Abstract：
:As 5-lipoxygenase (5-LO) is an emerging target in obesity and insulin resistance, we have investigated whether this arachidonate pathway is also implicated in the progression of obesity-related fatty liver disease. Our results show that 5-LO activity and 5-LO-derived product levels are significantly elevated in the liver of obese ob/ob mice with respect to wild-type controls. Treatment of ob/ob mice with a selective 5-LO inhibitor exerted a remarkable protection from hepatic steatosis as revealed by decreased oil red-O staining and reduced hepatic triglyceride (TG) concentrations. In addition, 5-LO inhibition in ob/ob mice downregulated genes involved in hepatic fatty acid uptake (i.e., L-FABP and FAT/CD36) and normalized peroxisome proliferator-activated receptor alpha (PPARalpha) and acyl-CoA oxidase expression, whereas the expression of lipogenic genes [i.e., fatty acid synthase (FASN) and SREBP-1c] remained unaltered. Furthermore, 5-LO inhibition restored hepatic microsomal TG transfer protein (MTP) activity in parallel with a stimulation of hepatic VLDL-TG and apoB secretion in ob/ob mice. Consistent with these findings, 5-LO products directly inhibited MTP activity and triggered cytosolic TG accumulation in CC-1 cells, a murine hepatocyte cell line. Taken together, these findings identify a novel steatogenic role for 5-LO in the liver through mechanisms involving the regulation of hepatic MTP activity and VLDL-TG and apoB secretion.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
López-Parra M,Titos E,Horrillo R,Ferré N,González-Périz A,Martínez-Clemente M,Planagumà A,Masferrer J,Arroyo V,Clària Jdoi
10.1194/jlr.M800101-JLR200subject
Has Abstractpub_date
2008-12-01 00:00:00pages
2513-23issue
12eissn
0022-2275issn
1539-7262pii
M800101-JLR200journal_volume
49pub_type
杂志文章abstract：:Hepatocytes express on their surfaces more than one class of receptors capable of mediating the internalization of lipoproteins. However, relatively little is known about the binding characteristics of hepatic receptors for various lipoproteins, about the regulation of the receptors, and about the consequences for int...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-12-01 00:00:00
abstract：:Cholesterol 7α-hydroxylase (CYP7A1) is the first and rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In addition to absorption and digestion of nutrients, bile acids play a critical role in the regulation of lipid, glucose, and energy homeostasis. We have backcrossed Cyp7a1(-/-) mice ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M064709
更新日期：2016-07-01 00:00:00
abstract：:The implication of cholesteryl ester transfer protein (CETP) in the high density lipoprotein (HDL) conversion process was studied by incubating HDL3 with a purified CETP preparation for 24 h at 37 degrees C. At a physiological plasma level, CETP induced a decrease of the HDL3 fraction (8.6 nm diameter) and the appeara...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual clas...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000950
更新日期：2020-07-09 00:00:00
abstract：:Lipoprotein lipase (LPL) and hepatic lipase (HL) mediate the hydrolysis of triglycerides and phospholipids present in circulating lipoprotein particles and are essential for normal lipid metabolism. Both enzymes have a similar primary amino acid structure and share requirements for intact catalytic, lipid binding, and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:The role of phosphodiesterase in glucagon resistance of large adipocytes was investigated. A comparison was made of phosphodiesterase activities of homogenates prepared from isolated small (mean diameter approximately 45 micro m) and large (mean diameter approximately 78 micro m) adipocytes, using various concentratio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-01-01 00:00:00
abstract：:The alpha-naphthylisothiocyanate (ANIT)-treated rat was evaluated as a model for lipoprotein metabolism in cholestatic liver disease. Alterations in lipoprotein composition over a period of 120 h after ANIT treatment (100 mg/kg) were studied. Eighteen hours after treatment, plasma bilirubin and bile acid levels began ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:Dysbetalipoproteinemia, an uncommon but highly atherogenic mixed hyperlipidemia due to the accumulation of remnants of triglyceride-rich lipoproteins, is characterized by cholesterol-enriched VLDL that migrates in the beta-position on agarose gels. The demonstration of a broad beta-band on agarose gel electrophoresis ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.d200013-jlr200
更新日期：2003-01-01 00:00:00
abstract：:The selective and reversible adsorption of bovine low density lipoproteins (LDL) by heparin-Sepharose has been exploited as the critical step in a procedure for the preparative isolation of very low density lipoproteins (VLDL)/chylomicrons, LDL, and high density lipoproteins (HDL) from bovine plasma. Molecular size ex...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:Previous studies from our laboratory have shown that oral administration of stigmastanyl-phosphocholine (Ro 16-6532) reduces plasma cholesterol levels in experimental animals on diets free of added cholesterol. In the present study, effects of Ro 16-6532 and lovastatin on lipoprotein levels and metabolism were investi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：:Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. To study the relationship of DGAT1, FAS, and LPL with insulin, we examined adipose mRNA expression of these genes in subjects with a wide range of insulin sen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600248-JLR200
