High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha

Zsofia Ban, Paul Maurischat, Verena Benz, Sarah Brix, Anna Sonnenburg, Gerhard Schuler, Robert Klopfleisch, Michael Rothe, Jan Åke Gustafsson, Anna Foryst-Ludwig, Ulrich Kintscher

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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-/+/ERαfl/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.

Original languageEnglish (US)
Article number43269
JournalScientific Reports
Volume7
DOIs
StatePublished - Feb 24 2017

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha'. Together they form a unique fingerprint.

Cite this