Abstract

Angiopoietin-like protein 4 (ANGPTL4) was identified as a peroxisome proliferator-activated receptor (PPAR)-induced gene. The genetic finding that mutation in ANGPTL3 causes hypolipidemia in mice moved us to test whether ANGPTL4 could also regulate lipid metabolism in vivo. We successfully proved that the introduction of ANGPTL4 as well as ANGPTL3 protein into mice rapidly induced hyperlipidemia. This suggests that the identification of novel PPAR-induced secreted proteins would contribute greatly to the elucidation of the molecular mechanisms of metabolic syndrome, including cardiovascular disease. In addition to lipid metabolism, ANGPTL4 is now regarded as a regulator of glucose metabolism. Emerging biochemical and genetic studies are expected to establish proof-of-evidence of ANGPTL4 as a promising drug development target.

Key words: Angiopoietin-like protein 4, peroxisome proliferator-activated receptor, lipid metabolism, drug target.