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

TitleSupplemental estrogen and caloric restriction reduce obesity-induced periprostatic white adipose inflammation in mice.
Publication TypeJournal Article
Year of Publication2019
AuthorsBhardwaj P, Ikeda T, Zhou XKathy, Wang H, Zheng XEmily, Giri DD, Elemento O, Verma A, Miyazawa M, Mukherjee S, Falcone DJ, Wendel NK, Scherr DS, Dannenberg AJ
Date Published2019 07 20
KeywordsAdipocytes, Animals, Caloric Restriction, Diet, High-Fat, Disease Models, Animal, Eating, Estradiol, Estrogens, Humans, Inflammation, Intra-Abdominal Fat, Male, Mice, Obesity, Prostate, Prostatic Neoplasms, Treatment Outcome, Weight Loss

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.

Alternate JournalCarcinogenesis
PubMed ID31067318
PubMed Central IDPMC7331453
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
P50 CA092629 / CA / NCI NIH HHS / United States