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Journal article
CRFR1 in AgRP Neurons Modulates Sympathetic Nervous System Activity to Adapt to Cold Stress and Fasting.
Cell Metabolism, Vol.23(6), pp.1185-1199
14/Jun/2016
Abstract
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.
Details
- Title
- CRFR1 in AgRP Neurons Modulates Sympathetic Nervous System Activity to Adapt to Cold Stress and Fasting.
- Creators
- Yael Kuperman (null) - 972WIS_INST___130Meira Weiss (null) - The Weizmann Institute of ScienceJulien Dine (null) - Max Planck Institute of PsychiatryKaty Staikin (null) - 972WIS_INST___123Ofra Golani (null) - 972WIS_INST___113Assaf Ramot (null) - 972WIS_INST___123Tali Nahum (null) - 972WIS_INST___123Claudia Kuhne (null) - Max Planck Institute of PsychiatryYair Shemesh (null) - 972WIS_INST___123Wolfgang Wurst (null) - Helmholtz Zentrum MünchenAlon Harmelin (null) - 972WIS_INST___130Jan M Deussing (null) - Max Planck Institute of PsychiatryMatthias Eder (null) - Max Planck Institute of PsychiatryAlon Chen (null) - 972WIS_INST___123
- Resource Type
- Journal article
- Publication Details
- Cell Metabolism, Vol.23(6), pp.1185-1199; 14/Jun/2016
- Number of pages
- 15
- Language
- English
- DOI
- https://doi.org/10.1016/j.cmet.2016.04.017
- Grant note
- A.C. is head of the Max Planck Society, Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics. Y.K. is the incumbent of the Sarah and Rolando Uziel Research Associate Chair. We thank Mr. Sharon Ovadia and Ms. Dalia Vaknin for their devoted assistance with animal care. We thank Dr. Jessica Keverne for professional English editing, formatting, and scientific input. This work is supported by an FP7 grant from the European Research Council (260463); research support from the Perlman Family Foundation, founded by Louis L. and Anita M. Perlman; a research grant from the Israel Science Foundation (803/11); research support from Roberto and Renata Ruhman; the Nella and Leon Benoziyo Center for Neurological Diseases; the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Adelis Foundation; the Irving I. Moskowitz Foundation; and the Helmholtz Alliance ICEMED, Imaging and Curing Environmental Metabolic Diseases, through the Initiative and Network Fund of the Helmholtz Association (to J.M.D. and W.W.). We dedicate this work to the memory of Professor W. Vale (Salk Institute for Biological Studies).
- Record Identifier
- 993264923003596
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