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Sensory neurons expressing calcitonin gene-related peptide α regulate adaptive thermogenesis and diet-induced obesity.

التفاصيل البيبلوغرافية
العنوان: Sensory neurons expressing calcitonin gene-related peptide α regulate adaptive thermogenesis and diet-induced obesity.
المؤلفون: Makwana K; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA., Chodavarapu H; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA., Morones N; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA., Chi J; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USA., Barr W; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USA., Novinbakht E; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA., Wang Y; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA., Nguyen PT; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA., Jovanovic P; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA., Cohen P; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USA., Riera CE; Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors of the Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, CA, USA; David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: celine.riera@cshs.org.
المصدر: Molecular metabolism [Mol Metab] 2021 Mar; Vol. 45, pp. 101161. Date of Electronic Publication: 2021 Jan 05.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier GmbH Country of Publication: Germany NLM ID: 101605730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2212-8778 (Electronic) Linking ISSN: 22128778 NLM ISO Abbreviation: Mol Metab Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [München] : Elsevier GmbH, 2012-
مواضيع طبية MeSH: Calcitonin Gene-Related Peptide/*genetics , Calcitonin Gene-Related Peptide/*metabolism , Obesity/*metabolism , Sensory Receptor Cells/*metabolism , Thermogenesis/*genetics , Thermogenesis/*physiology, Adipose Tissue, Brown/metabolism ; Adipose Tissue, Brown/pathology ; Adipose Tissue, White/metabolism ; Adipose Tissue, White/pathology ; Animals ; Body Temperature Regulation/genetics ; Body Temperature Regulation/physiology ; Cold Temperature ; Diet, High-Fat/adverse effects ; Energy Metabolism/genetics ; Energy Metabolism/physiology ; Female ; Insulin Resistance ; Lipolysis/genetics ; Lipolysis/physiology ; Male ; Mice ; Neurons
مستخلص: Objectives: Heat-sensory neurons from the dorsal root ganglia (DRG) play a pivotal role in detecting the cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis remains elusive. It is also unknown whether these neurons play a role in obesity and energy metabolism.
Methods: We used genetic ablation of heat-sensing neurons expressing calcitonin gene-related peptide α (CGRPα) to assess whole-body energy expenditure, weight gain, glucose tolerance, and insulin sensitivity in normal chow and high-fat diet-fed mice. Exvivo lipolysis and transcriptional characterization were combined with adipose tissue-clearing methods to visualize and probe the role of sensory nerves in adipose tissue. Adaptive thermogenesis was explored using infrared imaging of intrascapular brown adipose tissue (iBAT), tail, and core temperature upon various stimuli including diet, external temperature, and the cooling agent icilin.
Results: In this report, we show that genetic ablation of heat-sensing CGRPα neurons promotes resistance to weight gain upon high-fat diet (HFD) feeding and increases energy expenditure in mice. Mechanistically, we found that loss of CGRPα-expressing sensory neurons was associated with reduced lipid deposition in adipose tissue, enhanced expression of fatty acid oxidation genes, higher exvivo lipolysis in primary white adipocytes, and increased mitochondrial respiration from iBAT. Remarkably, mice lacking CGRPα sensory neurons manifested increased tail cutaneous vasoconstriction at room temperature. This exacerbated cold perception was not associated with reduced core temperature, suggesting that heat production and heat conservation mechanisms were engaged. Specific denervation of CGRPα neurons in intrascapular BAT did not contribute to the increased metabolic rate observed upon global sensory denervation.
Conclusions: Taken together, these findings highlight an important role of cutaneous thermoreceptors in regulating energy metabolism by triggering counter-regulatory responses involving energy dissipation processes including lipid fuel utilization and cutaneous vasodilation.
(Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
معلومات مُعتمدة: R01 DK120649 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: CGRP; Energy expenditure; Lipolysis; Obesity; Spinal sensory ganglion; Thermoregulation
المشرفين على المادة: 0 (Calca protein, mouse)
JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
تواريخ الأحداث: Date Created: 20210107 Date Completed: 20211025 Latest Revision: 20211213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7820934
DOI: 10.1016/j.molmet.2021.101161
PMID: 33412345
قاعدة البيانات: MEDLINE
الوصف
تدمد:2212-8778
DOI:10.1016/j.molmet.2021.101161