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Journal of Lipid Research

Eric L Klett, Shufen Chen, Alekhya Yechoor, Fred B Lih, Rosalind A Coleman
Because the signaling eicosanoids, epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs), are esterified to membrane phospholipids, we asked which long-chain acyl-CoA synthetase (ACSL) isoforms would activate these molecules and whether the apparent fatty acid substrate preferences of each ACSL isoform might differ depending on whether it was assayed in mammalian cell membranes or as a purified bacterial recombinant protein. We found that all five ACSL isoforms were able to use EETs and HETEs as substrates and showed by LC-MS that ACSLs produce EET-CoAs...
February 16, 2017: Journal of Lipid Research
Blake R Hopiavuori, Martin-Paul Agbaga, Richard S Brush, Michael T Sullivan, William E Sonntag, Robert E Anderson
We present herein a quantitative molecular blueprint of the three major glycerophospholipid (GPL) classes phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE) in retina and six regions of the brain in C57Bl6 mice at 2, 10, and 26 months of age. We found an age-related increase in molecular species containing saturated and monoenoic fatty acids and an overall decrease in the longer chain polyunsaturated fatty acid (PUFA) molecular species across brain regions, with loss of docosahexaenoic acid (DHA)-containing molecular species as the most consistent and dramatic finding...
February 15, 2017: Journal of Lipid Research
Nina H Pipalia, Kanagaraj Subramanian, Shu Mao, Harold Ralph, Darren M Hutt, Samantha M Scott, William E Balch, Frederick R Maxfield
Niemann Pick C disease (NPC) is an autosomal recessive disorder that leads to excessive storage of cholesterol and other lipids in late endosomes and lysosomes. The large majority of NPC disease is caused by mutations in NPC1, a large polytopic membrane protein that functions in late endosomes. There are many disease-associated mutations in NPC1, and most patients are compound heterozygotes. The most common mutation NPC1I1061T has been shown to cause endoplasmic reticulum associated degradation of the NPC1 protein...
February 13, 2017: Journal of Lipid Research
Ilke Vermeulen, Mark Baird, Juma Al-Dulayymi, Muriel Smet, Jan Verschoor, Johan Grooten
The differentiation of macrophages into lipid-filled foam cells is a hallmark of the lung granuloma that forms in patients with active tuberculosis (TB). Mycolic acids (MAs), the abundant lipid virulence factors in the cell wall of Mycobacterium tuberculosis (Mtb), can induce this foam phenotype possibly as a way to perturb host cell lipid homeostasis to support the infection. It is not exactly clear how MAs allow differentiation of foam cells during Mtb infection. Here we investigated how chemically synthetic MAs, each with a defined stereochemistry similar to natural Mtb-associated mycolates, influence cell foamy phenotype and mycobacterial proliferation in murine host macrophages...
February 13, 2017: Journal of Lipid Research
Hui Qi, Shrestha Priyadarsini, Sarah E Nicholas, Akhee Sarker-Nag, Jeremy Allegood, Charles E Chalfant, Nawajes A Mandal, Dimitrios Karamichos
The pathophysiology of human keratoconus (KC), a bilateral progressive corneal disease, leading to protrusion of the cornea, stromal thinning, and scarring is not well understood. In this study we investigated a novel Sphingolipid (SPL) signaling pathway through which KC may be regulated. Using human corneal fibroblasts (HCF) and human keratoconus cells (HKC) we examined the SPL pathway modulation. Both cell types were stimulated by the three TGF-β isoforms: TGF-B1 (T1), B2 (T2), and B3 (T3). All samples were analyzed using lipidomics, and real time-PCR...
February 10, 2017: Journal of Lipid Research
Mingwei Liu, Rui Ge, Wanlin Liu, Qiongming Liu, Xia Xia, Mi Lai, Lizhu Liang, Chen Li, Lei Song, Bei Zhen, Jun Qin, Chen Ding
Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets (LD) enclosed in a monolayer of phospholipids and associated proteins (LDP). Growing evidence has demonstrated that LDPs play important roles in the pathogenesis of liver diseases. However, the composition of liver LDPs and role of their alterations in hepatosteatosis is not well understood. In this study, we performed liver proteome and lipid droplet sub-proteome profiling to identify enriched proteins in LD as LDPs, and quantified their changes in a high fat diet induced (HFD) fatty liver model...
February 8, 2017: Journal of Lipid Research
Kensuke Iwasa, Shinji Yamamoto, Sosuke Yagishita, Kei Maruyama, Keisuke Yoshikawa
Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD2, PGE2 and PGF2alpha are produced by Cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration...
