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

Marino, Joseph S
Iler, Jeffrey
Dowling, Abigail R
Chua, Streamson
Bruning, Jens C
Hill, Jennifer W
Published in PloS one. 2012, vol. 7, no. 10, e48643
Abstract 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.
Keywords Adipocytes/metabolism/pathologyAdipose Tissue/metabolism/pathologyAnimalsBlood Glucose/metabolismDisease Models, AnimalFemaleGene ExpressionHumansHypertrophyInflammation/genetics/metabolismInterleukin-1beta/blood/genetics/metabolismInterleukin-6/blood/genetics/metabolismLiver/metabolism/pathologyMagnetic Resonance ImagingMaleMiceMice, KnockoutOvary/metabolism/pathologyOvulation/geneticsPolycystic Ovary Syndrome/blood/genetics/metabolismPregnancyReceptor, Insulin/genetics/metabolismReceptors, Leptin/genetics/metabolismReverse Transcriptase Polymerase Chain ReactionTomography, X-Ray Computed
PMID: 23119079
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Article (Published version) (794 Kb) - public document Free access
Research group La biologie du métabolisme dans la santé et la maladie (921)
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MARINO, Joseph S et al. Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS): evidence of adipocyte hypertrophy and tissue-specific inflammation. In: PloS one, 2012, vol. 7, n° 10, p. e48643. doi: 10.1371/journal.pone.0048643 https://archive-ouverte.unige.ch/unige:32259

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Deposited on : 2013-12-17

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