Activation of the hypothalamic-pituitary-adrenal axis by exogenous and endogenous GDF15.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
06 07 2021
Historique:
entrez: 30 6 2021
pubmed: 1 7 2021
medline: 15 12 2021
Statut: ppublish

Résumé

An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic-pituitary-adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of

Identifiants

pubmed: 34187898
pii: 2106868118
doi: 10.1073/pnas.2106868118
pmc: PMC8271778
pii:
doi:

Substances chimiques

GFRAL protein, mouse 0
Glial Cell Line-Derived Neurotrophic Factor Receptors 0
Glucocorticoids 0
Growth Differentiation Factor 15 0
Lipopolysaccharides 0
Tunicamycin 11089-65-9
Cisplatin Q20Q21Q62J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust
ID : WT 095515/Z/11/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N02995X/1
Pays : United Kingdom
Organisme : Department of Health
ID : CL-2019-14-504
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT 107064
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220268/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100574/Z/12/Z
Pays : United Kingdom

Informations de copyright

Copyright © 2021 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

Competing interest statement: S.O. undertakes remunerated consultancy work for Pfizer, AstraZeneca, GSK. H.K., S.B.J., D.B., D.M.B., and K.K.B. are employed by Pfizer. S.B.J. and K.P. are employed at Novo Nordisk A/S, a pharmaceutical company, manufacturing and vending medicine. E.C.L. and H.L. are employed at and are shareholders of Kymab Ltd.

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Auteurs

Irene Cimino (I)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

Hanna Kim (H)

Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139.

Y C Loraine Tung (YCL)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

Kent Pedersen (K)

Global Obesity and Liver Disease Research, Novo Nordisk A/S, DK-2760 Maaloev, Denmark.

Debra Rimmington (D)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

John A Tadross (JA)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.

Sara N Kohnke (SN)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

Ana Neves-Costa (A)

Innate Immunity and Inflammation Laboratory, Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.

André Barros (A)

Innate Immunity and Inflammation Laboratory, Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.

Stephanie Joaquim (S)

Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139.

Don Bennett (D)

Biostatistics, Early Clinical Development, Pfizer Inc., Cambridge, MA 02139.

Audrey Melvin (A)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

Samuel M Lockhart (SM)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

Anthony J Rostron (AJ)

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
Integrated Critical Care Unit, Sunderland Royal Hospital, South Tyneside and Sunderland NHS Foundation Trust, Sunderland SR4 7TP, United Kingdom.

Jonathan Scott (J)

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.

Hui Liu (H)

Kymab Ltd., Cambridge CB22 3AT, United Kingdom.

Keith Burling (K)

Core Biochemical Assay Laboratories, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom.

Peter Barker (P)

Core Biochemical Assay Laboratories, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom.

Menna R Clatworthy (MR)

Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom.
Cambridge Institute of Therapeutic Immunology and Infectious Diseases, University of Cambridge, Cambridge CB2 0AW, United Kingdom.
Cellular Genetics, Wellcome Sanger Institute, Hinxton CB10 1RQ, United Kingdom.

E-Chiang Lee (EC)

Kymab Ltd., Cambridge CB22 3AT, United Kingdom.

A John Simpson (AJ)

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.

Giles S H Yeo (GSH)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

Luís F Moita (LF)

Innate Immunity and Inflammation Laboratory, Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisboa, Portugal.

Kendra K Bence (KK)

Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139.

Sebastian Beck Jørgensen (SB)

Global Obesity and Liver Disease Research, Novo Nordisk A/S, DK-2760 Maaloev, Denmark.

Anthony P Coll (AP)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom.

Danna M Breen (DM)

Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139.

Stephen O'Rahilly (S)

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0SL, United Kingdom; so104@medschl.cam.ac.uk.

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