Abstract：
:Lipid metabolism plays an important role in the regulation of cellular homeostasis. However, because it is difficult to measure the actual rates of synthesis and degradation of individual lipid species, lipid compositions are often used as a surrogate to evaluate lipid metabolism even though they provide only static snapshots of the lipodome. Here, we designed a simple method to determine the turnover rate of phospholipid and acylglycerol species based on the incorporation of 13C6-glucose combined with LC-MS/MS. We labeled adult Drosophila melanogaster with 13C6-glucose that incorporates into the entire lipidome, derived kinetic parameters from mass spectra, and studied effects of deletion of CG6718, the fly homolog of the calcium-independent phospholipase A2β, on lipid metabolism. Although 13C6-glucose gave rise to a complex pattern of 13C incorporation, we were able to identify discrete isotopomers in which 13C atoms were confined to the glycerol group. With these isotopomers, we calculated turnover rate constants, half-life times, and fluxes of the glycerol backbone of multiple lipid species. To perform these calculations, we estimated the fraction of labeled molecules in glycerol-3-phosphate, the lipid precursor, by mass isotopomer distribution analysis of the spectra of phosphatidylglycerol. When we applied this method to D. melanogaster, we found a range of lipid half-lives from 2 to 200 days, demonstrated tissue-specific fluxes of individual lipid species, and identified a novel function of CG6718 in triacylglycerol metabolism. This method provides fluxomics-type data with significant potential to improve the understanding of complex lipid regulation in a variety of research models.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Schlame M,Xu Y,Erdjument-Bromage H,Neubert TA,Ren Mdoi
10.1194/jlr.D119000318subject
Has Abstractpub_date
2020-01-01 00:00:00pages
95-104issue
1eissn
0022-2275issn
1539-7262pii
jlr.D119000318journal_volume
61pub_type
杂志文章abstract：:Most mammalian neoplasms have a defect in ether lipid content manifested by the presence of abnormally large quantities of 0-alkyl glyceryl ethers, in contrast to normal tissues in which the alk-1-enyl structure predominates. These lipids are for the most part structural. The manner in which tumor cell plasma membrane...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:Membranes of mammalian cells contain lysophosphatidic acid acyltransferase (LPAAT) activities that catalyze the acylation of sn-1-acyl lysophosphatidic acid (lysoPA) to form phosphatidic acid. As the biological roles and biochemical properties of the six known LPAAT isoforms have yet to be fully elucidated, we have ch...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500435-JLR200
更新日期：2006-03-01 00:00:00
abstract：:Hyperlipidemia and marrow fat are associated with lowering bone density in vivo, suggesting that lipid contributes to bone loss. Using bone marrow-derived macrophages, we investigated the effect of saturated fatty acids (SFA) on osteoclastogenesis. The level of free fatty acids and adiposity in bone marrow was signifi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800626
更新日期：2010-05-01 00:00:00
abstract：:In this work, we investigated the impact of testosterone deficiency and cholesteryl ester transfer protein (CETP) expression on lipoprotein metabolism and diet-induced atherosclerosis. CETP transgenic mice and nontransgenic (nTg) littermates were studied 4 weeks after bilateral orchidectomy or sham operation. Castrate...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600135-JLR200
更新日期：2006-07-01 00:00:00
abstract：:Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in choles...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M045294
更新日期：2014-03-01 00:00:00
abstract：:Leukotrienes (LTs) play major roles in lung immune responses, and LTD4 is the most potent agonist for cysteinyl LT1, leading to bronchoconstriction and tissue remodeling. Here, we studied LT crosstalk between myeloid cells and pulmonary epithelial cells. Monocytic cells (Mono Mac 6 cell line, primary dendritic cells) ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M066910
更新日期：2016-09-01 00:00:00
abstract：:The pregnane X receptor (PXR, also known as SXR) is a nuclear hormone receptor activated by xenobiotics as well as diverse sterols and their metabolites. PXR functions as a xenobiotic sensor to coordinately regulate xenobiotic metabolism via transcriptional regulation of xenobiotic-detoxifying enzymes and transporters...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M017376
更新日期：2011-09-01 00:00:00
abstract：:In the present study, the relative positions of 11 anti-apolipoprotein B monoclonal antibodies have been mapped onto the surface of human low density lipoproteins by electron microscopy. As the epitopes recognized by these antibodies have been previously located on the primary sequence of apoB, these data provide a ma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:An amino group of phosphatidylethanolamine (PE) is considered as a target for nonenzymatic glycation, and the potential involvement of lipid glycation in the pathogenesis of diabetic complications has generated interest. However, unlike an early glycation product of PE (Amadori-PE), the occurrence and roles of advance...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D004564
更新日期：2010-08-01 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：:Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxi-dative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M046961
更新日期：2014-12-01 00:00:00
abstract：:There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for this "HDL hypothesi...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R001610
更新日期：2010-08-01 00:00:00
abstract：:In vitro experiments have demonstrated that exogenous phospholipid transfer protein (PLTP), i.e. purified PLTP added to macrophage cultures, influences ABCA1-mediated cholesterol efflux from macrophages to HDL. To investigate whether PLTP produced by the macrophages (i.e., endogenous PLTP) is also part of this process...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600051-JLR200
