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.
Level 5 - mechanism / opinion, no new human data
Mechanistic laboratory study combining in vitro cell models, rodent tissue/electroporation experiments, and human muscle biopsies without clinical trial outcomes
PubMed 19387610 · doi:10.1007/s00125-009-1364-1
What was done
Human skeletal muscle was analyzed for BDNF mRNA and protein expression and circulating release following exercise. To model contraction and downstream signaling in vitro and ex vivo, C2C12 myotubes were electrically stimulated, and L6 myotubes as well as isolated rat extensor digitorum longus muscles were treated with BDNF to assess fatty acid oxidation (FAO) and phosphorylation of AMPK (Thr172) and ACCbeta (Ser79). The requirement for AMPK was tested using a dominant-negative adenovirus and Compound C. Additionally, a Bdnf expression vector was electroporated into mouse tibialis cranialis muscle in vivo to observe local TrkB, ERK, and ACCbeta activation.
What was found
The abstract reports directional and pathway-level findings without providing numerical values, confidence intervals, or sample sizes. Exercise increased BDNF mRNA and protein in human skeletal muscle without detectable release into the circulation. Electrical stimulation induced Bdnf expression in muscle cells. BDNF treatment increased AMPK and ACCbeta phosphorylation and increased FAO both in vitro and ex vivo; this FAO increase was abolished by AMPK inhibition. In mice, Bdnf electroporation elevated BDNF protein, phosphorylated TrkB and ERK, and markedly increased ACCbeta phosphorylation.
Why it matters
This study defines muscle-derived BDNF as an autocrine or paracrine myokine that directly promotes lipid oxidation within skeletal muscle via AMPK activation rather than acting as a systemic endocrine signal.
Limits
The abstract reports no sample sizes or quantitative effect estimates for the human, animal, or cell experiments. The metabolic effects on fatty acid oxidation were directly demonstrated only in cell and rodent models, leaving the quantitative contribution to whole-body human metabolism unmeasured.
Cited by
- supports Brain-derived neurotrophic factor (BDNF) is produced in both skeletal muscle and the brain.