Abstract:
:SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synthesis of sterols and fatty acids is reduced, but mice are otherwise healthy. To determine whether Scap loss is tolerated in the intestine, we generated a mouse model (Vil-Scap(-)) in which tamoxifen-inducible Cre-ER(T2), a fusion protein of Cre recombinase with a mutated ligand binding domain of the human estrogen receptor, ablates Scap in intestinal mucosa. After 4 days of tamoxifen, Vil-Scap(-) mice succumb with a severe enteropathy and near-complete collapse of intestinal mucosa. Organoids grown ex vivo from intestinal crypts of Vil-Scap(-) mice are readily killed when Scap is deleted by 4-hydroxytamoxifen. Death is prevented when culture medium is supplemented with cholesterol and oleate. These data show that, unlike the liver, the intestine requires Scap to sustain tissue integrity by maintaining the high levels of lipid synthesis necessary for proliferation of intestinal crypts.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
McFarlane MR,Cantoria MJ,Linden AG,January BA,Liang G,Engelking LJdoi
10.1194/jlr.M059709subject
Has Abstractpub_date
2015-08-01 00:00:00pages
1560-71issue
8eissn
0022-2275issn
1539-7262pii
jlr.M059709journal_volume
56pub_type
杂志文章abstract::A reliable method for purifying envelope-stripped nuclei from immortalized murine embryonic fibroblasts (iMEFs) was established. Quantitative profiling of the glycerophospholipids (GPLs) in envelope-free iMEF nuclei yields several conclusions. First, we find the endonuclear glycerophospholipidome differs from that of ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M068734
更新日期:2016-08-01 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::Over the past several years, considerable progress has been made in the development of gene therapy as a therapeutic strategy for a variety of inherited metabolic diseases, including neuropathic lysosomal storage disorders (LSDs). The premise of gene therapy for this group of diseases is borne of findings that genetic...
journal_title:Journal of lipid research
pub_type: 杂志文章,评审
doi:10.1194/jlr.R047175
更新日期:2014-09-01 00:00:00
abstract::To assess the possible role of altered hepatic processing of free fatty acids in dietary sucrose-induced accumulation of triglyceride in the liver and blood plasma, livers from rats fed commercial laboratory stock and high sucrose diets were perfused both with and without oleic acid substrate. Consumption of the sucro...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Rat serum lipoproteins were separated into at least four fractions by agarose-starch gel electrophoresis. The system used was discontinuous in that glycine and sodium barbitone buffer was used in the reservoirs and Tris buffer was used for the gels. The four major bands could be related to the pattern obtained by ultr...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-05-01 00:00:00
abstract::Cholesterol 7alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse colony, as young a...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M200489-JLR200
更新日期:2003-05-01 00:00:00
abstract::A glycerophospholipid (1-O-tuberculostearoyl-2-O-palmitoyl-sn-glycero-3-phosphoethanolamine) from Mycobacterium tuberculosis was isolated from the reference strain H37Rv. The molecular structure of this tuberculostearoyl [(R)-10-methyloctadecyl] and palmitoyl containing phosphatidylethanolamine (PE) has been resolved....
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M001982
更新日期:2010-05-01 00:00:00
abstract::A positive effect of all-trans retinoic acid (ATRA) on white adipose tissue (WAT) oxidative and thermogenic capacity has been described and linked to an in vivo fat-lowering effect of ATRA in mice. However, little is known about the effects of ATRA on mitochondria in white fat. Our objective has been to characterize t...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M053652
更新日期:2015-06-01 00:00:00
abstract::Subcellular localization of nonesterified cholesterol has been determined in normal human fibroblasts from cultures incubated with human low density lipoprotein (LDL). Nonesterified and esterified cholesterol content of fibroblasts, grown initially in the absence of cholesterol, increased significantly after a 1-hour ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::14C-labeled oleic acid and (3)H-labeled monoether in a bile salt solution were perfused through three types of plastic tubing. Large proportions of lipid were lost to the walls of silicone rubber and polyvinyl chloride tubes. The major portion of the lipid lost was recoverable only when chloroform-methanol was perfuse...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-09-01 00:00:00
abstract::Inositol lipid kinases have been studied extensively in both plant and animal systems. However, major limitations for in vitro studies of recombinant lipid kinases are the low specific activity and instability of the purified proteins. Our goal was to determine if cyclodextrins would provide an effective substrate del...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.D400005-JLR200
更新日期:2004-09-01 00:00:00
abstract::Membranes of mammalian cells contain lysophosphatidic acid acyltransferase (LPAAT) activities that catalyze the acylation of sn-1-acyl lysophosphatidic acid (lysoPA) to form phosphatidic acid. As the biological roles and biochemical properties of the six known LPAAT isoforms have yet to be fully elucidated, we have ch...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M500435-JLR200
更新日期:2006-03-01 00:00:00
abstract::Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid derived from dietary sources and broken down in the peroxisome to pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) via alpha-oxidation. Pristanic acid then undergoes beta-oxidation in peroxisomes. Phytanic acid naturally occu...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::Mammalian spermatogenesis is a complex developmental program in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. One intriguing aspect of sperm production is the dynamic change in membrane lipid composition that occurs throughout spermatogenesis. Cholesterol content, as well as its ...
