Lactate administration reproduces specific brain and liver exercise-related changes

Area of Science:

• Exercise Physiology
• Molecular Biology
• Metabolic Research

Background:

• Exercise benefits extend beyond muscle, influencing chronic disease mitigation.
• Understanding exercise's non-muscle tissue effects is crucial for clinical trials and exercise mimetics.
• Lactate, an exercise byproduct, is investigated for its role in mediating these effects.

Purpose of the Study:

• To investigate lactate's role in mediating exercise-induced changes in liver and brain bioenergetic parameters.
• To determine if exogenous lactate can replicate observed physiological adaptations in the liver and brain.
• To explore lactate as a potential exercise mimetic.

Main Methods:

• Mice underwent 7 weeks of treadmill exercise exceeding lactate threshold.
• Plasma lactate accumulation was induced by running mice to exhaustion.
• Changes in liver and brain gene expression, PGC-1α/β, and mitochondrial DNA were analyzed.
• Exogenous lactate administration effects were compared to exercise-induced changes.

Main Results:

• Exercise increased liver gluconeogenesis gene expression and PGC-1α, while decreasing PGC-1β and respiratory chain genes.
• In the brain, exercise increased PGC-1-related co-activator expression and mitochondrial DNA copy number, decreasing TNF-α and increasing VEGF-A.
• Exogenous lactate partially reproduced these liver and brain adaptations.

Conclusions:

• Lactate mediates some exercise effects on the liver and brain.
• Lactate acts as a partial exercise mimetic, influencing key metabolic and molecular pathways.
• Findings support further research into lactate-based interventions and exercise mimetics.