Estrogen protects against obesity-induced mammary gland inflammation in mice

Priya Bhardwaj, Baoheng Du, Kathy Xi Zhou, Erika Sue, Dilip Giri, Michael D. Harbus, Domenick J. Falcone, Clifford A. Hudis, Kotha Subbaramaiah, Andrew J. Dannenberg

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Obesity is a risk factor for the development of hormone receptor (HR)-positive breast cancer in postmenopausal women. Obesity causes subclinical inflammation in white adipose tissue (WAT), characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures (CLS). Estrogen synthesis is catalyzed by aromatase. Previously, we demonstrated CLS and elevated levels of proinflammatory mediators and aromatase in the mammary glands of obese mice and breast tissue of obese women. Here, we tested the hypothesis that supplemental estrogen could prevent or reverse WAT inflammation (WATi) and related molecular changes in the mammary gland. C57BL/6J mice were ovariectomized (OVX) to simulate the postmenopausal state. Supplementation with 17β-estradiol (E2) protected against high fat diet (HFD)-induced weight gain and mammary glands WATi. Expression of proinflammatory mediators (Cox-2, TNFα, IL1β) and aromatase were also reduced in the mammary glands of mice that received supplemental E2. Next, to determine whether E2 supplementation can reverse WATi, obese OVX mice were treated with E2 or placebo and then continued on HFD. E2 supplementation induced weight loss, reversed mammary gland inflammation, and downregulated expression of proinflammatory mediators and aromatase. Finally, we determined whether the protective effects of E2 were mediated by estrogen receptor-α (ERα). Knocking out ERα in ovary intact mice fed a HFD led to weight gain, WATi and elevated levels of proinflammatory mediators and aromatase mimicking the effects of OVX. Taken together, our findings indicate that estrogen via ERα protects against weight gain, WATi and associated increases in proinflammatory mediators and aromatase in the mammary gland.

Original languageEnglish (US)
Pages (from-to)751-759
Number of pages9
JournalCancer Prevention Research
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Estrogen protects against obesity-induced mammary gland inflammation in mice'. Together they form a unique fingerprint.

Cite this