Lipid Neuroprotectants and Traumatic Glaucomatous Neurodegeneration

DTIC Science & Technology

2016-05-01

alter elastic TM, modulus and binding and functional assays with potential protein targets. Endogenous lipids, Aqueous humor, Trabecular meshwork...Intraocular pressure, sphingolipids, primary cell culture, elastic modulus, protein targets. Major goal 1. Test the hypothesis that selected lipids...glaucomatous TM with and without these lipids and atomic force microscope (AFM). Further elastic modulus using high flow and low flow areas of glaucomatous

Modeling and optimization of lipid accumulation by Yarrowia lipolytica from glucose under nitrogen depletion conditions.

PubMed

Robles-Rodríguez, Carlos E; Muñoz-Tamayo, Rafael; Bideaux, Carine; Gorret, Nathalie; Guillouet, Stéphane E; Molina-Jouve, Carole; Roux, Gilles; Aceves-Lara, César A

2018-05-01

Oleaginous yeasts have been seen as a feasible alternative to produce the precursors of biodiesel due to their capacity to accumulate lipids as triacylglycerol having profiles with high content of unsaturated fatty acids. The yeast Yarrowia lipolytica is a promising microorganism that can produce lipids under nitrogen depletion conditions and excess of the carbon source. However, under these conditions, this yeast also produces citric acid (overflow metabolism) decreasing lipid productivity. This work presents two mathematical models for lipid production by Y. lipolytica from glucose. The first model is based on Monod and inhibition kinetics, and the second one is based on the Droop quota model approach, which is extended to yeast. The two models showed good agreements with the experimental data used for calibration and validation. The quota based model presented a better description of the dynamics of nitrogen and glucose dynamics leading to a good management of N/C ratio which makes this model interesting for control purposes. Then, quota model was used to evaluate, by means of simulation, a scenario for optimizing lipid productivity and lipid content. For that, a control strategy was designed by approximating the flow rates of glucose and nitrogen with piecewise linear functions. Simulation results achieved productivity of 0.95 g L -1  hr -1 and lipid content fraction of 0.23 g g -1 , which indicates that this strategy is a promising alternative for the optimization of lipid production. © 2017 Wiley Periodicals, Inc.

A diffusive ink transport model for lipid dip-pen nanolithography.

PubMed

Urtizberea, A; Hirtz, M

2015-10-14

Despite diverse applications, phospholipid membrane stacks generated by dip-pen nanolithography (DPN) still lack a thorough and systematic characterization that elucidates the whole ink transport process from writing to surface spreading, with the aim of better controlling the resulting feature size and resolution. We report a quantitative analysis and modeling of the dependence of lipid DPN features (area, height and volume) on dwell time and relative humidity. The ink flow rate increases with humidity in agreement with meniscus size growth, determining the overall feature size. The observed time dependence indicates the existence of a balance between surface spreading and the ink flow rate that promotes differences in concentration at the meniscus/substrate interface. Feature shape is controlled by the substrate surface energy. The results are analyzed within a modified model for the ink transport of diffusive inks. At any humidity the dependence of the area spread on the dwell time shows two diffusion regimes: at short dwell times growth is controlled by meniscus diffusion while at long dwell times surface diffusion governs the process. The critical point for the switch of regime depends on the humidity.

Development of droplet microfluidic platforms for the synthesis of monodisperse lipid vesicles and polymer particles

NASA Astrophysics Data System (ADS)

Teh, Shia-Yen

This body of work presents my approaches to the design and development of microfluidic platforms for synthesizing monodisperse polymer particles and phospholipid vesicles. There is interest in both of these particles for use in a variety of biomedical applications. Poly(D,L-lactide-co-glycolic acid) (PLGA) particles in particular have been sought out as vehicles for drug delivery due to their biocompatibility and because the rate of degradation -- hence cargo release - can be controlled. On the other hand, liposomes possess membrane structures resembling that of cells, an ability to adopt both hydrophilic and hydrophobic molecules, and are easily functionalized, which make lipid vesicles the ideal candidate for applications ranging from targeted therapeutic delivery to formation of artificial cells. However, current methods of production for both of these particles result in a wide range of sizes and poor cargo uptake efficiency. We address these challenges by utilizing a flow focusing droplet generation design, which allows for fine control over droplet size and improves encapsulation efficiencies. The size of these droplets can be determined by channel geometry and the ratio of fluid flow rates. I will discuss the work I have done to improve upon current technologies to form nano- to micrometer sized PLGA particles and cell-sized lipid vesicles. Solvent evaporation and solvent extraction methods were implemented and tested in several device designs to optimize the formation process. The particles produced were characterized for their stability, size variation, and ability to encapsulate a model drug. The release profiles of PLGA particles were also measured to determine the length of delivery. In addition, I worked on the generation of monodisperse lipid vesicles to investigate the application of liposomes as an artificial cell. As a proof of principle, expression of green fluorescent protein (GFP) was successfully carried out in the lipid vesicles. This demonstrates the versatility of the microfluidic device for generating a range of particles of controlled size for therapeutic agent delivery and artificial cell applications.

