Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol.

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.

• Authors: Vineeta Sharma, Trudy M Forte, Robert O Ryan
• Journal: Current opinion in lipidology (Curr Opin Lipidol) Vol. 24 Issue 2 Pg. 153-9 (Apr 2013) ISSN: 1473-6535 [Electronic] England
• PMID: 23241513 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Apoa5 protein, mouse
• Apolipoprotein A-V
• Apolipoproteins
• GPI-HBP1 protein, mouse
• Receptors, Lipoprotein
• Triglycerides

Topics

• Animals
• Apolipoprotein A-V
• Apolipoproteins (genetics, metabolism)
• Cell Line, Tumor
• Cytosol (metabolism)
• Endoplasmic Reticulum (metabolism)
• Humans
• Intracellular Membranes (metabolism)
• Liver (metabolism, pathology)
• Mice
• Polymorphism, Genetic
• Protein Interaction Mapping
• Receptors, Lipoprotein (genetics, metabolism)
• Structure-Activity Relationship
• Triglycerides (genetics, metabolism)