Abstract：
:We previously reported that liver-specific overexpression of ABCG5/G8 in mice is not atheroprotective, suggesting that increased biliary cholesterol secretion must be coupled with decreased intestinal cholesterol absorption to increase net sterol loss from the body and reduce atherosclerosis. To evaluate this hypothesis, we fed low density lipoprotein receptor-knockout (LDLr-KO) control and ABCG5/G8-transgenic (ABCG5/G8-Tg)xLDLr-KO mice, which overexpress ABCG5/G8 only in liver, a Western diet containing ezetimibe to reduce intestinal cholesterol absorption. On this dietary regimen, liver-specific ABCG5/G8 overexpression increased hepatobiliary cholesterol concentration and secretion rates (1.5-fold and 1.9-fold, respectively), resulting in 1.6-fold increased fecal cholesterol excretion, decreased hepatic cholesterol, and increased (4.4-fold) de novo hepatic cholesterol synthesis versus LDLr-KO mice. Plasma lipids decreased (total cholesterol, 32%; cholesteryl ester, 32%; free cholesterol, 30%), mostly as a result of reduced non-high density lipoprotein-cholesterol and apolipoprotein B (apoB; 36% and 25%, respectively). ApoB-containing lipoproteins were smaller and lipid-depleted in ABCG5/G8-TgxLDLr-KO mice. Kinetic studies revealed similar 125I-apoB intermediate density lipoprotein/LDL fractional catabolic rates, but apoB production rates were decreased 37% in ABCG5/G8-TgxLDLr-KO mice. Proximal aortic atherosclerosis decreased by 52% (male) and 59% (female) in ABCG5/G8-TgxLDLr-KO versus LDLr-KO mice fed the Western/ezetimibe diet. Thus, increased biliary secretion, resulting from hepatic ABCG5/G8 overexpression, reduces atherogenic risk in LDLr-KO mice fed a Western diet containing ezetimibe. These findings identify distinct roles for liver and intestinal ABCG5/G8 in modulating sterol metabolism and atherosclerosis.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Basso F,Freeman LA,Ko C,Joyce C,Amar MJ,Shamburek RD,Tansey T,Thomas F,Wu J,Paigen B,Remaley AT,Santamarina-Fojo S,Brewer HB Jrdoi
10.1194/jlr.M600353-JLR200subject
Has Abstractpub_date
2007-01-01 00:00:00pages
114-26issue
1eissn
0022-2275issn
1539-7262pii
M600353-JLR200journal_volume
48pub_type
杂志文章abstract：:The direct non-endocytotic uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) plays a major role in HDL CE metabolism in rats and rabbits. In vitro evidence indicates it may also play such a role in humans. However, a study in mice (tracing the CE and apoA-I moieties of HDL) concluded that, while se...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:In promoting oxidation of 0.02 m potassium linoleate in a buffered (pH 7.0) aqueous dispersion at 37 degrees C, ascorbic acid at low concentrations (1.8 x 10(-6) and 1.8 x 10(-5) m) in combination with copper (1.3 x 10(-7) to 1.3 x 10(-3) m) had greater catalytic activity than the additive activity of the two catalyst...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-09-01 00:00:00
abstract：:A reliable method for purifying envelope-stripped nuclei from immortalized murine embryonic fibroblasts (iMEFs) was established. Quantitative profiling of the glycerophospholipids (GPLs) in envelope-free iMEF nuclei yields several conclusions. First, we find the endonuclear glycerophospholipidome differs from that of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M068734
更新日期：2016-08-01 00:00:00
abstract：:It is becoming increasingly accepted that removal of cellular cholesterol occurs by at least two pathways, one involving the well-described aqueous diffusion mechanism and another promoted by lipid-free apolipoproteins. We compared the contribution of apolipoprotein-dependent and -independent pathways, taking into con...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:Studies on plasma triglycerides (TG) were performed in 10 nonobese and 16 obese patients with hypothyroidism and in 13 with hyperthyroidism. Nonobese, hypothyroid patients generally had normal levels of TG, but obese patients often had hypertriglyceridemia. In most hypothyroid patients 1-thyroxine treatment lowered pl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:The human apolipoprotein C-II locus exhibits genetically determined structural polymorphism in United States and African blacks. In the present study, we have investigated the effect of the apoC-II polymorphism on quantitative serum levels of total cholesterol, total high density lipoprotein (HDL) cholesterol, cholest...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:Lipid concentrations are heritable traits. Recently, the number of known genetic loci associated with lipid levels in adults increased from 95 to 157. The effects of these 157 loci have not been tested in children. Considering that lipid levels track from childhood to adulthood, we studied to determine whether these v...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P066902
