Mediation of the Acute Stress Response by the Skeleton

Julian Meyer Berger; Parminder Singh; Lori Khrimian; Donald A Morgan; Subrata Chowdhury; Emilio Arteaga-Solis; Tamas L Horvath; Ana I Domingos; Anna L Marsland; Vijay Kumar Yadav; Kamal Rahmouni; Xiao-Bing Gao; Gerard Karsenty

doi:10.1016/j.cmet.2019.08.012

Back

Mediation of the Acute Stress Response by the Skeleton

Journal article

Open access

Peer reviewed

Mediation of the Acute Stress Response by the Skeleton

Julian Meyer Berger, Parminder Singh, Lori Khrimian, Donald A Morgan, Subrata Chowdhury, Emilio Arteaga-Solis, Tamas L Horvath, Ana I Domingos, Anna L Marsland, Vijay Kumar Yadav, …

Cell metabolism, Vol.30(5), pp.890-902.e8

11/05/2019

DOI: 10.1016/j.cmet.2019.08.012

PMCID: PMC6834912

PMID: 31523009

Files and links (1)

url

https://doi.org/10.1016/j.cmet.2019.08.012View

Published (Version of record) Open Access

Abstract

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.

Parasympathetic Nervous System - cytology

Stress, Physiological - genetics

Humans

Mice, Inbred C57BL

Middle Aged

Cells, Cultured

Osteocalcin - genetics

Rats

Male

Mice, Transgenic

Healthy Volunteers

Rats, Sprague-Dawley

Adrenalectomy

Adrenal Insufficiency - metabolism

Osteocalcin - blood

Animals

Bone and Bones - metabolism

Adult

Female

Glutamic Acid - metabolism

Mice

Neurons - metabolism

Osteoblasts - metabolism

Details

Title: Subtitle: Mediation of the Acute Stress Response by the Skeleton
Creators: Julian Meyer Berger - Department 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
Parminder Singh - Metabolic Research Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India
Lori Khrimian - Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA
Donald A Morgan - Department of Pharmacology, University of Iowa and Veteran Health Care System, Iowa City, IA 52242, USA
Subrata Chowdhury - Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA
Emilio Arteaga-Solis - Department 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
Tamas L Horvath - Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA
Ana I Domingos - Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
Anna L Marsland - Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA
Vijay Kumar Yadav - Department 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
Kamal Rahmouni - Department of Pharmacology, University of Iowa and Veteran Health Care System, Iowa City, IA 52242, USA
Xiao-Bing Gao - Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA
Gerard Karsenty - Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: gk2172@cumc.columbia.edu
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.30(5), pp.890-902.e8
Publisher: United States
DOI: 10.1016/j.cmet.2019.08.012
PMID: 31523009
PMCID: PMC6834912
ISSN: 1550-4131
eISSN: 1932-7420
Grant note: R01 AR073180 / NIAMS NIH HHS 208576/Z/17/Z / Wellcome Trust P30 CA013696 / NCI NIH HHS R21 DA040782 / NIDA NIH HHS T32 DK007328 / NIDDK NIH HHS P01 AG032959 / NIA NIH HHS UL1 TR001863 / NCATS NIH HHS P01 HL084207 / NHLBI NIH HHS T32 AI106711 / NIAID NIH HHS I01 BX004249 / BLRD VA R01 DK104727 / NIDDK NIH HHS
Language: English
Date published: 11/05/2019
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984070655602771

Metrics

22 Record Views

110 Times Cited - Web of Science

See more details