title: 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 Angptl3 gene, and analyzed the lipid metabolism. Angptl3-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 Angptl3-null mice and wild-type mice. Angptl3-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 Angptl3-null mice was caused by an accelerated clearance of triglyceride. In fact, lipoprotein lipase and hepatic lipase activities in the post-heparin plasma of Angptl3-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.
authors.affiliation: Medicinal Safety Research Laboratories, Sankyo Co., Ltd., Fukuroi, Shizuoka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Ryuta
authors.initials: R
authors.lastname: Koishi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shimizugawa
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ando
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000473:pathology; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D048429:Cell Size; D004041:Dietary Fats / Q000008:administration & dosage; D004822:Epididymis / Q000473:pathology; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D004041:Dietary Fats; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D014280:Triglycerides; D008071:Lipoprotein Lipase