The Dual Role of Lactate in the Exercising Brain: Fueling Energy and Signaling Fatigue.

Historically regarded as a "fatigue substance" that impedes muscle contraction, lactate has undergone a paradigm shift in its scientific perception. Currently, it is acknowledged as an indispensable substrate for aerobic ATP synthesis, functioning as a pivotal intermediate in the glycolysis pathway. Within the brain context, lactate derived from glycogen in astrocytes is instrumental in augmenting exercise endurance and enhancing memory formation via the astrocyte-neuron lactate shuttle. This glia-neuron interaction mechanism underscores the expansive influence of lactate beyond mere muscular physiology. Contemporary investigations have pivoted toward elucidating a novel hypothesis: the role of lactate as a ligand for the G protein-coupled receptor (GPR) 81, posited to orchestrate a "fatigue signal" amid exercise capabilities. This hypothesized function in neural inhibition underscores the comprehensive impact of lactate on physiological responses to prolonged exercise. This evolving perspective of lactate not only accentuates its central role in metabolic processes but also paves the way for advanced exploration into the whole-body's sophisticated mechanisms for managing and adapting to physical exhaustion and central fatigue.