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/LepRPOMC 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/LepRPOMC mice showed reduced or absent ovulation. IR/LepRPOMC 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/LepRPOMC mice, which develop a PCOS-like phenotype. Thus, IR/LepRPOMC 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. © 2012 Marino et al.
Marino, J. S., Iler, J., Dowling, A. R., Chua, S., Bruning, J. C., Coppari, R., & Hill, J. W. (2012). Adipocyte Dysfunction in a Mouse Model of Polycystic Ovary Syndrome (PCOS): Evidence of Adipocyte Hypertrophy and Tissue-Specific Inflammation. PLoS ONE, 7(10). https://doi.org/10.1371/journal.pone.0048643