Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

Matthews, V, Astrom, M, Chan, S, Bruce, C, Krabbe, K, Akerstrom, T, Yfanti, C, Broholm, C, Mortensen, O, Penkowa, M, Hojman, P, Zankari, A, Watt, M, Bruunsgaard, H, Pedersen, B and Febbraio, M 2009, 'Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase', Diabetologia, vol. 52, no. 7, pp. 1409-1418.


Document type: Journal Article
Collection: Journal Articles

Title Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase
Author(s) Matthews, V
Astrom, M
Chan, S
Bruce, C
Krabbe, K
Akerstrom, T
Yfanti, C
Broholm, C
Mortensen, O
Penkowa, M
Hojman, P
Zankari, A
Watt, M
Bruunsgaard, H
Pedersen, B
Febbraio, M
Year 2009
Journal name Diabetologia
Volume number 52
Issue number 7
Start page 1409
End page 1418
Total pages 10
Publisher Springer
Abstract Aims/hypothesis: Brain-derived neurotrophic factor (BDNF) is produced in skeletal muscle, but its functional significance is unknown. We aimed to determine the signalling processes and metabolic actions of BDNF. Methods: We first examined whether exercise induced BDNF expression in humans. Next, C2C12 skeletal muscle cells were electrically stimulated to mimic contraction. L6 myotubes and isolated rat extensor digitorum longus muscles were treated with BDNF and phosphorylation of the proteins AMP-activated protein kinase (AMPK) (Thr172) and acetyl coenzyme A carboxylase ß (ACCß) (Ser79) were analysed, as was fatty acid oxidation (FAO). Finally, we electroporated a Bdnf vector into the tibialis cranialis muscle of mice. Results: BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released into the circulation. Bdnf mRNA and protein expression was increased in muscle cells that were electrically stimulated. BDNF increased phosphorylation of AMPK and ACCß and enhanced FAO both in vitro and ex vivo. The effect of BDNF on FAO was AMPK-dependent, since the increase in FAO was abrogated in cells infected with an AMPK dominant negative adenovirus or treated with Compound C, an inhibitor of AMPK. Electroporation of a Bdnf expression vector into the tibialis cranialis muscle resulted in increased BDNF protein production and tropomyosin-related kinase B (TrkBTyr706/707) and extracellular signal-regulated protein kinase (p44/42 Thr202/Tyr204) phosphorylation in these muscles. In addition, phosphorylation of ACCß was markedly elevated in the Bdnf electroporated muscles. Conclusions/ interpretation: 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.
Subject Pharmacology and Pharmaceutical Sciences not elsewhere classified
Keyword(s) Cytokines
lipid metabolism
metabolism
neuropeptides
physical activity
DOI - identifier 10.1007/s00125-009-1364-1
Copyright notice © 2009 Springer-Verlag.
ISSN 0012-186X
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