Abstract:Obesity is a risk factor for the development of hormone receptor–positive breast cancer in post-menopausal 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 pro-inflammatory mediators and aromatase in the mammary glands (MG) of obese mice and breast tissue of obese women. Here we te… Show more
“…Studies using animal models and breast tissues of women suggest that their presence is associated with obesity and a pro-inflammatory, pro-carcinogenic process characterized by increased aromatase expression and activity and elevated signaling through ER-mediated pathways [10–12]. Data also suggest that the presence of CLS adversely affects outcomes among women with ER-positive breast cancers, and, in mice, CLS-related pro-inflammatory and carcinogenic processes may be reversible with weight-loss or chemopreventive agents [13, 14]. Accordingly, CLS in breast adipose tissue may represent one mechanism of increased local estrogen production, which would support the hypothesized role of local hormone levels in breast cancer development and progression.Fig.…”
BackgroundPostmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients.MethodsFormalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS.ResultsCLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03–0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04–0.72).ConclusionsCLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0791-4) contains supplementary material, which is available to authorized users.
“…Studies using animal models and breast tissues of women suggest that their presence is associated with obesity and a pro-inflammatory, pro-carcinogenic process characterized by increased aromatase expression and activity and elevated signaling through ER-mediated pathways [10–12]. Data also suggest that the presence of CLS adversely affects outcomes among women with ER-positive breast cancers, and, in mice, CLS-related pro-inflammatory and carcinogenic processes may be reversible with weight-loss or chemopreventive agents [13, 14]. Accordingly, CLS in breast adipose tissue may represent one mechanism of increased local estrogen production, which would support the hypothesized role of local hormone levels in breast cancer development and progression.Fig.…”
BackgroundPostmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients.MethodsFormalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS.ResultsCLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03–0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04–0.72).ConclusionsCLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0791-4) contains supplementary material, which is available to authorized users.
“…Estrogens possess anti-inflammatory effects and have been used to treat men with PC (13)(14)(15)30). Here, treatment with E2 led to reduced calorie consumption and weight loss with associated decreases in adipocyte size, periprostatic WAT inflammation and levels of pro-inflammatory mediators.…”
Section: Discussionmentioning
confidence: 99%
“…Although these effects of exogenous estrogen on periprostatic fat were previously unknown, the findings are consistent with the known biological effects of estrogen. Supplemental estrogen has been reported to suppress appetite via direct effects on the hypothalamus, protect against adipocyte hypertrophy and reduce adipose inflammation in other fat depots in mice (12,13,(31)(32)(33). The reduction in weight may be due to both reduced appetite and increased metabolism (11,34,35).…”
Section: Discussionmentioning
confidence: 99%
“…Supplemental estrogen is known to suppress appetite and to possess anti-inflammatory properties (10)(11)(12). Previously, we showed that 17β-estradiol (E2) reversed obesity-induced WAT inflammation in the mammary glands of female mice (13). Because estrogens have been used to treat men with advanced PC (14,15), the first aim of this study was to test the hypothesis that supplemental estrogen will attenuate periprostatic WAT inflammation in obese male mice.…”
AbstractObesity 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.
“…Menopausal women can suffer from physical and psychological symptoms such as obesity, hypertension, dyslipidemia, cardiovascular morbidity, and depression [2,3]. In the menopause, estrogen deficiency is associated with increased prevalence of obesity [4,5]. E2, the primary female sex hormone, has been known to protect against fat accumulation in adipose tissues [6,7].…”
Menopausal women are associated with an increase in obesity accompanying changes in the body's condition and composition. Polygonatum stenophyllum (PS) rhizome, which is a traditional herbal remedy, has been used to treat various diseases including obesity. However, the effect of PS on menopausal obesity remains unclear. Female C57BL/6 mice were ovariectomized (OVX) and fed on high fat diet (HFD) to induce menopausal obesity. Aqueous extract of PS of 1, 10, and 100 mg/kg was orally administrated for 6 weeks after 7 weeks of induction. The weights of body, uterine, and ovarian fat were investigated. Histological analysis was performed to monitor the changes of liver and fat. In addition, lipid profiles were measured in serum and the expression of lipolysis-related enzymes was analyzed in uterine tissues. PS significantly decreased the weights of body and ovarian fat and increased the uterine weight compared to control group. Administration of PS significantly decreased the adipocyte diameter and the lipid droplets within the hepatocytes. In addition, PS-treated mice had lower levels of triglyceride (TG), total cholesterol, and LDL-cholesterol than control mice. The expression of lipolysis-related genes, including adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), was increased in PS-treated groups. Taken together, these results demonstrate that PS might have efficacy on menopausal obesity by activating ATGL and HSL.
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