Tissue-specific roles of brain-derived neurotrophic factor in metabolism

Abstract

Brain-derived neurotrophic factor (BDNF) can be readily detected in peripheral organs such as skeletal muscle but its functions in these tissues remain largely unknown. Our recent study shows that BDNF is a fasting-induced myokine to modulate systemic energy metabolism. We found that skeletal muscle-specific Bdnf knockout (MBKO) mice were incapable of shifting the fuel source from fatty acid to carbohydrates during nutrient stress, which resulted in the accumulation of acylcarnitines and reduced energy production in glycolytic muscle. Moreover, fasting-induced autophagy was abolished in the Bdnf-ablated muscle. MBKO mice thus displayed reduced muscle strength, decreased physical activity, metabolic inflexibility and muscle-specific insulin resistance. Our findings demonstrate that BDNF is an essential metabolic regulator in skeletal muscle to link autophagy and metabolic flexibility.