Abstract：
:Our previous studies have demonstrated the activity of oncostatin M (OM) in stimulating the transcription of the human LDL receptor (LDLR) gene in HepG2 cells through a sterol-independent regulatory mechanism. The current studies were designed to determine whether this in vitro property of OM could be recapitulated in vivo to increase LDLR expression in cholesterol-loaded livers and consequently decrease plasma levels of LDL-cholesterol (LDL-C) and total cholesterol (TC) using hypercholesterolemic hamsters as an experimental model. We show that administration of human recombinant OM for 7 days in hamsters fed a high-fat diet significantly reduced plasma levels of TC, LDL-C, and triglyceride in dose- and time-dependent manners. This lipid-lowering effect was associated with increased hepatic LDLR mRNA expression, as determined by quantitative real-time RT-PCR. Additionally, hepatic fat storage and cholesterol content in the hypercholesterolemic animals were substantially reduced by OM treatment. As a consequence, the increased aminotransferase levels in the high-fat diet-fed hamsters were normalized nearly to baseline values. These results not only corroborate the in vitro finding of OM in the regulation of LDLR but also, for the first time, demonstrate that OM has a strong lipid-lowering effect under in vivo conditions in which the levels of circulating LDL-C are high and liver LDLR transcription is repressed.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Kong W,Abidi P,Kraemer FB,Jiang JD,Liu Jdoi
10.1194/jlr.M400425-JLR200keywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
1163-71issue
6eissn
0022-2275issn
1539-7262pii
M400425-JLR200journal_volume
46pub_type
杂志文章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：:Experimental approaches involving the perfusion of tissues and organs offer the advantage of improved physiological relevance over the use of isolated tissues or cells while at the same time being much more controlled and tissue-specific than studies in vivo. Nevertheless, there have been few metabolic studies perform...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D500016-JLR200
更新日期：2005-08-01 00:00:00
abstract：:Various detergents can be used to dissolve phospholipids, resulting in very narrow 31PNMR resonances. The resonances are well resolved, allowing identification and quantitative analysis of phospholipids in a mixture. The chemical shift depends strongly on pH, reflecting changes in the state of ionization of the phosph...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-03-01 00:00:00
abstract：:A woman with primary lipoprotein lipase (LPL) deficiency developed marked hypertriglyceridemia, pancreatitis, eruptive xanthomas, and unusual palmar xanthomas during pregnancy. Hypotheses to account for the palmar xanthomas were that oxidative modification of triglyceride (TG)-rich lipoproteins occurred due to increas...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:This study was undertaken to determine the mechanisms that regulate cholesterol synthesis in vivo and to quantitate the relative importance of the liver and extrahepatic tissues as sites for sterol synthesis. Rats were administered [3H]water intravenously and killed 1 hour later. The amount of [3H]water incorporated i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-03-01 00:00:00
abstract：:The recognition that the 7 alpha-hydroxylation of 27-hydroxycholesterol is catalyzed by an enzyme that is different from cholesterol 7 alpha-hydroxylase raises the question as to the number of similar enzymes that may be present in liver and subserve bile acid synthesis. Thus, both 3 beta-hydroxy-5-cholestenoic acid a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Lipid-containing deposits within the swim bladders of Coryphaenoides acrolepis and Antimora rostrata were investigated. Lipid analysis of this material, which was quite uniform from the two species, yielded the following data: neutral lipids, 36.0-41.7%; phospholipids, 53.6-56.7%; and glycolipids, 4.3-8.9%. Cholestero...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-05-01 00:00:00
abstract：:Apolipoprotein A-IV (apoA-IV) is involved in the metabolism of chylomicrons and high density lipoproteins. It displays genetic polymorphism due to two co-dominant alleles apoA-IV1 and apoA-IV2. The mutation that causes the polymorphism is a G to T substitution in the third base of codon 360 in the apoA-IV2 allele whic...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:We report on the effect of human apolipoprotein (apo) A-II transgene expression on atherosclerosis susceptibility in two transgenic lines (25.3 and 11.1) whose plasma human apoA-II concentrations (approximately 23 and 96 mg/dl, respectively) span the normal range in humans. After 9 months of an atherogenic diet, 25.3 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:This report describes the chemical synthesis of isoursocholic acid (3 beta, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid) from its corresponding 3 alpha-analog. The method consists of refluxing a mixture of ursocholic acid, triphenylphosphine, and diethyl azodicarboxylate in benzene solution with an acid such as ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
