Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity.
Cell Metab
; 33(11): 2215-2230.e8, 2021 11 02.
Article
en En
| MEDLINE
| ID: mdl-34592133
ABSTRACT
Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift toward a slow MN identity. In muscle, NRTN increased capillary density and oxidative capacity and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1É1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neurturina
/
Neuronas Motoras
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2021
Tipo del documento:
Article
País de afiliación:
Suecia