February 7, 2017: Journal of Lipid Research
Marina Cuchel, Anna C Raper, Donna M Conlon, Daniel A Pryma, Richard H Freifelder, Rahul Poria, Debra Cromley, Xiaoyu Li, Richard L Dunbar, Benjamin French, Liming Qu, William Farver, Ching-Chiang Su, Sissel Lund-Katz, Amanda Baer, Giancomo Ruotolo, Peter Akerblad, Carol S Ryan, Lan Xiao, Todd G Kirchgessner, John S Millar, Jeffrey T Billheimer, Daniel J Rader
AIM: Reverse cholesterol transport (RCT) is thought to be an atheroprotective function of HDL, and macrophage-specific RCT in mice is inversely associated with atherosclerosis. We developed a novel method using 3H-cholesterol nanoparticles to selectively trace macrophage-specific RCT in vivo in humans. METHODS: Use of 3H-cholesterol nanoparticles was initially tested in mice to assess the distribution of tracer and response to interventions known to increase RCT...
February 6, 2017: Journal of Lipid Research
Kelly M Hines, Josi Herron, Libin Xu
Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report the combination of hydrophilic interaction liquid chromatography (HILIC) with traveling wave IM-MS (TWIM-MS) for comprehensive lipidomics analysis. Main lipid categories such as glycerolipids, sphingolipids, and glycerophospholipids are separated on the basis of their lipid backbones in the IM dimension while sub-classes of each category are mostly separated based on their headgroups in the HILIC dimension, demonstrating the orthogonality of HILIC and IM separations...
February 6, 2017: Journal of Lipid Research
Nathan L Meyers, Mikael Larsson, Evelina Vorrsjö, Gunilla Olivecrona, Donald M Small
Plasma apolipoprotein C-III (apoC-III) levels correlate with triglyceride (TG) levels and are a strong predictor of cardiovascular disease outcomes. ApoC-III elevates TG in part by inhibiting lipoprotein lipase (LPL). ApoC-III likely inhibits LPL by competing for lipid-binding. To probe this, we used oil-drop tensiometry to characterize binding of six apoC-III variants to lipid/water interfaces. This technique monitors the dependence of lipid-binding on surface pressure; which increases during TG hydrolysis by LPL...
February 3, 2017: Journal of Lipid Research
Javeed J Jattan, Cayla N Rodia, Diana Li, Adama C Diakhate, Hongli Dong, Amy M Bataille, Noah F Shroyer, Alison B Kohan
Since its initial report in 2009, the intestinal enteroid culture system has been a powerful tool used to study stem cell biology and development in the gastrointestinal tract. However, a major question is whether enteroids retain intestinal function and physiology. There have been significant contributions describing ion transport physiology of human intestinal organoid cultures, as well as physiology of gastric organoids, but critical studies on dietary fat absorption and chylomicron synthesis in primary intestinal enteroids have not been undertaken...
February 3, 2017: Journal of Lipid Research
Jelske N van der Veen, Susanne Lingrell, Xia Gao, Abhijit Takawale, Zamaneh Kassiri, Dennis E Vance, René L Jacobs
BACKGROUND AND AIMS: Mice lacking phosphatidylethanolamine N-methyltransferase (PEMT) are protected from high-fat diet (HFD)-induced obesity and insulin resistance. However, these mice develop severe non-alcoholic fatty liver disease (NAFLD) when fed the HFD, which is mainly due to inadequate secretion of VLDL particles. Our aim was to prevent NAFLD development in mice lacking PEMT. METHODS: We treated Pemt-/- mice with either ezetimibe or fenofibrate to see if either could ameliorate liver disease in these mice...
February 3, 2017: Journal of Lipid Research
Prabuddha Dey, Wen-Min Su, Gil-Soo Han, George M Carman
Protein kinase C in Saccharomyces cerevisiae, i.e., Pkc1, is an enzyme that plays an important role in signal transduction and the regulation of lipid metabolic enzymes. Pkc1 is structurally similar to its counterparts in higher eukaryotes, but its requirement of phosphatidylserine and diacylglycerol for catalytic activity has been unclear. In this work, we examined the role of these lipids in Pkc1 activity with protein and peptide substrates. In agreement with previous findings, yeast Pkc1 did not require phosphatidylserine and diacylglycerol for its activity on the peptide substrates derived from lipid metabolic proteins such as Pah1 (phosphatidate phosphatase), Nem1 (phosphatidate phosphatase phosphatase), and Spo7 (protein phosphatase catalytic subunit)...
