Liu, Y.* ; Lin, D.* ; Najam, S.S.* ; Huang, S.* ; Song, M.* ; Sirakawin, C.* ; Zhao, C.* ; Jiang, H.* ; Konopka, W.* ; Herzig, S. ; Vinnikov, I.A.*
     
 
    
        
Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin-releasing hormone neurons protects from obesity.
    
    
        
    
    
        
        Obesity 32, 1885-1896 (2024)
    
    
		
		
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			 möglich sobald  bei der ZB eingereicht worden ist.
		
     
    
		
		
			
				OBJECTIVE: Here, we aimed to investigate the role of glucocorticoid and mineralocorticoid receptors (GRs and MRs, respectively) in the regulation of energy homeostasis. METHODS: We used three mouse models with simultaneous deletion of GRs and MRs in either forebrain neurons, the paraventricular nucleus, or corticotropin-releasing hormone (CRH) neurons and compared them with wild-type controls or isolated knockout groups. In addition to body weight, food intake, energy expenditure, insulin sensitivity, fat/lean mass distribution, and plasma corticosterone levels, we also performed transcriptomic analysis of CRH neurons and assessed their response to melanocortinergic stimulation. RESULTS: Similar to global double-knockout models, deletion of GRs and MRs specifically in mature CRH neurons resulted in obesity. Importantly, the latter was accompanied by insulin resistance, but not increased plasma corticosterone levels. Transcriptomic analysis of these neurons revealed upregulation of several genes involved in postsynaptic signal transduction, including the Ptk2b gene, which encodes proline-rich tyrosine kinase 2. Knockout of both nuclear receptors leads to upregulation of Ptk2b in CRH neurons, which results in their diminished responsiveness to melanocortinergic stimulation. CONCLUSIONS: Our data demonstrate the functional redundancy of GRs and MRs in CRH neurons to maintain energy homeostasis and prevent obesity. Simultaneous targeting of both receptors might represent an unprecedented approach to counteract obesity.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        Melanocyte-stimulating Hormone; Immunoreactive Innervation; Neuropeptide-y; Dna-binding; C-fos; Stress; Hypothalamus; Alpha; Rat; Expression
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2024
    
 
    
        Prepublished im Jahr 
        0
    
 
    
        HGF-Berichtsjahr
        2024
    
 
    
    
        ISSN (print) / ISBN
        1930-7381
    
 
    
        e-ISSN
        1930-739X
    
 
    
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	    Band: 32,  
	    Heft: 10,  
	    Seiten: 1885-1896 
	    Artikelnummer: ,  
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Wiley
        
 
        
            Verlagsort
            111 River St, Hoboken 07030-5774, Nj Usa
        
 
	
        
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        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        90000 - German Center for Diabetes Research
    
 
    
        Forschungsfeld(er)
        Helmholtz Diabetes Center
    
 
    
        PSP-Element(e)
        G-501900-251
    
 
    
        Förderungen
        National Natural Science Foundation of China (NSFC)
National Natural Science Foundation of China
    
 
    
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        Erfassungsdatum
        2024-10-29