Abstract：
:The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Gorden DL,Myers DS,Ivanova PT,Fahy E,Maurya MR,Gupta S,Min J,Spann NJ,McDonald JG,Kelly SL,Duan J,Sullards MC,Leiker TJ,Barkley RM,Quehenberger O,Armando AM,Milne SB,Mathews TP,Armstrong MD,Li C,Melvin WV,Clemendoi
10.1194/jlr.P056002subject
Has Abstractpub_date
2015-03-01 00:00:00pages
722-36issue
3eissn
0022-2275issn
1539-7262pii
jlr.P056002journal_volume
56pub_type
临床试验,杂志文章,多中心研究abstract：:The transfer or exchange of cholesteryl esters, triglycerides, and phospholipids between plasma very low (VLDL), low (LDL), and high (HDL) density lipoproteins is facilitated by specific lipid transfer proteins. The present report describes a method to separate donor and acceptor lipoprotein pools used in assays for l...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:PPARs regulate the expression of genes for energy metabolism in a ligand-dependent manner. PPARs can influence fatty acid oxidation, the level of circulating triglycerides, glucose uptake and insulin sensitivity. Here, we demonstrate that 5-hydroxyeicosapentaenoic acid (HEPE), 8-HEPE, 9-HEPE, 12-HEPE and 18-HEPE (hydr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M047514
更新日期：2014-05-01 00:00:00
abstract：:Changes in the cellularity of various adipose tissues in growing cattle were analyzed. Fifty male cattle were slaughtered between 15 and 65% of mature weight. The whole adipose mass, separated by dissection, was divided into three parts: subcutaneous, intermuscular, and internal adipose tissues. Lipid content, cell si...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M082362
更新日期：2018-02-01 00:00:00
abstract：:The conversion of alpha-linolenate (18:3n-3) to docosahexaenoate (22:6n-3) in the presence of low and high dietary levels of linoleate (18:2n-6) is reported in young rats using [U-13C]-alpha-linolenic acid (18:2n-3*) and high precision gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS). After con...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-05-01 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：: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：:Bile acids labeled with 3H on the sterol nucleus lose a substantial fraction of label during enterohepatic cycling and conversion to secondary bile acids. We tested the isotopic stability of a side-chain 3H label, [22,23-3H]cholic acid in humans. The 3H-labeled compound was administered simultaneously with [24-14C]cho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:The mammalian FA-binding proteins (FABPs) bind long-chain FA with high affinity. The large number of FABP types is suggestive of distinct functions in specific tissues. Multiple experimental approaches have shown that individual FABPs possess both unique and overlapping functions, some of which are based on specific e...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800084-JLR200
更新日期：2009-04-01 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：:The surface area, A, of contracting fatty acid monolayers was measured as a function of time, t, at constant surface pressure. In the initial temporal phase, ln A was linear with radical t. In a subsequent steady-state phase, ln A was linear with t. The initial desorption coefficient for sodium palmitate, K(i), and th...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-01-01 00:00:00
abstract：:Lilly PCSK9 antibody LY3015014 (LY) is a monoclonal antibody (mAb) that neutralizes proprotein convertase subtilisin-kexin type 9 (PCSK9). LY decreases LDL cholesterol in monkeys and, unlike other PCSK9 mAbs, does not cause an accumulation of intact PCSK9 in serum. Comparing the epitope of LY with other clinically tes...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M061903
更新日期：2015-11-01 00:00:00
abstract：:Remnant-like emulsions were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice the remnant-like emulsions labeled with cholesteryl[13C]oleate were metabolized in the liver and the appearance of 13CO2 in the breath wa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by nor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:A series of cholesterol hydroperoxides has been prepared and tested as inactivators of calmodulin. Two previously undescribed compounds, tentatively identified as 20-(R)-25-dihydroperoxy-5-cholesten-3 beta-ol and its 20-(S) isomer inactivate calmodulin with 50% loss of activity at 5-10 microM. Cholesterol derivatives ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:The in vivo formation of the sulfate ester of glycolithocholate is a critical step in the elimination of this hepatotoxic bile salt. Rhesus monkeys fed chenodeoxycholate or ursodeoxycholate, the precursors of lithocholate, develop frank cirrhosis in association with accumulation of nonsulfated glycolithocholate in bil...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
