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Journal of Lipid Research

Valentin Blanchard, Stephane Ramin-Mangata, Stephanie Billon-Crossouard, Audrey Aguesse, Manon Durand, Kevin Chemello, Brice Nativel, Laurent Flet, Maud Chetiveaux, David Jacobi, Jean-Marie Bard, Khadija Ouguerram, Gilles Lambert, Michel Krempf, Mikael Croyal
Human apolipoprotein E (apoE) exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the APOE gene. Total plasma apoE concentrations are closely related to these isoforms but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discriminate between isoforms by identifying specific peptide sequences in subjects (3 E2/E3, 3 E3/E3 and 3 E3/E4 phenotypes) who received a primed constant infusion of2 H3 -leucine for 14 hours...
March 14, 2018: Journal of Lipid Research
Takashi Baba, J Larry Campbell, J C Yves Le Blanc, Paul R S Baker, Kazutaka Ikeda
We report a method for comprehensive structural characterization of lipids in animal tissues using a combination of differential Ion mobility spectrometry (DMS) with electron-impact excitation of ions from organics (EIEIO) mass spectrometry. Singly charged lipid ions in protonated or sodiated forms were dissociated by an electron beam having a kinetic energy of 10 eV in a branched radio-frequency ion trap. We established a comprehensive set of diagnostics to characterize structures of glycerophospholipids, sphingolipids, and acylglycerols, including glycosylated, plasmalogen, and ester forms...
March 14, 2018: Journal of Lipid Research
Ernst R Werner, Markus A Keller, Sabrina Sailer, Daniele Seppi, Georg Golderer, Gabriele Werner-Felmayer, Raphael A Zoeller, Katrin Watschinger
Plasmanylethanolamine desaturase (E.C. introduces the 1-prime double bond into plasmalogens, one of the most abundant phospholipids in the human body. This labile membrane enzyme has not been purified and its coding sequence is unknown. Previous assays for this enzyme used radiolabeled substrates followed by multistep processing. We describe here a straight-forward method for the quantification of plasmanylethanolamine desaturase in enzyme incubation mixtures using pyrene-labeled substrates and reversed phase high performance liquid chromatography (HPLC) with fluorescence detection...
March 14, 2018: Journal of Lipid Research
Di-Li-Da-Er Mu-Han-Ha-Li, Tian-Yu Zhai, Yan Ling, Xin Gao
The connection between lipoprotein(a) [Lp(a)] levels and the risks of cardiovascular disease and diabetes remains poorly understood. Lp(a) is encoded by the LPA gene, and evidence suggests that the kringle IV type 2 (KIV-2) variant is particularly important to Lp(a) isoform size. A large isoform size, represented as a high number of KIV-2 repeats in LPA, is associated with low serum Lp(a) concentrations and an increased risk of type 2 diabetes. We investigated the associations among Lp(a) concentrations, LPA KIV-2 repeats, and type 2 diabetes in a Chinese population of 1,863 consecutive patients with very high cardiovascular risk, as identified by coronary angiography...
March 6, 2018: Journal of Lipid Research
Yasuhiro Horibata, Orly Elpeleg, Ayelet Eran, Yoshio Hirabayashi, David Savitzki, Galit Tal, Hanna Mandel, Hiroyuki Sugimoto
Ethanolamine phosphotransferase 1 (EPT1), also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate (CDP)-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids such as diacyl-linked phosphatidylethanolamine (PE) and ether-linked plasmalogen (plasmenyl-PE). However, to date there has been no analysis of the metabolomic consequence of the mutation of EPT1 on the concentration of ethanolamine glycerophospholipids in mammalian cells...
March 2, 2018: Journal of Lipid Research
Sudichhya Shrestha, Ben J Wu, Liam Guiney, Philip J Barter, Kerry-Anne Rye
Most of the cholesterol in plasma is in an esterified form that is generated in potentially cardioprotective high density lipoproteins (HDLs). Cholesteryl ester transfer protein (CETP) mediates bidirectional transfers of cholesteryl esters (CE) and triglycerides (TG) between plasma lipoproteins. Since CE originates in HDLs, and TG enters the plasma as a component of very low density lipoproteins (VLDLs), activity of CETP results in a net mass transfer of CE from HDLs to VLDLs and low density lipoproteins (LDLs), and of TG from VLDLs to LDLs and HDLs...
