Objectives: Our objective is to investigate the independent and synergistic effect of acute exercise and the GLP-1/GIP agonist(Tirzepatide) on fatty liver and other metabolic biomarkers in the high-fat diet mice.
Methods: We fed male C57BL/6 mice high-fat diet(HFD) for 12 weeks. We divided the mice into four groups(exercise/Tirzepatide, non-exercise/Tirzepatide, exercise/saline, and non-exercise/Tirzepatide, n=3/group). Then, the mice were observed in metabolic cage to develop a profile of activity and metabolism at both the beginning and end of the study. Also, measures of daily body weight and plasma samples were obtained. At the end of the study, abdominal ultrasound was performed, relevant tissues were harvested, and protein multiplex analysis and metabolite analysis were performed.
Results: Acute exercise for 7 days only doesn't affect weight change, but once injection of Tirzepatide showed significant weight loss in our study. There were no differences in the energy expenditure rate and respiratory exchange ratio(week 2) between the four groups. Our results showed a statistically significant decrease of 65%(p<0.001) in ALT(60U/L, p<0.05) after the once injection of Tirzepatide and 7 days of acute exercise. Analysis of serum inflammatory markers showed a 43% of decrease(3pg/ml) in TNF-α levels in the Tirzepatide/exercise group as compared with the control group(p<0.05). Tirzepatide/acute exercise group showed a trend of 10% reduction in liver fattiness(measured by brightness), but no statistical significance in the ultrasonography at the end of the study as compared with control group.
Conclusion: In this study, we found that the significant decreased in serum ALT level and serum TNF-α level after the once injection of Tirzepatide and 7 days of acute exercise in the high-fat diet mice. Synergistic intervention with Tirzepatide and acute exercise which may be mediated by their anti-inflammatory effects, appears to be an effective therapy against fatty liver.