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：:Remnant-like emulsions were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice the remnant-like emulsions labeled with cholesteryl[13C]oleate were metabolized in the liver and the appearance of 13CO2 in the breath wa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:Apolipoprotein E plays a critical role in plasma lipoprotein clearance. Peptide models of a highly conserved, N-terminal domain of this protein have been shown to increase the binding of low density lipoprotein (LDL) to fibroblast cell surfaces independently of the low density lipoprotein receptor. Here we provide dat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:A higher incidence of coronary artery disease is associated with a lower level of HDL-cholesterol. We searched for genetic loci influencing HDL-cholesterol in F2 mice from a cross between MRL/MpJ and SM/J mice. Quantitative trait loci (QTL) mapping revealed one significant HDL QTL (Apoa2 locus), four suggestive QTL on...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M025833
更新日期：2012-06-01 00:00:00
abstract：:The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M082362
更新日期：2018-02-01 00:00:00
abstract：:Ursodeoxycholic acid (UDCA, ursodiol) is used to prevent damage to the liver in patients with primary biliary cirrhosis. The drug also prevents the progression of colorectal cancer and the recurrence of high-grade colonic dysplasia. However, the molecular mechanism by which UDCA elicits its beneficial effects is not e...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M021733
更新日期：2012-04-01 00:00:00
abstract：:Diseases such as obesity, diabetes, and atherosclerosis result from multiple genetic and environmental factors, and importantly, interactions between genetic and environmental factors. Identifying susceptibility genes for these diseases using genetic and genomic technologies is accelerating, and the expectation over t...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R600026-JLR200
更新日期：2006-12-01 00:00:00
abstract：:The purpose of the present study was to examine the regulation of levels of apolipoprotein B (apoB) mRNA and its protein by cytokines in HepG2 cells. A dose-dependent increase in apoB mRNA levels was observed in the presence of either interleukin-1beta (IL-1beta) or IL-6 alone. This increase occurred as early as 1 h a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:Apolipoprotein (apo)A-I is the major protein component of HDL and the cofactor for LCAT. We describe a large Spanish kindred, living in the Mediterranean Island of Mallorca, that presents a dominant form of hypoalphalipoproteinemia. The lipid profile of this family was studied because the proband, a 40-year-old male p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-01-01 00:00:00
abstract：:Using thin-layer chromatography and glass capillary gas-liquid chromatography, we have quantitated the lipids in the germinative, differentiating, and fully cornified layers in human epidermis. As previously noted in nonhuman species, we found progressive depletion of phospholipids coupled with repletion of sterols an...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-02-01 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：:Apolipoprotein A-II (apoA-II) is the second major apolipoprotein following apolipoprotein A-I (apoA-I) in HDL. ApoA-II has multiple physiological functions and can form senile amyloid fibrils (AApoAII) in mice. Most circulating apoA-II is present in lipoprotein A-I/A-II. To study the influence of apoA-I on apoA-II and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M013235
更新日期：2011-08-01 00:00:00
abstract：:The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-09-01 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：:Chylomicron metabolism is critical for determining plasma levels of triacylglycerols (TAGs) and cholesterol, both of which are risk factors for CVD. The rates of chylomicron secretion and remnant clearance are controlled by intracellular and extracellular factors, including apoC-III. We have previously shown that huma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M092460
更新日期：2019-09-01 00:00:00
abstract：:The class B scavenger receptors SR-BI and CD36 exhibit a broad ligand binding specificity. SR-BI is well characterized as a HDL receptor that mediates selective cholesteryl ester uptake from HDL. CD36, a receptor for oxidized LDL, also binds HDL and mediates selective cholesteryl ester uptake, although much less effic...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300417-JLR200
更新日期：2004-04-01 00:00:00
abstract：:The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hyp...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P026005
更新日期：2012-07-01 00:00:00
abstract：:Ceramides containing phytosphingosine as base and one of the fatty acids 16:0, 18:0, 20:0, 22:0, 23:0, and 24:0, were prepared by direct coupling in the presence of a mixed carbodiimide. The ceramides were analyzed as the 1,3,4-tri-O-trimethylsilyl ether derivatives by gas-liquid chromatography-mass spectrometry. Gas ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-05-01 00:00:00
abstract：:Binding of the medium-chain fatty acids (MCFA), octanoic (OCT) and decanoic (DEC) acid, to human serum albumin (HSA) has been studied by 13C NMR spectroscopy. NMR spectra at 35 degrees C showed an apparently homogeneous binding environment (a single, narrow resonance for the 13C-enriched carboxyl carbon) at different ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
