Dietary-dependent sensitization of neuronal leptin signaling promotes neural repair after injury via cAMP and gene transcription
File(s)
Published version
Author(s)
Chadwick, Jessica S
Decourt, Charlotte
Muller, Franziska
Maldonado-Lasuncion, Ines
Serger, Elisabeth
Type
Journal Article
Abstract
Dietary-dependent shifts, ranging from metabolic dysfunction to health, involve transitions in key signaling pathways. Dietary regimens can influence nervous system repair, but whether conserved, diet-specific mechanisms can enhance neuronal regeneration by directly sensitizing neuronal signaling remains unclear. We found that in mice, in contrast to a neuropathy-inducing high-fat diet that causes leptin resistance, intermittent fasting (IF) enhances leptin sensitivity in dorsal root ganglia sensory neurons. Deletion of leptin receptors in sensory neurons impairs IF-induced regeneration. Systemic leptin or leptin neuronal overexpression promote axonal repair after sciatic nerve crush and spinal cord injury via endocrine or autocrine mechanism, respectively. Leptin-dependent axon growth requires cyclic AMP (cAMP) signaling, transcriptional activity, and regenerative gene expression to support axon growth after injury. Unexpectedly, leptin, whose canonical function is to control feeding, promotes neuronal regenerative signaling, highlighting a novel role in nervous system regeneration and providing insights into diet-dependent neurorepair mechanisms.
Date Issued
2025-09-03
Date Acceptance
2025-07-14
Citation
Neuron, 2025, 113 (17), pp.2839-2855.e8
ISSN
0896-6273
Publisher
Cell Press
Start Page
2839
End Page
2855.e8
Journal / Book Title
Neuron
Volume
113
Issue
17
Copyright Statement
© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40812302
PII: S0896-6273(25)00523-9
Subjects
AXON REGENERATION
FUNCTIONAL RECOVERY
INCREASE
Life Sciences & Biomedicine
LIFE-SPAN
MECHANISMS
METABOLISM
Neurosciences
Neurosciences & Neurology
PLASTICITY
RESISTANCE
RESTRICTION
Science & Technology
SPINAL-CORD-INJURY
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-08-13