Proton Gradients as a Key Physical Factor in the Evolution of the Forced Transport Mechanism Across the Lipid Membrane.

PubMed

Strbak, Oliver; Kanuchova, Zuzana; Krafcik, Andrej

2016-11-01

A critical phase in the transition from prebiotic chemistry to biological evolution was apparently an asymmetric ion flow across the lipid membrane. Due to imbalance in the ion flow, the early lipid vesicles could selectively take the necessary molecules from the environment, and release the side-products from the vesicle. Natural proton gradients played a definitively crucial role in this process, since they remain the basis of energy transfer in the present-day cells. On the basis of this supposition, and the premise of the early vesicle membrane's impermeability to protons, we have shown that the emergence of the proton gradient in the lipid vesicle could be a key physical factor in the evolution of the forced transport mechanism (pore formation and active transport) across the lipid bilayer. This driven flow of protons across the membrane is the result of the electrochemical proton gradient and osmotic pressures on the integrity of the lipid vesicle. At a critical number of new lipid molecules incorporated into the vesicle, the energies associated with the creation of the proton gradient exceed the bending stiffness of the lipid membrane, and overlap the free energy of the lipid bilayer pore formation.

A diffusive ink transport model for lipid dip-pen nanolithography

NASA Astrophysics Data System (ADS)

Urtizberea, A.; Hirtz, M.

2015-09-01

Despite diverse applications, phospholipid membrane stacks generated by dip-pen nanolithography (DPN) still lack a thorough and systematic characterization that elucidates the whole ink transport process from writing to surface spreading, with the aim of better controlling the resulting feature size and resolution. We report a quantitative analysis and modeling of the dependence of lipid DPN features (area, height and volume) on dwell time and relative humidity. The ink flow rate increases with humidity in agreement with meniscus size growth, determining the overall feature size. The observed time dependence indicates the existence of a balance between surface spreading and the ink flow rate that promotes differences in concentration at the meniscus/substrate interface. Feature shape is controlled by the substrate surface energy. The results are analyzed within a modified model for the ink transport of diffusive inks. At any humidity the dependence of the area spread on the dwell time shows two diffusion regimes: at short dwell times growth is controlled by meniscus diffusion while at long dwell times surface diffusion governs the process. The critical point for the switch of regime depends on the humidity.Despite diverse applications, phospholipid membrane stacks generated by dip-pen nanolithography (DPN) still lack a thorough and systematic characterization that elucidates the whole ink transport process from writing to surface spreading, with the aim of better controlling the resulting feature size and resolution. We report a quantitative analysis and modeling of the dependence of lipid DPN features (area, height and volume) on dwell time and relative humidity. The ink flow rate increases with humidity in agreement with meniscus size growth, determining the overall feature size. The observed time dependence indicates the existence of a balance between surface spreading and the ink flow rate that promotes differences in concentration at the meniscus/substrate interface. Feature shape is controlled by the substrate surface energy. The results are analyzed within a modified model for the ink transport of diffusive inks. At any humidity the dependence of the area spread on the dwell time shows two diffusion regimes: at short dwell times growth is controlled by meniscus diffusion while at long dwell times surface diffusion governs the process. The critical point for the switch of regime depends on the humidity. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04352b

Flow cytometric analysis of crayfish haemocytes activated by lipopolysaccharides

USGS Publications Warehouse

Cardenas, W.; Dankert, J.R.; Jenkins, J.A.

