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Diabetologia (2009) 52:14091418 DOI 10.1007/s00125-009-1364-1
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
V. B. Matthews & M.-B. strm & M. H. S. Chan & C. R. Bruce & K. S. Krabbe &
O. Prelovsek & T. kerstrm & C. Yfanti & C. Broholm & O. H. Mortensen &
M. Penkowa & P. Hojman & A. Zankari & M. J. Watt & H. Bruunsgaard &
B. K. Pedersen & M. A. Febbraio
Received: 25 February 2009 /Accepted: 16 March 2009 /Published online: 22 April 2009 # Springer-Verlag 2009
AbstractAims/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 (ACC) (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 ACC 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
V. B. Matthews and M.-B. strm contributed equally to this study.
B. K. Pedersen and M. A. Febbraio co-directed this study.
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s00125-009-1364-1
Web End =10.1007/s00125-009-1364-1 ) contains supplementary material, which is available to authorised users.
V. B. Matthews : M. H. S. Chan : C. R. Bruce : O. Prelovsek :
M. A. Febbraio (*)
Cellular and Molecular Metabolism Laboratory, Diabetes and Metabolism Division, Baker Heart Research Institute,PO...