abstract：:Severe endothelial abnormalities are a prominent feature in sepsis with cytokines such as tumor necrosis factor (TNF)alpha being implicated in the pathogenesis. As mimic to inflammation, human umbilical vascular endothelial cells (HUVEC) were incubated with TNFalpha for 22 h, in the absence or presence of the omega-6 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-06-01 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：:Four different lipolytic preparations have been isolated from rat skeletal muscle. Two of these, provisionally designated monopalmitin lipase (MPL) and monomyristin lipase (MML), are associated with insoluble cellular particulate fractions. The other two enzymes, provisionally designated tricaproin lipase (TCL) and mo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-03-01 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：:The lipin protein family, consisting of three members, was first identified early this century. In the last few years, the lipin proteins have been shown to have important roles in glycerolipid biosynthesis and gene regulation, and mutations in the corresponding genes cause lipodystrophy, myoglobinuria, and inflammato...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800052-JLR200
更新日期：2009-04-01 00:00:00
abstract：:Human apolipoprotein E (apoE) is a constituent of plasma very low density and high density lipoproteins and is important in modulating the catabolism of remnants of triglyceride-rich lipoproteins. There are three common isoforms of apoE, designated apoE-2, E-3, and E-4, which are coded by three separate alleles (epsil...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:In Refsum disease, disorders of peroxisome biogenesis, and rhizomelic chondrodysplasia punctata, pathological accumulation of phytanic acid results from impaired alpha-oxidation of this branched-chain fatty acid. Previous studies from this laboratory indicated that activation of phytanic acid to its CoA derivative pre...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:Male Sprague-Dawley rats were fed diets that contained 20% by weight soybean oil or rapeseed oil (21% and 43% erucic acid) for 7 days. The rapeseed oil diets increased the cardiac triacylglycerol content 5-fold and 25-fold, respectively, above control values. Hearts were removed from the animals and perfused with modi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:The report that sweat of certain schizophrenics contains the branched chain fatty acid, trans-3-methyl-2-hexenoic acid (TMHA), stimulated an investigation to evaluate the relationship between this fatty acid and schizophrenia. A sensitive and specific gas-liquid chromatography-mass spectroscopic procedure was develope...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-07-01 00:00:00
abstract：:The characteristics of 7 alpha-dehydroxylase, a bile acid-biotransforming enzyme, were determined using dialyzed cell extracts of Eubacterium sp. V.P.I. 12708. 7 alpha-Dehydroxylase was induced by cholic acid in this organism. Induction by cholic acid resulted in the differential synthesis of at least five new polypep...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:This report describes the chemical synthesis of isoursocholic acid (3 beta, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid) from its corresponding 3 alpha-analog. The method consists of refluxing a mixture of ursocholic acid, triphenylphosphine, and diethyl azodicarboxylate in benzene solution with an acid such as ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Apolipoprotein L is a newly recognized component of human plasma lipoproteins. Mainly associated with apoA-I-containing lipoproteins, it is a marker of distinct HDL subpopulations. In an effort to gain inference as to its as yet unknown function, we studied biological determinants of apoL levels in human plasma. The d...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-08-01 00:00:00
abstract：:Here, we present an improved method for sensitive profiling of lipids in a single high-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry experiment. The approach consists of i) sensitive isocratic elution, which takes advantage of C18 column material that is resistan...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700060-JLR200
更新日期：2007-09-01 00:00:00
abstract：:Two procedures were used to isolate hepatocytic Golgi fractions from rat liver. One procedure yields a light Golgi fraction (GF1 + 2) and the other "intact" stacks of cisternae. Triglyceride fatty acids in nascent very low density lipoproteins (VLDL) were labeled by injection of [3H]palmitate intravenously, and radiol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