journal_title:Journal of lipid research
pub_type: 杂志文章,评审
doi:10.1194/jlr.R032326
更新日期:2013-01-01 00:00:00
abstract::An improved preparation of proteolipid from bovine brain white matter is described. The product obtained by repeated acetone precipitation is completely soluble in chloroform-methanol and has a fairly constant composition: 35% protein, 40% galactocerebroside, and about 25% phospholipid. ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1967-01-01 00:00:00
abstract::ATP-citrate lyase (ACL) is a key lipogenic enzyme that converts citrate in the cytoplasm to acetyl-CoA, the initial precursor that yields malonyl-CoA for fatty acid biosynthesis. As cytosolic citrate is derived from the tricarboxylic acid cycle in the mitochondrion, ACL catalyzes a critical reaction linking cellular g...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M003335
更新日期:2010-09-01 00:00:00
abstract::LCAT plays a key role in the maturation of HDL, as evidenced by low HDL-cholesterol levels in carriers of deleterious mutations in LCAT. However, the role of LCAT in atherosclerosis is unclear. We set out to study this in a prospective study. Plasma LCAT levels, which strongly correlate with LCAT activity, were measur...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/P900038-JLR200
更新日期:2010-02-01 00:00:00
abstract::The effect of various levels of the oral contraceptive drug, Enovid E, on serum and liver lipid levels of adult female rats has been investigated. Doses ranging from 0.052 to 1.04 mg/day have been employed in rats fed control or cholesterol-containing diets. It has been confirmed that after administration of even low,...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-05-01 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::Acyl-CoA:monoglyceride acyltransferase in microsomal preparations from the small intestine of the rat has been measured by means of continuous recording spectrophotometry. The reaction of 5,5'-dithiobis(2-nitrobenzoic acid) with CoA has been employed for this assay and optimal conditions for the reaction have been def...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1969-07-01 00:00:00
abstract::A new method for the purification of apolipoprotein H by affinity chromatography followed by continuous-elution electrophoresis is described. It is both simpler and less complicated than the chromatographic and electrophoretic methods usually used. In addition, apolipoprotein H is isolated in a pure, structurally uncl...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::The cellular content of total and individual phospholipids and gangliosides was measured in fibroblasts cultured from four normal subjects, three patients with lysosomal lipid storage diseases, and two subjects with homozygous familial hypercholesterolemia. Measurements were made on cells grown in medium containing fe...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1978-03-01 00:00:00
abstract::Apart from exhibiting the presence of lipoprotein [a] in its plasma, another interest of the European hedgehog in lipoprotein research lies in the quantitative prominence of a complex spectrum of high density lipoproteins (HDL) and very high density lipoproteins (VHDL) as cholesterol transporters in plasma (Laplaud, P...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::We elucidated the mechanisms of action of two n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in Jurkat T-cells. Both DHA and EPA were principally incorporated into phospholipids in the following order: phosphatidylcholine < phosphatidylethanolamine < phosphatidylinositol/phosphatidylserine. Fur...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M400444-JLR200
更新日期:2005-04-01 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::HDL and its major component, apolipoprotein A-I (apoA-I), play a central role in reverse cholesterol transport. We recently reported the involvement of a glycosylphosphatidylinositol anchor (GPI anchor) in the binding of HDL and apoA-I on human macrophages, and purified an 80 kDa HDL/apoA-I binding protein. In the pre...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M500425-JLR200
更新日期:2006-01-01 00:00:00
abstract::Chemokines are a family of cytokines inducing cell migration and inflammation. Recent reports have implicated the roles of chemokines in cell differentiation. However, little is known about the functional roles of chemokines in adipocytes. Here, we explored gene expression levels of chemokines and chemokine receptors ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M067207
更新日期:2016-10-01 00:00:00
abstract::The concept that hepatic cholesterol synthesis regulates hepatocyte assembly and secretion of apoB-containing lipoproteins remains controversial. The present study was carried out in HepG2 cells to examine the regulation of apoB secretion by the HMG-CoA reductase inhibitor atorvastatin. ApoB accumulation in the media ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-06-01 00:00:00
abstract::Human monocyte-derived macrophages secrete lipoprotein lipase (LPL) in culture. The regulation of human macrophage LPL production is poorly understood. Since bacterial lipopolysaccharide (LPS) alters production of several macrophage secretory products, its effect on human monocyte-derived macrophage LPL was tested. LP...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Triacylglycerols (TG) are the major storage form of energy in eukaryotic organisms and are synthesized primarily by acyl CoA:1,2-diacylglycerol acyltransferase (DGAT) enzymes. In vitro DGAT activity has previously been quantified by measuring the incorporation of either radiolabeled fatty acyl CoA or diacylglycerol (D...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.D016626
更新日期:2011-09-01 00:00:00