Mediation of the Acute Stress Response by the Skeleton.

Author: Berger JM1, Singh P2, Khrimian L3, Morgan DA4, Chowdhury S3, Arteaga-Solis E5, Horvath TL6, Domingos AI7, Marsland AL8, Kumal Yadav V9, Rahmouni K4, Gao XB6, Karsenty G10
Affiliation:
1Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Program in Microbiology, Immunology and Infection, Columbia University Irving Medical Center, New York, NY 10032, USA.
2Metabolic Research Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
3Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA.
4Department of Pharmacology, University of Iowa and Veteran Health Care System, Iowa City, IA 52242, USA.
5Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Pediatric Pulmonary, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
6Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
7Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
8Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
9Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Metabolic Research Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
10Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: gk2172@cumc.columbia.edu.
Conference/Journal: Cell Metab.
Date published: 2019 Sep 4
Other: Pages: S1550-4131(19)30441-3 , Special Notes: doi: 10.1016/j.cmet.2019.08.012. [Epub ahead of print] , Word Count: 169

We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and selective surge of circulating bioactive osteocalcin because stressors favor the uptake by osteoblasts of glutamate, which prevents inactivation of osteocalcin prior to its secretion. Osteocalcin permits manifestations of the ASR to unfold by signaling in post-synaptic parasympathetic neurons to inhibit their activity, thereby leaving the sympathetic tone unopposed. Like wild-type animals, adrenalectomized rodents and adrenal-insufficient patients can develop an ASR, and genetic studies suggest that this is due to their high circulating osteocalcin levels. We propose that osteocalcin defines a bony-vertebrate-specific endocrine mediation of the ASR.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Glast; Vglut2; adrenal; bone; fight or flight; glutamate; osteoblast; osteocalcin; parasympathetic; stress response

PMID: 31523009 DOI: 10.1016/j.cmet.2019.08.012

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