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
| Autor: | M H S Chan, Oja Prelovsek, Helle Bruunsgaard, M-B Astrom, Pernille Hojman, Alaa Zankari, Clinton R. Bruce, K. S. Krabbe, Mark A. Febbraio, Christina Yfanti, Ole Hartvig Mortensen, Vance Matthews, Thorbjorn Akerstrom, Matthew J. Watt, Bente Klarlund Pedersen, Christa Broholm, Milena Penkowa |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Muscle Fibers Skeletal Gene Expression Tropomyosin receptor kinase B AMP-Activated Protein Kinases Cell Line Fats Mice AMP-activated protein kinase Internal medicine Internal Medicine medicine Animals Humans Receptor trkB Myocyte Phosphorylation Extracellular Signal-Regulated MAP Kinases Muscle Skeletal Protein kinase A Brain-derived neurotrophic factor biology Brain-Derived Neurotrophic Factor AMPK Skeletal muscle Lipid Metabolism Rats Mice Inbred C57BL Endocrinology medicine.anatomical_structure nervous system Exercise Test biology.protein medicine.symptom Oxidation-Reduction Acetyl-CoA Carboxylase Muscle Contraction Signal Transduction Muscle contraction |
| Zdroj: | Diabetologia. 52:1409-1418 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-009-1364-1 |
| Popis: | 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.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) (Thr(172)) and acetyl coenzyme A carboxylase beta (ACCbeta) (Ser(79)) were analysed, as was fatty acid oxidation (FAO). Finally, we electroporated a Bdnf vector into the tibialis cranialis muscle of mice.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 ACCbeta 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 Thr(202)/Tyr(204)) phosphorylation in these muscles. In addition, phosphorylation of ACCbeta was markedly elevated in the Bdnf electroporated muscles.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. |
| Databáze: | OpenAIRE |
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