February 27, 2018: Journal of Lipid Research
Zhenzhen Zhang, Song Wu, Saeed Muhammad, Qian Ren, Chao Sun
Both miR-103 and 107 have been demonstrated to restrain cell proliferation, regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocytes apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocytes apoptosis. We found that miR-103/107 aggravated Endoplasmic Reticulum (ER) stress mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted Wnt3a (WNT family member 3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes...
February 26, 2018: Journal of Lipid Research
Godfrey S Getz
No abstract.
February 26, 2018: Journal of Lipid Research
Mohamed A Zayed, Fong-Fu Hsu, Bruce W Patterson, Yan Yan, Uzma Naim, Malik Darwesh, Gayan De Silva, Chao Yang, Clay F Semenkovich
Patients with diabetes are at higher risk of developing carotid artery stenosis and resultant stroke. Arachidonoyl phospholipids affect plaque inflammation and vulnerability, but whether diabetic patients have unique carotid artery phospholipidomic profiles is unknown. We performed a comprehensive paired analysis of phospholipids in extracranial carotid endarterectomy (CEA) plaques of matched diabetic and nondiabetic patients and analyzed mass spectrometry-derived profiles of three phospholipids - plasmenyl-phosphatidylethanolamine (pPE), phosphatidylserine (PS), and phosphatidylinositol (PI) - in minimally diseased (MIN) and maximally diseased (MAX) CEA segments...
February 24, 2018: Journal of Lipid Research
Xiaoyan Wang, Van A Villar, Andrew Tiu, Kiran K Upadhyay, Santiago Cuevas
Leptin is a pro-inflammatory cytokine secreted by the adipose tissue. Dopamine D2 receptors (D2R) have anti-inflammatory effects in the brain and kidney tissues. Mouse and human adipocytes express the (D2R); D2R protein was 10-fold greater in adipocytes from human visceral than subcutaneous tissue. However, the function of D2R in adipocytes is not well understood. The D2-like receptor agonist Quinpirole increased the protein expression of leptin and IL-6, not adiponectin and Visfatin, along with their mRNA expression (24 hr)...
February 22, 2018: Journal of Lipid Research
Tamas Kriska, Michael J Thomas, John R Falck, William B Campbell
Polarization of macrophages to pro-inflammatory M1 and to anti-inflammatory alternatively activated M2 states has physiological implications in development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acids (HETE) are essential in the process since disruption of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE into products that are incapable of promoting vasoconstriction...
February 22, 2018: Journal of Lipid Research
Fu-Han Gong, Wen-Lin Cheng, Haiping Wang, Maomao Gao, Juan-Juan Qin, Yan Zhang, Xia Li, Xueyong Zhu, Hao Xia, Zhi-Gang She
Atherosclerosis is generally considered a chronic inflammatory response that can lead to several severe clinical cardiovascular events. MiR-150 is a small non-coding RNA that has been reported to play an important role in regulating endothelial cell proliferation and migration and intravascular environmental homeostasis. However, the exact role that miR-150 plays in atherosclerosis remains unknown. In the present study, miR-150-/-ApoE-/- mice were generated to evaluate the impact of miR-150 deficiency on atherosclerosis development...
February 20, 2018: Journal of Lipid Research
Xin Geng, Marguerite R Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis Frazier-Wood, Hemant K Tiwari, Tushar Dave, Kathleen Ryan, Jose M Ordovas, Robert J Straka, Mary F Feitosa, Paul N Hopkins, Ingrid Borecki, Michael A Province, Braxton D Mitchell, Donna K Arnett, Degui Zhi
Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting low-density lipoprotein cholesterol (LDL-C) response to FFB (P=1...
February 20, 2018: Journal of Lipid Research
Haruto Yamanashi, William E Boeglin, Christophe Morisseau, Robert W Davis, Gary A Sulikowski, Bruce D Hammock, Alan R Brash
Lipoxygenase-catalyzed oxidation of the essential fatty acid linoleate represents a vital step in construction of the mammalian epidermal permeability barrier. Analysis of epidermal lipids indicates the linoleate is converted to a trihydroxy derivative by hydrolysis of an epoxy-hydroxy precursor. We evaluated different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty acid epoxides and compared the products to those of acid-catalyzed hydrolysis. In the absence of enzyme, exposure to pH 5 or pH 6 at 37 deg C for 30 min hydrolyzed fatty acid allylic epoxyalcohols to four trihydroxy products...
