Abstract:
:The differentiation of macrophages into lipid-filled foam cells is a hallmark of the lung granuloma that forms in patients with active tuberculosis (TB). Mycolic acids (MAs), the abundant lipid virulence factors in the cell wall of Mycobacterium tuberculosis (Mtb), can induce this foam phenotype possibly as a way to perturb host cell lipid homeostasis to support the infection. It is not exactly clear how MAs allow differentiation of foam cells during Mtb infection. Here we investigated how chemically synthetic MAs, each with a defined stereochemistry similar to natural Mtb-associated mycolates, influence cell foamy phenotype and mycobacterial proliferation in murine host macrophages. Using light and laser-scanning-confocal microscopy, we assessed the influence of MA structure first on the induction of granuloma cell types, second on intracellular cholesterol accumulation, and finally on mycobacterial growth. While methoxy-MAs (mMAs) effected multi-vacuolar giant cell formation, keto-MAs (kMAs) induced abundant intracellular lipid droplets that were packed with esterified cholesterol. Macrophages from mice treated with kMA were permissive to mycobacterial growth, whereas cells from mMA treatment were not. This suggests a separate yet key involvement of oxygenated MAs in manipulating host cell lipid homeostasis to establish the state of TB.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Vermeulen I,Baird M,Al-Dulayymi J,Smet M,Verschoor J,Grooten Jdoi
10.1194/jlr.M073171subject
Has Abstractpub_date
2017-04-01 00:00:00pages
709-718issue
4eissn
0022-2275issn
1539-7262pii
jlr.M073171journal_volume
58pub_type
杂志文章abstract::We describe new methods for analyzing the apolipoproteins (apo) of the high density lipoproteins (HDL) of several species by two modes of capillary electrophoresis: size separation using a molecular sieving buffer, and capillary zone electrophoresis (CZE) using neutral coated capillaries. By either mode HDL apos were ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::In addition to its role in the uptake of apolipoprotein B (apoB)-containing lipoproteins, apoE promotes hepatic very low density lipoprotein-triglyceride (VLDL-TG) production in animal models. However, it is not known if apoE increases the amount of TG per VLDL particle or the number of VLDL particles secreted. VLDL-a...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract::The regulation of hepatic and intestinal 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and acyl-CoA; cholesterol acyltransferase (ACAT) activities by dietary fish oil was examined in the rabbit. Rabbits were fed 10% menhaden oil or menhaden oil plus 1% cholesterol for 14 days. They were compared with animals fed ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Lipoprotein lipase has been found to efficiently mediate binding of lipoproteins to cell surfaces and to the low density lipoprotein (LDL) receptor-related protein (LRP) under cell culture conditions (Beisiegel et al. 1991. Proc. Natl. Acad. Sci. USA. 88: 8242-8346). This supports the previously proposed idea that the...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Previously, we identified the low density lipoprotein receptor (LDLR) promoter region -17 to -1 as a novel sterol-independent regulatory element (SIRE) that mediates the stimulating effect of oncostatin M (OM). The goal of this study was to identify the OM-induced transcription activator that binds to the SIRE sequenc...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.m200126-jlr200
更新日期:2002-09-01 00:00:00
abstract::Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are the two most common familial dyslipidemias predisposing to premature coronary heart disease (CHD). These dyslipidemias share many phenotypic features, suggesting a partially overlapping molecular pathogenesis. This was supported by our p...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M400141-JLR200
更新日期:2004-10-01 00:00:00
abstract::Endothelial lipase (EL) is a triglyceride lipase gene family member that has high phospholipase and low triglyceride lipase activity. The aim of this study was to determine whether the phospholipase activity of EL is sufficient to remodel HDLs into small particles and mediate the dissociation of apolipoprotein A-I (ap...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M400212-JLR200
更新日期:2005-05-01 00:00:00
abstract::The ATP binding cassette (ABC) half-transporters ABCG5 and ABCG8 facilitate biliary and intestinal removal of neutral sterols. Here, we identify a binding site for the orphan nuclear receptor liver receptor homolog-1 (LRH-1) at nt 134-142 of the ABCG5/ABCG8 intergenic region necessary for the activity of both the ABCG...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.C400002-JLR200
更新日期:2004-07-01 00:00:00
abstract::A method has been developed for rapidly quantitating the cholesterol concentration of normal and certain variant lipoproteins in a large number of patients (over 240 in one week). The method employs a microcomputer interfaced to the vertical autoprofiler (VAP) described earlier (Chung et al. 1981. J. Lipid Res. 22: 10...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract::Conjugated linoleic acid (CLA), a mixture of isomers of linoleic acid, has previously been shown to be able to decrease porcine subcutaneous (SC) adipose tissue levels while increasing the count of intramuscular (IM) adipose tissue in vivo. However, the underlying mechanisms through which it acts are poorly understood...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M600525-JLR200
更新日期:2007-08-01 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 initial studies of the metabolism of arachidonic acid (AA) by the cytochrome P450 (P450) hemeproteins sought to: a) elucidate the roles for these enzymes in the metabolism of endogenous pools of the FA, b) identify the P450 isoforms involved in AA epoxidation and ω/ω-1 hydroxylation, and c) explore the biological ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.R087882
更新日期:2018-11-01 00:00:00
abstract::Lipoprotein electrophoresis on agarose gel has been modified to allow estimation of the absolute quantity of each fraction. The reproducibility of the method is illustrated by 12 determinations in a single day on serum from one normal subject: mean total dye uptake was 302 +/- 9 (sd "corrected dye units," and the perc...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-07-01 00:00:00
