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CRFR1 in AgRP neurons modulates sympathetic nervous system activity to adapt to cold stress and fasting.
Cell Metab. 23, 1185-1199 (2016)
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
Publisher
Elsevier
Publishing Place
Cambridge
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)
POF-Topic(s)
30204 - Cell Programming and Repair
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-500500-001
WOS ID
WOS:000378000600027
Scopus ID
84975465813
PubMed ID
27211900
Erfassungsdatum
2016-06-01