February 19, 2018: Journal of Lipid Research
Mikael Larsson, Christopher M Allan, Patrick J Heizer, Yiping Tu, Norma P Sandoval, Rachel S Jung, Rosemary L Walzem, Anne P Beigneux, Stephen G Young, Loren G Fong
GPIHBP1, an endothelial cell protein, binds lipoprotein lipase (LPL) in the subendothelial spaces and transports it to the capillary lumen. In Gpihbp1-/- mice, LPL remains stranded in the subendothelial spaces, causing hypertriglyceridemia, but how Gpihbp1-/- mice respond to metabolic stress (e.g., cold exposure) has never been studied. In wild-type mice, cold exposure increases LPL-mediated processing of triglyceride-rich lipoproteins (TRLs) in brown adipose tissue (BAT), providing fuel for thermogenesis and leading to lower plasma triglyceride levels...
February 15, 2018: Journal of Lipid Research
Heike Gottschall, Christoph Schmoecker, Dirk Hartmann, Nadine Rohwer, Katharina Rund, Laura Kutzner, Fabian Nolte, Annika I Ostermann, Nils Helge Schebb, Karsten H Weylandt
Eicosanoids, including prostaglandins and thromboxanes, are broadly bioactive lipid mediators and increase colon tumorigenesis possibly through chronic inflammatory mechanisms. Epidemiological and experimental data suggest that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly through cyclooxygenase (COX)-mediated suppression of eicosanoid - particularly prostaglandin E2 (PGE2) - formation. Recent studies suggest that statins prevent CRC and improve survival after diagnosis. We identified patients on ASA and/or statin treatment undergoing routine colonoscopy and measured eicosanoid levels in colonic mucosa with targeted metabolomics technology (LC-MS/MS)...
February 14, 2018: Journal of Lipid Research
Wanze Tang, Weilie Ma, Hang Ding, Margarita Lin, Le Xiang, Guorong Lin, Zhizhen Zhang
HDL apolipoprotein A-1-mediated cholesterol efflux pathway requires multiple cellular proteins and signal transduction pathways, including adenylyl cyclase (AC) / cAMP signaling. Due to the existence of multiple transmembrane AC isoforms, it was not known how many AC isoforms are expressed and which ones are essential for cholesterol efflux in macrophage foam cells. These questions were investigated in THP-1 macrophages in this study. QRT-PCR detected mRNAs for all nine transmembrane AC isoforms, but only the mRNA and protein of AC1 isoform were consistently upregulated by cholesterol loading and apoA-1...
February 14, 2018: Journal of Lipid Research
Mark A Duerr, Elisa N D Palladino, Celine L Hartman, James A Lambert, Jacob D Franke, Carolyn J Albert, Sadis Matalon, Rakesh P Patel, Arne Slungaard, David A Ford
α-Chlorofatty aldehydes (α-ClFALD) and α-bromofatty aldehydes (α-BrFALD) are produced in activated neutrophils and eosinophils. This study investigated the ability of α-BrFALD and α-ClFALD to react with the thiols of GSH and protein cysteinyl residues. Initial studies showed 2-bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared to 2-ClHDA as precursor...
February 14, 2018: Journal of Lipid Research
Marco G Casteleijn, Petteri Parkkila, Tapani Viitala, Artturi Koivuniemi
Lecithin-cholesterol acyltransferase (LCAT) is an enzyme responsible for the formation of cholesteryl esters from unesterified cholesterol (UE) and phospholipid (PL) molecules in high-density lipoprotein (HDL) particles. However, it is poorly understood how LCAT interacts with lipoproteins and how apolipoprotein A-I (apoA-I) activates it. Here we have studied the interactions between LCAT and lipids through molecular simulations. In addition, we studied the binding of LCAT to apoA-I derived peptides, and their effect on LCAT lipid association utilizing experiments...
February 8, 2018: Journal of Lipid Research
Xian-Cheng Jiang
PLTP is one of the major modulators of lipoprotein metabolism and atherosclerosis development in humans; however, we still do not quite understand the mechanisms. In mouse models, PLTP overexpression induces atherosclerosis, while its deficiency reduces it. Thus, mouse models were used to explore the mechanisms. In this review, we summarized the major progresses made in the PLTP research field and emphasized its impact on lipoprotein metabolism and atherosclerosis, as well as its own regulation.
February 8, 2018: Journal of Lipid Research
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