Understanding the Role of Exercise and Probiotic Interventions on Non-Alcoholic Fatty Liver Disease Alleviation in Zebrafish: Dialogue Between the Gut and Liver

Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver illness, is characterized by hepatic steatosis. Exercise and probiotics can regulate the gut microbiota to treat NAFLD; however, their combined effects and the mechanisms of gut-liver communication remain unclear. Inconsistent results on probiotic efficacy further warrant investigation. In this study, zebrafish fed a high-fat diet (HFD) for six weeks were subjected to swimming exercise (HFDE), probiotic intervention (HFDP), or a combination of both (HFDEP) for 10 weeks to explore their effects on NAFLD and the corresponding mechanism. The results showed that NAFLD alleviation followed the order HFDEP > HFDE > HFDP. HFDEP and HFDE treatments effectively reduced Body Mass Index (BMI), relative liver weight, liver vacuolation density, lipid droplets in liver sections, triglyceride, free fatty acid, glucose, and pyruvic acid. In contrast, a single probiotic treatment had limited impact, suggesting a complementary role in NAFLD treatment. Glucose and fatty acid metabolism were central to the "gut-liver" axis. The reduced conversion of glucose to pyruvic acid, decreased fatty acid synthesis and esterification, and accelerated fatty acid transformation to CO₂ contributed to NAFLD improvement under HFDE and HFDEP treatments. This study provides promising theoretical groundwork for potential prevention and treatment strategies for NAFLD.