Abstract：
:The mechanisms involved in the development of alcoholic liver disease (ALD) are not well established. We investigated the involvement of acyl-CoA: diacylglycerol acyltransferase 2 (DGAT2) upregulation in mediating hepatic fat accumulation induced by chronic alcohol consumption. Chronic alcohol feeding caused fatty liver and increased hepatic DGAT2 gene and protein expression, concomitant with a significant suppression of hepatic MAPK/ERK kinase/extracellular regulated kinase 1/2 (MEK/ERK1/2) activation. In vitro studies demonstrated that specific inhibitors of the MEK/ERK1/2 pathway increased DGAT2 gene expression and triglyceride (TG) contents in HepG2 cells, whereas epidermal growth factor, a strong ERK1/2 activator, had the opposite effect. Moreover, chronic alcohol feeding decreased hepatic S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio, an indicator of disrupted transmethylation reactions. Mechanistic investigations revealed that N-acetyl-S-farnesyl-L-cysteine, a potent inhibitor of isoprenylcysteine carboxyl methyltransferase, suppressed ERK1/2 activation, followed by an enhanced DGAT2 expression and an elevated TG content in HepG2 cells. Lastly, we demonstrated that the beneficial effects of betaine supplementation in ALD were associated with improved SAM/SAH ratio, alleviated ERK1/2 inhibition, and attenuated DGAT2 upregulation. In conclusion, our data suggest that upregulation of DGAT2 plays an important role in the pathogenesis of ALD, and that abnormal methionine metabolism contributes, at least partially, to DGAT2 upregulation via suppression of MEK/ERK1/2 activation.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Wang Z,Yao T,Song Zdoi
10.1194/jlr.M007948subject
Has Abstractpub_date
2010-11-01 00:00:00pages
3158-65issue
11eissn
0022-2275issn
1539-7262pii
jlr.M007948journal_volume
51pub_type
杂志文章abstract：:Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are the two most common familial dyslipidemias predisposing to premature coronary heart disease (CHD). These dyslipidemias share many phenotypic features, suggesting a partially overlapping molecular pathogenesis. This was supported by our p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400141-JLR200
更新日期：2004-10-01 00:00:00
abstract：:Apolipoprotein (apo)A-IV is synthesized in the small intestine during fat absorption and is incorporated onto the surface of nascent chylomicrons. In circulation, apoA-IV is displaced from the chylomicron surface by high density lipoprotein-associated C and E apolipoproteins; this exchange is critical for activation o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:Five samples from three different types of 1500-year-old Mediterranean amphorae, as well as from a contemporary oil lamp found in the same deposit, were analyzed for the presence of lipid residues. Each sample of finely ground amphorae powder weighed 1-2 g. The abundance of interfering secondary products makes thin-la...
journal_title：Journal of lipid research
pub_type： 历史文章,杂志文章
doi：
更新日期：1981-07-01 00:00:00
abstract：:Extracts of urine and serum from children with cholestatic liver disease were analyzed by fast atom bombardment (FAB) mass spectrometry. About half of all spectra showed a peak at m/z 657, compatible with the presence of a glucuronidated cholestenediol sulfate. Separation by ion exchange chromatography before and afte...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:Several studies indicate that cholesterol esterification is deregulated in cancers. The present study aimed to characterize the role of cholesterol esterification in proliferation and invasion of two tumor cells expressing an activated cholecystokinin 2 receptor (CCK2R). A significant increase in cholesterol esterific...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800668-JLR200
更新日期：2009-11-01 00:00:00
abstract：:The present study was undertaken to investigate the potentiation by p-chlorophenoxyisobutyrate (CPIB) of the antilipolytic effect of insulin in isolated adipocytes from rats fed a (1) sucrose diet, (2) glycerol-lard diet, or (3) chow diet. CPIB supplementation in the diet consistently resulted in decreased serum trigl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
abstract：:Accumulation of foam cells in the neointima represents a key event in atherosclerosis. We previously demonstrated that Tanshinone IIA (Tan), a lipophilic bioactive compound extracted from Salvia miltiorrhiza Bunge, inhibits experimental atherogenesis, yet the detailed mechanisms are not fully understood. In this study...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M040394
更新日期：2014-02-01 00:00:00
abstract：:Mutations in the genes coding for patatin-like phospholipase domain-containing 1 (PNPLA1) and α/β-hydrolase domain-containing 5 (ABHD5), also known as comparative gene identification 58, are causative for ichthyosis, a severe skin barrier disorder. Individuals with mutations in either of these genes show a defect in e...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089771
更新日期：2018-12-01 00:00:00
abstract：:In a randomized, cross-over feeding trial involving 10 men with polygenic hypercholesterolemia, a control, Mediterranean-type cholesterol-lowering diet, and a diet of similar composition in which walnuts replaced approximately 35% of energy from unsaturated fat, were given for 6 weeks each. Compared with the control d...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2001-12-01 00:00:00
abstract：:Normal human plasma HDL was applied to a column of heparin-Sepharose in the presence of MnCl(2) and three fractions were obtained by stepwise elution with increasing NaCl concentrations: a non-retained fraction (NR, 78% of protein) and two retained fractions (R(1) and R(2), 18 and 2.5% of protein, respectively). Both ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:Lipids secreted form the bovine meibomian glands were assigned to following classes: cholesteryl esters (A) (fatty acyl chain lengths from 15 to 27 carbon atoms), 41%; wax esters, 29%; triacylglycerols, 10%; and cholesteryl ester (B) (fatty acyl chain lengths from 14 to 18 carbons), 15%. The remaining 5% consisted of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-07-01 00:00:00
