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 - Funding Information:
This work was supported by National Institutes of Health Grants HL135737, HL136275, HL088093 (Y.I.M.), HL114734, and HL132155 (L.F.); American Heart Association Grants 15BGIA25550111 (P.L.S.M.G.) and SDG14710028 (S.-H.C.); and Foundation Leducq Grant 16CVD01 (P.L.S.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing financial interests. Manuscript received 18 January 2018 and in revised form 20 March 2018. Published, JLR Papers in Press, March 20, 2018 DOI https://doi.org/10.1194/jlr.M083618
Funding Information:
This work was supported by National Institutes of Health Grants HL135737, HL136275, HL088093 (Y.I.M.), HL114734, and HL132155 (L.F.); American Heart Association Grants 15BGIA25550111 (P.L.S.M.G.) and SDG14710028 (S.-H.C.); and Foundation Leducq Grant 16CVD01 (P.L.S.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing financial interests.
Publisher Copyright:
Copyright © 2018 Schneider et al. Published under exclusive license by The American
PY - 2018
Y1 - 2018
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
VL - 59
SP - 854
EP - 863
JO - Journal of lipid research
JF - Journal of lipid research
SN - 0022-2275
IS - 5
ER -