Abstract：
:The bioactive sphingolipid metabolite, ceramide, regulates physiological processes important for inflammation and elevated levels of ceramide have been implicated in IL-1-mediated events. Although much has been learned about ceramide generation by activation of sphingomyelinases in response to IL-1, the contribution of the de novo pathway is not completely understood. Because yeast ORM1 and ORM2 proteins negatively regulate ceramide levels through inhibition of serine palmitoyltransferase, the first committed step in ceramide biosynthesis, we examined the functions of individual mammalian ORM orthologs, ORM (yeast)-like (ORMDL)1-3, in regulation of ceramide levels. In HepG2 liver cells, downregulation of ORMDL3 markedly increased the ceramide precursors, dihydrosphingosine and dihydroceramide, primarily from de novo biosynthesis based on [U-(13)C]palmitate incorporation into base-labeled and dual-labeled dihydroceramides, whereas downregulation of each isoform increased dihydroceramides [(13)C]labeled in only the amide-linked fatty acid. IL-1 and the IL-6 family cytokine, oncostatin M, increased dihydroceramide and ceramide levels in HepG2 cells and concomitantly decreased ORMDL proteins. Moreover, during irritant-induced sterile inflammation in mice leading to induction of the acute-phase response, which is dependent on IL-1, expression of ORMDL proteins in the liver was strongly downregulated and accompanied by increased ceramide levels in the liver and accumulation in the blood. Together, our results suggest that ORMDLs may be involved in regulation of ceramides during IL-1-mediated sterile inflammation.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Cai L,Oyeniran C,Biswas DD,Allegood J,Milstien S,Kordula T,Maceyka M,Spiegel Sdoi
10.1194/jlr.M065920subject
Has Abstractpub_date
2016-08-01 00:00:00pages
1412-22issue
8eissn
0022-2275issn
1539-7262pii
jlr.M065920journal_volume
57pub_type
杂志文章abstract：:In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate specie...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M019927
更新日期：2012-01-01 00:00:00
abstract：:Circulating triacylglycerol (TG) arises mainly from dietary fat. However, little is known about the entry of dietary fat into the major TG pool, very low-density lipoprotein (VLDL) TG. We used a novel method to study the specific incorporation of dietary fatty acids into postprandial VLDL TG in humans. Eight healthy v...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.M300167-JLR200
更新日期：2003-11-01 00:00:00
abstract：:Retinoic acid (RA), the active metabolite of vitamin A, is required for spermatogenesis and many other biological processes. RA formation requires irreversible oxidation of retinal to RA by aldehyde dehydrogenase enzymes of the 1A family (ALDH1A). While ALDH1A1, ALDH1A2, and ALDH1A3 all form RA, the expression pattern...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054718
更新日期：2015-02-01 00:00:00
abstract：:An in vitro assay to study lipolysis of very low density lipoproteins (VLDL) by heparan sulfate proteoglycan (HSPG-bound lipoprotein lipase (LPL) was developed. Optimal conditions for VLDL lipolysis by HSPG-bound LPL were obtained by incubating plastic wells with 0.5 microg HSPG and 1.5 microg LPL, subsequently. Contr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:(13)C-Cholesterol was produced with high efficiency by a genetically engineered yeast strain. The method produces ∼ 1 mg of cholesterol per gram of glucose using 100 ml of culture medium. Uniform 94% enrichment where the most abundant product is the fully enriched isotopomer (u-(13)C(27)) is obtained using (u-(13)C(6)...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D014209
更新日期：2011-05-01 00:00:00
abstract：:We report a new genetic defect in the lecithin:cholesterol acyltransferase (LCAT) gene associated with classical clinical and biochemical features of fish eye disease. The 63-year-old Australian female proband also suffers from non-insulin-dependent (type II) diabetes mellitus. She presented with corneal opacities, ma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Cerebrotendinous xanthomatosis (CTX) is a rare, recessively inherited lipid storage disease characterized by a markedly reduced production of chenodeoxycholic acid and an increased formation of 25-hydroxylated bile alcohols and cholestanol. Patients with this disease are known to have mutations in the sterol 27-hydrox...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL's ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000767
更新日期：2020-11-03 00:00:00
abstract：:Prostaglandin (PG)E(2) is relevant in tumor biology, and interactions between tumor and stroma cells dramatically influence tumor progression. We tested the hypothesis that cross-talk between head and neck squamous cell carcinoma (HNSCC) cells and fibroblasts could substantially enhance PGE(2) biosynthesis. We observe...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M019695
更新日期：2012-04-01 00:00:00
abstract：:We have previously observed that the Ya subunit-containing glutathione (GSH) S-transferases from rat liver exhibit a common high affinity binding site for lithocholic acid, bilirubin, and sulfobromophthalein (BSP) (1984. J. Lipid Res. 25: 1177-1183). Subsequently we found that cholic acid and its amidates bound to a s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:This study describes a variant of familial apoA-I deficiency associated with a moderate risk for premature coronary artery disease. The proband, a 25-year-old man of Philippine origin, and his 62-year-old maternal aunt had peripheral corneal opacification, xanthelasma, and planar xanthoma; the aunt had coronary artery...