Abstract：
:The CYP27A gene encodes a mitochondrial cytochrome P450 enzyme, sterol 27-hydroxylase, that is expressed in many different tissues and plays an important role in cholesterol and bile acid metabolism. In humans, CYP27A deficiency leads to cerebrotendinous xanthomatosis. To gain insight into the roles of CYP27A in the regulation of cholesterol and bile acid metabolism, cyp27A gene knockout heterozygous, homozygous, and wild-type littermate mice were studied. In contrast to homozygotes, heterozygotes had increased body weight and were mildly hypercholesterolemic, with increased numbers of lipoprotein particles in the low density lipoprotein size range. Cyp7A expression was not increased in heterozygotes but was in homozygotes, suggesting that parts of the homozygous phenotype are secondary to increased cyp7A expression and activity. Homozygotes exhibited pronounced hepatomegaly and dysregulation in hepatic cholesterol, bile acid, and fatty acid metabolism. Hepatic cholesterol synthesis and synthesis of bile acid intermediates were increased; however, side chain cleavage was impaired, leading to decreased bile salt concentrations in gallbladder bile. Expression of Na-taurocholate cotransporting polypeptide, the major sinusoidal bile salt transporter, was increased, and that of bile salt export pump, the major canalicular bile salt transporter, was decreased. Gender played a modifying role in the homozygous response to cyp27A deficiency, with females being generally more severely affected. Thus, both cyp27A genotype and gender affected the regulation of hepatic bile acid, cholesterol, and fatty acid metabolism.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Dubrac S,Lear SR,Ananthanarayanan M,Balasubramaniyan N,Bollineni J,Shefer S,Hyogo H,Cohen DE,Blanche PJ,Krauss RM,Batta AK,Salen G,Suchy FJ,Maeda N,Erickson SKdoi
10.1194/jlr.M400219-JLR200keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
76-85issue
1eissn
0022-2275issn
1539-7262pii
M400219-JLR200journal_volume
46pub_type
杂志文章abstract：:A gas-liquid chromatographic-mass spectrometric method of determining the position of oxygen atoms on polyfunctional fatty acids has been explored. The method consists of reduction of keto, hydroperoxy, epoxy, and carboxylic acid groups with LiAlH(4) to the corresponding alcohols; trimethylsilylation with bis(trimethy...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-03-01 00:00:00
abstract：:The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-12-01 00:00:00
abstract：:Murine strains susceptible to atherosclerosis provide valuable models to study factors involved in atherogenesis. In some murine models, limited hypercholesterolemia can be achieved and lesions develop primarily in the aortic origin, in the vicinity of the aortic valve. In other models such as LDL receptor-deficient a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption consider...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M085043
更新日期：2018-09-01 00:00:00
abstract：:The isolated perfused rat liver was used to study the 300-800 A electron-opaque bodies which had previously been described in the liver cell Golgi apparatus, smooth endoplasmic reticulum, and space of Disse. When the perfusion medium was enriched with linoleate, the number and electron opacity of these particles incre...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-09-01 00:00:00
abstract：:Cerebrosides have been isolated from adult human aortic tissue. Each aorta was divided into portions classified as normal, fatty streaks, fibrous plaques, or complicated lesions. The cerebrosides were isolated by Florisil column chromatography, mild alkaline methanolysis, a second Florisil column, and preparative thin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-07-01 00:00:00
abstract：:At onset of egg-laying in the chicken, plasma levels of apolipoprotein VLDL-II (apoII) increase dramatically, suggesting a function of apoII in yolk deposition of triglyceride-rich lipoproteins. Thus, the possibility that this female-specific homodimeric protein (Mr of subunit, 9500) is recognized by the oocyte recept...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:ABCA1 plays a key role in the initial lipidation of apoA-I, which generates circulating HDL cholesterol. Whereas it is known that the transcriptional upregulation of ABCA1 promotes HDL formation and reverse cholesterol transport (RCT), it is not known how the inhibition of ABCA1 protein degradation impacts HDL functio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054742
更新日期：2015-05-01 00:00:00
abstract：:The rate-limiting step in the transit of dietary fat across the intestinal absorptive cell is its exit from the endoplasmic reticulum (ER) in a specialized ER-to-Golgi transport vesicle, the prechylomicron transport vesicle (PCTV). PCTV bud off from the ER membranes and have unique features; they are the largest ER-de...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M002758
更新日期：2010-05-01 00:00:00
abstract：:Type 1 diabetes mellitus is a devastating disorder affecting both glucose and lipid metabolism. Using the nonobese diabetic (NOD) mouse model, we found that diabetic mice had a liver-specific increase in steady state mRNA levels for enzymes involved in oxidation of fatty acids. Increased mRNA abundance was observed in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:SW-13 adrenal tumor cells that lack detectable intermediate filaments (IF-free) exhibit an impaired capacity to esterify lipoprotein-derived cholesterol compared with cells that contain vimentin filaments. IF-free cells were found to synthesize and secrete significant amounts of apoE, while apoE secretion was nearly u...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：:HDL cholesterol levels are decreased in Crohn's disease, a tumor necrosis factor-alpha (TNF-alpha)-driven chronic inflammatory condition involving the gastrointestinal tract. ATP-binding cassette transporter A1 (ABCA1), one of several liver X receptor (LXR) target genes, is a cell surface transporter that mediates the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M002410
