Figure 2.

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Dietary factors and obesity, important for the development of insulin resistance, increase the lipolysis of adipose tissue and de novo lipogenesis (DNL) in hepatocytes. An excess of free fatty acids from circulating blood enters the liver, which, together with increased DNL in hepatocytes, leads to hepatocyte steatosis and lipotoxicity. The latter can affect the normal functioning of mitochondria and endoplasmic reticulum, leading to oxidative stress and endoplasmic reticulum stress, which can increase hepatocyte apoptosis. Apoptotic hepatocytes increase the production of proinflammatory cytokines, recruit inflammatory cells to the liver, activate Kupfer cells, and lead to inflammation, which is a hallmark of NASH. At the same time, inflammation and hepatocyte apoptosis promote the activation of hepatic stellate cells (HSCs), which will transform into myofibroblasts and produce extracellular matrix. Excessive deposition of extracellular matrix leads to the occurrence of liver fibrosis.