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dc.contributor.authorVan Sinderen, ML
dc.contributor.authorSteinberg, GR
dc.contributor.authorJorgensen, SB
dc.contributor.authorHoneyman, J
dc.contributor.authorChow, JD
dc.contributor.authorHerridge, KA
dc.contributor.authorWinship, AL
dc.contributor.authorDimitriadis, E
dc.contributor.authorJones, MEE
dc.contributor.authorSimpson, ER
dc.contributor.authorBoon, WC
dc.date.accessioned2020-12-17T03:59:05Z
dc.date.available2020-12-17T03:59:05Z
dc.date.issued2015-08-28
dc.identifierpii: PONE-D-14-53696
dc.identifier.citationVan 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.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/255117
dc.description.abstractThe 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEffects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0136143
melbourne.affiliation.departmentSchool of BioSciences
melbourne.affiliation.departmentObstetrics and Gynaecology
melbourne.source.titlePLoS One
melbourne.source.volume10
melbourne.source.issue8
melbourne.identifier.nhmrc628553
dc.rights.licenseCC BY
melbourne.elementsid1237146
melbourne.contributor.authorBoon, Wah Chin
melbourne.contributor.authorDimitriadis, Evdokia
dc.identifier.eissn1932-6203
melbourne.identifier.fundernameidNHMRC, 628553
melbourne.accessrightsOpen Access


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