Supplemental estrogen and caloric restriction reduce obesity-induced periprostatic white adipose inflammation in mice

Priya Bhardwaj, Takahiro Ikeda, Xi Kathy Zhou, Hanhan Wang, Xi Emily Zheng, Dilip D. Giri, Olivier Elemento, Akanksha Verma, Miki Miyazawa, Sushmita Mukherjee, Domenick J. Falcone, Nils K. Wendel, Douglas S. Scherr, Andrew J. Dannenberg

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Obesity is associated with an increased incidence of high-grade prostate cancer (PC) and worse prognosis for PC patients. Recently, we showed in men that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures, was associated with high-grade PC. Possibly, interventions that suppress periprostatic WAT inflammation will improve outcomes for men with PC. Here, we tested the hypothesis that supplemental 17β-estradiol (E2) could decrease periprostatic WAT inflammation in obese male mice. Mice were fed a high-fat diet to induce periprostatic WAT inflammation before being treated with supplemental E2. E2 supplementation suppressed caloric intake, induced weight loss, decreased periprostatic WAT inflammation and downregulated the expression of genes linked to inflammation including Cd68, Mcp1 and Tnf. Similar to the effects of E2 supplementation, treatment with diethylstilbestrol, a synthetic estrogen, also suppressed caloric intake and reduced periprostatic WAT inflammation. To determine whether the observed effects of supplemental estrogen could be reproduced by caloric restriction (CR) alone, obese mice were put on a 30% CR diet. Like estrogen treatment, CR was effective in reducing body weight, periprostatic WAT inflammation and the expression of pro-inflammatory genes. Transcriptomic analyses of periprostatic fat showed that obesity was associated with enrichment in inflammatory response pathways, which were normalized by both supplemental E2 and CR. Taken together, these findings strengthen the rationale for future efforts to determine whether either CR or supplemental estrogen will decrease periprostatic WAT inflammation and thereby improve outcomes for men with PC.

Original languageEnglish (US)
Pages (from-to)914-923
Number of pages10
JournalCarcinogenesis
Volume40
Issue number7
DOIs
StatePublished - Jul 1 2019

ASJC Scopus subject areas

  • Cancer Research

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