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 species, and four nonhuman primate (NHP) species, and both healthy animals and animals with metabolic disorders. Dyslipidemic humans were assessed by the same measures. Plasma lipoprotein profiles, eight major plasma lipid fractions, and FA compositions within these lipid fractions were compared both qualitatively and quantitatively across the species. Given the importance of statins in decreasing plasma low-density lipoprotein cholesterol for treatment of dyslipidemia in humans, the responses of these measures to simvastatin treatment were also assessed for each species and compared with dyslipidemic humans. NHPs, followed by dog, were the models that demonstrated closest overall match to dyslipidemic humans. For the subset of the dyslipidemic population with high plasma triglyceride levels, the data also pointed to hamster and db/db mouse as representative models for practical use in target validation. Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Yin W,Carballo-Jane E,McLaren DG,Mendoza VH,Gagen K,Geoghagen NS,McNamara LA,Gorski JN,Eiermann GJ,Petrov A,Wolff M,Tong X,Wilsie LC,Akiyama TE,Chen J,Thankappan A,Xue J,Ping X,Andrews G,Wickham LA,Gai CL,Trinhdoi
10.1194/jlr.M019927subject
Has Abstractpub_date
2012-01-01 00:00:00pages
51-65issue
1eissn
0022-2275issn
1539-7262pii
jlr.M019927journal_volume
53pub_type
杂志文章abstract：:The effect of fatty acids on secretion of triglyceride-rich lipoprotein (d less than 1.006 g/ml) by CaCo-2 cells was studied. Of the fatty acids studied, oleic acid (18:1) was the most potent stimulator of newly synthesized triglyceride secretion in triglyceride-rich lipoproteins followed in descending order by 18:2, ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:Of the six fatty acid elongase (Elovl) subtypes expressed in mammals, adult rat liver expresses four subtypes: Elovl-5 > Elovl-1 = Elovl-2 = Elovl-6. Overnight starvation and fish oil-enriched diets repressed hepatic elongase activity in livers of adult male rats. Diet-induced changes in elongase activity correlate wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400335-JLR200
更新日期：2005-04-01 00:00:00
abstract：:Recent discovery and characterization of APOAV suggests a role in metabolism of triglyceride (TG)-rich lipoproteins. Previously, variation at the APOAV locus was shown to modestly influence plasma TGs in normolipidemic samples. The aims of this study were to assess the effects of a polymorphism in APOAV (T-1131C) in t...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200480-JLR200
更新日期：2003-06-01 00:00:00
abstract：:To study the mechanism of alcoholic hypertriglyceridemia, baboons were pair-fed liquid diets containing 50% of energy as ethanol or as additional carbohydrate for 5-16 months. Alcohol-fed animals developed hypertriglyceridemia and early stages of alcoholic injury, namely fatty liver with or without perivenular fibrosi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-10-01 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：:Black tea is one of the world's most popular beverages, and its health-promoting effects have been intensively investigated. The antiobesity and hypolipidemic effects of black tea have attracted increasing interest, but the mechanisms underlying these phenomena remain unclear. In the present study, the black tea major...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700128-JLR200
更新日期：2007-11-01 00:00:00
abstract：:Skeletal muscle has two circulatory routes, nutritive (in contact with muscle) and non-nutritive (part of which is located in the connective tissue), and the balance of flow between the two is controlled by neural input and circulating vasomodulators. The purpose of this study was to assess muscle triglyceride hydroly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：:The two oxysterols, 27-hydroxycholesterol (27OH) and 24S-hydroxycholesterol (24OH), are both inhibitors of cholesterol synthesis and activators of the liver X receptor (LXR) in vitro. Their role as physiological regulators under in vivo conditions is controversial, however. In the present work, we utilized a previousl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034124
更新日期：2013-04-01 00:00:00
abstract：:The effects of vitamin E on the activity of membrane-dependent enzymes suggest that it acts indirectly by modifying some properties of the lipid host. The effects of alpha-tocopherol (alpha-T) and alpha-tocopherol hemisuccinate (alpha-THS) on phospholipid monolayer structure, curvature, and bending elasticity were exa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300146-JLR200
更新日期：2003-10-01 00:00:00
abstract：:The activity of phospholipase A on phosphatidyl choline and phosphatidal choline spread as monolayers on phosphate buffers containing snake venom (Crotalus atrox or Naja naja) was studied by measuring the fall of surface potential as a function of time, pH, film pressure, temperature, and concentrations of phosphate a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-03-01 00:00:00
abstract：:Cellular membranes are composed of numerous kinds of glycerophospholipids with different combinations of polar heads at the sn-3 position and acyl moieties at the sn-1 and sn-2 positions, respectively. The glycerophospholipid compositions of different cell types, organelles, and inner/outer plasma membrane leaflets ar...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R046094
更新日期：2014-05-01 00:00:00
abstract：:Hepatic steatosis is one of the most common liver disorders in the general population. The main cause of hepatic steatosis is nonalcoholic fatty liver disease (NAFLD), representing the hepatic component of the metabolic syndrome, which is characterized by type 2 diabetes, obesity, and dyslipidemia. Insulin resistance ...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R008896
更新日期：2011-04-01 00:00:00
abstract：:The extent to which cholesterol synthesis is modulated in macrophage foam cells by changes in cholesterol influx and efflux was determined using thioglycollate-elicited peritoneal macrophages from normal and cholesterol-fed White Carneau (WC) and Show Racer (SR) pigeons. In peritoneal macrophages from normocholesterol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:The amphipathic alpha helix is an often-encountered secondary structural motif in biologically active peptides and proteins. An amphipathic helix is defined as an alpha helix with opposing polar and nonpolar faces oriented along the long axis of the helix. In a recent review article we grouped amphipathic helixes into...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：:Delta-5 and delta-6 desaturases (D5D and D6D) are key enzymes in endogenous synthesis of long-chain PUFAs. In this sample of healthy subjects (n = 310), genotypes of single nucleotide polymorphisms (SNPs) rs174537, rs174561, and rs3834458 in the FADS1-FADS2 gene cluster were strongly associated with proportions of LC-...
