Abstract：
:Cystic fibrosis (CF) patients and model systems exhibit consistent abnormalities in PUFA metabolism, including increased metabolism of linoleate to arachidonate. Recent studies have connected these abnormalities to increased expression and activity of the Δ6- and Δ5-desaturase enzymes. However, the mechanism connecting these changes to the CF transmembrane conductance regulator (CFTR) mutations responsible for CF is unknown. This study tests the hypothesis that increased activity of AMP-activated protein kinase (AMPK), previously described in CF bronchial epithelial cells, causes these changes in fatty acid metabolism by driving desaturase expression. Using CF bronchial epithelial cell culture models, we confirm elevated activity of AMPK in CF cells and show that it is due to increased phosphorylation of AMPK by Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ). We also show that inhibition of AMPK or CaMKKβ reduces desaturase expression and reverses the metabolic alterations seen in CF cells. These results signify a novel AMPK-dependent mechanism linking the genetic defect in CF to alterations in PUFA metabolism.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Umunakwe OC,Seegmiller ACdoi
10.1194/jlr.M050369subject
Has Abstractpub_date
2014-07-01 00:00:00pages
1489-97issue
7eissn
0022-2275issn
1539-7262pii
jlr.M050369journal_volume
55pub_type
杂志文章abstract：:ABCB4, which is specifically expressed on the canalicular membrane of hepatocytes, exports phosphatidylcholine (PC) into bile. Because SM depletion increases cellular PC content and stimulates PC and cholesterol efflux by ABCA1, a key transporter involved in generation of HDL, we predicted that SM depletion also stimu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M056622
更新日期：2015-03-01 00:00:00
abstract：:Rod outer segments (ROSs) are specialized light-sensitive organelles in vertebrate photoreceptor cells. Lipids in ROS are of considerable importance, not only in providing an adequate environment for efficient phototransduction, but also in originating the second messengers involved in signal transduction. ROSs have t...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R001891
更新日期：2010-04-01 00:00:00
abstract：:Two novel mutations were identified in a compound heterozygous male with lecithin:cholesterol acyltransferase (LCAT) deficiency. Exon sequence determination of the LCAT gene of the proband revealed two novel heterozygous mutations in exons one (C110T) and six (C991T) that predict non-conservative amino acid substituti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:This study aimed at measuring the influence of a low salt diet on the development of experimental atherosclerosis in moderately hyperlipidemic mice. Experiments were carried out on LDL receptor (LDLR) knockout (KO) mice, or apolipoprotein E (apoE) KO mice on a low sodium chloride diet (LSD) as compared with a normal s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200330-JLR200
更新日期：2003-04-01 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 apoE gene exhibits two common polymorphisms that have been associated with both coronary artery disease and Alzheimer's disease. The polymorphisms create the three allelic isoforms E2, E3, and E4 which are encoded by Cys;-Cys, Cys;-Arg, and Arg;-Arg at amino acid positions 112 and 158, respectively. Numerous metho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
abstract：:Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholest...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M053439
更新日期：2015-01-01 00:00:00
abstract：:Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder (OMIM #270400) caused by autosomal recessive mutations in the Dhcr7 gene, which encodes the enzyme 3β-hydroxysterol-∆7 reductase. SLOS patients present clinically with dysmorphology and neurological, behavioral and cognitive defects, with characteristically...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120001101
更新日期：2020-11-17 00:00:00
abstract：:Percent cholesterol absorption was measured in 94 normal subjects aged 17- 80 years while consuming diets generally low in cholesterol (mean intake = 226 +/- 126 mg/day). A new dual stable isotope method was used where a cholesterol tracer containing 6 extra mass units was given intravenously and another tracer with 5...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:Diet-induced changes in high density lipoprotein (HDL) density and size were studied in patas monkeys. When the animals were switched from a moderate fat-low cholesterol diet to a high fat-high cholesterol (HFHC) diet, the plasma apoA-I levels increased initially in all of the animals. The apoA-I levels remained eleva...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:It has been suggested that phytosterol and phytostanol esters possess similar cholesterol-lowering properties, however, whether mechanisms responsible are identical has not been addressed. To address this question, cholesterol plasma levels, absorption, biosynthesis, and turnover were measured in 15 hypercholesterolem...