2004-01-01

Lipopolysaccharides (LPS) from Gram-negative bacteria are strong stimulators of white river crayfish, Procambarus zonangulus, haemocytes in vitro. Following haemocyte treatment with LPS and with LPS from rough mutant R5 (LPS Rc) from Salmonella minnesota, flow cytometric analysis revealed a conspicuous and reproducible decrease in cell size as compared to control haemocytes. These LPS molecules also caused a reduction in haemocyte viability as assessed by flow cytometry with the fluorescent dyes calcein-AM and ethidium homodimer. The onset of cell size reduction was gradual and occurred prior to cell death. Haemocytes treated with LPS from S. minnesota without the Lipid A moiety (detoxified LPS) decreased in size without a reduction of viability. The action of LPS on crayfish haemocytes appeared to be related to the activation of the prophenoloxidase system because phenoloxidase (PO)-specific activity in the supernatants from control and detoxified LPS-treated cells was significantly lower than that from LPS and LPS-Rc treated cells (P < 0.05). Furthermore, addition of trypsin inhibitor to the LPS treatments caused noticeable delays in cell size and viability changes. These patterns of cellular activation by LPS formulations indicated that crayfish haemocytes react differently to the polysaccharide and lipid A moieties of LPS, where lipid A is cytotoxic and the polysaccharide portion is stimulatory. These effects concur with the general pattern of mammalian cell activation by LPS, thereby indicting commone innate immune recognition mechanisms to bacterial antigens between cells from mammals and invertebrates. These definitive molecular approaches used to verify and identify mechanisms of invertbrate haemocyte responses to LPS could be applied with other glycoconjugates, soluble mediators, or xenobiotic compounds.

Size fractionation and size characterization of nanoemulsions of lipid droplets and large unilamellar lipid vesicles by asymmetric-flow field-flow fractionation/multi-angle light scattering and dynamic light scattering.

PubMed

Vezočnik, Valerija; Rebolj, Katja; Sitar, Simona; Ota, Katja; Tušek-Žnidarič, Magda; Štrus, Jasna; Sepčić, Kristina; Pahovnik, David; Maček, Peter; Žagar, Ema

2015-10-30

Asymmetric-flow field-flow fractionation technique coupled to a multi-angle light-scattering detector (AF4-MALS) was used together with dynamic light-scattering (DLS) in batch mode and transmission electron microscopy (TEM) to study the size characteristics of the trioleoylglycerol lipid droplets covered by a monolayer of sphingomyelin and cholesterol, in water phase. These lipid droplet nanoemulsions (LD) were formed by ultrasonication. In parallel, the size characteristics of large unilamellar lipid vesicles (LUV) prepared by extrusion and composed of sphingomyelin and cholesterol were determined. LD and LUV were prepared at two different molar ratios (1/1, 4/1) of sphingomyelin and cholesterol. In AF4-MALS, various cross-flow conditions and mobile phase compositions were tested to optimize the separation of LD or LUV particles. The particle radii, R, as well as the root-mean-square radii, Rrms, of LD and LUV were determined by AF4-MALS, whereas the hydrodynamic radii, Rh, were obtained by DLS. TEM visualization revealed round shape particles of LD and LUV. Copyright © 2015 Elsevier B.V. All rights reserved.

Functionalization Pattern of Graphene Oxide Sheets Controls Entry or Produces Lipid Turmoil in Phospholipid Membranes.

PubMed

Dallavalle, Marco; Bottoni, Andrea; Calvaresi, Matteo; Zerbetto, Francesco

2018-05-09

Molecular dynamics, coarse-grained to the level of hydrophobic and hydrophilic interactions, shows that graphene oxide sheets, GOSs, can pierce through the phospholipid membrane and navigate the double layer only if the hydrophilic groups are randomly dispersed in the structure. Their behavior resembles that found in similar calculations for pristine graphene sheets. If the oxidation is located at the edge of the sheets, GOSs hover over the membrane and trigger a major reorganization of the lipids. The reorganization is the largest when the radius of the edge-functionalized sheet is similar to the length of the lipophilic chain of the lipids. In the reorganization, the heads of the lipid chains form dynamical structures that pictorially resemble the swirl of water flowing down a drain. All effects maximize the interaction between hydrophobic moieties on the one hand and lipophilic fragments on the other and are accompanied by a large number of lipid flip-flops. Possible biological consequences are discussed.

Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion.

