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

Autor: Jennifer W. Hill, Jens C. Brüning, Jeffrey Iler, Streamson C. Chua, Joseph S. Marino, Abigail R. Dowling, Roberto Coppari
Rok vydání: 2012
Předmět:
Blood Glucose
Male
Central Nervous System
Anatomy and Physiology
Mouse
Receptor
Insulin/genetics/metabolism
Interleukin-1beta
lcsh:Medicine
Adipose tissue
Gene Expression
Adipocytes/metabolism/pathology
Pathogenesis
chemistry.chemical_compound
Mice
0302 clinical medicine
Pregnancy
Reproductive Physiology
Adipocyte
Adipocytes
lcsh:Science
Interleukin-6/blood/genetics/metabolism
Mice
Knockout
0303 health sciences
030219 obstetrics & reproductive medicine
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Ovary/metabolism/pathology
Polycystic ovary syndrome (PCOS)
Leptin
Animal Models
Polycystic ovary
Magnetic Resonance Imaging
3. Good health
Adipose Tissue
Liver
Receptors
Leptin
Medicine
Female
Polycystic Ovary Syndrome
Research Article
Ovulation
medicine.medical_specialty
Ovulation/genetics
Neurophysiology
Endocrine System
Biology
Polycystic Ovary Syndrome/blood/genetics/metabolism
Receptors
Leptin/genetics/metabolism
03 medical and health sciences
Insulin resistance
Model Organisms
Internal medicine
medicine
Animals
Humans
Reproductive Endocrinology
Interleukin-1beta/blood/genetics/metabolism
ddc:612
030304 developmental biology
Inflammation
Adipose Tissue/metabolism/pathology
Liver/metabolism/pathology
Blood Glucose/metabolism
Endocrine Physiology
Interleukin-6
lcsh:R
Ovary
Reproductive System
Immunity
Hypertrophy
Inflammation/genetics/metabolism
medicine.disease
Receptor
Insulin
Disease Models
Animal
Endocrinology
chemistry
Women's Health
lcsh:Q
Clinical Immunology
Adipocyte hypertrophy
Tomography
X-Ray Computed
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 10, p e48643 (2012)
PLOS ONE, Vol. 7, No 10 (2012) P. e48643
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: