Insulin induces SREBP-1c maturation via a proteolytic mechanism started in the endoplasmic reticulum (ER), wherein hepatic IR is highly associated with hepatic steatosis.118 Over-expression of liver SREBP-1c has been described in several IR models of including IRS2 knockout,119 lipodystrophic and ob/ob mice.120 In addition, hepatic glucose lead to a deficiency in the transcription factor carbohydrate responsive element binding protein (ChREBP) resulting in reduced mRNA levels of glycolytic and lipogenic enzymes, as well as SREBP-1c levels. Here, SREBF1 is linked to fatty liver disease.