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Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1.
Cell Metab. 35, 438-455.e7 (2023)
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
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
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)
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)
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)