abstract::Studies on the effects of longitudinal lipid trajectories on end-stage renal disease (ESRD) development and deaths among patients with chronic kidney disease (CKD) are limited. We conducted a registry-based prospective study using data from a 13-year multidisciplinary pre-ESRD care program. The final study population ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.P084590
更新日期:2019-03-01 00:00:00
abstract::The extent and site(s) of inhibition of cholesterol absorption by plant sterols, sitosterol and fucosterol, were studied in rats. The intragastric administration of a single emulsified lipid meal containing 25 mg [3H]cholesterol and 25 mg of either sitosterol or fucosterol inhibited the lymphatic absorption of cholest...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::Hepatocytes and hepatic stellate cells play important roles in retinoid storage and metabolism. Hepatocytes process postprandial retinyl esters and are responsible for secretion of retinol bound to retinol-binding protein (RBP) to maintain plasma retinol levels. Stellate cells are the body's major cellular storage sit...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::We analysed the sensitivity to beta-adrenoceptor agonists in epididymal adipose cells from rats submitted to a stress protocol previously reported to induce alterations in sensitivity to catecholamines in cardiac tissue from rats. Food intake and body weight were lower, whereas adipocytes basal lipolysis was higher (c...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::A multiplexed assay was developed by MS to analyze, in a single run, six major human Apos involved in lipoprotein metabolism: ApoA-I, ApoA-II, ApoB100, ApoC-II, ApoC-III, and ApoE. This method was validated in vivo in six subjects who received a 14 h constant infusion of [5,5,5-(2)H3]L-leucine at 10 μM/kg/h. Plasma li...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.D064618
更新日期:2016-03-01 00:00:00
abstract::We determined the effect of storage at -70 degrees C on the determination of plasma high density lipoprotein (HDL)-cholesterol. Plasma from 106 subjects was stored for 1, 6, and 12 months, then treated with heparin and MnCl2 to remove other lipoproteins, and HDL-cholesterol was measured. The mean HDL-cholesterol level...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::14C-labeled oleic acid and (3)H-labeled monoether in a bile salt solution were perfused through three types of plastic tubing. Large proportions of lipid were lost to the walls of silicone rubber and polyvinyl chloride tubes. The major portion of the lipid lost was recoverable only when chloroform-methanol was perfuse...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-09-01 00:00:00
abstract::HDL subspecies Lp(A-I) and Lp(A-I,A-II) have different anti-atherogenic potentials. To determine the role of lipoprotein lipase (LPL) and hepatic lipase (HL) in regulating these particles, we measured these enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and studied their relationship wi...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M300091-JLR200
更新日期:2003-08-01 00:00:00
abstract::The novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor CP-113,818 has been characterized in vitro against ACAT isolated from liver and intestine from a variety of species including human subjects, and in vivo in cholesterol-fed rats, hamsters, rabbits, and two species of nonhuman primates. CP-113,818 is a pot...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Tetradecylthioacetic acid (TTA), which cannot be beta-oxidized, exerts growth-limiting properties in glioma cells. In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatt...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.m200312-jlr200
更新日期:2003-01-01 00:00:00
abstract::A novel metabolite of d-delta-tocopherol was isolated from the urine of rats given d-3,4-[3H2]-delta-tocopherol intravenously. The metabolite was collected from the urine of rats given d-delta-tocopherol in the same manner as that of the labeled compound. It was found that the metabolites consisted of sulfate conjugat...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::ABCA1 plays a key role in the initial lipidation of apoA-I, which generates circulating HDL cholesterol. Whereas it is known that the transcriptional upregulation of ABCA1 promotes HDL formation and reverse cholesterol transport (RCT), it is not known how the inhibition of ABCA1 protein degradation impacts HDL functio...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M054742
更新日期:2015-05-01 00:00:00
abstract::The genetic variability of apolipoprotein E (apoE) influences plasma lipoprotein levels, and allele frequencies differ between African Americans and Caucasians. As African Americans have higher lipoprotein [a] (Lp[a]) levels than Caucasians, we investigated the effects of the apoE gene on allele-specific apolipoprotei...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M600431-JLR200
更新日期:2007-03-01 00:00:00
abstract::Analyses have been made of glycosphingolipids from visceral organs and brain of a patient with an unusual lipid storage disorder diagnosed initially as classical Tay-Sachs disease. Levels of the lipids from fresh-frozen sections of gray and white matter, kidney, spleen, liver, and heart from this patient were compared...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1972-01-01 00:00:00
abstract::Using solid phase systems, the kinetics of binding of monoclonal antibody (LRB 45, IgG2b,kappa) to apoC-I and apoC-I on lipoproteins were investigated. At 25 degrees C, the association constant of LRB 45 antibody to apoC-I (3.56 X 10(6) M-1 X sec-1) was almost three times slower than the association constant LRB 45 an...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract::This work describes the molecular mechanisms of fatty acid and hormonal modulations of the retinoid X receptor alpha (RXRalpha) in rat liver cells. We examined the effects of different fatty acids (myristic, stearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and several hormon...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::The recognition that the 7 alpha-hydroxylation of 27-hydroxycholesterol is catalyzed by an enzyme that is different from cholesterol 7 alpha-hydroxylase raises the question as to the number of similar enzymes that may be present in liver and subserve bile acid synthesis. Thus, both 3 beta-hydroxy-5-cholestenoic acid a...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00