TY - JOUR

T1 - Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals

AU - Pedersen, Bente K

AU - Pedersen, Maria

AU - Krabbe, Karen S

AU - Bruunsgaard, Helle

AU - Matthews, Vance B

AU - Febbraio, Mark A

N1 - Keywords: AMP-Activated Protein Kinases; Animals; Brain-Derived Neurotrophic Factor; Diabetes Mellitus, Type 2; Energy Metabolism; Exercise; Homeostasis; Humans; Lipid Metabolism; Muscle Contraction; Muscle, Skeletal; Neurodegenerative Diseases; Physical Conditioning, Animal

PY - 2009

Y1 - 2009

N2 - Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal development and plasticity and plays a role in learning and memory. Moreover, it is well established that BDNF plays a role in the hypothalamic pathway that controls body weight and energy homeostasis. Recent evidence identifies BDNF as a player not only in central metabolism, but also in regulating energy metabolism in peripheral organs. Low levels of BDNF are found in patients with neurodegenerative diseases, including Alzheimer's disease and major depression. In addition, BDNF levels are low in obesity and independently so in patients with type 2 diabetes. Brain-derived neurotrophic factor is expressed in non-neurogenic tissues, including skeletal muscle, and exercise increases BDNF levels not only in the brain and in plasma, but in skeletal muscle as well. Brain-derived neurotrophic factor mRNA and protein expression was increased in muscle cells that were electrically stimulated, and BDNF increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl coenzyme A carboxylase-beta (ACCbeta) and enhanced fatty oxidation both in vitro and ex vivo. These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing lipid oxidation in skeletal muscle via activation of AMPK. Thus, BDNF appears to play a role both in neurobiology and in central as well as peripheral metabolism. The finding of low BDNF levels both in neurodegenerative diseases and in type 2 diabetes may explain the clustering of these diseases. Brain-derived neurotrophic factor is likely to mediate some of the beneficial effects of exercise with regard to protection against dementia and type 2 diabetes.

AB - Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal development and plasticity and plays a role in learning and memory. Moreover, it is well established that BDNF plays a role in the hypothalamic pathway that controls body weight and energy homeostasis. Recent evidence identifies BDNF as a player not only in central metabolism, but also in regulating energy metabolism in peripheral organs. Low levels of BDNF are found in patients with neurodegenerative diseases, including Alzheimer's disease and major depression. In addition, BDNF levels are low in obesity and independently so in patients with type 2 diabetes. Brain-derived neurotrophic factor is expressed in non-neurogenic tissues, including skeletal muscle, and exercise increases BDNF levels not only in the brain and in plasma, but in skeletal muscle as well. Brain-derived neurotrophic factor mRNA and protein expression was increased in muscle cells that were electrically stimulated, and BDNF increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl coenzyme A carboxylase-beta (ACCbeta) and enhanced fatty oxidation both in vitro and ex vivo. These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing lipid oxidation in skeletal muscle via activation of AMPK. Thus, BDNF appears to play a role both in neurobiology and in central as well as peripheral metabolism. The finding of low BDNF levels both in neurodegenerative diseases and in type 2 diabetes may explain the clustering of these diseases. Brain-derived neurotrophic factor is likely to mediate some of the beneficial effects of exercise with regard to protection against dementia and type 2 diabetes.

U2 - 10.1113/expphysiol.2009.048561

DO - 10.1113/expphysiol.2009.048561

M3 - Journal article

C2 - 19748969

VL - 94

SP - 1153

EP - 1160

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 12

ER -