Physical Activity and Muscle–Brain Crosstalk
Key points
· Exercise can indirectly be sensed by the brain via adipose tissue (adiponectin) or the liver (fibroblast growth factor 21 and insulin-like growth factor 1).
· Myokines mediate muscle–organ crosstalk to the liver, gut, pancreas, adipose tissue, bone, vascular bed, skin and brain.
· Cathepsin B is an exercise-induced myokine required for exercise-induced improvement in memory and adult neurogenesis.
· Exercise enhances neuronal gene expression of FNDC5, the protein product of which might stimulate brain-derived neurotrophic factor in the hippocampus.
· Serum levels of the myokine IL-6 increase with exercise, and this myokine might regulate central mechanisms for food intake.
· Exercise increases muscular expression of kynurenine aminotransferases, which convert blood levels of neurotoxic kynurenine to the neuroprotective kynurenic acid, thereby reducing depression-like symptoms.
Pedersen BK. Physical activity and muscle–brain crosstalk. Nature Reviews Endocrinology 2019;15:383-92. https://doi.org/10.1038/s41574-019-0174-x
Neurological and mental illnesses account for a considerable proportion of the global burden of disease. Exercise has many beneficial effects on brain health, contributing to decreased risks of dementia, depression and stress, and it has a role in restoring and maintaining cognitive function and metabolic control.
The fact that exercise is sensed by the brain suggests that muscle-induced peripheral factors enable direct crosstalk between muscle and brain function. Muscle secretes myokines that contribute to the regulation of hippocampal function.
Evidence is accumulating that the myokine cathepsin B passes through the blood–brain barrier to enhance brain-derived neurotrophic factor production and hence neurogenesis, memory and learning. Exercise increases neuronal gene expression of FNDC5 (which encodes the PGC1α-dependent myokine FNDC5), which can likewise contribute to increased brain-derived neurotrophic factor levels.
Serum levels of the prototype myokine, IL-6, increase with exercise and might contribute to the suppression of central mechanisms of feeding. Exercise also increases the PGC1α-dependent muscular expression of kynurenine aminotransferase enzymes, which induces a beneficial shift in the balance between the neurotoxic kynurenine and the neuroprotective kynurenic acid, thereby reducing depression-like symptoms.
Myokine signalling, other muscular factors and exercise-induced hepatokines and adipokines are implicated in mediating the exercise-induced beneficial impact on neurogenesis, cognitive function, appetite and metabolism, thus supporting the existence of a muscle–brain endocrine loop.
Key points
· Exercise can indirectly be sensed by the brain via adipose tissue (adiponectin) or the liver (fibroblast growth factor 21 and insulin-like growth factor 1).
· Myokines mediate muscle–organ crosstalk to the liver, gut, pancreas, adipose tissue, bone, vascular bed, skin and brain.
· Cathepsin B is an exercise-induced myokine required for exercise-induced improvement in memory and adult neurogenesis.
· Exercise enhances neuronal gene expression of FNDC5, the protein product of which might stimulate brain-derived neurotrophic factor in the hippocampus.
· Serum levels of the myokine IL-6 increase with exercise, and this myokine might regulate central mechanisms for food intake.
· Exercise increases muscular expression of kynurenine aminotransferases, which convert blood levels of neurotoxic kynurenine to the neuroprotective kynurenic acid, thereby reducing depression-like symptoms.
Pedersen BK. Physical activity and muscle–brain crosstalk. Nature Reviews Endocrinology 2019;15:383-92. https://doi.org/10.1038/s41574-019-0174-x
Neurological and mental illnesses account for a considerable proportion of the global burden of disease. Exercise has many beneficial effects on brain health, contributing to decreased risks of dementia, depression and stress, and it has a role in restoring and maintaining cognitive function and metabolic control.
The fact that exercise is sensed by the brain suggests that muscle-induced peripheral factors enable direct crosstalk between muscle and brain function. Muscle secretes myokines that contribute to the regulation of hippocampal function.
Evidence is accumulating that the myokine cathepsin B passes through the blood–brain barrier to enhance brain-derived neurotrophic factor production and hence neurogenesis, memory and learning. Exercise increases neuronal gene expression of FNDC5 (which encodes the PGC1α-dependent myokine FNDC5), which can likewise contribute to increased brain-derived neurotrophic factor levels.
Serum levels of the prototype myokine, IL-6, increase with exercise and might contribute to the suppression of central mechanisms of feeding. Exercise also increases the PGC1α-dependent muscular expression of kynurenine aminotransferase enzymes, which induces a beneficial shift in the balance between the neurotoxic kynurenine and the neuroprotective kynurenic acid, thereby reducing depression-like symptoms.
Myokine signalling, other muscular factors and exercise-induced hepatokines and adipokines are implicated in mediating the exercise-induced beneficial impact on neurogenesis, cognitive function, appetite and metabolism, thus supporting the existence of a muscle–brain endocrine loop.