更新日期：2010-06-01 00:00:00
abstract：:Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in adipocyte lipolysis. The activity of HSL is thought to be primarily regulated by reversible phosphorylation. However, the regulation of HSL activity by pre-translational mechanisms has been poorly studied. The present studies were undertaken to explore...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:The rate of lipolytic enzyme-catalyzed reactions yielding water-soluble products can be measured by isobaric titration. The method is based upon the measurement of the amount of substrate that must be added to a monalayer to maintain constant surface pressure during the course of the enzymatic reaction. The rate const...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-01-01 00:00:00
abstract：:Recently we evaluated an isotope ratio method (IRM) for measurement of cholesterol absorption in 14 patients (15 experiments) hospitalized in the metabolic ward by comparing it to simultaneous measurements with a fecal radioactivity method (FRM) and found good to excellent agreement between two procedures (Samuel, P.,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:The major high density lipoprotein (HDL) apolipoprotein, apoA-I, was knocked out by gene targeting in ES cells to provide a model for the study of HDL metabolism and its relationship to plasma and tissue cholesterol metabolism. HDL and non-HDL cholesterol (HDL-C) were reduced in apoA-I-deficient mice. Feeding a high f...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:Essential fatty acids (EFA) are important structural and functional components of cell membranes. Their deficiency has been associated with several clinical and biochemical abnormalities. In the present study, the lipid profile as well as the concentration, composition, and metabolism of lipoproteins were examined in ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M074997
更新日期：2017-05-01 00:00:00
abstract：:It is becoming increasingly accepted that removal of cellular cholesterol occurs by at least two pathways, one involving the well-described aqueous diffusion mechanism and another promoted by lipid-free apolipoproteins. We compared the contribution of apolipoprotein-dependent and -independent pathways, taking into con...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:The immunoreactivities of LDL (low density lipoprotein) samples obtained from a variety of subjects were analyzed by comparing their capacities to compete with 125I-labeled LDL for binding to various monoclonal anti-LDL antibodies in competitive binding assays. A marked variation in epitope expression was observed. In...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:Apolipoprotein (apo) A-I-containing lipoproteins can be separated into two subfractions, pre-beta HDL and alpha HDL (high density lipoproteins), based on differences in their electrophoretic mobility. In this report we present results indicating that these two subfractions are metabolically linked. When plasma was inc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-12-01 00:00:00
abstract：:Fatty acid compositions of glycerophosphatides of developing chick embryonic brain and liver were compared. In brain, ethanolamine and serine glycerophosphatides contained 30-40% polyunsaturated fatty acids, lecithin almost none (except for arachidonic). In the liver, these acids were equally distributed in the phosph...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-09-01 00:00:00
abstract：:Plasma phospholipid transfer protein (PLTP) interacts with HDL particles and facilitates the transfer of phospholipids from triglyceride (TG)-rich lipoproteins to HDL. Overexpressing human PLTP in mice increases the susceptibility to atherosclerosis. In human plasma, high-active and low-active forms of PLTP exist. To ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800080-JLR200
更新日期：2008-12-01 00:00:00
abstract：:We used a mouse C57BL/6J×CASA/Rk intercross to map a locus on chromosome 14 that displayed a gender-dependent effect on cholesterol absorption from the intestine. Studies in congenic animals revealed a complex locus with multiple operating genetic determinants resulting in alternating gender-dependent phenotypic effec...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034579
更新日期：2013-03-01 00:00:00
abstract：:Tissue-specific regulation of LPL has been widely studied in rats. Previous studies reported that in vivo administration of adrenaline and acute stress cause an increase in plasma LPL activity coinciding with a decrease in white adipose tissue (WAT) LPL activity. We studied the speed of LPL activity changes during 30 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600487-JLR200
更新日期：2007-04-01 00:00:00
abstract：:Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and en...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R900010-JLR200
更新日期：2009-10-01 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：: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：:The objectives of this study were to characterize the effects of plasma lipoproteins on prostacyclin (PGI2) production by the Langendorff-perfused rabbit heart, and to determine the mechanism of lipoprotein-induced cardiac PGI2 production. PGI2 production by perfused rabbit hearts was stimulated by injections of rabbi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-05-01 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
