Abstract：
:Previous studies have shown that reduced levels of the adipocyte fatty acid binding protein (FABP)4 (AFABP/aP2), result in metabolic improvement including potentiated insulin sensitivity and attenuated atherosclerosis. Mechanistically, pharmacologic or genetic inhibition of FABP4 in macrophages upregulates UCP2, attenuates reactive oxygen species (ROS) production, polarizes cells toward the anti-inflammatory M2 state, and reduces leukotriene (LT) secretion. At the protein level, FABP4 stabilizes LTA4 toward chemical hydrolysis, thereby potentiating inflammatory LTC4 synthesis. Herein, we extend the FABP4-LT axis and demonstrate that genetic knockout of FABP4 reduces expression of the major macrophage LT receptor, LTB4 receptor 1 (BLT1R), via a ROS-dependent mechanism. Consistent with inflammation driving BLT1R expression, M1 polarized macrophages express increased levels of BLT1R relative to M2 polarized macrophages and treatment with proinflammatory lipopolysaccharide increased BLT1R mRNA and protein expression. In FABP4 knockout macrophages, silencing of UCP2, increased ROS levels and led to increased expression of BLT1R mRNA. Similarly, addition of exogenous H2O2 upregulated BLT1R expression, whereas the addition of a ROS scavenger, N-acetyl cysteine, decreased BLT1R levels. As compared with WT macrophages, LTB4-BLT1R-dependent JAK2-phosphorylation was reduced in FABP4 knockout macrophages. In summary, these results indicate that FABP4 regulates the expression of BLT1R and its downstream signaling via control of oxidative stress in macrophages.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Hertzel AV,Xu H,Downey M,Kvalheim N,Bernlohr DAdoi
10.1194/jlr.M074542subject
Has Abstractpub_date
2017-07-01 00:00:00pages
1354-1361issue
7eissn
0022-2275issn
1539-7262pii
jlr.M074542journal_volume
58pub_type
杂志文章abstract：:HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmac...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M073270
更新日期：2017-08-01 00:00:00
abstract：:Groups of gerbils were fed purified diets containing either 10 or 20% of safflower, olive, or coconut oil. Each diet was fed without cholesterol and with 0.1 and 0.2% of added cholesterol. The animals were bled after 2, 4, and 8 wk for the determination of the level of serum cholesterol. The major factors affecting th...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-05-01 00:00:00
abstract：:The intestinal bacterium Eubacterium sp. strain VPI 12708 has been shown to have a bile acid 7 alpha/7 beta-dehydroxylation pathway. A large bile acid inducible (bai) operon encoding at least 9 open reading frames has been cloned and sequenced from this bacterium. The baiE gene from this operon has been subcloned and ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:N-3 trans geometrical isomers of 20:5 n-3 and 22:6 n-3 were isolated from rats fed heated linseed oil. The ability of these acids to inhibit 20:4 n-6 metabolism by human platelets was examined. The concentrations required to inhibit 50% of platelet aggregation (IC50) induced by 2.5 microM 20:4 n-6 were higher for the ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Hyperlipoproteinemia contributes both to kidney disease progression and the development of atherosclerosis. Elevated high density lipoprotein cholesterol and apolipoprotein A-I (apoA-I) serum levels are independent factors protective against the atherosclerotic process. We examined the effects in a transgenic rat mode...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：:In isolated fat cells, the same maximal rate of glycerol production can be induced by epinephrine or ACTH, alone or in combination with each other or with glucagon. With fat cells from rats weighing 150-175 g, the maximal rate of lipolysis attained with glucagon was 75-80% of that produced by epinephrine or ACTH, and ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-01-01 00:00:00
abstract：:Group IVA cytosolic phospholipase A(2)alpha (cPLA(2)alpha) plays a role in the microbicidal machinery of immune cells by translocating to phagosomes to initiate the production of antimicrobial eicosanoids. In this work, we have studied the involvement of the cationic cluster of cPLA(2)alpha (Lys(488)/Lys(541)/Lys(543)...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M001461
更新日期：2010-02-01 00:00:00
abstract：:Studies were carried out to determine whether apolipoprotein (apo) A-II, like apoA-I, can recruit phospholipid and cholesterol from cell membranes, thereby forming nascent apoA-II-specific HDL. ApoA-II and apoA-I were purified from plasma and each was incubated with CHO cells at a concentration of 10 micrograms/ml. Li...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated metabolic dysregulation. This concept is fundamental to our understanding of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here,...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R700005-JLR200
更新日期：2007-06-01 00:00:00
abstract：:Inositol lipid kinases have been studied extensively in both plant and animal systems. However, major limitations for in vitro studies of recombinant lipid kinases are the low specific activity and instability of the purified proteins. Our goal was to determine if cyclodextrins would provide an effective substrate del...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D400005-JLR200
更新日期：2004-09-01 00:00:00
abstract：:When NH(4)OH-NH(4)Cl extracts of adipose acetone powder were applied to agarose gel chromatography columns, two peaks of lipoprotein lipase were eluted. The first activity peak (LPL(a)) was eluted with an elution volume of a protein of molecular weight approximately five times that of the second (LPL(b)). Addition of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-01-01 00:00:00
abstract：:The methanolyzed lipids of the extreme halophile, Halobacterium cutirubrum, were separated into glycerol diether and glycerol monoether fractions. The diether was shown by synthesis to be 2,3-di-O-(3'R,7'R,11'R,15'-tetramethylhexadecyl)-sn-glycerol. The monoether fraction was separated by thin-layer chromatography on ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-11-01 00:00:00