PubMed

Patil, Hemlata; Kulkarni, Vijay; Majumdar, Soumyajit; Repka, Michael A

2014-08-25

Solid lipid nanoparticles (SLN) can either be produced by hot homogenization of melted lipids at higher temperatures or by a cold homogenization process. This paper proposes and demonstrates the formulation of SLN for pharmaceutical applications by combining two processes: hot melt extrusion (HME) technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. This work aimed at developing continuous and scalable processes for SLN by mixing a lipid and aqueous phase containing an emulsifier in the extruder barrel at temperatures above the melting point of the lipid and further reducing the particle size of emulsion by HPH linked to HME in a sequence. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm (for 60 mg/ml lipid solution at a flow rate of 100ml/min). Among the several process parameters investigated, the lipid concentration, residence time and screw design played major roles in influencing the size of the SLN. This new process demonstrates the potential use of hot melt extrusion technology for continuous and large-scale production of SLN. Copyright © 2014 Elsevier B.V. All rights reserved.

Droplet interface bilayer reconstitution and activity measurement of the mechanosensitive channel of large conductance from Escherichia coli.

PubMed

Barriga, Hanna M G; Booth, Paula; Haylock, Stuart; Bazin, Richard; Templer, Richard H; Ces, Oscar

2014-09-06

Droplet interface bilayers (DIBs) provide an exciting new platform for the study of membrane proteins in stable bilayers of controlled composition. To date, the successful reconstitution and activity measurement of membrane proteins in DIBs has relied on the use of the synthetic lipid 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC). We report the functional reconstitution of the mechanosensitive channel of large conductance (MscL) into DIBs composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), a lipid of significantly greater biological relevance than DPhPC. MscL functionality has been demonstrated using a fluorescence-based assay, showing that dye flow occurs across the DIB when MscL is gated by the cysteine reactive chemical 2-(trimethylammonium)ethyl methane thiosulfonate bromide (MTSET). MscL has already been the subject of a number of studies investigating its interaction with the membrane. We propose that this method will pave the way for future MscL studies looking in detail at the effects of controlled composition or membrane asymmetry on MscL activity using biologically relevant lipids and will also be applicable to other lipid-protein systems, paving the way for the study of membrane proteins in DIBs with biologically relevant lipids.

Contactless Stimulation and Control of Biomimetic Nanotubes by Calcium Ion Gradients.

PubMed

Kirejev, Vladimir; Ali Doosti, Baharan; Shaali, Mehrnaz; Jeffries, Gavin D M; Lobovkina, Tatsiana

2018-04-17

Membrane tubular structures are important communication pathways between cells and cellular compartments. Studying these structures in their native environment is challenging, due to the complexity of membranes and varying chemical conditions within and outside of the cells. This work demonstrates that a calcium ion gradient, applied to a synthetic lipid nanotube, triggers lipid flow directed toward the application site, resulting in the formation of a bulge aggregate. This bulge can be translated in a contactless manner by moving a calcium ion source along the lipid nanotube. Furthermore, entrapment of polystyrene nanobeads within the bulge does not tamper the bulge movement and allows transporting of the nanoparticle cargo along the lipid nanotube. In addition to the synthetic lipid nanotubes, the response of cell plasma membrane tethers to local calcium ion stimulation is investigated. The directed membrane transport in these tethers is observed, but with slower kinetics in comparison to the synthetic lipid nanotubes. The findings of this work demonstrate a novel and contactless mode of transport in lipid nanotubes, guided by local exposure to calcium ions. The observed lipid nanotube behavior can advance the current understanding of the cell membrane tubular structures, which are constantly reshaped during dynamic cellular processes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam.

PubMed

Khalil, Rawia M; Abd-Elbary, A; Kassem, Mahfoz A; Ghorab, Mamdouh M; Basha, Mona

2014-05-01

The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX). The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application. The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430 nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of -19.1 to -25.7 mV. The release profiles of all formulations exhibited sustained release characteristics over 48 h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel. It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.

Membrane Heterogeneity in Akt Activation in Prostate Cancer

DTIC Science & Technology

2009-11-01

promote oncogenesis by altering the nature of Akt1 signals that flow through lipid raft microdomains. The purpose of this project was to identify the...altering the nature of Akt1 signals that flow through lipid raft microdomains. The purpose of this project was to identify the mecha- nism of Akt1...predominantly in lipid rafts. Consequently, I was able to identify an important function for serine 473 and lysine 179 in regulating the admission

Concurrent studies of the flow of digesta in the duodenum and of exocrine pancreatic secretion of calves. 7. Influence of milk substitutes on abomasal lipolysis and biliary secretion.

