Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol
- 1 April 2013
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Lipidology
- Vol. 24 (2), 153-159
- https://doi.org/10.1097/mol.0b013e32835c8c1a
Abstract
Purpose of review Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Recent findings Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion. ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. Summary ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (∼150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein1's other ligand, lipoprotein lipase.Keywords
This publication has 49 references indexed in Scilit:
- Polymorphisms in the APOA1/C3/A4/A5 gene cluster and cholesterol responsiveness to dietary changecclm, 2007
- The Novel Apolipoprotein A5 Is Present in Human Serum, Is Associated with VLDL, HDL, and Chylomicrons, and Circulates at Very Low Concentrations Compared with Other ApolipoproteinsClinical Chemistry, 2005
- Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart StudyJournal of Lipid Research, 2004
- Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11Genomics, 2004
- Structure and Interfacial Properties of Human Apolipoprotein A-VPublished by Elsevier BV ,2003
- A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemiaHuman Molecular Genetics, 2003
- Expression Cloning and Characterization of a Novel Glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding Protein, GPI-HBP1Journal of Biological Chemistry, 2003
- Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.Human Molecular Genetics, 2002
- An Apolipoprotein Influencing Triglycerides in Humans and Mice Revealed by Comparative SequencingScience, 2001
- Biosynthesis and secretion of triacylglycerol in rat liver after partial hepatectomyBiochemical Journal, 1991