Abstract：
:Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we investigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyceridemia. Here, we studied the role of LPL and two potent modifiers, the LPL inhibitor apoC-III and the LPL activator apoA-V, in APOE2-knockin (APOE2) mice. Injection of heparin in APOE2 mice reduced plasma TG by 53% and plasma total cholesterol (TC) by 18%. Adenovirus-mediated overexpression of LPL reduced plasma TG by 85% and TC by 40%. Both experiments indicate that the TG in apoE2-enriched particles is a suitable substrate for LPL. Indirect activation of LPL activity via deletion of Apoc3 in APOE2 mice did not affect plasma TG levels, whereas overexpression of Apoa5 in APOE2 mice did reduce plasma TG by 81% and plasma TC by 41%. In conclusion, the hypertriglyceridemia in APOE2 mice can be ameliorated by the direct activation of LPL activity. Indirect activation of LPL via overexpression of apoA-V does, whereas deletion of apoC-III does not, affect the plasma TGs in APOE2 mice. These data indicate that changes in apoA-V levels have a dominant effect over changes in apoC-III levels in the improvement of APOE2-associated hypertriglyceridemia.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Gerritsen G,van der Hoogt CC,Schaap FG,Voshol PJ,Kypreos KE,Maeda N,Groen AK,Havekes LM,Rensen PC,van Dijk KWdoi
10.1194/jlr.M800009-JLR200subject
Has Abstractpub_date
2008-05-01 00:00:00pages
1048-55issue
5eissn
0022-2275issn
1539-7262pii
M800009-JLR200journal_volume
49pub_type
杂志文章abstract：:We report the molecular basis of familial chylomicronemia and recurrent pancreatitis in five members of a large Dutch family. All patients had normal plasma hepatic lipase and apoC-II levels, but absent lipoprotein lipase (LPL) catalytic activity and low LPL mass in postheparin plasma. The mutation in the LPL gene was...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:Guinea pig gallbladder bile contains chenodeoxycholic acid (62 +/- 5%), ursodeoxycholic acid (8 +/- 5%), and 7-ketolithocholic acid (30 +/- 5%). All three bile acids became labeled to the same specific activity within 30 min after [3H]cholesterol was injected into bile fistula guinea pigs. When a mixture of [3H]ursode...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Apolipoprotein (apo) E, via its receptor binding domain contained in residues 140-150, mediates hepatic and peripheral tissue binding of cholesterol-rich lipoproteins. Previously, we reported that a synthetic peptide representing a linear tandem repeat of amino acids 141-155, the 141-155 dimer, binds the low density l...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:The identification of three highly conserved phosphorylation sites in the cytoplasmic domain of each of the monomeric subunits of the macrophage scavenger receptor suggests that protein phosphorylation may regulate this receptor pathway. To investigate this, mouse peritoneal macrophages were pretreated with either the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:Oxidized forms of cholesterol (oxysterols) are present in atherosclerotic lesions and may play an active role in lesion development. For example, 7-ketocholesterol (7KC) inhibits cholesterol efflux from macrophage foam cells induced by apolipoprotein A-I (apoA-I). Such oxysterols may promote foam cell formation in ath...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-09-01 00:00:00
abstract：:Conditions leading to oxidation of LDL in vivo are still unknown. While the occurrence of oxidized lipoproteins and catalytic free iron in advanced atherosclerotic lesions has been demonstrated, the origin of both is unclear. In vivo, iron metabolism is tightly regulated by iron-binding proteins that ensure that virtu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-07-01 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：: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：:We measured the amount of apoA-I in serum by isotope dilution, finding 1.33 mg/ml (standard deviation 0.177) in six normolipidemic, healthy subjects. We developed this method by adapting published techniques to purify apoA-I from 3 ml of serum in two steps: density gradient ultracentrifugation and high performance liq...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
abstract：:Structurally specific very low density lipoprotein (VLDL) particles are presumed to redirect VLDL uptake during yolk deposition. Egg production is an energy intensive process, but energy excess negatively affects egg production. This study sought to determine whether overfeeding changed hen lipoprotein profiles, and i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:An enzyme (phosphatidyl glycerophosphate phosphatase) that catalyzes the formation of phosphatidyl glycerol from phosphatidyl glycerophosphate has been rendered soluble by treatment of the particulate fraction of E. coli with Triton X-100 in the presence of EDTA, and has been partially purified. The enzyme is specific...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-09-01 00:00:00
