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

Hongfei Ge, Ji Young Cha, Harini Gopal, Christopher Harp, Xinxin Yu, Joyce J. Repa, Cai Li

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1484-1490
Number of pages7
JournalJournal of lipid research
Volume46
Issue number7
DOIs
StatePublished - 2005

Keywords

  • Angptl3
  • Angptl4
  • Gel filtration
  • LPL
  • Liver X receptor
  • Nutritional status
  • Peroxisome proliferator-activated receptor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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