• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Journal of the Endocrine Society >Breast Cancer Endocrine Therapy Exhausts Adipocyte Progenitors Promoting Weight Gain and Glucose Intolerance
【2h】

Breast Cancer Endocrine Therapy Exhausts Adipocyte Progenitors Promoting Weight Gain and Glucose Intolerance

机译：乳腺癌内分泌治疗废止脂肪细胞祖细胞促进体重增加和葡萄糖不耐受

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Breast cancer survivors treated with anti-estrogen therapies report weight gain and have an elevated risk of type 2 diabetes. Here, we show that current tamoxifen use did not influence body mass index but associated with larger breast adipocyte diameter only in women with obesity, suggesting adipose tissue may be targeted by breast cancer therapies. To understand the mechanisms behind these clinical findings, we investigated the impact of estrogen deprivation and tamoxifen in a relevant pre-clinical murine model of obesity. Specifically, mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression of Esr1 observed in single-cell RNA sequencing of mesenchymal stem cells from mouse adipose tissue, endocrine therapies associated with adipose accumulation and preadipocyte expansion, but resulted in adipocyte progenitor depletion only in the context of HFHS. Consequently, 7-week endocrine therapy supported adipocyte hypertrophy and was associated with hepatic steatosis, hyperinsulinemia, insulin resistance, and glucose intolerance, particularly in HFHS fed females. We administered HFHS fed females either metformin or pioglitazone, glucose lowering drugs used to treat diabetes, or treadmill interval exercise during endocrine therapy with the goal of improving whole body metabolism. All interventions prevented the effects of tamoxifen but not estrogen deprivation on adipocyte size and insulin resistance in HFHS-fed mice. This translational study suggests that endocrine therapies may act via ER-alpha to directly disrupt adipocyte progenitors and support adipocyte hypertrophy, leading to ectopic lipid deposition that may promote hyperinsulinemia, insulin resistance and type 2 diabetes. Interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer.
机译：用抗雌激素疗法治疗的乳腺癌幸存者报告体重增加并具有2型糖尿病的风险升高。在这里，我们表明目前的他莫昔芬使用不影响体重指数，而是与肥胖妇女仅在患有肥胖的女性中，脂肪组织可以通过乳腺癌疗法靶向，并且患有较大的乳腺脂肪细胞直径。为了了解这些临床发现背后的机制，我们研究了雌激素剥夺和制革毒素在肥胖的相关前鼠模型中的影响。具体地，成熟的雌性小鼠饲养在热屈光蛋白下，并喂食低脂/低蔗糖（LFL）或高脂肪/高蔗糖（HFHS）饮食。与小鼠脂肪组织的间充质干细胞单细胞RNA测序中观察到的ESR1的高表达一致，与脂肪积聚和前脂肪细胞膨胀相关的内分泌疗法，但仅导致脂肪细胞祖细胞耗尽仅在HFHS的背景下。因此，7周内分泌治疗支持脂肪细胞肥大，与肝脏脂肪变性，高胰岛素血症，胰岛素抵抗和葡萄糖不耐受相关，特别是在喂养女性的HFHS中。我们施用HFHS喂养女性二甲双胍或吡格列酮，葡萄糖降低药物用于治疗糖尿病，或在内分泌治疗期间的跑步机间隔运动，目的是改善全身代谢。所有干预措施都阻止了Tamoxifen但不是雌激素剥夺对HFHS-FED小鼠的脂肪细胞尺寸和胰岛素抗性的影响。该转化研究表明，内分泌疗法可以通过ER-α行动，直接破坏脂肪细胞祖细胞并支持adipocyte肥大，导致异位脂质沉积，可促进高胰岛素血症，胰岛素抵抗和2型糖尿病。应考虑靶向胰岛素诉讼的干预措施，用于一些接受乳腺癌救生内分泌疗法的妇女。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号