FIGURE 3.

Mediators of hepatic de novo lipogenesis in obese individuals with NAFLD & insulin resistance. Dietary glucose stimulates insulin secretion from pancreatic beta cells. With hepatic IR, insulin fails to suppress hepatic gluconeogenesis; however, stimulation of DNL continues through residual activation of SREBP-1c. Dietary fructose is transported through the hepatic portal vein directly to the liver, where it stimulates de novo lipogenesis through non-insulin–mediated activation of ChREBP. Additionally, IR in adipose and muscle tissue prevents peripheral glucose uptake. Overall, these processes promote hyperglycemia and hyperlipidemia, driving NAFLD progression.^65–67 Abbreviations: ChREBP, carbohydrate-responsive element–binding protein; DNL, de novo lipogenesis; IR, insulin resistance; SREBP-1c, sterol regulatory element–binding transcription factor 1; TG, triglycerides. Figure created using Biorender.