We compared the effects of chronic exogenous lactate and exercise training, which influence energy substrate utilization and body composition improvements at rest and during exercise, and investigated the availability of lactate as a metabolic regulator. The mice were divided into four groups: CON (sedentary + saline), LAC (sedentary + lactate), EXE (exercise + saline), and EXLA (exercise + lactate). The total experimental period was set at 4 weeks, the training intensity was set at 60–70% VO₂max, and each exercise group was administered a solution immediately after exercise. Changes in the energy substrate utilization at rest and during exercise, the protein levels related to energy substrate utilization in skeletal muscles, and the body composition were measured. Lactate intake and exercise increased carbohydrate oxidation as a substrate during exercise, leading to an increased energy expenditure and increased protein levels of citrate synthase and malate dehydrogenase 2, key factors in the TCA(tricarboxylic acid) cycle of skeletal muscle. Exercise, but not lactate intake, induced the upregulation of the skeletal muscle glucose transport factor 4 and a reduction in body fat. Hence, chronic lactate administration, as a metabolic regulator, influenced energy substrate utilization by the skeletal muscle and increased energy expenditure during exercise through the activation of carbohydrate metabolism-related factors. Therefore, exogenous lactate holds potential as a metabolic regulator.

Several studies have suggested that lactate mediates exercise-induced hippocampal neurogenesis. To investigate this, we used a monocarboxylate transporter (MCT) inhibitor, alpha-cyano-4-hydroxycinnamic acid (4CIN), to attenuate the signaling effect of endogenous lactate in the hippocampus. Ten-week-old ICR mice were intraperitoneally injected with 100 mg/kg 4CIN before beginning moderate-intensity treadmill exercise 5 days a week for 8 weeks. After 8 weeks of intervention, we evaluated hippocampal neurogenesis, hippocampal protein expression relevant to neurogenesis, and learning and memory function using histology, western blotting, and behavioral tests, respectively. We found that the inhibition of MCT2 by 4CIN led to a reduction in the number of exercise-induced newly generated neurons in the dentate gyrus, and the hippocampal protein expression level of the neurogenesis marker was in line with these histological results. Furthermore, we showed that the inhibition of MCT2 negated the improvements in learning and memory induced by exercise training. Based on these results, we propose that lactate is a potential mediator of exercise-induced hippocampal neurogenesis.

Recent studies suggest that lactate intake has a positive effect on glycogen recovery after exercise. However, it is important to verify the effect of lactate supplementation alone and the timing of glycogen recovery. Therefore, in this study, we aimed to examine the effect of lactate supplementation immediately after exercise on glycogen recovery in mice liver and skeletal muscle at 1, 3, and 5 h after exercise. Mice were randomly divided into the sedentary, exercise-only, lactate, and saline-treated groups. mRNA expression and activation of glycogen synthesis and lactate transport-related factors in the liver and skeletal muscle were assessed using real-time polymerase chain reaction. Skeletal muscle glycogen concentration showed an increasing trend in the lactate group compared with that in the control group at 3 and 5 h after post-supplementation. Additionally, exogenous lactate supplementation significantly increased the expression of core glycogen synthesis enzymes, lactate transporters, and pyruvate dehydrogenase E1 alpha 1 in the skeletal muscles. Conversely, glycogen synthesis, lactate transport, and glycogen oxidation to acetyl-CoA were not significantly affected in the liver by exogenous lactate supplementation. Overall, these results suggest that post-exercise lactate supplement enables glycogen synthesis and recovery in skeletal muscles.

Background/Objectives: Alternate-day fasting (ADF) combined with exercise has been suggested as an effective lifestyle strategy for reducing fat mass while preserving lean mass. However, whether exercise preconditioning before ADF plus concurrent exercise affects subsequent body-composition and substrate-utilization responses remains unclear. This study aimed to evaluate the effects of exercise preconditioning during a subsequent ADF plus concurrent exercise intervention. Methods: Seven-week-old male ICR mice were assigned to the non-exercise preconditioning (Non-ExPC) or exercise preconditioning (ExPC) group (n = 8/group). After the 4-week preconditioning period, both groups underwent 7 days of ADF plus concurrent exercise. Resting energy metabolism was measured during the intervention, and body composition, exercise energy metabolism, muscle and motor function, blood biomarker concentrations, and plasma hormone levels were assessed before and after the intervention. Results: Both groups showed significant reductions in body weight, body fat percentage, and fat mass after the intervention. Lean mass decreased in both groups without between-group differences. The ExPC group maintained significantly lower body fat percentage and fat mass than the Non-ExPC group and showed significantly higher resting oxygen uptake, carbon dioxide production, respiratory exchange ratio, carbohydrate oxidation, and energy expenditure during the intervention. During exercise, the respiratory exchange ratio and carbohydrate oxidation significantly increased in both groups, whereas fat oxidation significantly decreased only in the ExPC group. Conclusions: Exercise preconditioning was associated with the maintenance of lower adiposity during short-term ADF combined with concurrent exercise, while differences in substrate utilization were observed under some conditions.