Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Mol Metab. 2018 Sep;15:20-34. doi: 10.1016/j.molmet.2018.06.013. Epub 2018 Jun 21.
The incidence of chronic disease is elevated in women after menopause. Natural variation in muscle expression of the estrogen receptor (ER)α is inversely associated with plasma insulin and adiposity. Moreover, reduced muscle ERα expression levels are observed in women and animals presenting clinical features of the metabolic syndrome (MetSyn). Considering that metabolic dysfunction impacts nearly a quarter of the U.S. adult population and elevates chronic disease risk including type 2 diabetes, heart disease, and certain cancers, treatment strategies to combat metabolic dysfunction and associated pathologies are desperately needed.
This review will provide evidence supporting a critical and protective role for skeletal muscle ERα in the regulation of metabolic homeostasis and insulin sensitivity, and propose novel ERα targets involved in the maintenance of metabolic health.
Studies identifying ERα-regulated pathways essential for disease prevention will lay the important foundation for the rational design of novel therapeutics to improve the metabolic health of women while limiting secondary complications that have plagued traditional hormone replacement interventions.
女性绝经后慢性病的发病率升高。雌激素受体（ER）α在肌肉中的自然表达变化与血浆胰岛素和肥胖呈负相关。此外，患有代谢综合征（MetSyn）临床特征的女性和动物中，肌肉 ERα 表达水平降低。考虑到代谢功能障碍影响了近四分之一的美国成年人口，并增加了包括 2 型糖尿病、心脏病和某些癌症在内的慢性病风险，因此急需治疗策略来对抗代谢功能障碍和相关的病理。
本综述将提供支持骨骼肌 ERα 在调节代谢稳态和胰岛素敏感性方面的关键和保护作用的证据，并提出参与维持代谢健康的新的 ERα 靶点。
确定 ERα 调节的对疾病预防至关重要的途径的研究将为合理设计新型疗法奠定重要基础，以改善女性的代谢健康，同时限制困扰传统激素替代干预的继发性并发症。
