The potential mechanisms of lactate in mediating exercise-enhanced cognitive function: a dual role as an energy supply substrate and a signaling molecule

Abstract

Lactate has previously been considered a metabolic waste and is mainly involved in exercise-induced fatigue. However, recent studies have found that lactate may be a mediator of the beneficial effects of exercise on brain health. Lactate plays a dual role as an energy supply substrate and a signaling molecule in this process. On the one hand, astrocytes can uptake circulating glucose or degrade glycogen for glycolysis to produce lactate, which is released into the extracellular space. Neurons can uptake extracellular lactate as an important supplement to their energy metabolism substrates, to meet the demand for large amounts of energy when synaptic activity is enhanced. Thus, synaptic activity and energy transfer show tight metabolic coupling. On the other hand, lactate acts as a signaling molecule to activate downstream signaling transduction pathways by specific receptors, inducing the expression of immediate early genes and cerebral angiogenesis. Moderate to high-intensity exercise not only increases lactate production and accumulation in muscle and blood but also promotes the uptake of skeletal muscle-derived lactate by the brain and enhances aerobic glycolysis to increase brain-derived lactate production. Furthermore, exercise regulates the expression or activity of transporters and enzymes involved in the astrocyte-neuron lactate shuttle to maintain the efficiency of this process; exercise also activates lactate receptor HCAR1, thus affecting brain plasticity. Rethinking the role of lactate in cognitive function and the regulatory effect of exercise is the main focus and highlights of the review. This may enrich the theoretical basis of lactate-related to promote brain health during exercise, and provide new perspectives for promoting a healthy aging strategy.

Alleviation of Cognitive and Physical Fatigue with Enzymatic Porcine Placenta Hydrolysate Intake through Reducing Oxidative Stress and Inflammation in Intensely Exercised Rats

“…Intense exercise generates both physical and cognitive fatigue [ 45 ], although long-term moderate exercise improves cognitive functions [ 46 ]. However, the mechanism of intense exercise to induce cognitive fatigue has remained controversial [ 45 , 47 , 48 ]. The present study demonstrated that EPPH improved physical and cognitive fatigue induced by exhaustive exercise.…”

The role of efferocytosis‐fueled macrophage metabolism in the resolution of inflammation

“…Exercise is well-known to generate lactate, promote anti-inflammatory signaling, and enhance tissue repair. [160][161][162] This exercise-induced resolution-repair program repairs skeletal muscle that becomes injured through exercise. 163 The process is initiated by the recruitment of pro-inflammatory Ly6c hi monocytes by the chemokine CCL2.…”

“…Aside from direct injection of lactate or boosting efferocytosis, lactate levels can be acutely raised through exercise. Exercise is well‐known to generate lactate, promote anti‐inflammatory signaling, and enhance tissue repair 160–162 . This exercise‐induced resolution‐repair program repairs skeletal muscle that becomes injured through exercise 163 .…”

Qigong Exercise Balances Oxygen Supply and Acid-Base to Modulate Hypoxia: A Perspective Platform toward Preemptive Health & Medicine

“…More importantly, burdensome specific metabolites (e.g., lactate) in one tissue may be important regulators in another organ, as lactate acts as a mediator of the beneficial effects of exercise on brain health. Lactate plays a dual role as an energy supply substrate and a signaling molecule in this metabolic coupling process [ 23 ]. This metabolic coupling process manifests.…”