Abstract：
:The LDL receptor-related protein-1 (LRP1) is highly expressed in numerous cell types, and its impairment is associated with obesity, diabetes, and fatty liver disease. However, the mechanisms linking LRP1 to metabolic disease are not completely understood. Here, we compared the metabolic phenotype of C57BL/6J wild type and LRP1 knock-in mice carrying an inactivating mutation in the distal NPxY motif after feeding a low fat (LF) diet or high fat diets with (HFHC) or without (HF) cholesterol supplementation. In response to HF feeding, both groups developed hyperglycemia, hyperinsulinemia, and hyperlipidemia, as well as increased adiposity with adipose tissue inflammation and liver steatosis. However, when animals were fed the HF diet supplemented with cholesterol, the LRP1 NPxY mutation prevents hypercholesterolemia, reduces adipose tissue and brain inflammation, and limits liver progression to steatohepatitis. Nevertheless, insulin signaling is impaired in LRP1 NPxY mutant hepatocytes and this mutation does not protect against HFHC-induced insulin resistance. The selective metabolic improvement observed in HFHC-fed LRP1 NPxY mutant mice is due to an apparent increase of hepatic LDL receptor levels, leading to an elevated rate of plasma lipoprotein clearance and lowering of plasma and hepatic cholesterol levels. The unique metabolic phenotypes displayed by LRP1 NPxY mutant mice in response to HF or HFHC diet feeding indicate an LRP1-cholesterol axis in modulating tissue inflammation. The LRP1 NPxY mutant mouse phenotype differs from phenotypes observed in mice with tissue-specific LRP1 inactivation, thus highlighting the importance of an integrative approach to evaluate how global LRP1 dysfunction contributes to metabolic disease development.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Jaeschke A,Haller A,Cash JG,Nam C,Igel E,Roebroek AJM,Hui DYdoi
10.1194/jlr.RA120001141subject
Has Abstractpub_date
2020-12-09 00:00:00eissn
0022-2275issn
1539-7262pii
jlr.RA120001141pub_type
杂志文章abstract：:A method has been described for the measurement of apoB concentration and specific activity in very low density lipoprotein (VLDL) and low density lipoprotein (LDL) during metabolic studies. For measurement of specific activity, apoB was separated from other apolipoproteins and lipids by precipitation in, and subseque...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:Fatty acid elongases and desaturases play an important role in hepatic and whole body lipid composition. We examined the role that key transcription factors played in the control of hepatic elongase and desaturase expression. Studies with peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice esta...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600177-JLR200
更新日期：2006-09-01 00:00:00
abstract：:The genetic variability of apolipoprotein E (apoE) influences plasma lipoprotein levels, and allele frequencies differ between African Americans and Caucasians. As African Americans have higher lipoprotein [a] (Lp[a]) levels than Caucasians, we investigated the effects of the apoE gene on allele-specific apolipoprotei...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600431-JLR200
更新日期：2007-03-01 00:00:00
abstract：:Oxidative stress promotes acute kidney injury (AKI). Higher concentrations of HDL cholesterol are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle size and number, paraoxonase-1 activity, and isofuran concentrations ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1016/j.jlr.2021.100024
更新日期：2021-01-13 00:00:00
abstract：:Apolipoprotein (apo) E, via its receptor binding domain contained in residues 140-150, mediates hepatic and peripheral tissue binding of cholesterol-rich lipoproteins. Previously, we reported that a synthetic peptide representing a linear tandem repeat of amino acids 141-155, the 141-155 dimer, binds the low density l...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Cholesterol exists within the hepatocyte as free cholesterol and cholesteryl ester. The proportion of intrahepatic cholesterol in the free or ester forms is governed in part by the rate of cholesteryl ester formation by acyl-coenzyme A:cholesterol acyltransferase (ACAT) and cholesteryl ester hydrolysis by neutral chol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is present in the blood plasma and acts as a pivotal intercellular signal transmitter in the immune system by recruiting lymphocytes from the thymus and secondary lymphoid tissues. The plasma S1P concentration is maintained by the supply of S1P from erythrocytes. Previously, we showed tha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D071068
更新日期：2016-11-01 00:00:00
abstract：:Familial hypobetalipoproteinemia (FHBL) exists in three forms: a) FHBL genetically linked to truncated forms of apolipoprotein B (apoB); b) FHBL linked to the apoB gene but with no apoB truncations; and c) FHBL not linked to the apoB gene. Mean production rate (PR) of apoB-100 in FHBL subjects heterozygous for apoB tr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-03-01 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 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：:Here, we present an improved method for sensitive profiling of lipids in a single high-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry experiment. The approach consists of i) sensitive isocratic elution, which takes advantage of C18 column material that is resistan...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700060-JLR200
更新日期：2007-09-01 00:00:00
abstract：:Genetic defects in SAR1B GTPase inhibit chylomicron (CM) trafficking to the Golgi and result in a huge intraenterocyte lipid accumulation with a failure to release CMs and liposoluble vitamins into the blood circulation. The central aim of this study is to test the hypothesis that SAR1B deletion (SAR1B-/- ) disturbs e...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000119
更新日期：2019-10-01 00:00:00
abstract：:The subcellular and submitochondrial localization of CTP:phosphatidate cytidylyltransferase is altered in the Morris 7777 hepatoma. Mitochondria in this poorly differentiated tumor are the principal sites of CDP-diacylglycerol synthesis, in contrast to normal rat liver where the endoplasmic reticulum is most active. T...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-07-01 00:00:00
