PMID- 19387610
OWN - NLM
STAT- MEDLINE
DCOM- 20090904
LR  - 20220410
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 52
IP  - 7
DP  - 2009 Jul
TI  - 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.
PG  - 1409-18
LID - 10.1007/s00125-009-1364-1 [doi]
AB  - 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) (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. 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 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. 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.
FAU - Matthews, V B
AU  - Matthews VB
AD  - Cellular and Molecular Metabolism Laboratory, Diabetes and Metabolism Division, 
      Baker Heart Research Institute, St Kilda Road Central, Melbourne, Victoria 8008, 
      Australia.
FAU - Astrom, M-B
AU  - Astrom MB
FAU - Chan, M H S
AU  - Chan MH
FAU - Bruce, C R
AU  - Bruce CR
FAU - Krabbe, K S
AU  - Krabbe KS
FAU - Prelovsek, O
AU  - Prelovsek O
FAU - Akerstrom, T
AU  - Akerstrom T
FAU - Yfanti, C
AU  - Yfanti C
FAU - Broholm, C
AU  - Broholm C
FAU - Mortensen, O H
AU  - Mortensen OH
FAU - Penkowa, M
AU  - Penkowa M
FAU - Hojman, P
AU  - Hojman P
FAU - Zankari, A
AU  - Zankari A
FAU - Watt, M J
AU  - Watt MJ
FAU - Bruunsgaard, H
AU  - Bruunsgaard H
FAU - Pedersen, B K
AU  - Pedersen BK
FAU - Febbraio, M A
AU  - Febbraio MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090422
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Fats)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
EIN - Diabetologia. 2012 Mar;55(3):864
EIN - Diabetologia. 2015 Apr;58(4):854-5. PMID: 25693750
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Acetyl-CoA Carboxylase/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism
MH  - Cell Line
MH  - Exercise Test
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fats/metabolism
MH  - Gene Expression/physiology
MH  - Humans
MH  - Lipid Metabolism/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle Contraction/*physiology
MH  - Muscle Fibers, Skeletal/physiology
MH  - Muscle, Skeletal/cytology/*physiology
MH  - Oxidation-Reduction
MH  - Phosphorylation/physiology
MH  - Rats
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction/physiology
EDAT- 2009/04/24 09:00
MHDA- 2009/09/05 06:00
CRDT- 2009/04/24 09:00
PHST- 2009/02/25 00:00 [received]
PHST- 2009/03/16 00:00 [accepted]
PHST- 2009/04/24 09:00 [entrez]
PHST- 2009/04/24 09:00 [pubmed]
PHST- 2009/09/05 06:00 [medline]
AID - 10.1007/s00125-009-1364-1 [doi]
PST - ppublish
SO  - Diabetologia. 2009 Jul;52(7):1409-18. doi: 10.1007/s00125-009-1364-1. Epub 2009 
      Apr 22.