更新日期：2006-08-01 00:00:00
abstract：:To determine the extent and microanatomical distribution of extramyocellular adipocytes associated with skeletal muscle, histological, biochemical, nuclear magnetic resonance proton spectroscopic and microcomputed tomography techniques were employed to analyze skeletal muscle samples from lean and obese Sprague-Dawley...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-07-01 00:00:00
abstract：:Various detergents can be used to dissolve phospholipids, resulting in very narrow 31PNMR resonances. The resonances are well resolved, allowing identification and quantitative analysis of phospholipids in a mixture. The chemical shift depends strongly on pH, reflecting changes in the state of ionization of the phosph...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-03-01 00:00:00
abstract：:Phospholipids serve as central structural components in cellular membranes and as potent mediators in numerous signaling pathways. There are six main classes of naturally occurring phospholipids distinguished by their distinct polar head groups that contain many unique molecular species with distinct fatty acid compos...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D051581
更新日期：2014-11-01 00:00:00
abstract：:Macrophages contain a neutral cholesteryl ester hydrolase that can be activated by cAMP-dependent protein kinase. Immunological studies strongly suggest that hormone-sensitive lipase (HSL) is probably responsible for the cholesteryl ester hydrolase activity in macrophages; however, due to the very low level of express...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:To assess the possible role of altered hepatic processing of free fatty acids in dietary sucrose-induced accumulation of triglyceride in the liver and blood plasma, livers from rats fed commercial laboratory stock and high sucrose diets were perfused both with and without oleic acid substrate. Consumption of the sucro...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:The accurate quantitation of high density lipoproteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma fraction of d > 1.063 g/ml. A more practical approach is...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:The quantitative isolation of total glycosphingolipids from crude lipid extracts without contamination from other lipid classes is described. The method consists of (a) acetylation of total lipids with pyridine and acetic anhydride, (b) separation of acetylated glycolipids from nonglycolipids on a magnesia-silica gel ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-03-01 00:00:00
abstract：:The objective of this study was to investigate the mobilization of individual fatty acids from human subcutaneous adipose tissue in vivo. Concentrations of individual non-esterified fatty acids were measured in arterialized plasma and in the venous drainage from subcutaneous abdominal adipose tissue in eight normal su...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Based on our previous observation that monoclonal antibody anti-apoD-4E11 reacted with several HDL proteins we studied them further with three questions in mind: i) is there common protein polymorphism in healthy individuals? ii) how many proteins are present and what are their characteristics? iii) are they all apoli...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:Apolipoprotein E plays a critical role in plasma lipoprotein clearance. Peptide models of a highly conserved, N-terminal domain of this protein have been shown to increase the binding of low density lipoprotein (LDL) to fibroblast cell surfaces independently of the low density lipoprotein receptor. Here we provide dat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:In this article we report the effects of low and high fat diets on the arterial thrombosis tendency in rats. The animal system used was the aorta loop model, in which we compared the effect of saturated (hardened coconut oil, HCO) and unsaturated (sunflower seed oil, SSO; corn oil, CO) fatty acids on the arterial thro...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-07-01 00:00:00
abstract：:The lipids of rat milk, the contents of 9-- 10-day-old rat stomach and intestine, lymph, plasma, and liver were quantitated and their fatty acids were analyzed. Rat milk consists of 97% triacylglycerols, of which 35% of the fatty acids are of medium chain length (C8-C12). However, stomach triacylglycerols show a 25% r...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-05-01 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：:This article presents a novel methodology for the analysis of ethanolamine glycerophospholipid (PE) and lysoPE molecular species directly from lipid extracts of biological samples. Through brief treatment of lipid extracts with fluorenylmethoxylcarbonyl (Fmoc) chloride, PE and lysoPE species were selectively derivatiz...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D500007-JLR200
更新日期：2005-07-01 00:00:00
abstract：:A positive effect of all-trans retinoic acid (ATRA) on white adipose tissue (WAT) oxidative and thermogenic capacity has been described and linked to an in vivo fat-lowering effect of ATRA in mice. However, little is known about the effects of ATRA on mitochondria in white fat. Our objective has been to characterize t...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M053652
更新日期：2015-06-01 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：:The in vivo total body cholesterol transport of homozygous apoE-deficient (-/-) and control (+/+) mice was evaluated by compartmental analysis of plasma cholesterol decay. Body cholesterol fractional catabolic rates of chow fed mutants were less (-/-, 0.17 +/- 0.02; +/+, 0.51 +/- 0.06 day-1) and body cholesterol conte...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