PubMed

Ternouth, J H; Thompson, S Y; Edwards-Webb, J D

1980-09-01

1. The abomasal hydrolysis of lipids and the flow of endogenous (biliary) lipids was studied in two Friesian calves given four milk-substitute diets, by sampling the duodenal digesta. The diets were: reconstituted, mildly preheated, spray-dried skim-milk powder with (SKF) or without (SK) margarine fat or with 500 g/kg skim-milk powder in diet SKF replaced by soy-beran flour (ASKF) or fish-protein concentrate (BSKF) together with dried whey. The diets were given ad lib. twice daily from 13 to 37 d of age, each diet being given for six consecutive days. Collections of duodenal digesta from the re-entrant cannula situated caudal to the bile duct were made for 12 h after feeding the 6th and 12th meals for each diet. Samples from one collection only were subjected to detailed analysis of the lipid classes. 2. The inclusion of non-milk protein (ASKF and BSKF) not only increased the rate of passage of lipid through the abomasum but also the proportion of the lipid present as triglyceride particularly, in the first 2 h after feeding. 3. In a 12 h period, 2.3-6.3 g 'polar' lipids (mainly biliary phospholipids) were estimated to have been secreted. The rate of flow was high during the first hour after feeding and constant thereafter. The quantity of 'polar' lipid was not related to the type of milk fed or the duodenal flow of lipid. 4. When diet SK was fed, the small amounts of lipid present were extensively hydrolysed so that free fatty acids represented 700 g/kg lipid of dietary origin passing through the duodenum. When margarine fat was included in the diets (SKF, ASKF and BSKF), the free fatty acids represented only 210 g/kg lipid of dietary origin. 5. The quantities of lipid and nitrogen passing through the duodenum were poorly related to the quantities ingested at the beginning of the 12 h experimental period but were closely related to each other.

Microfluidic based high throughput synthesis of lipid-polymer hybrid nanoparticles with tunable diameters

PubMed Central

Feng, Qiang; Zhang, Lu; Liu, Chao; Li, Xuanyu; Hu, Guoqing; Sun, Jiashu; Jiang, Xingyu

2015-01-01

Core-shell hybrid nanoparticles (NPs) for drug delivery have attracted numerous attentions due to their enhanced therapeutic efficacy and good biocompatibility. In this work, we fabricate a two-stage microfluidic chip to implement a high-throughput, one-step, and size-tunable synthesis of mono-disperse lipid-poly (lactic-co-glycolic acid) NPs. The size of hybrid NPs is tunable by varying the flow rates inside the two-stage microfluidic chip. To elucidate the mechanism of size-controllable generation of hybrid NPs, we observe the flow field in the microchannel with confocal microscope and perform the simulation by a numerical model. Both the experimental and numerical results indicate an enhanced mixing effect at high flow rate, thus resulting in the assembly of small and mono-disperse hybrid NPs. In vitro experiments show that the large hybrid NPs are more likely to be aggregated in serum and exhibit a lower cellular uptake efficacy than the small ones. This microfluidic chip shows great promise as a robust platform for optimization of nano drug delivery system. PMID:26180574

Analysis of factors affecting volatile compound formation in roasted pumpkin seeds with selected ion flow tube-mass spectrometry (SIFT-MS) and sensory analysis.

PubMed

Bowman, T; Barringer, S

2012-01-01

Pumpkin (Cucurbita pepo and maxima) seeds are uniquely flavored and commonly consumed as a healthy roasted snack. The objective was to determine dominant volatiles in raw and roasted pumpkin seeds, and the effect of seed coat, moisture content, fatty acid ratio, total lipids, reducing sugars, and harvest year on volatile formation. Sensory was conducted to evaluate overall liking of seed variety and texture. Seed processing included extraction from the fruit, dehydration, and roasting (150 °C). Oil extraction was done using soxhlet, fatty acid profile using Gas Chromatography Flame Ionization Detector, and reducing sugars using 3,5-dinitrosalicylic acid and UV-spectroscopy. Headspace analysis of seeds was performed by selected ion flow tube-mass spectrometry (SIFT-MS). Volatiles dominating in raw pumpkin seeds were lipid aldehydes, ethyl acetate, 2,3-butandione, and dimethylsulfide. Compounds contributing to roasted aroma include alkylpyrazines and Strecker and lipid aldehydes. Overall, hull-less seeds had higher volatile lipid aldehydes and Strecker aldehydes. Seeds dehydrated to a moisture content of 6.5% before roasting had higher initial and final volatile concentrations than seeds starting at 50% moisture. Higher oil content resulted in higher lipid aldehyde formation during roasting with a moderate correlation between free fatty acid ratio and corresponding lipid aldehyde. Harvest year (2009 compared with 2010) had a significant impact on volatile formation in hull-less seeds, but not as much as variety differences. No significant correlation was found between reducing sugars and volatile formation. Sensory showed that hull-less seeds were liked significantly more than hulled seeds. Elucidation of aromatic flavor development during roasting with SIFT-MS provides information on flavor release and offers better control during processing. Knowledge of volatiles in raw and roasted pumpkin seeds and effects of seed coat, moisture content, seed composition, and harvest date will allow for better control over the production/storage/transportation process and a more educated decision during selection of a variety for production of pumpkin seeds in the snack food industry. © 2011 Institute of Food Technologists®

