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Gonzales García, I. ; Garcia-Clavé, E. ; Cebrian Serrano, A. ; Le Thuc, O. ; Contreras, R. ; Xu, Y. ; Gruber, T. ; Schriever, S.C. ; Legutko, B. ; Lintelmann, J. ; Adamski, J. ; Wurst, W. ; Müller, T.D. ; Woods, S.C.* ; Pfluger, P.T. ; Tschöp, M.H. ; Fisette, A. ; García-Cáceres, C.

Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1.

Cell Metab. 35, 438-455.e7 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Arc ; Pomc ; Diet-induced Obesity ; Estradiol ; Hypothalamus ; Leptin; Estrogen-receptor-alpha; Agouti-related Protein; Signal Transducer; Energy Homeostasis; Gene-expression; Cross-talk; Transcription-3; Activator; P300/cbp; Neurons
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 35, Issue: 3, Pages: 438-455.e7 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
Grants German Research Foundation DFG
Helmholtz Excellence Network
Deutsche Forschungsgemeinschaft
Helmholtz Association - Initiative and Networking Fund
European Union
European Research Council ERC
Canadian Institutes of Health Research
German Center for Diabetes Research (DZD e.V.)
European Research Council ERC-CoG

European Research Council (ERC)