abstract：:Mutational inactivation of NPC1 largely blocks the movement of LDL-derived cholesterol from the lysosome to the metabolically active, cytosolic pool of sterol that is the substrate for steroid hormone production. Such a block might, in theory, lead to deficiencies in circulating levels of testosterone, progesterone, a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500534-JLR200
更新日期：2006-05-01 00:00:00
abstract：:Three 14C-labeled 22-carbon polyunsaturated fatty acids, 7,10,13,16-[14C]docosatetraenoic acid (22:4(n-6)), 7,10,13,16,19-[14C]docosapentaenoic acid (22:5(n-3)), and 4,7,10,13,16,19-[14C]docosahexaenoic acid (22:6(n-3)), were compared with [3H]arachidonic acid (20:4(n-6] and [14C]linoleic acid (18:2(n-6)) to character...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
abstract：:Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experimen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:We designed a rapid method for determining mRNA content of cholesterol biosynthesis enzymes and LDL receptor (LDLR) using a ribonuclease protection assay (RPA). 32P-labeled cRNA fragments for genes of human LDLR and the enzymes HMG-CoA synthase (HMGS), HMG-CoA reductase (HMGR), mevalonate kinase (MK), farnesyl pyropho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:The bioactive sphingolipid metabolite, ceramide, regulates physiological processes important for inflammation and elevated levels of ceramide have been implicated in IL-1-mediated events. Although much has been learned about ceramide generation by activation of sphingomyelinases in response to IL-1, the contribution o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M065920
更新日期：2016-08-01 00:00:00
abstract：:Biliary secretion of bile acid glucuronides was studied in control rats and in rats with a congenital defect in hepatobiliary transport of organic anions (GY rats). In control animals, hepatobiliary transport of [3H]lithocholic acid 3-O-glucuronide and [3H]cholic acid 3-O-glucuronide was efficient (greater than 95% in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-12-01 00:00:00
abstract：:Egg triglycerides chromatographed on silicic acid are eluted in a skew curve in which fatty acid composition varies. The triglycerides were cleaved by sodium methoxide in chloroform-methanol at 0 degrees C to yield diglycerides (11.3%) and monoglycerides (17.5% of original triglycerides) after 3 min. Complete cleavage...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-11-01 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：:N-arachidonylethanolamine (AEA) accumulates during brain injury and postmortem. Because fatty acid amide hydrolase (FAAH) regulates brain AEA content, the purpose of this study was to determine its role in the postmortal accumulation of AEA using FAAH null mice. As expected, AEA content in immediately frozen brain tis...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400377-JLR200
更新日期：2005-02-01 00:00:00
abstract：:Native interactions between lysophospholipids (LPs) and their cognate LP receptors are difficult to measure because of lipophilicity and/or the adhesive properties of lipids, which contribute to high levels of nonspecific binding in cell membrane preparations. Here, we report development of a free-solution assay (FSA)...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D120000880
更新日期：2020-08-01 00:00:00
abstract：:Very few studies have investigated the interrelations between proprotein convertase subtilisin/kexin type 9 (PCSK9) metabolism, cholesterol synthesis, and cholesterol absorption. We aimed to address this issue in a large clinical trial of 245 patients with hypercholesterolemia. Serum lipids, PCSK9, lathosterol (choles...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P088583
更新日期：2019-01-01 00:00:00
abstract：:When NH(4)OH-NH(4)Cl extracts of adipose acetone powder were applied to agarose gel chromatography columns, two peaks of lipoprotein lipase were eluted. The first activity peak (LPL(a)) was eluted with an elution volume of a protein of molecular weight approximately five times that of the second (LPL(b)). Addition of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-01-01 00:00:00
abstract：:Optically active 1- or 3-acyl-sn-glycerols were synthesized from 2,3- or 1,2-isopropylidene-sn-glycerols, respectively. The 2,3- or 1,2-isopropylidene-sn-glycerols were condensed with appropriate long saturated or unsaturated fatty acids and the resulting acyl isopropylidene compounds were treated with dimethylboronbr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
abstract：:The transport of LDL-derived cholesterol from lysosomes to peroxisomes is facilitated by membrane contacts formed between the lysosomal protein synaptotagmin VII and the peroxisomal lipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2]. Here, we used RNA interference to search for regulators of PI(4,5)P2 and to stu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M082149
更新日期：2018-03-01 00:00:00
abstract：:To study the role of phospholipids in the lipophorin structure, they were removed by phospholipase A2 treatment. Fluorescence lifetimes and accessibility to acrylamide quenching of different diphenylhexatrienyl derivatives, which were used as analogues of the different lipid components, indicate a surface localization...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Bile acids labeled with 3H on the sterol nucleus lose a substantial fraction of label during enterohepatic cycling and conversion to secondary bile acids. We tested the isotopic stability of a side-chain 3H label, [22,23-3H]cholic acid in humans. The 3H-labeled compound was administered simultaneously with [24-14C]cho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:Autosomal dominant Stargardt-like macular dystrophy (STGD3) in humans results from mutations in elongation of very long chain FAs-like 4 (ELOVL4), which leads to vision loss in young adults. ELOVL4 is an integral endoplasmic reticulum (ER) protein that mediates the elongation of very long chain (VLC) FAs. Mutations in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M045443
更新日期：2014-04-01 00:00:00
