title: Differential regulation and properties of angiopoietin-like proteins 3 and 4.
abstract: Angiopoietin-like protein 3 and 4 (Angptl3 and Angptl4) are two members of the angiopoietin-like family of proteins. These two closely related proteins have been reported to similarly affect lipid metabolism through their capacity to inhibit lipoprotein lipase. We undertook a series of studies to compare the structure, function, and regulation of Angptl3 and Angptl4. Previously, we reported that Angptl4 exists as variable-sized oligomers that contain intermolecular disulfide bonds. We now have evidence that although there are no intermolecular disulfide bonds evident in Angptl3, higher molecular weight forms do exist. In addition, Angptl4 exhibits a widespread distribution of tissue expression, while Angptl3 is exclusively expressed in the liver. Treatments with various ligands of nuclear receptors reveal that Angptl3 is a target gene of liver X receptor, while Angptl4 expression is activated by ligands of all peroxisome proliferator-activated receptors. Expression of Angptl4 in adipose tissue and liver is induced by fasting, while Angptl3 expression is not appreciably affected by nutritional status. We suggest that the differential regulation of Angptl3 and Angptl4 by sites of expression, nutritional status, and ligands of nuclear receptors may confer unique roles of each in lipoprotein metabolism.
authors.affiliation: Touchstone Center for Diabetes Research, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8854, USA.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Ge
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Cha
authors.forename: Harini
authors.initials: H
authors.lastname: Gopal
authors.forename: Christopher
authors.initials: C
authors.lastname: Harp
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yu
authors.forename: Joyce J
authors.initials: JJ
authors.lastname: Repa
authors.forename: Cai
authors.initials: C
authors.lastname: Li
mesh_terms: D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis / Q000502:physiology*; D011345:Fenofibrate / Q000494:pharmacology; D005508:Food Deprivation; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D047493:PPAR alpha / Q000819:agonists; D047494:PPAR delta / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D020836:Protein Structure, Quaternary; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D001798:Blood Proteins; D011345:Fenofibrate; D036341:Intercellular Signaling Peptides and Proteins; D008071:Lipoprotein Lipase; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D000077205:Pioglitazone; D013844:Thiazoles; D045162:Thiazolidinediones; C404495:Angptl3 protein, mouse; C407088:Angptl4 protein, mouse; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds