Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1

Gonzalez-Garcia, Ismael; Garcia-Clave, Elena; Cebrian-Serrano, Alberto; Le Thuc, Ophlia; Contreras, Raian E.; Xu, Yanjun; Gruber, Tim; Schriever, Sonja C.; Legutko, Beata; Lintelmann, Jutta; Adamski, Jerzy; Wurst, Wolfgang; Mueller, Timo D.; Woods, Stephen C.; Pfluger, Paul T.; Tschoep, Matthias H.; Fisette, Alexandre und Garcia-Caceres, Cristina (2023): Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1. In: Cell Metabolism, Bd. 35, Nr. 3: 438-+

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 molec-ular 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-ERa-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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198