Exercise-induced BDNF promotes PPARδ-dependent reprogramming of lipid metabolism in skeletal muscle during exercise recovery, 2024, WING SUEN CHAN

Editor’s summary
Intracellular lipids are an important energy source for skeletal muscle during exercise and must be replenished afterward. Chan et al. investigated the role of the myokine BDNF in post-exercise metabolic reprogramming and recovery in skeletal muscle. Mice with a muscle-specific deficiency in BDNF had reduced intramuscular lipid content, needed more time to recover from exercise, and did not show improvements in endurance capacity. Unexercised mice fed a bioavailable BDNF mimetic showed adaptations typically induced by exercise. Thus, BDNF generated by skeletal muscle promotes metabolic reprogramming that enables recovery after exercise. —Wei Wong

Abstract
Post-exercise recovery is essential to resolve metabolic perturbations and promote long-term cellular remodeling in response to exercise. Here, we report that muscle-generated brain-derived neurotrophic factor (BDNF) elicits post-exercise recovery and metabolic reprogramming in skeletal muscle. BDNF increased the post-exercise expression of the gene encoding PPARδ (peroxisome proliferator–activated receptor δ), a transcription factor that is a master regulator of lipid metabolism. After exercise, mice with muscle-specific Bdnf knockout (MBKO) exhibited impairments in PPARδ-regulated metabolic gene expression, decreased intramuscular lipid content, reduced β-oxidation, and dysregulated mitochondrial dynamics. Moreover, MBKO mice required a longer period to recover from a bout of exercise and did not show increases in exercise-induced endurance capacity. Feeding naïve mice with the bioavailable BDNF mimetic 7,8-dihydroxyflavone resulted in effects that mimicked exercise-induced adaptations, including improved exercise capacity. Together, our findings reveal that BDNF is an essential myokine for exercise-induced metabolic recovery and remodeling in skeletal muscle.

https://www.science.org/doi/10.1126/scisignal.adh2783