Kupffer cells: increasingly significant role in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation of liver metabolic damage and is related to insulin resistance and genetic susceptibility. Inflammation mediated by Kupffer cells (KCs) is of critical importance to the development of NAFLD. The primary role of KCs in NAFLD is considered to be the perturbation of the C-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) pathways as a result of lipopolysaccharide (LPS) recognition by Toll-like receptor 4 (TLR4). Simultaneously, the activation of NF-κB, as mediated by oxidative and endoplasmic reticulum (ER) stress and free fatty acid (FFA) or free cholesterol (FC) crystal formation, heavily relies on NF-κB regulatory factors and TLR4. Additionally, the imbalance of certain pro-inflammatory cytokines and chemokines released by innate immunity is deemed to promote the steatosis of hepatocytes. In conclusion, this review indicates that the inflammatory and oxidative stress of KCs play a significant role in the development of NAFLD.