Unlabeled lysophosphatidic acid receptor binding in free solution as determined by a compensated interferometric reader [Methods]
In conclusion, FSA-CIR offers a new increased-throughput approach to assess quantitatively label-free lipid ligand-receptor binding, including nonactivating antagonist binding, under near-native conditions. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Ray, M., Nagai, K., Kihara, Y., Kussrow, A., Kammer, M. N., Frantz, A., Bornhop, D. J., Chun, J. Tags: Methods Source Type: research

Yeast phosphatidic acid phosphatase Pah1 hops and scoots along the membrane phospholipid bilayer [Research Articles]
PA phosphatase, encoded by PAH1 in the yeast Saccharomyces cerevisiae, catalyzes the Mg2+-dependent dephosphorylation of PA, producing DAG at the nuclear/ER membrane. This enzyme plays a major role in triacylglycerol synthesis and in the regulation of phospholipid synthesis. As an interfacial enzyme, PA phosphatase interacts with the membrane surface, binds its substrate, and catalyzes its reaction. The Triton X-100/PA-mixed micellar system has been utilized to examine the activity and regulation of yeast PA phosphatase. This system, however, does not resemble the in vivo environment of the membrane phospholipid bilayer. W...
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Kwiatek, J. M., Carman, G. M. Tags: Research Articles Source Type: research

Locations and contributions of the phosphotransferases EPT1 and CEPT1 to the biosynthesis of ethanolamine phospholipids [Research Articles]
The final step of the CDP-ethanolamine pathway is catalyzed by ethanolamine phosphotransferase 1 (EPT1) and choline/EPT1 (CEPT1). These enzymes are likely involved in the transfer of ethanolamine phosphate from CDP-ethanolamine to lipid acceptors such as 1,2-diacylglycerol (DAG) for PE production and 1-alkyl-2-acyl-glycerol (AAG) for the generation of 1-alkyl-2-acyl-glycerophosphoethanolamine. Here, we investigated the intracellular location and contribution to ethanolamine phospholipid (EP) biosynthesis of EPT1 and CEPT1 in HEK293 cells. Immunohistochemical analyses revealed that EPT1 localizes to the Golgi apparatus and ...
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Horibata, Y., Ando, H., Sugimoto, H. Tags: Research Articles Source Type: research

Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids [Research Articles]
Angiopoietin-like protein (ANGPTL)8 has been implicated in metabolic syndrome and reported to regulate adipose FA uptake through unknown mechanisms. Here, we studied how complex formation of ANGPTL8 with ANGPTL3 or ANGPTL4 varies with feeding to regulate LPL. In human serum, ANGPTL3/8 and ANGPTL4/8 complexes both increased postprandially, correlated negatively with HDL, and correlated positively with all other metabolic syndrome markers. ANGPTL3/8 also correlated positively with LDL-C and blocked LPL-facilitated hepatocyte VLDL-C uptake. LPL-inhibitory activity of ANGPTL3/8 was>100-fold more potent than that of ANGPTL3,...
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Chen, Y. Q., Pottanat, T. G., Siegel, R. W., Ehsani, M., Qian, Y.-W., Zhen, E. Y., Regmi, A., Roell, W. C., Guo, H., Luo, M. J., Gimeno, R. E., vant Hooft, F., Konrad, R. J. Tags: Research Articles Source Type: research

Crystal structure of human lysosomal acid lipase and its implications in cholesteryl ester storage disease [Research Articles]
Lysosomal acid lipase (LAL) is a serine hydrolase that hydrolyzes cholesteryl ester (CE) and TGs delivered to the lysosomes into free cholesterol and fatty acids. LAL deficiency due to mutations in the LAL gene (LIPA) results in accumulation of TGs and cholesterol esters in various tissues of the body leading to pathological conditions such as Wolman’s disease and CE storage disease (CESD). Here, we present the first crystal structure of recombinant human LAL (HLAL) to 2.6 Å resolution in its closed form. The crystal structure was enabled by mutating three of the six potential glycosylation sites. The overall s...
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Rajamohan, F., Reyes, A. R., Tu, M., Nedoma, N. L., Hoth, L. R., Schwaid, A. G., Kurumbail, R. G., Ward, J., Han, S. Tags: Research Articles Source Type: research

