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

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• 作者：Hironori Adachi^a ; Tatsuya Kondo^a ; Gou Young Koh^c ; Andras Nagy^d ; Yuichi Oike^b ; Eiichi Araki^a ; ^{earaki@gpo.kumamoto-u.ac.jp"" rel=""nofollow}
• 关键词：Diabetes mellitus ; Familial hypercholesterolemia ; Lipoprotein lipase ; Postprandial hypertriglyceridemia ; Angptl4
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：3 June 2011
• 年：2011
• 卷：409
• 期：2
• 页码：177-180
• 全文大小：261 K

文摘

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.