abstract：:We propose a simple mathematical model to account for the coupling of secretion rates of bile salts, lecithin, and cholesterol into bile. The model assumes that: 1) molecules of "biliary" lecithin and cholesterol enter a functional compartment located in the endoplasmic reticulum of the hepatocyte from which they are ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 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：:Percent cholesterol absorption was measured in 94 normal subjects aged 17- 80 years while consuming diets generally low in cholesterol (mean intake = 226 +/- 126 mg/day). A new dual stable isotope method was used where a cholesterol tracer containing 6 extra mass units was given intravenously and another tracer with 5...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:We have previously demonstrated the potential usefulness of capillary columns coated with a high temperature polarizable phenylmethylsilicone liquid phase in plasma lipid profiling (Kuksis, A., J.J. Myher, and P. Sandra. 1990. J. Chromatogr. 500: 427-441). The present study reports improved operating conditions along ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-06-01 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：:We have studied the rate of phospholipid synthesis and turnover in mouse peritoneal macrophages in reaction to cholesterol influx and high density lipoprotein (HDL)-mediated cholesterol efflux, using three different radioactive precursors, 32PO4(3-), [3H]choline, and [14C]oleic acid. The cells were loaded with cholest...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:To study the effect of an unstirred layer (UL), we have investigated the exchange efflux kinetics of anandamide at 0 degrees C, pH 7.3, from albumin-free as well as from albumin-filled human red blood cell ghosts to media of various BSA concentrations ([BSA](o)). The rate constant (k(m)) of unidirectional flux from th...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500411-JLR200
更新日期：2006-03-01 00:00:00
abstract：:Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has been applied primarily to the analysis of glycosphingolipids separated from other complex mixtures by TLC, but it is difficult to obtain quantitative profiling of each glycosphingolipid among the different spots on TLC by MALDI-MS. Thus, the ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D800038-JLR200
更新日期：2008-12-01 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：:Since the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) as an attractive target in the treatment of hypercholesterolemia, multiple anti-PCSK9 therapeutic modalities have been pursued in drug development. The objective of this research is to set the stage for the quantitative benchmarking of two an...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M092486
更新日期：2019-09-01 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：:Although the synthesis pathways of intracellular triacylglycerol (TAG) species have been well elucidated, assessment of the contribution of an individual pathway to TAG pools in different mammalian organs, particularly under pathophysiological conditions, is difficult, although not impossible. Herein, we developed and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M033837
更新日期：2013-04-01 00:00:00
abstract：:Lymph chylomicrons of different sizes are known to be cleared at different rates, but the underlying mechanism for this effect has not been resolved. To investigate the differences in clearance rates between small and large particles, chylomicron-like lipid emulsions labeled with radioactive triolein and cholesteryl o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Conventional ideas concerning the unidirectional movement of triacylglycerol from intestinal lumen to lymph with sn-2-monoacylglycerol being the major glyceride-glycerol precursor were challenged by our finding that steady state specific activities of radiolabeled triacylglycerol (glyceryl moiety) in the intestinal mu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：:Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experimen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:A reproducible cell culture system is described that allows the study of adipose conversion in fibroblast-like cells isolated by collagenase digestion of epididymal and perirenal adipose tissue from male rats weighing 70-200 g. Adipose conversion as measured by lipid accumulation and increase in glycerophosphate dehyd...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
abstract：:Thioesterase superfamily member 1 (Them1; synonyms acyl-CoA thioesterase 11 and StarD14) is highly expressed in brown adipose tissue and limits energy expenditure in mice. Them1 is a putative fatty acyl-CoA thioesterase that comprises tandem hot dog-fold thioesterase domains and a lipid-binding C-terminal steroidogeni...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M029538
更新日期：2012-12-01 00:00:00
abstract：:Epoxyeicosatrienoic acids were isolated and purified from female rabbit kidneys. They were identified as a group, prior to resolution, by packed column gas-liquid chromatography-mass spectroscopic techniques as their methyl esters as well as their trimethylsilyl bromohydrin methyl esters. Initial capillary gas-liquid ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
abstract：:Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies agai...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