abstract：:The acylation of glycerol-3-phosphate by acyl-CoA is regarded as the first committed step for the synthesis of the lipoidal moiety in glycerolipids. The direct acylation of glycerol in mammalian tissues has not been demonstrated. In this study, lipid biosynthesis in myoblasts and hepatocytes was reassessed by conducti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-12-01 00:00:00
abstract：:Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder populati...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M008359
更新日期：2010-09-01 00:00:00
abstract：:Steroid balance studies were conducted on 24 conventional and 12 germfree male rats, 90-120 days old, fed diets containing either 20% safflower or 20% coconut oil. Both germfree and conventional rats fed the safflower oil diets had significantly lower serum cholesterol levels and significantly higher liver cholesterol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-11-01 00:00:00
abstract：:Macrophage infiltration of white adipose tissue (WAT) is implicated in the metabolic complications of obesity. The precipitating event(s) and function(s) of macrophage infiltration into WAT are unknown. We demonstrate that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500294-JLR200
更新日期：2005-11-01 00:00:00
abstract：:Human high density lipoprotein enriched in free cholesterol was obtained by exposing the lipoprotein to lipid dispersions having a free cholesterol/lecithin molar ratio greater than two. The metabolism of cholesterol was studied in tissue culture cells exposed to normal and cholesterol-enriched lipoproteins. Incubatio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-03-01 00:00:00
abstract：:The antitumor effect of daily individual administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2 g/kg body weight) in Balb/c mice bearing a transplantable thymoma was investigated. Mice received oleic acid (control group), EPA and DHA ethyl esters starting 10 days before tumor inoculation. Anal...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:ABCA1 exports cholesterol and phospholipids from cells by a multistep pathway that involves forming cell surface lipid domains, solubilizing these lipids by apolipoproteins, binding of apolipoproteins to ABCA1, and activating signaling processes. Here we used a mutational analysis approach to evaluate the relationship...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800366-JLR200
更新日期：2009-02-01 00:00:00
abstract：:3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis, exists in one active (dephosphorylated) and one inactive (phosphorylated) form in liver microsomes obtained from several animal species. The present study was undertaken in order to dete...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholest...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M053439
更新日期：2015-01-01 00:00:00
abstract：:A preparation of cerebral microvessels was used to demonstrate the presence of lipoprotein lipase and acid lipase activity in the microvasculature of rabbit brain. Microvessels, consisting predominantly of capillaries, small arterioles, and venules, were islated from rabbit brain. Homogenates were assayed for lipolyti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-05-01 00:00:00
abstract：:We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simpl...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:Recent discovery and characterization of APOAV suggests a role in metabolism of triglyceride (TG)-rich lipoproteins. Previously, variation at the APOAV locus was shown to modestly influence plasma TGs in normolipidemic samples. The aims of this study were to assess the effects of a polymorphism in APOAV (T-1131C) in t...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200480-JLR200
更新日期：2003-06-01 00:00:00
abstract：:Ceramides (Cers) with ultralong (∼32-carbon) chains and ω-esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ∼10 mol%; diminished concentrations, along with altered or miss...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000420
更新日期：2020-02-01 00:00:00
abstract：:Bovine aortic endothelial cells take up 12-hydroxyeicosatetraenoic acid (12-HETE), a lipoxygenase product formed from arachidonic acid. The uptake of [3H]12-HETE reached a maximum in 2 to 4 h. At this time, from 75 to 80% of the incorporated radioactivity was contained in phospholipids, about 85% of the esterified rad...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:The transcriptional regulation of the rat cholesterol 7 alpha-hydroxylase gene (CYP7) by hormones and signal transduction pathways was studied by transient transfection assay of the promoter activity. HepG2 cells were transfected with deletion mutants of the CYP7 upstream region linked to the luciferase reporter gene....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Elevated serum levels of triglyceride-rich remnant lipoproteins (TRL) are a major risk factor predisposing a subject to atherosclerosis. Apolipoprotein C-III (apoC-III) is a major constituent of TRL that impedes triglyceride hydrolysis and remnant clearance and, as such, may exert pro-atherogenic activities. In the pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200386-jlr200
更新日期：2002-12-01 00:00:00
abstract：:Biosynthetic pathways of phosphatidylcholine and triglyceride were studied in proliferating hepatic endoplasmic reticulum of rats pretreated with phenobarbital. Phosphatidylcholine accounted for the major increment in membrane phospholipid. In vitro measurements of hepatic microsomal enzymes which catalyze phosphatidy...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-01-01 00:00:00
abstract：:Four hours after intraportal injection of retinoic acid-(14)C into bile duct-cannulated rats, less than 10% of the radioactivity was recovered in the liver, intestine, and kidneys. Within 6 hr, 40% of the radioactivity had appeared in bile. When suspensions of retinol-(14)C or retinal were similarly injected, 25-35% o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-01-01 00:00:00