February 2, 2017: Journal of Lipid Research
Meei-Hua Lin, Jeffery Miner, John Turk, Fong-Fu Hsu
1-O-acylceramide is a new class of epidermal ceramide found in humans and mice. Here, we report ESI linear ion-trap (LIT) multiple stage mass spectrometric (MSn) approach with high resolution towards structural characterization of this lipid family isolated from mice. Molecular species desorbed as the [M + H]+ ions was subjected to LIT MS2 to yield predominately the [M + H - H2O]+ ions, followed by MS3 to cleave the 1-O-acyl residue to yield the [M + H - H2O - (1-O-fatty acid)]+ ions. The structures of the N-acyl chain and long-chain base (LCB) of the molecule were determined by MS4 on ([M + H - H2O - (1-O-fatty acid)]+) ions that yielded multiple sets of specific ions...
February 2, 2017: Journal of Lipid Research
Debin Wan, Jun Yang, Bogdan Barnych, Sung Hee Hwang, Kin Sing Stephen Lee, Yongliang Cui, Jun Niu, Mitchell A Watsky, Bruce D Hammock
There is an increased demand in the comprehensive analysis of vitamin D metabolites. This is a major challenge, especially for 1 α,25(OH)2VitD since it is biologically active at picomolar concentrations. 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) was a revolutionary reagent in dramatically increasing sensitivity of all diene metabolites and allowing the routine analysis of the bioactive but minor vitamin D metabolites. A second generation of reagents used large fixed charge groups in the dienophile that increased sensitivity at the cost of a deterioration in chromatographic separation of the vitamin D derivatives...
February 1, 2017: Journal of Lipid Research
Clara Stiebing, Lisa Schmoelz, Maria Wallert, Christian Matthaeus, Stefan Lorkowski, Juergen Popp
Raman spectroscopic imaging was used to investigate the uptake of oxidized low-density lipoproteins (oxLDL) by human macrophages. To better understand the receptor-mediated pathway and the intracellular fate of modified lipoproteins is of foremost interest with regard to the development of atherosclerotic plaques. To obtain information on the storage process of lipids caused by oxLDL uptake, Raman spectroscopic imaging was used because of its unique chemical specificity, especially for lipids. For the present study, a protocol was established to incorporate deuterated tripalmitate into oxLDL...
January 31, 2017: Journal of Lipid Research
Shigenobu Emoto, Makoto Kurano, Kuniyuki Kano, Keisuke Matsusaki, Hiroharu Yamashita, Masako Nishikawa, Koji Igarashi, Hitoshi Ikeda, Junken Aoki, Joji Kitayama, Yutaka Yatomi
Lysophosphatidic acid (LysoPA) has been proposed to be involved in the pathogenesis of various cancers. Moreover, glycero-lysophospholipids other than LysoPA are now emerging as novel lipid mediators. Therefore, we aimed to elucidate the possible involvement of glycero-lysophospholipids in the pathogenesis of gastric cancer by measuring glycero-LPLs, autotaxin, and phosphatidylserine-specific phospholipase A1 (PS-PLA1) in ascites obtained from patients with gastric cancer and those with cirrhosis (as a control)...
January 31, 2017: Journal of Lipid Research
Takashi Kuwano, Xin Bi, Eleonora Cipollari, Tomoyuki Yasuda, William R Lagor, Hannah J Szapary, Junichiro Tohyama, John S Millar, Jeffrey T Billheimer, Nicholas N Lyssenko, Daniel J Rader
Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of high-density lipoprotein (HDL). Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral vector, and control and PLTP deletion animals were injected with AAV-null...
January 30, 2017: Journal of Lipid Research
Kazuyuki Kasahara, Takeshi Tanoue, Tomoya Yamashita, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Taiji Mizoguchi, Tomohiro Hayashi, Naoki Kitano, Naoto Sasaki, Koji Atarashi, Kenya Honda, Ken-Ichi Hirata
The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free (GF) or conventionally raised (Conv) Apolipoprotein E deficient (ApoE(-/-)) mice were fed chow diet and sacrificed at twenty weeks of age. We found lack of gut microbiota in ApoE(-/-) mice caused a significant increase in the plasma and hepatic cholesterol levels compared to ConvR ApoE(-/-) mice...
January 27, 2017: Journal of Lipid Research
Misbaudeen Abdul-Hammed, Bernadette Breiden, Günter Schwarzmann, Konrad Sandhoff
Glucosylceramide is the primary storage lipid in the lysosomes of Gaucher patients and a secondary one in Niemann-Pick disease types A, B and C. The regulatory roles of lipids on the hydrolysis of membrane bound glucosylceramide by glucocerebrosidase GBA1 was probed using a detergent-free liposomal assay. The degradation rarely occurs at uncharged liposomal surfaces in the absence of Sap C. However, anionic lipids stimulate glucosylceramide hydrolysis at low pH by up to 1000 fold depending on the nature and position of the negative charges in their head groups while cationic lipids inhibit the degradation, thus showing the importance of electrostatic interactions between the polycationic GBA1 and the negatively charged vesicle surfaces at low pH...
January 26, 2017: Journal of Lipid Research
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