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.
|Number of pages||4|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 3 Jun 2011|
- Diabetes mellitus
- Familial hypercholesterolemia
- Lipoprotein lipase
- Postprandial hypertriglyceridemia