The protein kinase PknB negatively regulates biosynthesis and trafficking of mycolic acids in mycobacteria [Research Articles]
Mycobacterium tuberculosis is the causative agent of tuberculosis and remains one of the most widespread and deadliest bacterial pathogens in the world. A distinguishing feature of mycobacteria that sets them apart from other bacteria is the unique architecture of their cell wall, characterized by various species-specific lipids, most notably mycolic acids (MAs). Therefore, targeted inhibition of enzymes involved in MA biosynthesis, transport, and assembly has been extensively explored in drug discovery. Additionally, more recent evidence suggests that many enzymes in the MA biosynthesis pathway are regulated by kinase-med...
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Le, N.-H., Locard-Paulet, M., Stella, A., Tomas, N., Molle, V., Burlet-Schiltz, O., Daffe, M., Marrakchi, H. Tags: Research Articles Source Type: research

The lipid transfer properties of CETP define the concentration and composition of plasma lipoproteins [Research Articles]
Cholesteryl ester transfer protein (CETP) facilitates the net transfer of cholesteryl esters (CEs) and TGs between lipoproteins, impacting the metabolic fate of these lipoproteins. Previous studies have shown that a CETP antibody can alter CETP’s preference for CE versus TG as transfer substrate, suggesting that CETP substrate preference can be manipulated in vivo. Hamster and human CETPs have very different preferences for CE and TG. To assess the effect of altering CETP’s substrate preference on lipoproteins in vivo, here, we expressed human CETP in hamsters. Chow-fed hamsters received adenoviruses expressing...
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Morton, R. E., Liu, Y. Tags: Research Articles Source Type: research

Aging and plasma triglyceride metabolism [Reviews]
The risk for metabolic disease, including metabolic syndrome, insulin resistance, and diabetes, increases with age. Altered plasma TG metabolism and changes in fatty acid partitioning are also major contributors to metabolic disease. Plasma TG metabolism itself is altered by age in humans and rodents. As discussed in this review, the age-induced changes in human TG metabolism include increased plasma TG levels, reduced postprandial plasma TG clearance rates, reduced postheparin LPL activity, decreased adipose tissue lipolysis, and elevated ectopic fat deposition, all of which could potentially contribute to age-associated ...
Source: The Journal of Lipid Research - August 1, 2020 Category: Lipidology Authors: Spitler, K. M., Davies, B. S. J. Tags: Reviews Source Type: research

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 - August 1, 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 - August 1, 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 - August 1, 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 - July 1, 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 - July 1, 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 - July 1, 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 - July 1, 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 - July 1, 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-...
Source: The Journal of Lipid Research - July 1, 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 - July 1, 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 - July 1, 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 - July 1, 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 - July 1, 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 - July 1, 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 - July 1, 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

Liver-specific ceramide reduction alleviates steatosis and insulin resistance in alcohol-fed mice [Research Articles]
We examined effects of alcohol on hepatic lipid metabolism, body composition, energy homeostasis, and insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Our results demonstrate that hepatic ceramide reduction ameliorates the effects of alcohol on hepatic lipid droplet (LD) accumulation by promoting VLDL secretion and lipophagy, the latter of which involves ceramide cross-talk between the lysosomal and LD compartments. We additionally demonstrate that hepatic ceramide reduction prevents alcohol’s inhibition of hepatic insulin signaling. These effects on the liver are associated with a reduction in o...
Source: The Journal of Lipid Research - July 1, 2020 Category: Lipidology Authors: Correnti, J., Lin, C., Brettschneider, J., Kuriakose, A., Jeon, S., Scorletti, E., Oranu, A., McIver-Jenkins, D., Kaneza, I., Buyco, D., Saiman, Y., Furth, E. E., Argemi, J., Bataller, R., Holland, W. L., Carr, R. M. Tags: Research Articles Source Type: research

Potential COVID-19 therapeutics from a rare disease: weaponizing lipid dysregulation to combat viral infectivity [Reviews]
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has resulted in the death of more than 328,000 persons worldwide in the first 5 months of 2020. Herculean efforts to rapidly design and produce vaccines and other antiviral interventions are ongoing. However, newly evolving viral mutations, the prospect of only temporary immunity, and a long path to regulatory approval pose significant challenges and call for a common, readily available, and inexpensive treatment. Strategic drug repurposing combined with rapid testing of established molecular targets could ...
Source: The Journal of Lipid Research - July 1, 2020 Category: Lipidology Authors: Sturley, S. L., Rajakumar, T., Hammond, N., Higaki, K., Marka, Z., Marka, S., Munkacsi, A. B. Tags: Reviews Source Type: research

