Therapeutic effects and mechanisms of two exercise modes on rats with nonalcoholic fatty liver disease

Background Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, which may lead to cirrhosis or even hepatoma. Regular exercise is an important non-drug intervention strategy for the prevention and treatment of NAFLD, but the optimal prescription for rehabilitation training has not yet been determined.

Objective To compare the therapeutic effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on rats with NAFLD and explore the possible mechanisms.

Methods Thirty-six 4-week-old male OLETF rats were raised to 20 weeks old and divided into three groups: a sedentary group, a MICT group, and a HIIT group (n=12 in each group) by random number table, at the same time, same strain 12 age- and sex-matched LETO rats were selected as normal control group. The rats in the normal control and the sedentary group were fed quietly in cages, while the rats in the MICT group (60% of maximal running speed, 60 min·d⁻¹, 5 d·week⁻¹) and the HIIT group (80% of maximal running speed for 1 min followed by 40% of maximal running speed for 1 min, alternately repeating 10 cycles, 5 d·week⁻¹) followed the designed exercise protocols for eight weeks by treadmill running. Forty-eight hours after the last training session, hepatic histopathology was observed and hepatic triglyceride and glycogen content, mitochondrial content and function. and protein expressions of markers related to metabolic regulation (glycogen synthesis, fatty acid transport, de novo lipogenesis, triglyceride transport and secretion, and macrophage polarization) were measured.

Results Compared with the sedentary group, the levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and hepatic triglyceride decreased (P<0.05), the activities of citrate synthase (CS) and fatty acid oxidation (FAO) increased (P<0.05), the protein expression levels of Elovl fatty acid elongase 6 (Elovl6), CD11c, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) decreased (P<0.05), the protein expression levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and CD206 increased (P<0.05), while the differences of liver glycogen and glycogen synthase (GS) protein expression levels showed no statistical significance (P>0.05) in the MICT group and the HIIT gtoup; the protein expression of fatty acid translocase (FAT/CD36) decreased in the MICT group (P<0.05); the protein expression of apolipoprotein B100 (ApoB100) were up-regulated (P<0.05) in the HIIT group (P<0.05).

Conclusion Long-term MICT (60 min·d⁻¹, 5 d·week⁻¹) and HIIT (20 min·d⁻¹, 5 d·week⁻¹) interventions have similar therapeutic effects on NAFLD in OLETF rats, and the mechanisms are related to the improvement of hepatic mitochondrial content and function, lipid metabolism, and macrophage polarization state. Because of its remarkable time efficiency, HIIT is expected to become an alternative mode of MICT, which is of great significance for optimizing exercise rehabilitation prescriptions for patients with NAFLD.