更新日期：2006-11-01 00:00:00
abstract：:The primary structure of apolipoprotein A-II (apoA-II) isolated from the plasma high density lipoprotein (HDL) fraction of the inbred mouse strain BALB/c is described in this work. The complete 78 amino acid protein sequence was determined by proteolytic fragmentation, gas-phase microsequence analysis, and fast atom b...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:Sphingoglycolipids (SGLs) are cell membrane constituents. As the ceramide structure influences the biological properties of the SGL, we characterized by electrospray ionization tandem mass spectrometry the molecular species of ceramides present in SGL of mouse brain. We report here for the first time the presence in m...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300331-JLR200
更新日期：2004-02-01 00:00:00
abstract：:We have developed a simplified and improved high performance liquid chromatography (HPLC) method for the detection and quantitation of tissue lipid using a new laser light-scattering detector (Varex model ELSD II). This detector has a limit of sensitivity of 50 ng for neutral lipid and 200 ng for most phospholipids wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000704
更新日期：2020-12-15 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
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：:Apolipoprotein A-I (apoA-I) induces the translocation of newly synthesized cholesterol as well as caveolin-1 to the cytosolic lipid-protein particle (CLPP) fraction in astrocytes before its appearance in high density lipoprotein generated in the medium (Ito, J., Y. Nagayasu, K. Kato, R. Sato, and S. Yokoyama. 2002. Ap...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400222-JLR200
更新日期：2004-12-01 00:00:00
abstract：:Labeled cholesterol esters were incorporated into chylomicrons in vitro by adding an acetone solution of the cholesterol ester to a suspension of washed chylomicrons. The physical and metabolic properties of the added labeled ester were the same as those of cholesterol esters incorporated into chylomicrons in vivo, ex...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-09-01 00:00:00
abstract：:Apheresis is a treatment option for patients with severe hypercholesterolemia and coronary artery disease. It is, however, unknown whether such therapy changes kinetic parameters of lipoprotein metabolism, such as apolipoprotein B (apoB) secretion rates, conversion rates, and fractional catabolic rates (FCR). We studi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:13C nuclear magnetic resonance (NMR) spectra were obtained at 50.3 and 100.5 MHz for methanolic and aqueous mixtures of sodium taurocholate, 1-monocapryloyl-rac-glycerol, and caprylic acid. Distortionless Enhancement by Polarization Transfer (DEPT) was used to improve spectral sensitivity and resolution, and to genera...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:In the chick, the large cholesteryl ester (CE) store present in the liver during the last period of embryonic life increases at hatching and is rapidly depleted after 2-7 days of postnatal life. In this study we asked whether these changes were associated with variations in the hepatic production of apoB-containing li...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Lysophospholipid acyltransferases (LPATs) incorporate fatty acyl chains into phospholipids via a CoA-dependent mechanism and are important in remodeling phospholipids to generate the molecular species of phospholipids found in cells. These enzymes use one lysophospholipid and one acyl-CoA ester as substrates. Traditio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D044636
更新日期：2014-04-01 00:00:00
abstract：:Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we investigate how one of these modifications, triglyceride (TG) enrichment, affects HDL and LDL function when this alteration occurs under conditions in which more polar components can naturally re-equilibrate. TG-enriched lipoproteins wer...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-08-01 00:00:00
abstract：:Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100254-jlr200
更新日期：2002-07-01 00:00:00
abstract：:Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000648
更新日期：2020-05-01 00:00:00
abstract：:The role of lipid transfer proteins during plasma membrane biogenesis was explored. Developing amphibia embryos were used because during their growth an active plasma membrane biosynthesis occurs together with negligible mitochondrial and endoplasmic reticulum proliferation. Sonicated vesicles, containing 14C-labeled ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:We investigated the formation and pharmacology of prostaglandin E(3) (PGE(3)) derived from fish oil eicosapentaenoic acid (EPA) in human lung cancer A549 cells. Exposure of A549 cells to EPA resulted in the rapid formation and export of PGE(3.) The extracellular ratio of PGE(3) to PGE(2) increased from 0.08 in control...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300455-JLR200
更新日期：2004-06-01 00:00:00
abstract：:The direct non-endocytotic uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) plays a major role in HDL CE metabolism in rats and rabbits. In vitro evidence indicates it may also play such a role in humans. However, a study in mice (tracing the CE and apoA-I moieties of HDL) concluded that, while se...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by ads...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P016816
更新日期：2011-12-01 00:00:00