Membrane Heterogeneity in Akt Activation in Prostate Cancer

DTIC Science & Technology

2009-07-01

oncogenesis by altering the nature of Akt1 signals that flow through lipid raft microdomains. The purpose of this project is to identify the mechanism of...nature of Akt1 signals that flow through lipid raft microdomains. The purpose of this project was to identify the mecha- nism of Akt1 recruitment to...predominantly in lipid rafts (for details see Annual Summary Report March 2008). Consequently, I was able to identify an im- portant function for

Effects of surface pressure and internal friction on the dynamics of shear-driven supported lipid bilayers.

PubMed

Jönsson, Peter; Höök, Fredrik

2011-02-15

Supported lipid bilayers (SLBs) are one of the most common model systems for cell membrane studies. We have previously found that when applying a bulk flow of liquid above an SLB the lipid bilayer and its constituents move in the direction of the bulk flow in a rolling type of motion, with the lower monolayer being essentially stationary. In this study, a theoretical platform is developed to model the dynamic behavior of a shear-driven SLB. In most regions of the moving SLB, the dynamics of the lipid bilayer is well explained by a balance between the hydrodynamic shear force arising from the bulk flow above the lipid bilayer and the friction between the upper and lower monolayers of the SLB. These two forces result in a drift velocity profile for the lipids in the upper monolayer of the SLB that is highest at the center of the channel and decreases to almost zero at the corners of the channel. However, near the front of an advancing SLB a very different flow behavior is observed, showing an almost constant drift velocity of the lipids over the entire bilayer front. In this region, the motion of the SLB is significantly influenced by gradients in the surface pressure as well as internal friction due to molecules that have accumulated at the front of the SLB. It is shown that even a modest surface fraction of accumulated molecules (∼1%) can drastically affect the behavior of the SLB near the bilayer front, forcing the advancing lipids in the SLB away from the center of the channel out toward the sides.

The development of flow-through bio-catalyst microreactors from silica micro structured fibers for lipid transformations.

PubMed

Anuar, Sabiqah Tuan; Villegas, Carla; Mugo, Samuel M; Curtis, Jonathan M

2011-06-01

This study demonstrates the utility of a flow-through enzyme immobilized silica microreactor for lipid transformations. A silica micro structured fiber (MSF) consisting of 168 channels of internal diameter 4-5 μm provided a large surface area for the covalent immobilization of Candida antartica lipase. The specific activity of the immobilized lipase was determined by hydrolysis of p-nitrophenyl butyrate and calculated to be 0.81 U/mg. The catalytic performance of the lipase microreactor was demonstrated by the efficient ethanolysis of canola oil. The parameters affecting the performance of the MSF microreactor, including temperature and reaction flow rate, were investigated. Characterization of the lipid products exiting the microreactor was performed by non-aqueous reversed-phased liquid chromatography (NARP-LC) with evaporative light scattering detector (ELSD) and by comprehensive two-dimensional gas chromatography (GC x GC). Under optimized conditions of 1 μL/min flow rate of 5 mg/mL trioleoylglycerol (TO) in ethanol and 50 °C reaction temperature, 2-monooleoylglycerol was the main product at > 90% reaction yield. The regioselectivity of the Candida antartica lipase immobilized MSF microreactor in the presence of ethanol was found to be comparable to that obtained under conventional conditions. The ability of these reusable flow-through microreactors to regioselectively form monoacylglycerides in high yield from triacylglycerides demonstrate their potential use in small-scale lipid transformations or analytical lipids profiling.

