammation in IR/LepR(POMC) mice, which develop a PCOS-like phenotype. Thus, IR/LepR(POMC) mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions.