[Effects of different swimming exercises on alcoholic fatty liver formation in mice]

Objective: To investigate the effects of 7-week swimming exercise with different loads on the improvement of liver lipid metabolism in mice with alcoholic fatty liver disease (AFLD) and its relationship with the regulation of miR-34a/PPARα. Methods: Fifty male KM mice were randomly divided into control group (K, n=10) and alcoholic fatty liver group (AFLD, n=40). The AFLD model was constructed after feeding with 50% alcohol for 7 weeks with 1 d rest per week. After successful model construction, the mice were divided into a model group (M), a 30-min swimming exercise group (LE), a 60-min swimming exercise group (ME), and a 90-min loaded swimming exercise group (HE, 5% of body mass as tail lead load), with 10 mice in each group, for a total of 7 weeks of intervention. After completion, the serum and liver tissues were collected, the liver index, visceral fat ratio, hepatocyte injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT), total cholesterol (TC), triglyceride (TG), and high/low density lipoprotein cholesterol (H/LDL-C) content were measured; HE staining was used to observe the changes in liver structure, Western blot was used to detect the protein levels of PPARα, FAS and TNF-α in liver tissues, and mRNA expression profiles were analyzed by sequencing After RT-PCR, the mRNA expressions of miR-34a, PPARα, FAS, TNF-α and CPT-1 were verified. Results: Compared with K group, the hepatic cord disorder, focal lipid vacuum, obvious lipid droplet vacuolation, abnormal ectopic nucleus were observed in AFLD group ; liver function was decreased significantly. Compared with the M group, the liver functions of the ME and HE groups were improved significantly, the serum levels of TG, TC and LDL-C were decreased, while the HDL-C level was increased (P<0.01 or P<0.05), and the liver index and visceral fat ratio were decreased (P< 0.01 or P<0.05), the focal lipid droplet degeneration of hepatocytes was decreased, and the structure of the hepatic cord was clearer; and the ME group showed a more significant intervention effect. Compared with the M group, the expression levels of PPARα protein in the liver tissues of the LE, ME, and HE groups were increased, while the protein expression levels of FAS and TNF-α were decreased (P<0.01 or P<0.05). Based on Illumina high-throughput sequencing and mRNA differential expression analysis, there are 38 differentially expressed genes in the PPARα pathway, including 9 up-regulated genes and 29 down-regulated genes, which are involved in liver fatty acid oxidation, lipid metabolism, and apoptosis inhibition. Compared with group M, the gene levels of miR-34a, FAS, and TNF-α in LE, ME, and HE groups were decreased, and the gene levels of PPARα and CPT-1 were increased (P<0.01 or P<0.05). Conclusion: Swimming with different loads can improve liver functions in AFLD mice, promote lipid droplet degradation, and regulate liver lipid metabolism. The mechanism may be related to the activation of miR-34a/PPARα, and the intervention effect of moderate-load swimming is better.