更新日期：2016-12-01 00:00:00
abstract：:The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators. Administration of these promotes an increased transport of endogenous fatty acids to these organelles and a higher capacity of beta-oxidation. Administration of 3-thia fatty acids to rats ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by impaired degradation of very long-chain fatty acids (VLCFAs) due to mutations in the ABCD1 gene responsible for VLCFA transport into peroxisomes. Lorenzo's oil, a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, has been used to reduce...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044586
更新日期：2014-03-01 00:00:00
abstract：:Serum paraoxonase (PON1) is a HDL-associated enzyme exhibiting potentially antiatherogenic properties. Here, we examined the common PON1-192R/Q human polymorphism. Despite numerous studies, the effect of this polymorphism on the antiatherogenic potential of PON1 is yet unresolved. Our structural model suggests that am...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600297-JLR200
更新日期：2006-11-01 00:00:00
abstract：:3alpha-Hydroxy-5-cholanoic acid (lithocholic acid) and some unidentified acids (one of them perhaps 3-hydroxy-cholest-5-en-26-oic acid) have been detected in the brains of guinea pigs afflicted with experimental "allergic" encephalomyelitis. None of the acids could be identified in comparable amounts of brain tissue f...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-01-01 00:00:00
abstract：:Treatment of native human Lp(a) under nondenaturing conditions with dithiothreitol yielded both a lipoprotein particle and a lipid-free protein component that could be separated by either ultracentrifugation at d 1.063 g/ml or heparin-Sepharose chromatography. The protein component only showed antigenicity against ant...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:To study the mechanisms of hepatic HDL formation, we investigated the roles of ABCA1, ABCG1, and SR-BI in nascent HDL formation in primary hepatocytes isolated from mice deficient in ABCA1, ABCG1, or SR-BI and from wild-type (WT) mice. Under basal conditions, in WT hepatocytes, cholesterol efflux to exogenous apoA-I w...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M017079
更新日期：2012-03-01 00:00:00
abstract：:It has been suggested that phytosterol and phytostanol esters possess similar cholesterol-lowering properties, however, whether mechanisms responsible are identical has not been addressed. To address this question, cholesterol plasma levels, absorption, biosynthesis, and turnover were measured in 15 hypercholesterolem...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2000-05-01 00:00:00
abstract：:The diurnal cycle of hepatic HMG CoA reductase activity was studied under conditions of controlled feeding where the percentage of dietary lipid, alone or in combination with 2% cholestyramine, was varied. Cholestyramine caused an increase in HMG CoA reductase activity that began soon after feeding started and peaked ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-11-01 00:00:00
abstract：:Apolipoprotein (apo) B-100, the protein constituent of low density lipoproteins (LDL), is the determinant responsible for LDL binding to the apoB,E(LDL) receptor on cells. The current study was designed to identify the region(s) of apoB-100 that interact with the apoB,E(LDL) receptor. Apolipoprotein B-100 was fragment...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:A synthetic analog of glucocerebroside, N-hexyl-O-glucosyl sphingosine, was found to inhibit the glucosidase in rat spleen that hydrolyzes glucocerebroside. At a concentration of 1 micro m, the analog inhibited the enzyme by 48%. The mode of action appeared to be competitive, probably aided by tight binding of the ami...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-03-01 00:00:00
abstract：:Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M074997
更新日期：2017-05-01 00:00:00
