title: Angptl4 deficiency decreases serum triglyceride levels in low-density lipoprotein receptor knockout mice and streptozotocin-induced diabetic mice.
abstract: 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.
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Adachi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
mesh_terms: D042682:Angiopoietins / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005215:Fasting / Q000097:blood; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics; D014280:Triglycerides / Q000097:blood*
chemical_list: D042682:Angiopoietins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides; C118117:angiopoietin 4; D002784:Cholesterol