**2.4 Inflammation and steatohepatitis**

Hepatic steatosis in NAFLD is primarily caused by systemic insulin resistance, while NASH is majorly caused by lipotoxicity of accumulating lipids and innate immune system activation. Inflammatory mechanisms, such as the production of proinflammatory extracellular vesicles and cell death, are activated due to lipidinduced sub-lethal and lethal stress [1, 14]. Steatosis and chronic hepatic inflammation are strongly linked to NAFLD, and the Iκκ-β/NF-κB signaling pathway is partially responsible for this association. FFA can directly activate the Ikk-/BNF-kB pathway in hepatocytes, providing another mechanism through which central obesity and the resultant increase in hepatic FFA supply promote inflammation (**Figures 1** and **2**). Additionally, the transformation of FFA into hepatic triglyceride might act to protect against the direct toxicity of lipoproteins to the liver. Existing evidence has demonstrated that the suppression of DGAT2, the enzyme that catalyzes the last stage in triglyceride synthesis, improved hepatic steatosis and IR while exacerbating damage and fibrosis in a mouse model of NAFLD [15].
