Roles of polyunsaturated fatty acids, from mediators to membranes [Reviews]
PUFAs, such as AA and DHA, are recognized as important biomolecules, but understanding their precise roles and modes of action remains challenging. PUFAs are precursors for a plethora of signaling lipids, for which knowledge about synthetic pathways and receptors has accumulated. However, due to their extreme diversity and the ambiguity concerning the identity of their cognate receptors, the roles of PUFA-derived signaling lipids require more investigation. In addition, PUFA functions cannot be explained just as lipid mediator precursors because they are also critical for the regulation of membrane biophysical properties. ...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Harayama, T., Shimizu, T. Tags: Reviews Source Type: research
Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings [Special Reports]
This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Norum, K. R., Remaley, A. T., Miettinen, H. E., Strom, E. H., Balbo, B. E. P., Sampaio, C. A. T. .L., Wiig, I., Kuivenhoven, J. A., Calabresi, L., Tesmer, J. J., Zhou, M., Ng, D. S., Skeie, B., Karathanasis, S. K., Manthei, K. A., Retterstol, K. Tags: Special Reports Source Type: research
Dispersed lipid droplets: an intermediate site for lipid transport and metabolism in primary human adipocytes [Images In Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Moren, B., Stenkula, K. G. Tags: Images In Lipid Research Source Type: research
A high-throughput mass spectrometry-based assay for large-scale profiling of circulating human apolipoproteins [Methods]
Apolipoproteins govern lipoprotein metabolism and are promising biomarkers of metabolic and cardiovascular diseases. Unlike immunoassays, MS enables the quantification and phenotyping of multiple apolipoproteins. Hence, here, we aimed to develop a LC-MS/MS assay that can simultaneously quantitate 18 human apolipoproteins [A-I, A-II, A-IV, A-V, B48, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a)] and determined apoE, apoL1, and apo(a) phenotypes in human plasma and serum samples. The plasma and serum apolipoproteins were trypsin digested through an optimized procedure and peptides were extracted and analyzed by...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Blanchard, V., Garcon, D., Jaunet, C., Chemello, K., Billon-Crossouard, S., Aguesse, A., Garfa, A., Famchon, G., Torres, A., Le May, C., Pichelin, M., Bigot-Corbel, E., Lambert, G., Cariou, B., Hadjadj, S., Krempf, M., Bach-Ngohou, K., Croyal, M. Tags: Methods Source Type: research
2-Chlorofatty acids are biomarkers of sepsis mortality and mediators of barrier dysfunction in rats [Research Articles]
Sepsis is defined as the systemic, dysregulated host immune response to an infection that leads to injury to host organ systems and, often, death. Complex interactions between pathogens and their hosts elicit microcirculatory dysfunction. Neutrophil myeloperoxidase (MPO) is critical for combating pathogens, but MPO-derived hypochlorous acid (HOCl) can react with host molecular species as well. Plasmalogens are targeted by HOCl, leading to the production of 2-chlorofatty acids (2-CLFAs). 2-CLFAs are associated with human sepsis mortality, decrease in vitro endothelial barrier function, and activate human neutrophil extracel...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Pike, D. P., Vogel, M. J., McHowat, J., Mikuzis, P. A., Schulte, K. A., Ford, D. A. Tags: Research Articles Source Type: research
Catalytic residues, substrate specificity, and role in carbon starvation of the 2-hydroxy FA dioxygenase Mpo1 in yeast [Research Articles]
The yeast protein Mpo1 belongs to a protein family that is widely conserved in bacteria, fungi, protozoa, and plants, and is the only protein of this family whose function has so far been elucidated. Mpo1 is an Fe2+-dependent dioxygenase that catalyzes the α-oxidation reaction of 2-hydroxy (2-OH) long-chain FAs (LCFAs) produced in the degradation pathway of the long-chain base phytosphingosine. However, several biochemical characteristics of Mpo1, such as its catalytic residues, membrane topology, and substrate specificity, remain unclear. Here, we report that yeast Mpo1 contains two transmembrane domains and that bo...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Mori, K., Obara, T., Seki, N., Miyamoto, M., Naganuma, T., Kitamura, T., Kihara, A. Tags: Research Articles Source Type: research
15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15-lipoxygenase-2 in biosynthesis of resolvin D5 [Research Articles]
The two oxylipins 7S,14S-dihydroxydocosahexaenoic acid (diHDHA) and 7S,17S-diHDHA [resolvin D5 (RvD5)] have been found in macrophages and infectious inflammatory exudates and are believed to function as specialized pro-resolving mediators (SPMs). Their biosynthesis is thought to proceed through sequential oxidations of DHA by lipoxygenase (LOX) enzymes, specifically, by human 5-LOX (h5-LOX) first to 7(S)-hydroxy-4Z,8E,10Z,13Z,16Z,19Z-DHA (7S-HDHA), followed by human platelet 12-LOX (h12-LOX) to form 7(S),14(S)-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-DHA (7S,14S-diHDHA) or human reticulocyte 15-LOX-1 (h15-LOX-1) to form RvD5. In th...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Perry, S. C., Kalyanaraman, C., Tourdot, B. E., Conrad, W. S., Akinkugbe, O., Freedman, J. C., Holinstat, M., Jacobson, M. P., Holman, T. R. Tags: Research Articles Source Type: research
Human GDPD3 overexpression promotes liver steatosis by increasing lysophosphatidic acid production and fatty acid uptake [Research Articles]
