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01.07.2009 | Article

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

verfasst von: V. B. Matthews, M.-B. Åström, M. H. S. Chan, C. R. Bruce, K. S. Krabbe, O. Prelovsek, T. Åkerström, C. Yfanti, C. Broholm, O. H. Mortensen, M. Penkowa, P. Hojman, A. Zankari, M. J. Watt, H. Bruunsgaard, B. K. Pedersen, M. A. Febbraio

Erschienen in: Diabetologia | Ausgabe 7/2009

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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 β (ACCβ) (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 ACCβ 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 (TrkB^Tyr706/707) and extracellular signal-regulated protein kinase (p44/42 Thr²⁰²/Tyr²⁰⁴) phosphorylation in these muscles. In addition, phosphorylation of ACCβ 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.

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Titel: 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
verfasst von: V. B. Matthews
M.-B. Åström
M. H. S. Chan
C. R. Bruce
K. S. Krabbe
O. Prelovsek
T. Åkerström
C. Yfanti
C. Broholm
O. H. Mortensen
M. Penkowa
P. Hojman
A. Zankari
M. J. Watt
H. Bruunsgaard
B. K. Pedersen
M. A. Febbraio
Publikationsdatum: 01.07.2009
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 7/2009
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-009-1364-1

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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

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Methods

Results

Conclusions/interpretation

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