Moderate endurance training reduced hepatic tumourigenesis associated with lower lactate overload compared to high-intensity interval training

The anti-tumour effects of exercise are still poorly understood. In recent years, high-intensity interval exercise has been recognised as one of the best choices for better health. However, high-intensity interval exercise induces lactate production in muscles and elevates blood lactic acid levels, and the resulting acidic microenvironment may promote tumour progression. Therefore, it is important to compare the anti-tumour effects of different types of exercise. Objective: In this study, we aimed to compare the anti-tumour effects of moderate endurance training and high-intensity interval training on diethylnitrosamine (DEN)-induced liver tumours and to explore the underlying mechanisms. Methods: Three-week‒old male C57BL/6 mice were injected intraperitoneally with DEN for 10 weeks to induce hepatocellular carcinoma. DEN-treated mice were grouped and subjected to moderate endurance training (MET) or high-intensity interval training (HIIT) for 18 weeks. We performed real-time PCR to evaluate the mRNA expressions of key enzymes involved in lactate metabolism pathway and western blotting to examine the protein expressions of LDHA, AMPK/P-AMPK, PCK1, and G6Pase in the paracancerous liver tissue. We performed high-performance liquid mass spectrometry (HPLC) to detect lactate in liver. Results: Our results revealed that compared with HIIT, MET decreased hepatic tumour incidence, as HIIT increased blood lactate concentration at rest. Moreover, MET reduced the transcript-level expression of LDH subunit and significantly increased the mRNA levels of COX1 and ND1 in liver. However, no significant changes were observed in liver lactate levels and the expression of LDHA among the groups. In addition, no significant differences in the mRNA levels of critical enzymes involved in the gluconeogenesis pathway in liver were observed among the groups. Additionally, no significant differences were observed in the mRNA levels of MPC2, pdha2, and pdk4 among the groups. Conclusions: Our findings suggest that MET may be more efficient than HIIT at reducing hepatic tumourigenesis, and that it is associated with improved mitochondrial function in liver and lower lactate load in the circulation at rest.