ANGPLT3: A novel modulator of lipid metabolism

Angiopoietin-like proteins (ANGPTLs) have emerged as an important regulator of lipid and glucose metabolism as well as insulin sensitivity. ANGPTL3 plays a key role in regulating circulating triglycerides (TG) and cholesterol levels through reversible inhibition of lipoprotein lipase (LPL) and endothelial lipase enzymes activity. Loss of function mutation of ANGPTL3 gene has been identified in many subjects with familial combined hypolipidemia. ANGPTL4 produces irreversible inhibition of LPL activity, while ANGPTL8 enhances the activity of ANGPTL3, which highlight the interplay between the different ANGPTLs in a coordinated manner to regulate lipid metabolism during different nutritional states. This new class of lipid modulators may serve as potential novel therapeutic target for reducing plasma lipoprotein and treatment of metabolic syndrome.