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

Abstract

<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>

17β-Estradiol Attenuates LPS-Induced Macrophage Inflammation In Vitro and Sepsis-Induced Vascular Inflammation In Vivo by Upregulating miR-29a-5p Expression

“…As a major female hormone, estrogen has been proved to have anti-inflammatory, antioxidant, and organ-protective effects. Estrogen has been used as a therapeutic drug in many diseases, such as inflammatory bowel disease [ 14 ], acute spinal cord injury [ 15 ], neurovascular disease [ 16 ], and obesity [ 17 ]. Our previous study found that 17 β -estradiol (E2) suppressed proinflammatory gene expression through promoting the interaction of estrogen receptor (ER) α with NF- κ B p50 and decreasing high glucose-induced interaction of KLF5 with NF- κ B p50 in vascular smooth muscle cells [ 18 ].…”

Prognostic Value of CT-Attenuation and 18F-Fluorodeoxyglucose Uptake of Periprostatic Adipose Tissue in Patients with Prostate Cancer

“…Considering that no significant correlation between BMI and either PPAT HU or SUV was observed in our study, these inconsistent results might be due to the confounding effects of qualitative features of PPAT. Recently, an attempt has been made to pharmacologically modify PPAT features with 5α-reductase inhibitors and estrogen, which is expected to affect the outcomes of prostate cancer [ 49 , 50 ]. Based on the results of the present study, PPAT HU and SUV might be used to select candidates and to monitor treatment response to future therapy that targets PPAT in patients with prostate cancer.…”

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

“…Specifically, DES was capable of inhibiting mitochondrial respiration and glycolysis as well as activating ERK in 3T3-L1 adipocytes in an ER-dependent manner [223]. In addition, DES exposure was shown to induce WAT inflammation in obese mice [224].…”