Publication Database

High-fat diet induces unexpected fatal uterine infections in mice with aP2-Cre-mediated deletion of estrogen receptor alpha (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Ban, Zsofia

Maurischat, Paul

Benz, Verena

Brix, Sarah

Sonnenburg, Anna

Schuler, Gerhard

Klopfleisch, Robert (WE 12)

Rothe, Michael

Gustafsson, Jan-Åke

Foryst-Ludwig, Anna

Kintscher, Ulrich

Quelle

Scientific reports

Bandzählung: 7

Seiten: Article number: 43269

ISSN: 2045-2322

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/srep43269

DOI: 10.1038/srep43269

Pubmed: 28233809

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.