Angptl3-null mice show low plasma lipid concentrations by enhanced lipoprotein lipase activity

Abstract

Angiopoietin-like 3 (ANGPTL3) is a secreted protein with both angiogenesis and lipid metabolism functions. We generated knockout mice that failed to express the Angpt13 gene, and analyzed the lipid metabolism. Angpt13-null mice, fed a normal diet or a high-fat, high-calorie (HFC) diet, revealed markedly low plasma lipid concentrations, especially plasma triglyceride concentration, although the body weight and liver weight were not different between Angpt13-null mice and wild-type mice. Angpt13-null mice fed an HFC diet also revealed a significantly reduced epididymal adipose tissue weight despite there being no difference in adipocyte size between them and wild-type mice. A triglyceride clearance study indicated that the lower plasma triglyceride concentration in Angpt13-null mice was caused by an accelerated clearance of triglycedde. In fact, lipoprotein lipase and hepatic lipase activities in the post-heparin plasma of Angpt13-null mice were 1.57 times and 1.42 times higher than those of wild-type mice, respectively. These results suggest that ANGPTL3 may have an effect not only on lipid metabolism but also on adipose formation. Copyright © 2006 Japanese Association for Laboratory Animal Science.