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Kuperman, Y.* ; Weiss, M.* ; Dine, J.* ; Staikin, K.* ; Golani, O.* ; Ramot, A.* ; Nahum, T.* ; Kühne, C.* ; Shemesh, Y.* ; Wurst, W. ; Harmelin, A.* ; Deussing, J.M.* ; Eder, M.* ; Chen, A.*

CRFR1 in AgRP neurons modulates sympathetic nervous system activity to adapt to cold stress and fasting.

Cell Metab. 23, 1185-1199 (2016)
Publ. Version/Full Text Supplement DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Signaling by the corticotropin-releasing factor receptor type 1 (CRFR1) plays an important role in mediating the autonomic response to stressful challenges. Multiple hypothalamic nuclei regulate sympathetic outflow. Although CRFR1 is highly expressed in the arcuate nucleus (Arc) of the hypothalamus, the identity of these neurons and the role of CRFR1 here are presently unknown. Our studies show that nearly half of Arc-CRFR1 neurons coexpress agouti-related peptide (AgRP), half of which originate from POMC precursors. Arc-CRFR1 neurons are innervated by CRF neurons in the hypothalamic paraventricular nucleus, and CRF application decreases AgRP(+)CRFR1(+) neurons' excitability. Despite similar anatomy in both sexes, only female mice selectively lacking CRFR1 in AgRP neurons showed a maladaptive thermogenic response to cold and reduced hepatic glucose production during fasting. Thus, CRFR1, in a subset of AgRP neurons, plays a regulatory role that enables appropriate sympathetic nervous system activation and consequently protects the organism from hypothermia and hypoglycemia.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Corticotropin-releasing-factor; Brown Adipose-tissue; Hypothalamic Arcuate Nucleus; Hormone Gene-expression; Paraventricular Nucleus; Neuropeptide-y; Factor Increases; Food-intake; Energy-expenditure; Glucose-production
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 23, Issue: 6, Pages: 1185-1199 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge
Reviewing status Peer reviewed
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500500-001
Scopus ID 84975465813
PubMed ID 27211900
Erfassungsdatum 2016-06-01