Figure 3.

The development and progression of NAFLD. The development of insulin resistance increases the supply of free fatty acids (FFA) to the liver causing increased TAG synthesis and hepatic steatosis. Oxidative stress may also contribute to this process. The steatosis leads to inflammation and increased oxidative stress, which in turn causes mitochondrial dysfunction. These conditions, together with other factors such as PNPLA3 gene polymorphism, result in the development of fibrosis and ultimately NASH. In the traditional 2 hit hypothesis [48] the initial steatosis is the first hit and the second hits are the resulting oxidative stress and inflammation. It is now clear, however, that multiple hits are involved in the process.