The glycerol phosphate pathway produces more than 90% of the liver triacylglycerol (TAG). LysoPA, an intermediate in this pathway, is produced by glycerol-3-phosphate acyltransferase. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), whose gene was recently cloned, contains lysophospholipase D activity, which produces LysoPA from lysophospholipids. Whether human GDPD3 plays a role in hepatic TAG homeostasis is unknown. We hypothesized that human GDPD3 increases LysoPA production and availability in the glycerol phosphate pathway, promoting TAG biosynthesis. To test our hypothesis, we infected C57BL/6J mi...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Key, C.-C. C., Bishop, A. C., Wang, X., Zhao, Q., Chen, G.-y., Quinn, M. A., Zhu, X., Zhang, Q., Parks, J. S. Tags: Research Articles Source Type: research
Alterations in plasma triglycerides and ceramides: links with cardiac function in humans with type 2 diabetes [Research Articles]
Cardiac dysfunction in T2D is associated with excessive FA uptake, oxidation, and generation of toxic lipid species by the heart. It is not known whether decreasing lipid delivery to the heart can effect improvement in cardiac function in humans with T2D. Thus, our objective was to test the hypothesis that lowering lipid delivery to the heart would result in evidence of decreased "lipotoxicity," improved cardiac function, and salutary effects on plasma biomarkers of cardiovascular risk. Thus, we performed a double-blind randomized placebo-controlled parallel design study of the effects of 12 weeks of fenofibrate-induced li...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Peterson, L. R., Jiang, X., Chen, L., Goldberg, A. C., Farmer, M. S., Ory, D. S., Schaffer, J. E. Tags: Research Articles Source Type: research
The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice [Research Articles]
In conclusion, we have identified an lncRNA Gm15622/miR-742-3p/SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Ma, M., Duan, R., Shen, L., Liu, M., Ji, Y., Zhou, H., Li, C., Liang, T., Li, X., Guo, L. Tags: Research Articles Source Type: research
Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs [Research Articles]
Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequenc...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Call, L., Molina, T., Stoll, B., Guthrie, G., Chacko, S., Plat, J., Robinson, J., Lin, S., Vonderohe, C., Mohammad, M., Kunichoff, D., Cruz, S., Lau, P., Premkumar, M., Nielsen, J., Fang, Z., Olutoye, O., Thymann, T., Britton, R., Sangild, P., Burrin, D. Tags: Research Articles Source Type: research
Sphingolipid distribution at mitochondria-associated membranes (MAMs) upon induction of apoptosis [Research Articles]
The levels and composition of sphingolipids and related metabolites are altered in aging and in common disorders such as diabetes and cancers, as well as in neurodegenerative, cardiovascular, and respiratory diseases. Changes in sphingolipids have been implicated as being an essential step in mitochondria-driven cell death. However, little is known about the precise sphingolipid composition and modulation in mitochondria or related organelles. Here, we used LC-MS/MS to analyze the presence of key components of the ceramide metabolic pathway in vivo and in vitro in purified ER, mitochondria-associated membranes (MAMs), and ...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Mignard, V., Dubois, N., Lanoe, D., Joalland, M.-P., Oliver, L., Pecqueur, C., Heymann, D., Paris, F., Vallette, F. M., Lalier, L. Tags: Research Articles Source Type: research
The plant dehydrin Lti30 stabilizes lipid lamellar structures in varying hydration conditions [Research Articles]
A major challenge to plant growth and survival are changes in temperature and diminishing water supply. During acute temperature and water stress, plants often express stress proteins, such as dehydrins, which are intrinsically disordered hydrophilic proteins. In this article, we investigated how the dehydrin Lti30 from Arabidopsis thaliana stabilizes membrane systems that are exposed to large changes in hydration. We also compared the effects of Lti30 on membranes with those of the simple osmolytes urea and trimethylamine N-oxide. Using X-ray diffraction and solid-state NMR, we studied lipid-protein self-assembly at varyi...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Andersson, J. M., Pham, Q. D., Mateos, H., Eriksson, S., Harryson, P., Sparr, E. Tags: Research Articles Source Type: research
Mass spectrometry imaging and LC/MS reveal decreased cerebellar phosphoinositides in Niemann-Pick type C1-null mice [Research Articles]
Niemann-Pick disease type C1 (NPC1) is a lipid storage disorder in which cholesterol and glycosphingolipids accumulate in late endosomal/lysosomal compartments because of mutations in the NPC1 gene. A hallmark of NPC1 is progressive neurodegeneration of the cerebellum as well as visceral organ damage; however, the mechanisms driving this disease pathology are not fully understood. Phosphoinositides are phospholipids that play distinct roles in signal transduction and vesicle trafficking. Here, we utilized a consensus spectra analysis of MS imaging data sets and orthogonal LC/MS analyses to evaluate the spatial distribution...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Pathmasiri, K. C., Pergande, M. R., Tobias, F., Rebiai, R., Rosenhouse-Dantsker, A., Bongarzone, E. R., Cologna, S. M. Tags: Research Articles Source Type: research
Metabolic regulation of the lysosomal cofactor bis(monoacylglycero)phosphate in mice [Research Articles]
In conclusion, our observations suggest that BMP concentrations adapt to the metabolic state in a tissue- and cell-type-specific manner in mice. Drastic changes observed in hepatocytes, pancreatic cells, and brown adipocytes suggest that BMP plays a role in the functional adaption to nutrient starvation and ambient temperature. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Grabner, G. F., Fawzy, N., Schreiber, R., Pusch, L. M., Bulfon, D., Koefeler, H., Eichmann, T. O., Lass, A., Schweiger, M., Marsche, G., Schoiswohl, G., Taschler, U., Zimmermann, R. Tags: Research Articles Source Type: research
