Oxamate suppresses whole-body energy metabolism at rest and during exercise in mice by inhibiting fat oxidation and altering lactate dynamics.

Purpose: Oxamate is a well-known inhibitor of glycolysis. However, its broad inhibitory effects on whole-body energy metabolism in vivo have not been identified. Therefore, we aimed to investigate its effects on wholebody energy metabolism in mice.

Methods: Ten-week-old male ICR mice were used in this study. The resting metabolic rate was measured for 3 h immediately after the intraperitoneal injection of oxamate (750 mg/kg) using a metabolic chamber system. In addition, resting blood glucose and lactate concentrations were measured. Next, the metabolism during exercise (10-25 m/min) was measured for 30 min immediately after oxamate injection using a metabolic treadmill chamber system. Post-exercise blood lactate concentrations were measured immediately after exercise sessions.

Results: The resting respiratory exchange rate remained unchanged, but fat and carbohydrate oxidation and energy expenditure (p = 0.003, 0.049, and 0.002, respectively) were significantly suppressed following oxamate injection. While the resting blood glucose levels were significantly reduced (p = 0.002), the lactate levels were significantly elevated (p = 0.005). The respiratory exchange rate during exercise significantly increased by oxamate injection (p = 0.02). Although fat oxidation during exercise significantly reduced (p = 0.009), carbohydrate oxidation remained unchanged. Consequently, energy expenditure during exercise was significantly reduced (p = 0.024) and post-exercise blood lactate levels were significantly elevated (p = 0.005) by oxamate injection.

Conclusion: Oxamate suppressed whole-body energy metabolism by inhibiting fat oxidation and altering lactate dynamics in vivo. These results provide novel insights into the systemic metabolic effects of oxamate and highlight the need for further investigation of its impact under different physiological conditions.