Fig. 6.

Proposed mechanism and NAFLD progression model. (Left) SREBP-1 resides complexed with SCAP and INSIG in the ER. Upon activation, INSIG dissociates and SCAP facilitates transport to Golgi where cleavage by S1P and S2P leads to mature SREBP-1 which translocates to the nucleus and activates lipogenic genes. Vitamin E blocks SREBP-1 translocation through reduced protein expression of S1P and S2P by lowering oxidative stress (OS). (Right) Intra-hepatic triglyceride accumulation (IHTG) induces OS which can lead to progression to non-alcoholic steatohepatitis (NASH) and fibrosis. Our data supports a bi-directional model in which oxidative stress contributes to disease progression and exacerbates IHTG.