journal_title：Journal of lipid research
pub_type： 杂志文章,随机对照试验
doi：10.1194/jlr.P032276
更新日期：2013-02-01 00:00:00
abstract：:We analyzed Niemann-Pick type C disease 1 (NPC1) gene in 12 patients with Niemann-Pick type C disease by sequencing both cDNA obtained from fibroblasts and genomic DNA. All the patients were compound heterozygotes. We found 15 mutations, eight of which previously unreported. The comparison of cDNA and genomic DNA reve...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200203-jlr200
更新日期：2002-11-01 00:00:00
abstract：:Recent studies suggest that 7-dehydrocholesterol (7-DHC)-derived oxysterols play important roles in the pathophysiology of Smith-Lemli-Opitz syndrome (SLOS), a metabolic disorder that is caused by defective 3β-hydroxysterol-Δ(7)-reductase (DHCR7). Although 14 oxysterols have been identified as the primary products of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M035733
更新日期：2013-04-01 00:00:00
abstract：:Plasma phospholipid transfer protein (PLTP) is an important regulator of plasma HDL levels and HDL particle distribution. PLTP is present in plasma in two forms, one with high and the other with low phospholipid transfer activity. We have used the human hepatoma cell line, HepG2, as a model to study PLTP secreted from...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300059-JLR200
更新日期：2003-09-01 00:00:00
abstract：:The chemical composition and metabolism of lipoproteins in a population of Benedictine nuns were studied after 5-month periods during which the predominant dietary fats were sunflower oil, peanut oil, palm oil, or milk fats (butter and cream). The population was divided into three groups. The control group (C) include...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:An elevated plasma concentration of lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. Life style modification and currently available drugs either fail to effectively lower plasma Lp(a) levels or do not result in clinical benefit. However, lipoprotein apheresis is very efficient in decr...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R056549
更新日期：2016-10-01 00:00:00
abstract：:Tuberculosis is a major cause of mortality and morbidity due to infectious disease. However, current clinical diagnostic methodologies such as PCR, sputum culture, or smear microscopy are not ideal. Antibody-based assays are a suitable alternative but require specific antibodies against a suitable biomarker. Mycolic a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D036137
更新日期：2013-10-01 00:00:00
abstract：:To identify novel fatty acid diol synthases, putative candidate sequences from Penicillium species were analyzed, and hydroxy fatty acid production by crude Penicillium enzyme extracts was assessed. Penicillium chrysogenum was found to produce an unknown dihydroxy fatty acid, a candidate gene implicated in this produc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M061341
更新日期：2016-02-01 00:00:00
abstract：:Fungal lipases and human pancreatic lipase (hPL) share a common tertiary structure termed the alpha/beta hydrolase fold. In contrast, the region C-terminal to the common tertiary structure does not share any common structural features with fungal lipases, leading to the hypothesis that the divergent C-terminal domain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
abstract：:A simple procedure is described for preparing lyso-GM1, a GM1 derivative that lacks the fatty acid moiety, starting from GM1 ganglioside using a one-pot reaction. Ganglioside deacylation was carried out in KOH/propan-1-ol in the absence of oxygen. The yield of lyso-GM1 under optimal conditions (6 h, 90 degrees C, 0.2 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:Hepatic lipase (HL) is a lipolytic enzyme, synthesized by hepatocytes and found localized at the surface of liver sinusoid capillaries. In humans, the enzyme is mostly bound onto heparan-sulfate proteoglycans at the surface of hepatocytes and also of sinusoid endothelial cells. HL shares a number of functional domains...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：
更新日期：2002-08-01 00:00:00
abstract：:Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (d...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M073882
更新日期：2017-07-01 00:00:00
abstract：:We studied the biogenesis of apolipoprotein B (apoB) in primary hepatocytes isolated from hamster liver, an animal model with striking resemblance to humans in lipoprotein metabolism. Hamster hepatocytes were found to assemble and secrete apoB-containing lipoproteins at a density of VLDL. Intracellular mechanisms of a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:Autosomal recessive polycystic kidney disease (ARPKD) is a severe, monogenetically inherited kidney and liver disease. PCK rats carrying the orthologous mutant gene serve as a model of human disease, and alterations in lipid profiles in PCK rats suggest that defined subsets of lipids may be useful as molecular disease...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M040014
更新日期：2013-10-01 00:00:00
abstract：:The diffusion of [2-(14)C]glucose out of liposomes prepared from extracted human erythrocyte lipids was examined. Increased glucose efflux was observed when the lipids were treated with hydrogen peroxide and CuCl(2) before liposome formation, and this phenomenon required both peroxide and metal. Peroxidation of these ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-05-01 00:00:00
abstract：:The apoproteins of serum lipoproteins and of lipoproteins present in a nonrecirculating perfusate of rat liver were compared by immunochemical, gel electrophoretic, and solubility techniques. Serum and perfusate very low density lipoprotein apoprotein composition were not different. No evidence for the presence of a l...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
