Angptl4 deficiency decreases serum triglyceride levels in low-density lipoprotein receptor knockout mice and streptozotocin-induced diabetic mice

作者：Adachi Hironori; Kondo Tatsuya; Koh Gou Young; Nagy Andras; Oike Yuichi; Araki Eiichi^*

来源：Biochemical and Biophysical Research Communications, 2011, 409(2): 177-180.

DOI：10.1016/j.bbrc.2011.04.110

• Diabetes mellitus
• Familial hypercholesterolemia
• Lipoprotein lipase
• Postprandial hypertriglyceridemia
• Angptl4

Angiopoietin-like protein family 4 (Angptl4) has been shown to regulate lipoprotein metabolism through the inhibition of lipoprotein lipase (LPL). In familial hypercholesterolemia (FH), individuals lacking low-density lipoprotein receptor (LDLR) present not only hypercholesterolemia, but also increased plasma triglyceride (TG)-rich lipoprotein remnants, and develop atherosclerosis. In addition, the most common type of dyslipidemia in individuals with diabetes is increased TG levels.
We first generated LDLR(-/-)Angptl4(-/-) mice to study the effect of Angptl4 deficiency on the lipid metabolism. Fasting total cholesterol, VLDL-C, LDL-C, HDL-C and TG levels were decreased in LDLR(-/-) Angptl4(-/-) mice compared with LDLR(-/-) Angptl4(+/+) mice. In particular, post olive oil-loaded TG excursion were largely attenuated in LDLR(-/-)Angptl4(-/-) mice compared with LDLR(-/-)Angptl4(+/+) mice. We next introduced diabetes by streptozotocin (STZ) treatment in Angptl4(-/-) mice and examined the impacts of Angptl4 deficiency. Compared with diabetic Angptl4(+/+) mice, diabetic Angptl4(-/-) mice showed the improvement of fasting and postprandial hypertriglyceridemia as well. Thus, targeted silencing of Angptl4 offers a potential therapeutic strategy for the treatment of dyslipidemia in individuals with FH and insulin deficient diabetes.

• 出版日期2011-6-3