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:A study was conducted to determine the levels of cellular retinol-binding protein (CRBP) mRNA and protein in various tissues of the rat, to explore relationship between CRBP mRNA and protein levels in different tissues, and to examine the effects of changes in retinol nutritional status on the tissue distribution and ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:Mouse plasma from strains C57BL/6J and C3H/HeJ includes a high density lipoprotein (HDL) fraction containing apolipoprotein A-I which migrates in the prebeta region upon agarose gel electrophoresis, similar to the prebeta HDL previously reported in humans. This prebeta A-I lipoprotein species has a buoyant density of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:In this study, we have documented immunochemical properties of apolipoprotein (apo) B-containing particles (LpB) extracted from human atherosclerotic lesions obtained during vascular reconstructive surgery of patients. These properties were compared to those of particles purified from corresponding atherosclerotic pla...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:The effect of various levels of the oral contraceptive drug, Enovid E, on serum and liver lipid levels of adult female rats has been investigated. Doses ranging from 0.052 to 1.04 mg/day have been employed in rats fed control or cholesterol-containing diets. It has been confirmed that after administration of even low,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-05-01 00:00:00
abstract：:Spectrophotometric techniques for determining the activities of lipases, lysophospholipases, and phospholipases are reviewed. These methods involve the use of thioester substrate analogs as well as omega-nitrophenyl derivatives of the corresponding lipids. The most promising results are obtained with the thioester sub...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：
更新日期：1984-12-15 00:00:00
abstract：:Lysosomal acid lipase (LAL) is essential for the hydrolysis of triglycerides (TG) and cholesteryl esters (CE) in lysosomes. A mouse model created by gene targeting produces no LAL mRNA, protein, or enzyme activity. The lal-/- mice appear normal at birth, survive into adulthood, and are fertile. Massive storage of TG a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:To examine the validity of the deuterium (D) incorporation technique for measurement of human cholesterol synthesis rates, D uptake from D2O into cholesterol was compared to sterol balance in 13 subjects each under three controlled diet settings. Subjects (age 62 +/- 3.6 yr, body weight 74 +/- 4.0 kg, BMI 27 +/- 1.4) ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:The acute-phase response (APR) leads to alterations in lipid metabolism and type II nuclear hormone receptors, which regulate lipid metabolism, are suppressed, in liver, heart, and kidney. Here, we examine the effect of the APR in adipose tissue. In mice, lipopolysaccharide produces a rapid, marked decrease in mRNA le...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500540-JLR200
更新日期：2006-10-01 00:00:00
abstract：:Macrophages and arterial chondroitin sulfate proteoglycans (CSPG) are probably associated with extracellular and intracellular lipoprotein deposition during atherogenesis. We found that human arterial CSPG can be used to select subclasses from low density lipoprotein (LDL) with different structural properties and capa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:The kinetics of lecithin exchange between native lipoproteins was characterized for individual molecular species of lecithins of rat mesenteric lymph chylomicrons and rat plasma HDL. Studies were performed in the absence of lipid transfer proteins. Donor (chylomicrons) and acceptor (HDL) particles were present in rati...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:An in vitro method is presented which measures valid, unidirectional uptake rates for lipids across the intestinal brush border. This method combines analysis by a newly devised, double isotope counting system for solubilized tissue with the use of a nonabsorbable marker to correct gross uptake determinations for cont...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-03-01 00:00:00
abstract：:Apart from exhibiting the presence of lipoprotein [a] in its plasma, another interest of the European hedgehog in lipoprotein research lies in the quantitative prominence of a complex spectrum of high density lipoproteins (HDL) and very high density lipoproteins (VHDL) as cholesterol transporters in plasma (Laplaud, P...
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 specialized cell types, lysosome-related organelles support regulated secretory pathways, whereas in nonspecialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089979
更新日期：2019-04-01 00:00:00
abstract：:The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-12-01 00:00:00
abstract：:AY 9944 is a novel inhibitor of cholesterol biosynthesis which appears to act on the Delta 7-reductase enzyme, interfering with the conversion of 7-dehydrocholesterol to cholesterol. In all tissues studied, with the exception of the lens, there was a reduction in cholesterol and a marked accumulation of 7-dehydrochole...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-01-01 00:00:00
abstract：:Phosphatidylcholine preparations containing saturated and unsaturated molecular species were subjected to KMnO(4)-NaIO(4) oxidation in aqueous acetic acid, which left only disaturated species intact. After the oxidation, the remaining intact phosphatidylcholine was separated by thin-layer chromatography. The procedure...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-09-01 00:00:00
abstract：:We investigated the role of caveolae in uptake and intracellular trafficking of long chain fatty acids (LCFA) in HepG2 human hepatoma cells. The uptake of [(3)H]oleic acid and [(3)H]stearic acid into HepG2 cells was measured by radioactive assays and internalization of the non-metabolizable fluorescent fatty acid 12-(...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100404-jlr200
更新日期：2002-09-01 00:00:00
abstract：:Phospholipase was isolated (in two fractions) from Vipera palestinae venom and it was shown to possess phospholipase A activity (hydrolyzing diacyl-sn-glycerophosphorylcholines, e.g., lecithin, in the 2-position) as well as lysophospholipase (phospholipase B) activity (hydrolyzing 1-monoacyl-sn-glycerophosphorylcholin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-05-01 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
