Fujimoto Kazunori, Koishi Ryuta, Shimizugawa Tetsuya, Ando Yosuke
Medicinal Safety Research Laboratories, Sankyo Co., Ltd., Fukuroi, Shizuoka, Japan.
Exp Anim. 2006 Jan;55(1):27-34. doi: 10.1538/expanim.55.27.
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.
血管生成素样3（ANGPTL3）是一种具有血管生成和脂质代谢功能的分泌蛋白。我们培育了无法表达Angptl3基因的基因敲除小鼠，并对其脂质代谢进行了分析。给Angptl3基因敲除小鼠喂食正常饮食或高脂、高热量（HFC）饮食后发现，尽管Angptl3基因敲除小鼠与野生型小鼠的体重和肝脏重量没有差异，但前者的血浆脂质浓度，尤其是血浆甘油三酯浓度显著降低。给喂食HFC饮食的Angptl3基因敲除小鼠的附睾脂肪组织重量也显著减轻，尽管它们与野生型小鼠的脂肪细胞大小没有差异。一项甘油三酯清除研究表明，Angptl3基因敲除小鼠血浆甘油三酯浓度较低是由于甘油三酯清除加速所致。事实上，Angptl3基因敲除小鼠肝素后血浆中的脂蛋白脂肪酶和肝脂肪酶活性分别比野生型小鼠高1.57倍和1.42倍。这些结果表明，ANGPTL3可能不仅对脂质代谢有影响，而且对脂肪形成也有影响。
