Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Biomed Pharmacother. 2022 Dec;156:113808. doi: 10.1016/j.biopha.2022.113808. Epub 2022 Oct 15.
Over the last two decades, it has become evident that estrogens preserve the integrity of energy homeostasis at central and peripheral levels. Estrogen deficiency, such as that caused by menopause or ovariectomy, has been linked to obesity and metabolic disorders that can be resolved or reversed by estrogen therapy. 17β-estradiol (E2), as the major estrogen in the body, primarily regulates energy balance via estrogen receptor alpha (ERα). At the central level, E2 plays its catabolic role predominantly by interacting with hypothalamic arcuate neurons and sending signals via ventromedial hypothalamic neurons to control brown adipose tissue-mediated thermogenesis. In peripheral tissues, several organs, particularly the liver, brown and white adipose tissues, and pancreatic β cells, have attracted considerable attention. In this review, we focused on the current state of knowledge of "central and peripheral" estrogen signaling in regulating energy balance via "nuclear and extranuclear pathways" in both "females and males". In this context, according to an exploratory approach, we tried to determine the principal estrogen receptor subtype/isoform in each section, the importance of extranuclear-initiated estrogen signaling on metabolic functions, and how sex differences related to ER signaling affect the prevalence of some of the metabolic disorders. Moreover, we discussed the data from a third viewpoint, understanding the clinical significance of estrogen signaling in abnormal metabolic conditions such as obesity or being on a high-fat diet. Collectively, this review exposes novel and important research gaps in our current understanding of dysmetabolic diseases and can facilitate finding more effective treatment options for these disorders.
在过去的二十年中，已经明显的是，雌激素可以维持中枢和外周水平的能量平衡的完整性。雌激素缺乏，如绝经或卵巢切除引起的雌激素缺乏，与肥胖和代谢紊乱有关，这些紊乱可以通过雌激素治疗来解决或逆转。17β-雌二醇（E2）作为体内主要的雌激素，主要通过雌激素受体α（ERα）来调节能量平衡。在中枢水平，E2 通过与下丘脑弓状核神经元相互作用并通过腹内侧下丘脑神经元发送信号来发挥其分解代谢作用，从而控制棕色脂肪组织介导的产热。在外周组织中，有几个器官，特别是肝脏、棕色和白色脂肪组织以及胰岛β细胞，引起了人们的极大关注。在这篇综述中，我们重点关注“中枢和外周”雌激素信号通过“核和核外途径”在“女性和男性”中调节能量平衡的最新知识状态。在这方面，根据探索性方法，我们试图确定每个部分中的主要雌激素受体亚型/异构体，核外起始的雌激素信号对代谢功能的重要性，以及与 ER 信号相关的性别差异如何影响一些代谢紊乱的患病率。此外，我们从第三个角度讨论了数据，即了解雌激素信号在肥胖或高脂肪饮食等异常代谢情况下的临床意义。总的来说，这篇综述揭示了我们对代谢紊乱疾病理解的新的和重要的研究空白，并可以促进寻找这些疾病更有效的治疗选择。
