TY - JOUR
T1 - AIBP protects against metabolic abnormalities and atherosclerosis
AU - Schneider, Dina A.
AU - Choi, S. H.
AU - Agatisa-Boyle, C.
AU - Zhu, Laurence
AU - Kim, Jungsu
AU - Pattison, Jennifer
AU - Sears, Dorothy D.
AU - Gordts, Philip L.S.M.
AU - Fang, Longhou
AU - Miller, Yury I.
N1 - Publisher Copyright:
Copyright © 2018 Schneider et al. Published under exclusive license by The American
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Hepatosteatosis
KW - Hypercholesterolemia
KW - Hypertriglyceridemia
KW - Lipid rafts
UR - http://www.scopus.com/inward/record.url?scp=85046580350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046580350&partnerID=8YFLogxK
U2 - 10.1194/jlr.M083618
DO - 10.1194/jlr.M083618
M3 - Article
C2 - 29559522
AN - SCOPUS:85046580350
SN - 0022-2275
VL - 59
SP - 854
EP - 863
JO - Journal of lipid research
JF - Journal of lipid research
IS - 5
ER -