Exercise Inducible Lactate Dehydrogenase B Regulates Mitochondrial Function in Skeletal Muscle

Area of Science:

• Exercise Physiology
• Muscle Metabolism
• Mitochondrial Biology

Background:

• Lactate dehydrogenase (LDH) interconverts pyruvate and lactate, crucial for skeletal muscle energy during exercise.
• The precise physiological role of LDH in muscle adaptation remains unclear.
• Exercise impacts muscle pH and metabolic profiles, but LDH's specific contribution is poorly understood.

Purpose of the Study:

• To investigate the role of lactate dehydrogenase B (LDHB) in exercise-induced muscle adaptation.
• To elucidate the regulatory mechanisms of LDHB expression during exercise.
• To determine the impact of enhanced LDHB on muscle function and mitochondrial adaptation.

Main Methods:

• Measured Ldhb expression in human muscle during isometric exercise.
• Investigated PGC-1α regulation of Ldhb using gene reporter assays with ERR and MEF2 binding sites.
• Utilized transgenic mice overexpressing Ldhb in skeletal muscle (MCK-Ldhb).
• Assessed exercise performance, oxygen consumption, mitochondrial enzyme activity, and gene expression in MCK-Ldhb mice and myotubes.

Main Results:

• Ldhb expression increased with exercise in human muscle and correlated inversely with intramuscular pH.
• Exercise-induced PGC-1α activates Ldhb expression via ERR and MEF2 binding sites.
• MCK-Ldhb mice showed improved exercise performance and oxygen consumption.
• MCK-Ldhb muscle exhibited enhanced mitochondrial enzyme activity, gene expression, and respiration, with reduced lactate production.

Conclusions:

• LDHB is induced by exercise and regulated by PGC-1α, ERR, and MEF2 pathways.
• Overexpression of LDHB promotes adaptive oxidative muscle transformation and improves exercise capacity.
• LDHB plays a significant role in modulating muscle mitochondrial function and metabolic response to exercise training.