Molecular Simulations of Sequence-Specific Association of Transmembrane Proteins in Lipid Bilayers

NASA Astrophysics Data System (ADS)

Doxastakis, Manolis; Prakash, Anupam; Janosi, Lorant

2011-03-01

Association of membrane proteins is central in material and information flow across the cellular membranes. Amino-acid sequence and the membrane environment are two critical factors controlling association, however, quantitative knowledge on such contributions is limited. In this work, we study the dimerization of helices in lipid bilayers using extensive parallel Monte Carlo simulations with recently developed algorithms. The dimerization of Glycophorin A is examined employing a coarse-grain model that retains a level of amino-acid specificity, in three different phospholipid bilayers. Association is driven by a balance of protein-protein and lipid-induced interactions with the latter playing a major role at short separations. Following a different approach, the effect of amino-acid sequence is studied using the four transmembrane domains of the epidermal growth factor receptor family in identical lipid environments. Detailed characterization of dimer formation and estimates of the free energy of association reveal that these helices present significant affinity to self-associate with certain dimers forming non-specific interfaces.

Flow-induced 2D protein crystallization: characterization of the coupled interfacial and bulk flows.

PubMed

Young, James E; Posada, David; Lopez, Juan M; Hirsa, Amir H

2015-05-14

Two-dimensional crystallization of the protein streptavidin, crystallizing below a biotinylated lipid film spread on a quiescent air-water interface is a well studied phenomenon. More recently, 2D crystallization induced by a shearing interfacial flow has been observed at film surface pressures significantly lower than those required in a quiescent system. Here, we quantify the interfacial and bulk flow associated with 2D protein crystallization through numerical modeling of the flow along with a Newtonian surface model. Experiments were conducted over a wide range of conditions resulting in a state diagram delineating the flow strength required to induce crystals for various surface pressures. Through measurements of the velocity profile at the air-water interface, we found that even in the cases where crystals are formed, the macroscopic flow at the interface is well described by the Newtonian model. However, the results show that even in the absence of any protein in the system, the viscous response of the biotinylated lipid film is complicated and strongly dependent on the strength of the flow. This observation suggests that the insoluble lipid film plays a key role in flow-induced 2D protein crystallization.

Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

PubMed Central

Han, Mingda

2016-01-01

Background Embryonic acute exposure to ethanol (EtOH), lithium, and homocysteine (HCy) induces cardiac defects at the time of exposure; folic acid (FA) supplementation protects normal cardiogenesis (Han et al., 2009, 2012; Serrano et al., 2010). Our hypothesis is that EtOH exposure and FA protection relate to lipid and FA metabolism during mouse cardiogenesis and placentation. Methods On the morning of conception, pregnant C57BL/6J mice were placed on either of two FA‐containing diets: a 3.3 mg health maintenance diet or a high FA diet of 10.5 mg/kg. Mice were injected a binge level of EtOH, HCy, or saline on embryonic day (E) 6.75, targeting gastrulation. On E15.5, cardiac and umbilical blood flow were examined by ultrasound. Embryonic cardiac tissues were processed for gene expression of lipid and FA metabolism; the placenta and heart tissues for neutral lipid droplets, or for medium chain acyl‐dehydrogenase (MCAD) protein. Results EtOH exposure altered lipid‐related gene expression on E7.5 in comparison to control or FA‐supplemented groups and remained altered on E15.5 similarly to changes with HCy, signifying FA deficiency. In comparison to control tissues, the lipid‐related acyl CoA dehydrogenase medium length chain gene and its protein MCAD were altered with EtOH exposure, as were neutral lipid droplet localization in the heart and placenta. Conclusion EtOH altered gene expression associated with lipid and folate metabolism, as well as neutral lipids, in the E15.5 abnormally functioning heart and placenta. In comparison to controls, the high FA diet protected the embryo and placenta from these effects allowing normal development. Birth Defects Research (Part A) 106:749–760, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27296863

Effects of thyroxine replacement on endothelial function and carotid artery intima-media thickness in female patients with mild subclinical hypothyroidism

PubMed Central

Cabral, Monica Dias; Teixeira, Patricia; Soares, Debora; Leite, Sandra; Salles, Elizabeth; Waisman, Mario

