BDNF secretion from C2C12 cells is enhanced by methionine restriction.

Area of Science:

• Molecular Biology
• Cell Metabolism
• Neuroscience

Background:

• Brain-derived neurotrophic factor (BDNF) is a myokine crucial for skeletal muscle metabolism.
• The precise mechanisms by which metabolic alterations influence skeletal muscle BDNF expression and release are not fully elucidated.
• Methionine restriction (MR), a form of dietary amino acid restriction, is explored as an alternative fasting strategy.

Purpose of the Study:

• To investigate the impact of methionine restriction (MR) on BDNF expression and release in C2C12 myotubes.
• To elucidate the underlying molecular and metabolic pathways involved in MR-induced BDNF modulation.

Main Methods:

• C2C12 myotubes were subjected to methionine restriction (MR).
• BDNF release was quantified using ELISA, RT-qPCR, immunostaining, and Western blot.
• The role of the protein transport pathway, glycolysis, and lactate was assessed using inhibitors (2-deoxy-D-glucose) and exogenous lactate treatment.

Main Results:

• MR significantly enhanced BDNF release from C2C12 myotubes via the classical protein secretory pathway.
• MR increased l-lactate production, indicative of enhanced glycolysis.
• Inhibition of glycolysis (2-DG) attenuated MR-induced BDNF release, while l-lactate treatment dose-dependently increased BDNF gene expression and release in control cells.

Conclusions:

• Methionine restriction promotes BDNF secretion in skeletal muscle cells.
• Enhanced glycolysis and subsequent lactate production appear to be key mediators of MR-induced BDNF release.
• This study reveals a novel link between metabolic reprogramming and neurotrophin secretion in skeletal muscle.