Lactate metabolism: historical context, prior misinterpretations, and current understanding

Area of Science:

• Metabolic research
• Exercise physiology
• Biochemistry

Background:

• Lactate (La^-) has historically been mischaracterized as a detrimental byproduct of hypoxia.
• The cell-to-cell lactate shuttle theory revolutionized the understanding of lactate's metabolic role starting in the 1980s.
• Current research increasingly recognizes lactate's significance beyond exercise contexts.

Purpose of the Study:

• To review and synthesize the current understanding of lactate metabolism.
• To highlight lactate's historical context, particularly in exercise physiology.
• To emphasize lactate's expanding roles in metabolism and potential clinical applications.

Main Methods:

• Appraisal of historical experimental data, focusing on exercise physiology.
• Synthesis of current scientific literature on lactate metabolism.
• Review of lactate's functions as both a fuel source and signaling molecule.

Main Results:

• Lactate is a vital, readily utilized fuel source actively transported throughout the body.
• Lactate acts as a potent signaling molecule, influencing processes like angiogenesis independently of oxygen levels.
• Elevated lactate levels in various conditions are not exclusively indicative of hypoxia, as demonstrated in exercise.

Conclusions:

• Lactate plays a central, dynamic role in coordinating whole-body metabolism.
• Understanding lactate's multifaceted functions is crucial for advancing research and clinical practice.
• Lactate's roles as a fuel, signaling molecule, and its non-hypoxic production have significant implications for diverse physiological and pathological states.