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High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha
Estrogen receptor alpha (ERα) is a major regulator of metabolic processes in obesity. In this study we aimed to define the relevance of adipose tissue ERα during high-fat diet (HFD)-induced obesity using female aP2-Cre(−/+)/ERα(fl/fl) mice (atERαKO). HFD did not affect body weight or glucose metabol...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324142/ https://www.ncbi.nlm.nih.gov/pubmed/28233809 http://dx.doi.org/10.1038/srep43269 |
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author | Ban, Zsofia Maurischat, Paul Benz, Verena Brix, Sarah Sonnenburg, Anna Schuler, Gerhard Klopfleisch, Robert Rothe, Michael Gustafsson, Jan-Åke Foryst-Ludwig, Anna Kintscher, Ulrich |
author_facet | Ban, Zsofia Maurischat, Paul Benz, Verena Brix, Sarah Sonnenburg, Anna Schuler, Gerhard Klopfleisch, Robert Rothe, Michael Gustafsson, Jan-Åke Foryst-Ludwig, Anna Kintscher, Ulrich |
author_sort | Ban, Zsofia |
collection | PubMed |
description | Estrogen receptor alpha (ERα) is a major regulator of metabolic processes in obesity. In this study we aimed to define the relevance of adipose tissue ERα during high-fat diet (HFD)-induced obesity using female aP2-Cre(−/+)/ERα(fl/fl) mice (atERαKO). HFD did not affect body weight or glucose metabolism in atERαKO- compared to control mice. Surprisingly, HFD feeding markedly increased mortality in atERαKO mice associated with a destructive bacterial infection of the uterus driven by commensal microbes, an alteration likely explaining the absence of a metabolic phenotype in HFD-fed atERαKO mice. In order to identify a mechanism of the exaggerated uterine infection in HFD-fed atERαKO mice, a marked reduction of uterine M2-macrophages was detected, a cell type relevant for anti-microbial defence. In parallel, atERαKO mice exhibited elevated circulating estradiol (E2) acting on E2-responsive tissue/cells such as macrophages. Accompanying cell culture experiments showed that despite E2 co-administration stearic acid (C18:0), a fatty acid elevated in plasma from HFD-fed atERαKO mice, blocks M2-polarization, a process known to be enhanced by E2. In this study we demonstrate an unexpected phenotype in HFD-fed atERαKO involving severe uterine bacterial infections likely resulting from a previously unknown negative interference between dietary FAs and ERα-signaling during anti-microbial defence. |
format | Online Article Text |
id | pubmed-5324142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53241422017-03-01 High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha Ban, Zsofia Maurischat, Paul Benz, Verena Brix, Sarah Sonnenburg, Anna Schuler, Gerhard Klopfleisch, Robert Rothe, Michael Gustafsson, Jan-Åke Foryst-Ludwig, Anna Kintscher, Ulrich Sci Rep Article Estrogen receptor alpha (ERα) is a major regulator of metabolic processes in obesity. In this study we aimed to define the relevance of adipose tissue ERα during high-fat diet (HFD)-induced obesity using female aP2-Cre(−/+)/ERα(fl/fl) mice (atERαKO). HFD did not affect body weight or glucose metabolism in atERαKO- compared to control mice. Surprisingly, HFD feeding markedly increased mortality in atERαKO mice associated with a destructive bacterial infection of the uterus driven by commensal microbes, an alteration likely explaining the absence of a metabolic phenotype in HFD-fed atERαKO mice. In order to identify a mechanism of the exaggerated uterine infection in HFD-fed atERαKO mice, a marked reduction of uterine M2-macrophages was detected, a cell type relevant for anti-microbial defence. In parallel, atERαKO mice exhibited elevated circulating estradiol (E2) acting on E2-responsive tissue/cells such as macrophages. Accompanying cell culture experiments showed that despite E2 co-administration stearic acid (C18:0), a fatty acid elevated in plasma from HFD-fed atERαKO mice, blocks M2-polarization, a process known to be enhanced by E2. In this study we demonstrate an unexpected phenotype in HFD-fed atERαKO involving severe uterine bacterial infections likely resulting from a previously unknown negative interference between dietary FAs and ERα-signaling during anti-microbial defence. Nature Publishing Group 2017-02-24 /pmc/articles/PMC5324142/ /pubmed/28233809 http://dx.doi.org/10.1038/srep43269 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Ban, Zsofia Maurischat, Paul Benz, Verena Brix, Sarah Sonnenburg, Anna Schuler, Gerhard Klopfleisch, Robert Rothe, Michael Gustafsson, Jan-Åke Foryst-Ludwig, Anna Kintscher, Ulrich High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha |
title | High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha |
title_full | High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha |
title_fullStr | High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha |
title_full_unstemmed | High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha |
title_short | High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha |
title_sort | high-fat diet induces unexpected fatal uterine infections in mice with ap2-cre-mediated deletion of estrogen receptor alpha |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324142/ https://www.ncbi.nlm.nih.gov/pubmed/28233809 http://dx.doi.org/10.1038/srep43269 |
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