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

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. [Display omitted] • Nerve repair after acute trauma involves Schwann cell leptin receptor signaling • Leptin receptor activation promotes glial metabolic adaptation post injury • Schwann cell leptin receptor signaling is activated by adipose tissue-derived leptin Peripheral nerves can regenerate after trauma, but full recovery is rare and critically relies on repair by Schwann cells. Here, Sundaram, Schütza, Schröter, et al. reveal that, after a nerve injury, adipocyte-derived leptin supports peripheral nerve repair. Leptin receptor signaling in Schwann cells adjusts catabolic processes, including mitochondrial respiration and autophagy, facilitating nerve repair. [ABSTRACT FROM AUTHOR]