Fatty acid synthesis in satellite glial cell promotes regenerative growth in sensory neurons

Peripheral sensory neurons switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Whether satellite glial cells (SGC), which completely surround the neuronal soma, contribute to the regenerative responses remains unexplored. Here we defined the transcriptional profile of SGC and identified Fabp7/BLBP as a novel marker of SGC. We report that nerve injury changes gene expression in SGC, which is mostly related to lipid metabolism, specifically fatty acid synthesis and PPARa signaling. Conditional deletion of Fatty acid synthase (Fasn), the committed enzyme in de novo fatty acid synthesis in SGC impairs axon regeneration. Treatment with the PPARa agonist fenofibrate rescues axon regeneration in mice lacking Fasn in SGC. This results indicates that PPARa functions downstream of fatty acid synthesis in SGC to promote axon regeneration. These results identify fatty acid synthesis in SGC as a fundamental novel mechanism mediating axon regeneration in adult peripheral nerves.