Sequential Effects of High-Fat Diet and Hypoxia on Angptl4 Upregulation in Kupffer Cells: potencial implications for Non-Alcoholic Fatty Liver Disease (NAFLD) Aggravation

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease globally, significantly influenced by hypoxia and high-fat diet intake. This study investigates how Angptl4, a protein associated with lipid metabolism and inflammation, modulates NAFLD progression through its effects on Kupffer cells. Using a Mus musculus NAFLD model and a Kupffer cell line treated with palmitic acid, we examined lipid accumulation, inflammation, and oxidative stress under hypoxic and high-fat conditions.Key findings indicate that both hypoxia and high-fat diet contribute to increased hepatic triglyceride levels, inflammation, and oxidative stress, exacerbating NAFLD. Notably, Angptl4 expression was significantly elevated in Kupffer cells under these conditions, and silencing Angptl4 led to reductions in lipid accumulation, oxidative stress, and inflammatory markers. These results suggest that Angptl4 may be a critical factor in NAFLD progression and a potential therapeutic target for mitigating disease exacerbation induced by hypoxia and high-fat diets.