Angiopoietin-like proteins 3, 4 and 8: regulating lipid metabolism and providing new hope for metabolic syndrome.

Angiopoietin-like proteins (ANGPTLs) are a group of eight proteins that share structural similarity to the members of the angiopoietin protein family. ANGPTL3 plays a vital role in the regulation of the plasma levels of triglyceride and cholesterol, mainly via reversible inhibition of the lipoprotein lipase activity. ANGPTL4, which functions as a homo-oligomer different from ANGPTL3 and ANGPTL8, not only regulates the plasma levels of triglyceride and prevents the uptake of dietary lipids into adipose tissues but also inhibits intravascular lipolysis. ANGPTL8 (also called betatrophin) has been identified as an important factor in regulating the triglyceride levels and adipose tissue mass as well as in replenishing the adipose tissue triglyceride store. ANGPTL8 acts together with ANGPTL3 to regulate the lipid metabolism, and ANGPTL8 promotes cleavage of ANGPTL3 to augment the activity of ANGPTL3. In addition, ANGPTL8 promotes proliferation of pancreatic β-cells and enhances insulin secretion. The properties of ANGPTLs in regulating the lipid metabolism suggest their application in the target therapy for metabolic syndrome. As ANGPTLs are regulated by several factors and may be involved in certain specific pathways of lipid metabolism, designing drugs that target ANGPTLs or factors regulating ANGPTLs may be an efficient approach to treat metabolic syndrome.