abstract：:The phase behavior and temperature-dependent molecular motions of three cholesteryl ethers (caproyl, myristyl, oleyl) and a cholesteryl carbonate (oleyl) were characterized. The properties of each ether were qualitatively similar to, but quantitatively different from, those of the corresponding cholesteryl ester. For ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Of the six fatty acid elongase (Elovl) subtypes expressed in mammals, adult rat liver expresses four subtypes: Elovl-5 > Elovl-1 = Elovl-2 = Elovl-6. Overnight starvation and fish oil-enriched diets repressed hepatic elongase activity in livers of adult male rats. Diet-induced changes in elongase activity correlate wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400335-JLR200
更新日期：2005-04-01 00:00:00
abstract：:Previous studies from our laboratory have shown that oral administration of stigmastanyl-phosphocholine (Ro 16-6532) reduces plasma cholesterol levels in experimental animals on diets free of added cholesterol. In the present study, effects of Ro 16-6532 and lovastatin on lipoprotein levels and metabolism were investi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：:The amphipathic alpha helix is an often-encountered secondary structural motif in biologically active peptides and proteins. An amphipathic helix is defined as an alpha helix with opposing polar and nonpolar faces oriented along the long axis of the helix. In a recent review article we grouped amphipathic helixes into...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：:The K146N/R147W substitutions in apoE3 were described in patients with a dominant form of type III hyperlipoproteinemia. The effects of these mutations on the in vivo functions of apoE were studied by adenovirus-mediated gene transfer in different mouse models. Expression of the apoE3[K146N/R147W] mutant in apoE-defic...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M048348
更新日期：2014-07-01 00:00:00
abstract：:Rabbits were fed either 10% coconut oil, 10% coconut oil and 1% beta-sitosterol, 10% coconut oil and 1% cholesterol, or 10% coconut oil and 1% beta-sitosterol plus 1% cholesterol for 4 weeks. Microsomal membranes from intestines of animals fed the 1% beta-sitosterol diet had 48% less cholesterol and were enriched twof...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-04-01 00:00:00
abstract：:Biliary amphipathic anionic polypeptide (APF) the major protein of the pigment-lipoprotein complex in bile, and calcium-binding protein (CBP) from gallstones are both small (less than 10 kDa), highly acidic, amphipathic proteins present in bile and closely associated also with pigmented areas in human gallstones. Poly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:Lipid-containing deposits within the swim bladders of Coryphaenoides acrolepis and Antimora rostrata were investigated. Lipid analysis of this material, which was quite uniform from the two species, yielded the following data: neutral lipids, 36.0-41.7%; phospholipids, 53.6-56.7%; and glycolipids, 4.3-8.9%. Cholestero...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-05-01 00:00:00
abstract：:Alzheimer's disease (AD) is characterized by an extensive accumulation of amyloid-β (Aβ) peptide, which triggers a set of deleterious processes, including synaptic dysfunction, inflammation, and neuronal injury, leading to neuronal loss and cognitive impairment. A large body of evidence supports that nuclear receptor ...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R075556
更新日期：2017-10-01 00:00:00
abstract：:The mitochondrial lipids from avocado fruit, cauliflower buds, and potato tubers, and the lipids of chloroplasts isolated from avocado fruit and from cauliflower leaves were identified and the concentrations were determined. The lipid composition was compared with that of beef heart mitochondria. Phospholipids constit...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-03-01 00:00:00
abstract：:Measurements of enzymatic activity have demonstrated that lipoprotein lipase (LPL), the principal enzyme responsible for hydrolysis of circulating triglyceride, is present in a number of tissues including brain, kidney, and adrenal gland. To determine the sites of synthesis of LPL in these tissues, in situ hybridizati...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Lipogenesis in vitro from acetate-1-(14)C was studied in human preputial skin and abdominal skin. Radioactive lipids were separated by column chromatography on Florisil and by thin-layer chromatography on silica gel. Radioactivity was incorporated chiefly into the triglyceride, sterol, and polar lipid fractions, while...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-09-01 00:00:00
