Long-term lactate ingestion and exercise training differentially modulate body composition, resting substrate metabolism, and tissue-specific metabolic remodeling in mice

[Purpose] This study investigated whether long-term lactate ingestion induces systemic and tissue-specific metabolic adaptations under normal physiological conditions and whether these responses differ from those induced by exercise training.[Methods] Thirty-two male mice were randomly assigned to saline control, lactate ingestion, exercise training with saline, or exercise training with lactate groups (n = 8/group). Lactate (3 g/kg) or saline was administered by oral gavage five times per week for 16 weeks. Exercise-trained mice performed moderate-intensity treadmill exercise five times per week. Body composition, 24-h resting substrate utilization and energy expenditure, and metabolic protein abundance in the soleus muscle and epididymal white adipose tissue were assessed.[Results] Lactate ingestion reduced body fat percentage and absolute fat mass in untrained mice. Exercise increased resting carbohydrate oxidation, total energy expenditure, and skeletal muscle HK2, PDHA1, and GLUT4 abundance. Lactate ingestion increased skeletal muscle abundance of FAT/CD36, PDK4, MCT1, and MCT4 under untrained conditions. In epididymal white adipose tissue, molecular responses were limited, with the most robust changes observed for CIDEA, whereas the supplementation effect on GPR81 did not remain significant after false discovery rate correction. The combined intervention did not consistently produce additional adaptations beyond those observed with exercise training alone.[Conclusion] Long-term lactate ingestion and exercise training produced distinct but partially overlapping systemic and molecular response patterns. Lactate ingestion was associated with lower adiposity and increased abundance of skeletal muscle proteins related to fatty acid handling and lactate transport, whereas exercise training increased carbohydrate oxidation, energy expenditure, and the abundance of proteins associated with glucose metabolism.