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    Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice

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    Author
    Van Sinderen, ML; Steinberg, GR; Jorgensen, SB; Honeyman, J; Chow, JD; Herridge, KA; Winship, AL; Dimitriadis, E; Jones, MEE; Simpson, ER; ...
    Date
    2015-08-28
    Source Title
    PLoS One
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Boon, Wah Chin; Dimitriadis, Evdokia
    Affiliation
    School of BioSciences
    Obstetrics and Gynaecology
    Metadata
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    Document Type
    Journal Article
    Citations
    Van Sinderen, M. L., Steinberg, G. R., Jorgensen, S. B., Honeyman, J., Chow, J. D., Herridge, K. A., Winship, A. L., Dimitriadis, E., Jones, M. E. E., Simpson, E. R. & Boon, W. C. (2015). Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice. PLOS ONE, 10 (8), https://doi.org/10.1371/journal.pone.0136143.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255117
    DOI
    10.1371/journal.pone.0136143
    Abstract
    The maintenance of glucose homeostasis within the body is crucial for constant and precise performance of energy balance and is sustained by a number of peripheral organs. Estrogens are known to play a role in the maintenance of glucose homeostasis. Aromatase knockout (ArKO) mice are estrogen-deficient and display symptoms of dysregulated glucose metabolism. We aim to investigate the effects of estrogen ablation and exogenous estrogen administration on glucose homeostasis regulation. Six month-old female wildtype, ArKO, and 17β-estradiol (E2) treated ArKO mice were subjected to whole body tolerance tests, serum examination of estrogen, glucose and insulin, ex-vivo muscle glucose uptake, and insulin signaling pathway analyses. Female ArKO mice display increased body weight, gonadal (omental) adiposity, hyperinsulinemia, and liver triglycerides, which were ameliorated upon estrogen treatment. Tolerance tests revealed that estrogen-deficient ArKO mice were pyruvate intolerant hence reflecting dysregulated hepatic gluconeogenesis. Analyses of skeletal muscle, liver, and adipose tissues supported a hepatic-based glucose dysregulation, with a down-regulation of Akt phosphorylation (a key insulin signaling pathway molecule) in the ArKO liver, which was improved with E2 treatment. Concurrently, estrogen treatment lowered ArKO serum leptin and adiponectin levels and increased inflammatory adipokines such as tumour necrosis factor alpha (TNFα) and interleukin 6 (IL6). Furthermore, estrogen deficiency resulted in the infiltration of CD45 macrophages into gonadal adipose tissues, which cannot be reversed by E2 treatment. This study describes the effects of estrogens on glucose homeostasis in female ArKO mice and highlights a primary phenotype of hepatic glucose dysregulation and a parallel estrogen modified adipokine profile.

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