Figure 7.

Interplay between glucose and lipid metabolism in the PRIM and SEC models of NAFLD. Liver-specific overexpression of SREBP-1c and increased hepatic DNL in the PRIM mouse model leads to accumulation of DAGs and triacylglycerols (TAG) and development of NAFLD. NAFLD in PRIM associates with decreased insulin signaling and higher hepatic glucose output. On the one hand, mitochondrial oxidative capacity (O₂ flux) is increased under fasted conditions while emission of ROS remains unchanged. ChREBP-mediated lipogenesis in adipose tissue and fat mass are increased, which could protect from hyperglycemia and peripheral IR. On the other hand, SEC mice are characterized by loss of adipose tissue and ectopic lipid (DAG, TAG) accumulation in both liver and skeletal muscle. Moreover, accumulation of extrahepatic lipids in SEC but not intrahepatic lipids in PRIM associates with portal and lobular inflammation of the liver. In SEC, hepatic O₂ flux is increased under fed conditions as well as systemic oxidative stress. Liver and skeletal muscle are both characterized by decreased insulin sensitivity. alb, albumin; AP2, adipocyte P2.