AIBP protects against metabolic abnormalities and atherosclerosis

Dina A. Schneider, S. H. Choi, C. Agatisa-Boyle, Laurence Zhu, Jungsu Kim, Jennifer Pattison, Dorothy D. Sears, Philip L.S.M. Gordts, Longhou Fang, Yury I. Miller

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Apolipoprotein A-I binding protein (AIBP) has been shown to augment cholesterol efflux from endothelial cells and macrophages. In zebrafish and mice, AIBP-mediated regulation of cholesterol levels in the plasma membrane of endothelial cells controls angiogenesis. The goal of this work was to evaluate metabolic changes and atherosclerosis in AIBP loss-of-function and gain-of-function animal studies. Here, we show that Apoa1bp/Ldlr/ mice fed a high-cholesterol, high-fat diet had exacerbated weight gain, liver steatosis, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, and larger atherosclerotic lesions compared with Ldlr/ mice. Feeding Apoa1bp/Ldlr/ mice a high-cholesterol, normal-fat diet did not result in significant differences in lipid levels or size of atherosclerotic lesions from Ldlr/ mice. Conversely, adeno-associated virus-mediated overexpression of AIBP reduced hyperlipidemia and atherosclerosis in high-cholesterol, high-fat diet-fed Ldlr/ mice. Injections of recombinant AIBP reduced aortic inflammation in Ldlr/ mice fed a short high-cholesterol, high-fat diet. Conditional overexpression of AIBP in zebrafish also reduced diet-induced vascular lipid accumulation. In experiments with isolated macrophages, AIBP facilitated cholesterol efflux to HDL, reduced lipid rafts content, and inhibited inflammatory responses to lipopolysaccharide.jlr Our data demonstrate that AIBP confers protection against diet-induced metabolic abnormalities and atherosclerosis.

Original languageEnglish (US)
Pages (from-to)854-863
Number of pages10
JournalJournal of Lipid Research
Volume59
Issue number5
DOIs
StatePublished - 2018

Keywords

  • Hepatosteatosis
  • Hypercholesterolemia
  • Hypertriglyceridemia
  • Lipid rafts

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Schneider, D. A., Choi, S. H., Agatisa-Boyle, C., Zhu, L., Kim, J., Pattison, J., Sears, D. D., Gordts, P. L. S. M., Fang, L., & Miller, Y. I. (2018). AIBP protects against metabolic abnormalities and atherosclerosis. Journal of Lipid Research, 59(5), 854-863. https://doi.org/10.1194/jlr.M083618