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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)

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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

Corresponding Author

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

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

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Developmental Genetics (IDG)