professor National Institute of Sports Science beijing, Beijing, China (People's Republic)
Objectives : Non-alcoholic fatty liver disease (NAFLD) can lead to liver fibrosis with TGFβ playing a crucial role . UBAP2L regulates the expression of TGFβ, but its role in NAFLD remains unclear. Aerobic and resistance training can alleviate fibrosis, and the metabolic regulatory effects of ECE have become a research focus. This study investigates whether ECE can ameliorate NAFLD fibrosis through the UBAP2L-mediated TGFβ/Smad2/3 pathway, providing scientific evidence for potential therapeutic strategies.
Design: Fifty 5-week-old SPF-grade male C57BL/6N mice were randomly divided into five groups: normal control (C), high-fat diet group (H), high-fat diet with cold exposure group (HC), high-fat diet with exercise group (HE), and high-fat diet with cold exposure and exercise group (HCE). After 8 weeks of high-fat diet feeding, an 8-week treadmill exercise intervention was performed in HE and HCE groups, 5 days per week, 50 minutes each session. Liver tissue structure and morphology were assessed using HE, Oil Red O, and Masson staining, while liver function was evaluated through biochemical tests for blood lipids, glucose, and liver function indicators. Differential protein analysis using proteomics, along with GO and KEGG analysis, was conducted to identify intersecting proteins and biological processes between NAFLD and ECE intervention. Key fibrosis-related proteins, including UBAP2L, TGFβ, α-SMA, Smad2, Smad3, and Col1a2, were validated across groups using Western Blot (WB) and RT-qPCR.
Results: Compared to H group, liver steatosis, inflammation, fibrosis, and structural function were significantly ameliorated in HC, HE and HCE groups, which demonstrated exercise with cold exposure (ECE) showing superior effects over exercise in normal temperature. Proteomics, WB, and RT-qPCR analyses indicated that exercise with cold exposure ameliorated NAFLD-induced liver fibrosis by downregulating UBAP2L and inhibiting the TGFβ/Smad2 pathway.
Conclusion: ECE has a greater effect on improving NAFLD fibrosis . The underlying pathway involves UBAP2L-mediated inhibition of the TGFβ/Smad2 pathway, thereby preventing NAFLD-induced liver fibrosis.
