Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), and increases plasma triglyceride and HDL cholesterol in rodents. ANGPTL3 inhibits endothelial lipase to catalyze HDL-phospholipid and increase HDL-PL levels. Circulating PL-rich HDL particles have high cholesterol efflux abilities.
Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state, likely through activation by Angptl8, a feeding-induced hepatokine, to inhibit postprandial LPL activity in cardiac and skeletal muscles, as suggested by the ANGPTL3-4-8 model.
In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.
In humans with genetic loss-of-function variants in one copy of ANGPTL3, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").
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