Sundaram 2023 Cell Metab

Sundaram VK, Schütza V, Schröter NH, Backhaus A, Bilsing A, Joneck L, Seelbach A, Mutschler C, Gomez-Sanchez JA, Schäffner E, Sánchez EE, Akkermann D, Paul C, Schwagarus N, Müller S, Odle A, Childs G, Ewers D, Kungl T, Sitte M, Salinas G, Sereda MW, Nave KA, Schwab MH, Ost M, Arthur-Farraj P, Stassart RM, Fledrich R (2023) Adipo-glial signaling mediates metabolic adaptation in peripheral nerve regeneration. https://doi.org/10.1016/j.cmet.2023.10.017

» Cell Metab 35(12):2136-2152.e9. PMID: 37989315 Open Access

Sundaram Venkat Krishnan, Schuetza Vlad, Schroeter Nele H, Backhaus Aline, Bilsing Annika, Joneck Lisa, Seelbach Anna, Mutschler Clara, Gomez-Sanchez Jose A, Schaeffner Erik, Sanchez Eva Ernst, Akkermann Dagmar, Paul Christina, Schwagarus Nancy, Mueller Silvana, Odle Angela, Childs Gwen, Ewers David, Kungl Theresa, Sitte Maren, Salinas Gabriela, Sereda Michael W, Nave Klaus-Armin, Schwab Markus H, Ost Mario, Arthur-Farraj Peter, Stassart Ruth M, Fledrich Robert (2023) Cell Metab

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 • Bioblast editor: Plangger M • O2k-Network Lab: DE Leipzip Ost M

Labels: MiParea: Respiration 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Intact cells 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2023-11