Figure 1.

Effect of dietary cholesterol on the progression of NAFLD to NASH. Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. A high-cholesterol diet promotes the progression toward non-alcoholic steatohepatitis (NASH) by several key mechanisms including hepatic stellate cell activation, oxidative stress, activation of inflammatory pathways and hepatocyte death. Dietary cholesterol promotes NASH by modulating the expression of hepatic metabolic genes such as FXR and ABCG5/8, as well as the expression of cytokines like TNFα, IL-1β, and MCP1. A change in macrophage phenotype in resident macrophages or Kupffer cells toward a M1 phenotype has been suggested. Other proposed mechanisms include the activation of TLR4-dependent pathways and the upregulation of ABCA1 by LXR nuclear receptors.