Differential regulation and properties of angiopoietin-like proteins 3 and 4

Angiopoietin-like protein 3 and 4 (Angpt13 and Angpt14) 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 Angpt13 and Angpt14. Previously, we reported that Angpt14 exists as variable-sized oligomers that contain intermolecular disulfide bonds. We now have evidence that although there are no intermolecular disulfide bonds evident in Angpt13, higher molecular weight forms do exist. In addition, Angpt14 exhibits a widespread distribution of tissue expression, while Angpt13 is exclusively expressed in the liver. Treatments with various ligands of nuclear receptors reveal that Angpt13 is a target gene of liver X receptor, while Angpt14 expression is activated by ligands of all peroxisome proliferator-activated receptors. Expression of Angpt14 in adipose tissue and liver is induced by fasting, while Angpt13 expression is not appreciably affected by nutritional status. We suggest that the differential regulation of Angpt13 and Angpt14 by sites of expression, nutritional status, and ligands of nuclear receptors may confer unique roles of each in lipoprotein metabolism. - Ge, H.,J.-Y. Cha, H. Gopal, C. Harp, X. Yu, J. J. Repa, and C. Li. Differential regulation and properties of angiopoietin-like proteins 3 and 4.