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雌二醇通过下丘脑的Cited1调节瘦素敏感性来控制进食
作者:小柯机器人 发布时间:2023/3/13 13:51:05


德国慕尼黑大学Cristina García-Cáceres等研究人员合作发现,雌二醇通过下丘脑的Cited1调节瘦素敏感性来控制进食。这一研究成果发表在2023年3月7日出版的国际学术期刊《细胞—代谢》上。

通过使用一系列胚胎、成年发病和组织/细胞特异性功能丧失的小鼠模型,研究人员记录了下丘脑Cbp/P300与富含Glu/Asp羧基末端结构域1(Cited1)相互作用的反式激活因子在介导雌二醇(E2)依赖性瘦素作用中发挥了前所未有的作用,该作用专门控制原肾上腺皮质激素(Pomc)神经元的摄食。研究人员发现,在弓形Pomc神经元内,Cited1通过直接的Cited1-ERα-Stat3相互作用,作为汇聚E2和瘦素信号的共同因子,驱动瘦素的厌食效应。总之,这些结果提供了关于黑皮素神经元如何通过Cited1整合来自性腺和脂肪轴的内分泌输入的新见解,从而促成了饮食诱导的肥胖性别二态性。

据了解,在绝经前,女性患代谢性疾病的倾向比男性低,这表明性激素的保护作用。尽管雌激素和瘦素的中心作用之间的功能协同作用已被证明可以保护人们免受代谢紊乱的影响,但介导这种串联的基本细胞和分子机制仍然难以捉摸。

附:英文原文

Title: Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1

Author: Ismael González-García, Elena García-Clavé, Alberto Cebrian-Serrano, Ophélia Le Thuc, Raian E. Contreras, Yanjun Xu, Tim Gruber, Sonja C. Schriever, Beata Legutko, Jutta Lintelmann, Jerzy Adamski, Wolfgang Wurst, Timo D. Müller, Stephen C. Woods, Paul T. Pfluger, Matthias H. Tschp, Alexandre Fisette, Cristina García-Cáceres

Issue&Volume: 2023/03/07

Abstract: Until menopause, women have a lower propensity to develop metabolic diseases than men, suggestive of a protective role for sex hormones. Although a functional synergy between central actions of estrogens and leptin has been demonstrated to protect against metabolic disturbances, the underlying cellular and molecular mechanisms mediating this crosstalk have remained elusive. By using a series of embryonic, adult-onset, and tissue/cell-specific loss-of-function mouse models, we document an unprecedented role of hypothalamic Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 (Cited1) in mediating estradiol (E2)-dependent leptin actions that control feeding specifically in pro-opiomelanocortin (Pomc) neurons. We reveal that within arcuate Pomc neurons, Cited1 drives leptin’s anorectic effects by acting as a co-factor converging E2 and leptin signaling via direct Cited1-ERα-Stat3 interactions. Together, these results provide new insights on how melanocortin neurons integrate endocrine inputs from gonadal and adipose axes via Cited1, thereby contributing to the sexual dimorphism in diet-induced obesity.

DOI: 10.1016/j.cmet.2023.02.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00040-2

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx