AMPK affects the development of early-stage NAFLD by activating autophagy and fatty acid oxidation.

Non-alcoholic fatty liver disease (NAFLD) ranks among the most common liver disorders, but the mechanisms underlying its early development are still not well understood. This study aims to compare the effects of varying degrees of lipid accumulation on autophagy and energy metabolism signaling pathways to further elucidate the early pathogenesis of NAFLD. Low-level and classical lipid accumulation models were generated in AML12 and HepG2 cells in vitro using various concentrations of oleic acid and palmitic acid. For in vivo models, Tyloxapol and high-fat diet were utilized to construct both low-level and classical lipid accumulation models. We used Western blot analysis to assess the phosphorylation status of peroxisome proliferator-activated receptor α (PPARα) and AMP-activated protein kinase (AMPK), as well as the expression levels of autophagy-related proteins. We found that low-level lipid accumulation models significantly promoted the expression of the lipid oxidation protein PPARα, and enhanced autophagy activity and AMPK phosphorylation. However, these positive effects were inhibited in classical lipid accumulation models. Our research identified a compensatory mechanism in the early stages of NAFLD. Appropriate lipid accumulation can increase the levels of fatty acid oxidation proteins and autophagy, potentially mediated by the energy metabolism regulator AMPK. This discovery offers additional theoretical insights into the onset and progression of early-stage NAFLD.