abstract：:The relationship between the cholesterol 7 alpha-hydroxylase activity and the pool of free cholesterol in rat liver microsomes was studied under experimental conditions aimed to stimulate (biliary drainage, cholestyramine treatment, and lymphatic drainage) as well as inhibit (chenodeoxycholic acid treatment) bile acid...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:The effects of polyunsaturated fatty acids (PUFA) on the structure of recombinant high density lipoprotein (rHDL) was investigated using homogeneous particles containing phosphatidylcholine (PC), [3H]cholesterol, and apolipoprotein A-I (apoA-I). The PC component of the rHDL contained sn -1 16:0 and sn -2 18:1 (POPC), ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:The transcriptional regulation of the rat cholesterol 7 alpha-hydroxylase gene (CYP7) by hormones and signal transduction pathways was studied by transient transfection assay of the promoter activity. HepG2 cells were transfected with deletion mutants of the CYP7 upstream region linked to the luciferase reporter gene....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:An enzyme-coupled, colorimetric method for the assay of acyl-CoA synthetase is described. Acyl-CoA formed from fatty acid and CoA by acyl-CoA synthetase was dehydrogenated by acyl-CoA oxidase. Hydrogen peroxide produced was then converted into formaldehyde in the presence of methanol by catalase. The formaldehyde reac...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:The effects of eicosapentaenoic acid and oleic acid on lipid synthesis and secretion by HepG2 cells were examined to identify fatty acid specific changes in lipid metabolism that might indicate a basis for the hypolipidemic effect attributed to eicosapentaenoic acid and related n-3 fatty acids. Cellular glycerolipid s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:Distinct isoforms of long-chain acyl-CoA synthetases (ACSLs) may partition fatty acids toward specific metabolic cellular pathways. For each of the five members of the rat ACSL family, we analyzed tissue mRNA distributions, and we correlated the mRNA, protein, and activity of ACSL1 and ACSL4 after fasting and refeedin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600150-JLR200
更新日期：2006-09-01 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：:The effect of fat feeding on adipocyte insulin binding was examined to expand a study of adaptive changes in plasma membrane functions. Cells from rats fed a high fat (L) diet for five to seven days bound less insulin and showed a decreased response to insulin (glucose oxidation) compared to those from rats fed a high...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-11-01 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：:Endothelial lipase (EL) has been shown to be a critical determinant for high density lipoprotein cholesterol levels in vivo; therefore, assays that measure EL activity have become important for the discovery of small molecule inhibitors that specifically target EL. Here, we describe fluorescent Bodipy-labeled substrat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D600041-JLR200
更新日期：2007-02-01 00:00:00
abstract：:X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by impaired degradation of very long-chain fatty acids (VLCFAs) due to mutations in the ABCD1 gene responsible for VLCFA transport into peroxisomes. Lorenzo's oil, a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, has been used to reduce...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044586
更新日期：2014-03-01 00:00:00
abstract：:ABCA12 mutations disrupt the skin barrier and cause harlequin ichthyosis. We previously showed Abca12(-/-) skin has increased glucosylceramide (GlcCer) and correspondingly lower amounts of ceramide (Cer). To examine why loss of ABCA12 leads to accumulation of GlcCer, de novo sphingolipid synthesis was assayed using [(...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044941
更新日期：2014-03-01 00:00:00
abstract：:Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was perfor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:We studied the effects of the lecithin:cholesterol acyltransferase reaction on the size and composition of the small spherical high density lipoproteins of patients afflicted with familial lecithin:cholesterol acyltransferase deficiency. We isolated these lipoproteins by preparative ultracentrifugation and rate zonal ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
abstract：:SREBP-2 activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in the intestine, we generated a mouse model (Vil-BP2-/- ) in which Cre recombinase ablates SREBP-2 in intestinal epithelia. Intestines of Vil-BP2-/- mice had reduced expression of genes required for sterol synt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M077610
更新日期：2017-10-01 00:00:00
abstract：:Previous studies from our laboratory indicated that pre-germinated brown rice (PR) contained certain unknown bioactive lipids that activated two enzymes related to diabetes: Na+/K+ATPase and homocysteine-thiolactonase. In this paper, we report on the isolation and structural characterization of the activator lipids fr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800257-JLR200
更新日期：2008-10-01 00:00:00
abstract：:Immunological tolerance is one of the fundamental aspects of the immune system. The CD4(+)CD25(+) regulatory T (Treg) cells have emerged as key players in the development of tolerance to self and foreign antigens. However, little is known about the endogenous factors and mechanisms controlling their suppressive capaci...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M900101-JLR200
更新日期：2009-12-01 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：:Free fat cells and stromal-vascular cells were prepared from rat adipose tissue by incubation with collagenase. NH(4)OH-NH(4)Cl extracts of acetone-ether powders prepared from fat cells contained lipoprotein lipase activity but extracts of stromal-vascular cells did not. Intact fat cells released lipoprotein lipase ac...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-07-01 00:00:00
