2. Academic Validation
  3. Adipo-glial signaling mediates metabolic adaptation in peripheral nerve regeneration

Adipo-glial signaling mediates metabolic adaptation in peripheral nerve regeneration

  • Cell Metab. 2023 Nov 16:S1550-4131(23)00386-8. doi: 10.1016/j.cmet.2023.10.017.
Venkat Krishnan Sundaram 1,  Vlad Schütza 1,  Nele H Schröter 2,  Aline Backhaus 2,  Annika Bilsing 2,  Lisa Joneck 2,  Anna Seelbach 3,  Clara Mutschler 4,  Jose A Gomez-Sanchez 5,  Erik Schäffner 3,  Eva Ernst Sánchez 2,  Dagmar Akkermann 3,  Christina Paul 2,  Nancy Schwagarus 3,  Silvana Müller 2,  Angela Odle 6,  Gwen Childs 7,  David Ewers 8,  Theresa Kungl 2,  Maren Sitte 9,  Gabriela Salinas 9,  Michael W Sereda 8,  Klaus-Armin Nave 10,  Markus H Schwab 3,  Mario Ost 1,  Peter Arthur-Farraj 4,  Ruth M Stassart 11,  Robert Fledrich 12
Affiliations

Affiliations

  • 1 Institute of Anatomy, Leipzig University, Leipzig, Germany; Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.
  • 2 Institute of Anatomy, Leipzig University, Leipzig, Germany.
  • 3 Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany.
  • 4 John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.
  • 5 Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain; Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, Spain.
  • 6 Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, Spain.
  • 7 Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Markham, AR, USA.
  • 8 Max Planck Institute of Experimental Medicine, Göttingen, Germany; Klinik für Neurologie, Universitätsmedizin Göttingen (UMG), Göttingen, Germany.
  • 9 NGS-Integrative Genomics Core Unit (NIG), Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
  • 10 Max Planck Institute of Experimental Medicine, Göttingen, Germany.
  • 11 Paul Flechsig Institute of Neuropathology, University Clinic Leipzig, Leipzig, Germany. Electronic address: [email protected].
  • 12 Institute of Anatomy, Leipzig University, Leipzig, Germany. Electronic address: [email protected].
PMID: 37989315 DOI: 10.1016/j.cmet.2023.10.017
Abstract

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.

Keywords

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

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