Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity

Area of Science:

• Exercise Physiology
• Molecular Biology
• Biochemistry

Background:

• Skeletal muscle is central to lactic acid production and metabolism, involving monocarboxylate transporters (MCTs) like MCT1 and MCT4.
• Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates antioxidant responses and energy metabolism, impacting skeletal muscle function.

Purpose of the Study:

• To investigate the effects of Nrf2 activation using sulforaphane (SFN) on exercise performance and molecular markers in skeletal muscle under hypoxic conditions.
• To determine if SFN influences lactate transport and metabolism during exercise.

Main Methods:

• C57BL/6 J mice were pretreated with SFN, an Nrf2 activator, before undergoing incremental treadmill exercise to exhaustion under hypoxia.
• Evaluated exercise endurance, gene/protein expression of MCT1, MCT4, CD147, antioxidant markers, and lactate dehydrogenase (LDH) activity.

Main Results:

• SFN pretreatment significantly enhanced exercise endurance under hypoxia.
• Increased expression of antioxidant genes, MCT1, and CD147, alongside elevated LDH-B activity and citrate synthase activity.
• Reduced blood lactate levels and LDH activity for pyruvate to lactate conversion were observed in SFN-treated mice.

Conclusions:

• SFN activation of Nrf2 increases MCT1 expression in skeletal muscle during acute hypoxic exercise.
• Nrf2 activation presents a promising strategy for enhancing exercise performance under hypoxic conditions.