Figure 1.

The ANGPTL3-4-8 model revisited. In the fasted state (left), ANGPTL4 is expressed in adipose tissue and inhibits lipoprotein lipase (LPL) locally, reducing LPL activity and fatty acid uptake in adipose. ANGPTL3 is secreted by the liver, but has little ability to inhibit LPL on its own. In the fed state (right), both ANGPTL3 and ANGPTL8 are expressed in the liver, forming a complex that is secreted into the circulation and can inhibit LPL in oxidative tissues. In the adipose tissue, ANGPTL4 expression is repressed and ANGPTL8 expression is induced, leading to formation of ANGPTL4-ANGPTL8 complexes that have little ability to inhibit LPL and may also protect LPL from inhibition by circulating ANGPTL3-ANGPTL8 complexes.