The Ebola virus matrix protein VP40 hijacks the host plasma membrane to form virus envelope [Images In Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - July 1, 2020 Category: Lipidology Authors: Amiar, S., Stahelin, R. V. Tags: Images In Lipid Research Source Type: research

Opening ASBMB publications freely to all [Editorials]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - July 1, 2020 Category: Lipidology Authors: Gierasch, L. M., Davidson, N. O., Rye, K.-A., Burlingame, A. L. Tags: Editorials Source Type: research

A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound [Methods]
MS-assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, a...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Rohrbach, T. D., Boyd, A. E., Grizzard, P. J., Spiegel, S., Allegood, J., Lima, S. Tags: Methods Source Type: research

A direct fluorometric activity assay for lipid kinases and phosphatases [Methods]
Lipid kinases and phosphatases play key roles in cell signaling and regulation, are implicated in many human diseases, and are thus attractive targets for drug development. Currently, no direct in vitro activity assay is available for these important enzymes, which hampers mechanistic studies as well as high-throughput screening of small molecule modulators. Here, we report a highly sensitive and quantitative assay employing a ratiometric fluorescence sensor that directly and specifically monitors the real-time concentration change of a single lipid species. Because of its modular design, the assay system can be applied to...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Sun, J., Singaram, I., Soflaee, M. H., Cho, W. Tags: Methods Source Type: research

Serum nonesterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil, and dairy in women [Methods]
Nutritional studies rely on various biological specimens for FA determination, yet it is unclear how levels of serum NEFAs correlate with other circulating lipid pools. Here, we used a high-throughput method (
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Azab, S. M., de Souza, R. J., Teo, K. K., (for the FAMILY investigators), Anand, S. S., Williams, N. C., Holzschuher, J., McGlory, C., Philips, S. M., Britz-McKibbin, P. Tags: Methods Source Type: research

LDL subclass lipidomics in atherogenic dyslipidemia: effect of statin therapy on bioactive lipids and dense LDL [Patient-Oriented and Epidemiological Research]
Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a)
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Chapman, M. J., Orsoni, A., Tan, R., Mellett, N. A., Nguyen, A., Robillard, P., Giral, P., Therond, P., Meikle, P. J. Tags: Patient-Oriented and Epidemiological Research Source Type: research

Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro [Research Articles]
In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Naser, E., Kadow, S., Schumacher, F., Mohamed, Z. H., Kappe, C., Hessler, G., Pollmeier, B., Kleuser, B., Arenz, C., Becker, K. A., Gulbins, E., Carpinteiro, A. Tags: Research Articles Source Type: research

Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS [Research Articles]
Ceramides are the predominant lipids in the stratum corneum (SC) and are crucial components for normal skin barrier function. Although the composition of various ceramide classes in the human SC has been reported, that in mice is still unknown, despite mice being widely used as animal models of skin barrier function. Here, we performed LC/MS/MS analyses using recently available ceramide class standards to measure 25 classes of free ceramides and 5 classes of protein-bound ceramides from human and mouse SC. Phytosphingosine- and 6-hydroxy sphingosine-type ceramides, which both contain an additional hydroxyl group, were abun...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Kawana, M., Miyamoto, M., Ohno, Y., Kihara, A. Tags: Research Articles Source Type: research

Metabolic phospholipid labeling of intact bacteria enables a fluorescence assay that detects compromised outer membranes [Research Articles]
Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPSs) on the outer leaflet and phospholipids (PLs) on the inner leaflet. The loss of this asymmetry due to mutations in the LPS biosynthesis or transport pathways causes the externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we used metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase expression in Escherichia coli allowed for the incorporation of exogenous propargylcholine into phosphatidyl(propargyl)choline and exogenous 1-azid...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Nilsson, I., Lee, S. Y., Sawyer, W. S., Baxter Rath, C. M., Lapointe, G., Six, D. A. Tags: Research Articles Source Type: research

Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities [Research Articles]
We examined two key enzymes involved in epidermal ceramide biosynthesis, β-glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) SC ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: van Smeden, J., Al-Khakany, H., Wang, Y., Visscher, D., Stephens, N., Absalah, S., Overkleeft, H. S., Aerts, J. M. F. G., Hovnanian, A., Bouwstra, J. A. Tags: Research Articles Source Type: research