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：2000-05-01 00:00:00
abstract：:Circulating triacylglycerol (TG) arises mainly from dietary fat. However, little is known about the entry of dietary fat into the major TG pool, very low-density lipoprotein (VLDL) TG. We used a novel method to study the specific incorporation of dietary fatty acids into postprandial VLDL TG in humans. Eight healthy v...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.M300167-JLR200
更新日期：2003-11-01 00:00:00
abstract：:In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic p...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R054114
更新日期：2015-06-01 00:00:00
abstract：:Imidazole catalyzed acylations of lysolipids by acyl-CoAs in water at room temperature and at a pH close to neutrality. In the presence of oleoyl-CoA and either lysophosphatidylcholine, 1-palmitoyl-sn-glycero-3-phosphocholine (LPC); lysophosphatidylglycerol, monoacyl-sn-glycero-3-phosphoglycerol; lysophosphatidyl acid...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200075-jlr200
更新日期：2002-07-01 00:00:00
abstract：:3alpha-Hydroxy-5-cholanoic acid (lithocholic acid) and some unidentified acids (one of them perhaps 3-hydroxy-cholest-5-en-26-oic acid) have been detected in the brains of guinea pigs afflicted with experimental "allergic" encephalomyelitis. None of the acids could be identified in comparable amounts of brain tissue f...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-01-01 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：:The regulation of hepatic and intestinal 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and acyl-CoA; cholesterol acyltransferase (ACAT) activities by dietary fish oil was examined in the rabbit. Rabbits were fed 10% menhaden oil or menhaden oil plus 1% cholesterol for 14 days. They were compared with animals fed ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-01-01 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：:We previously reported that liver-specific overexpression of ABCG5/G8 in mice is not atheroprotective, suggesting that increased biliary cholesterol secretion must be coupled with decreased intestinal cholesterol absorption to increase net sterol loss from the body and reduce atherosclerosis. To evaluate this hypothes...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600353-JLR200
更新日期：2007-01-01 00:00:00
abstract：:Glycerolipid and apoB synthesis and secretion were examined in hepatocytes obtained from fetal, suckling (day 6), and adult rats in order to examine the developmental regulation of lipoprotein production. The capacity to synthesize [3H]triacylglycerol (from [3H]glycerol) followed the order: adult greater than day 6 gr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
abstract：:A reversed phase high performance liquid chromatographic (HPLC) method was developed for direct profiling and determination of adrenal cholesteryl ester composition. Cholesteryl adrenate and cholesteryl cervonate, which are not commercially available, were synthesized as markers. Lipid extracts of rat adrenal homogena...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:In human serum, polymorphism of apoA-II predominantly in HDL3 could be demonstrated. HDL3-apoA-II was composed of four isoproteins, each with a molecular weight of 8600 (reduced form) and identical immunological properties. The isoproteins are designated apoA-II-1 (pI 5.16), apoA-II-2 (pI 4.89) corresponding to the al...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-08-01 00:00:00
abstract：:The effect of inhibiting lysosomal protein degradation on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was determined using a mouse mammary cell line (TS-85) which expresses a temperature-sensitive mutation in the ubiquitin degradative pathway. Incubating cells for 18 hr in medium containi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Acyl-CoA-dependent O-acyltransferases catalyze reactions in which fatty acyl-CoAs are joined to acyl acceptors containing free hydroxyl groups to produce neutral lipids. In this report, we characterize a human multifunctional O-acyltransferase (designated MFAT) that belongs to the acyl-CoA:diacylglycerol acyltransfera...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500168-JLR200
更新日期：2005-11-01 00:00:00
abstract：:The total nitrogen and L-hydroxyproline concentrations of two intra-abdominal and two subcutaneous sites of adipose tissue were measured in male and female Wistar rats. At 100 g body weight the nitrogen concentration of intra-abdominal adipose tissue was slightly lower than that of subcutaneous adipose tissue. As age ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-07-01 00:00:00
abstract：:Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation. PCSK9 is transcriptionally activated by sterol response element-bin...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P009860
更新日期：2010-11-01 00:00:00
abstract：:LPL is an enzyme involved in the breakdown and uptake of lipoprotein triglycerides. In the present study, we examined how the transgenic (Tg) overexpression of human LPL in mouse skeletal muscle affected tolerance to cold temperatures, cold-induced thermogenesis, and fuel utilization during this response. Tg mice and ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700519-JLR200
更新日期：2008-04-01 00:00:00
abstract：:The rate of removal of phosphatidylethanolamine and phosphatidylcholine from the plasma of rats treated with antiserum to hepatic lipase was measured. The hepatic lipase antiserum was injected intravenously into animals prior to injection of 32P-labeled chylomicrons or 32P-labeled high density lipoproteins. In experim...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-06-01 00:00:00
abstract：:The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M045989
更新日期：2014-10-01 00:00:00
abstract：:This study determined the effects of apoA-I, HDL3, or hydroxy-beta-cyclodextrin on apoB-100 secretion and bile acid synthesis by HepG2 cells. The principal observations were that: 1) ApoB-100 secretion into the medium was significantly less after the addition of any of the three agents. 2) Triglyceride mass was not si...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200187-JLR200
更新日期：2003-03-01 00:00:00
