Adipo-glial signaling mediates metabolic adaptation in peripheral nerve regeneration.

Schwann cell adipocytes energy metabolism leptin leptin receptor metabolic adaptation mitochondrial respiration myelin autophagy myelinophagy nerve repair oxidative phosphorylation peripheral nerve injury regeneration remyelination

Journal

Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170

Informations de publication

Date de publication:
05 12 2023
Historique:
received: 02 12 2022
revised: 21 08 2023
accepted: 30 10 2023
medline: 11 12 2023
pubmed: 22 11 2023
entrez: 21 11 2023
Statut: ppublish

Résumé

The peripheral nervous system harbors a remarkable potential to regenerate after acute nerve trauma. Full functional recovery, however, is rare and critically depends on peripheral nerve Schwann cells that orchestrate breakdown and resynthesis of myelin and, at the same time, support axonal regrowth. How Schwann cells meet the high metabolic demand required for nerve repair remains poorly understood. We here report that nerve injury induces adipocyte to glial signaling and identify the adipokine leptin as an upstream regulator of glial metabolic adaptation in regeneration. Signal integration by leptin receptors in Schwann cells ensures efficient peripheral nerve repair by adjusting injury-specific catabolic processes in regenerating nerves, including myelin autophagy and mitochondrial respiration. Our findings propose a model according to which acute nerve injury triggers a therapeutically targetable intercellular crosstalk that modulates glial metabolism to provide sufficient energy for successful nerve repair.

Identifiants

pubmed: 37989315
pii: S1550-4131(23)00386-8
doi: 10.1016/j.cmet.2023.10.017
pmc: PMC10722468
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2136-2152.e9

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : P20 GM103425
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD059056
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD087057
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM011070
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Venkat Krishnan Sundaram (VK)

Institute of Anatomy, Leipzig University, Leipzig, Germany; Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Vlad Schütza (V)

Institute of Anatomy, Leipzig University, Leipzig, Germany; Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Nele H Schröter (NH)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Aline Backhaus (A)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Annika Bilsing (A)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Lisa Joneck (L)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Anna Seelbach (A)

Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Clara Mutschler (C)

John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.

Jose A Gomez-Sanchez (JA)

Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain; Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, Spain.

Erik Schäffner (E)

Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Eva Ernst Sánchez (EE)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Dagmar Akkermann (D)

Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Christina Paul (C)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Nancy Schwagarus (N)

Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Silvana Müller (S)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Angela Odle (A)

Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, Spain.

Gwen Childs (G)

Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Markham, AR, USA.

David Ewers (D)

Max Planck Institute of Experimental Medicine, Göttingen, Germany; Klinik für Neurologie, Universitätsmedizin Göttingen (UMG), Göttingen, Germany.

Theresa Kungl (T)

Institute of Anatomy, Leipzig University, Leipzig, Germany.

Maren Sitte (M)

NGS-Integrative Genomics Core Unit (NIG), Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.

Gabriela Salinas (G)

NGS-Integrative Genomics Core Unit (NIG), Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.

Michael W Sereda (MW)

Max Planck Institute of Experimental Medicine, Göttingen, Germany; Klinik für Neurologie, Universitätsmedizin Göttingen (UMG), Göttingen, Germany.

Klaus-Armin Nave (KA)

Max Planck Institute of Experimental Medicine, Göttingen, Germany.

Markus H Schwab (MH)

Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Mario Ost (M)

Institute of Anatomy, Leipzig University, Leipzig, Germany; Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.

Peter Arthur-Farraj (P)

John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.

Ruth M Stassart (RM)

Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany. Electronic address: ruth.stassart@medizin.uni-leipzig.de.

Robert Fledrich (R)

Institute of Anatomy, Leipzig University, Leipzig, Germany. Electronic address: robert.fledrich@medizin.uni-leipzig.de.

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Classifications MeSH