Roles of endogenous ether lipids and associated PUFAs in the regulation of ion channels and their relevance for disease [Research Articles]
Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage [i.e., plasmalogens (Pls)] at the sn1 position of the glycerol backbone, and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs) and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are e...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Fontaine, D., Figiel, S., Felix, R., Kouba, S., Fromont, G., Maheo, K., Potier-Cartereau, M., Chantome, A., Vandier, C. Tags: Research Articles Source Type: research

Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease [Research Articles]
Niemann-Pick type C (NPC)1 disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key factor in the development of atherosclerosis and NASH. In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of patholog...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Magro dos Reis, I., Houben, T., Oligschläger, Y., Bücken, L., Steinbusch, H., Cassiman, D., Lütjohann, D., Westerterp, M., Prickaerts, J., Plat, J., Shiri-Sverdlov, R. Tags: Research Articles Source Type: research

Circulating oxidized LDL, increased in patients with acute myocardial infarction, is accompanied by heavily modified HDL [Research Articles]
This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(–)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(–) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(–) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission elect...
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Sawada, N., Obama, T., Koba, S., Takaki, T., Iwamoto, S., Aiuchi, T., Kato, R., Kikuchi, M., Hamazaki, Y., Itabe, H. Tags: Research Articles Source Type: research

The fatty acids from LPL-mediated processing of triglyceride-rich lipoproteins are taken up rapidly by cardiomyocytes [images in Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Jiang, H., He, C., Fong, L. G., Young, S. G. Tags: images in Lipid Research Source Type: research

Phosphatidylinositol metabolism, phospholipases, lipidomics, and cancer: In Memoriam: Michael J. O. Wakelam (1955-2020) [Tribute]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - June 1, 2020 Category: Lipidology Authors: Dennis, E. A., ODonnell, V. B. Tags: Tribute Source Type: research

SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles]
Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focu...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Jay, A. G., Simard, J. R., Huang, N., Hamilton, J. A. Tags: Research Articles Source Type: research

Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells [Research Articles]
Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been sugge...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Tabata, Y., Shidoji, Y. Tags: Research Articles Source Type: research

A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice [Research Articles]
In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­ (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: DeLeon, C., Wang, H. H., Gunn, J., Wilhelm, M., Cole, A., Arnett, S., Wang, D. Q.-H., Arnatt, C. K. Tags: Research Articles Source Type: research

Nanodomains can persist at physiologic temperature in plasma membrane vesicles and be modulated by altering cell lipids [Research Articles]
The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing FoĢˆrster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persis...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Li, G., Wang, Q., Kakuda, S., London, E. Tags: Research Articles Source Type: research

Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation [Research Articles]
The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerat...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Jun, D.-J., Schumacher, M. M., Hwang, S., Kinch, L. N., Grishin, N. V., DeBose-Boyd, R. A. Tags: Research Articles Source Type: research

Slc43a3 is a regulator of free fatty acid flux [Research Articles]
Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, incre...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Hasbargen, K. B., Shen, W.-J., Zhang, Y., Hou, X., Wang, W., Shuo, Q., Bernlohr, D. A., Azhar, S., Kraemer, F. B. Tags: Research Articles Source Type: research

The grease trap: uncovering the mechanism of the hydrophobic lid in Cutibacterium acnes lipase [Research Articles]
Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, b...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Kim, H. J., Lee, B.-J., Kwon, A.-R. Tags: Research Articles Source Type: research

Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice [Research Articles]
Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. Al...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Hasenour, C. M., Kennedy, A. J., Bednarski, T., Trenary, I. A., Eudy, B. J., da Silva, R. P., Boyd, K. L., Young, J. D. Tags: Research Articles Source Type: research

Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice [Research Articles]
In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXRMyeLDLR–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXRMyeLDLR–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR defici...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Sui, Y., Meng, Z., Park, S.-H., Lu, W., Livelo, C., Chen, Q., Zhou, T., Zhou, C. Tags: Research Articles Source Type: research

Lipid rafts as a therapeutic target [Thematic Reviews]
Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting p...
Source: The Journal of Lipid Research - May 1, 2020 Category: Lipidology Authors: Sviridov, D., Mukhamedova, N., Miller, Y. I. Tags: Thematic Reviews Source Type: research