2011-01-01

BACKGROUND: Previous studies have suggested an association between subclinical hypothyroidism and coronary artery disease that could be related to changes in serum lipids or endothelial dysfunction. METHODS: Thirty-two female subclinical hypothyroidism patients were randomly assigned to 12 months of L-thyroxine replacement or no treatment. Endothelial function was measured by the flow-mediated vasodilatation of the brachial artery, as well as mean carotid artery intima-media thickness, and lipid profiles were studied at baseline and after 12 months of follow-up. RESULTS: The mean (±SD) serum thyroid-stimulating hormone levels in the L-thyroxine replacement and control groups were 6.09±1.32 and 6.27±1.39 µUI/ml, respectively. No relationship between carotid artery intima-media thickness or brachial flow-mediated vasodilatation and free T4 and serum thyroid-stimulating hormone was found. The median L-T4 dose was 44.23±18.13 µg/day. After 12 months, there was a significant decrease in the flow-mediated vasodilatation in the subclinical hypothyroidism control group (before: 17.33±7.88 to after: 13.1±4.75%, p = 0.03), but there were no significant differences in flow-mediated vasodilatation in the L-thyroxine treated group (before: 16.81±7.0 to after: 18.52±7.44%, p = 0.39). We did not find any significant change in mean carotid intima-media thickness after 12 months of L-thyroxine treatment. CONCLUSION: Replacement therapy prevents a decline in flow-mediated vasodilatation with continuation of the subclinical hypothyroidism state. Large prospective multicenter placebo-controlled trials are necessary to investigate endothelial physiology further in subclinical hypothyroidism patients and to define the role of L-thyroxine therapy in improving endothelial function in these patients. PMID:21915478

Validation of a CD1b tetramer assay for studies of human mycobacterial infection or vaccination.

PubMed

Layton, Erik D; Yu, Krystle K Q; Smith, Malisa T; Scriba, Thomas J; De Rosa, Stephen C; Seshadri, Chetan

2018-07-01

CD1 tetramers loaded with lipid antigens facilitate the identification of rare lipid-antigen specific T cells present in human blood and tissue. Because CD1 proteins are structurally non-polymorphic, these tetramers can be applied to genetically diverse human populations, unlike MHC-I and MHC-II tetramers. However, there are no standardized assays to quantify and characterize lipid antigen-specific T cells present within clinical samples. We incorporated CD1b tetramers loaded with the mycobacterial lipid glucose monomycolate (GMM) into a multi-parameter flow cytometry assay. Using a GMM-specific T-cell line, we demonstrate that the assay is linear, reproducible, repeatable, precise, accurate, and has a limit of detection of approximately 0.007%. Having formally validated this assay, we performed a cross-sectional study of healthy U.S. controls and South African adolescents with and without latent tuberculosis infection (LTBI). We show that GMM-specific T cells are specifically detected in South African subjects with LTBI and not in U.S. healthy controls. This assay can be expanded to include additional tetramers or phenotypic markers to characterize GMM-specific T cells in studies of mycobacterial infection, disease, or vaccination. Copyright © 2018 Elsevier B.V. All rights reserved.

Lipid shedding from single oscillating microbubbles.

PubMed

Luan, Ying; Lajoinie, Guillaume; Gelderblom, Erik; Skachkov, Ilya; van der Steen, Antonius F W; Vos, Hendrik J; Versluis, Michel; De Jong, Nico

2014-08-01

Lipid-coated microbubbles are used clinically as contrast agents for ultrasound imaging and are being developed for a variety of therapeutic applications. The lipid encapsulation and shedding of the lipids by acoustic driving of the microbubble has a crucial role in microbubble stability and in ultrasound-triggered drug delivery; however, little is known about the dynamics of lipid shedding under ultrasound excitation. Here we describe a study that optically characterized the lipid shedding behavior of individual microbubbles on a time scale of nanoseconds to microseconds. A single ultrasound burst of 20 to 1000 cycles, with a frequency of 1 MHz and an acoustic pressure varying from 50 to 425 kPa, was applied. In the first step, high-speed fluorescence imaging was performed at 150,000 frames per second to capture the instantaneous dynamics of lipid shedding. Lipid detachment was observed within the first few cycles of ultrasound. Subsequently, the detached lipids were transported by the surrounding flow field, either parallel to the focal plane (in-plane shedding) or in a trajectory perpendicular to the focal plane (out-of-plane shedding). In the second step, the onset of lipid shedding was studied as a function of the acoustic driving parameters, for example, pressure, number of cycles, bubble size and oscillation amplitude. The latter was recorded with an ultrafast framing camera running at 10 million frames per second. A threshold for lipid shedding under ultrasound excitation was found for a relative bubble oscillation amplitude >30%. Lipid shedding was found to be reproducible, indicating that the shedding event can be controlled. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

An in situ optical imaging system for measuring lipid uptake, vessel contraction, and lymph flow in small animal lymphatic vessels

NASA Astrophysics Data System (ADS)

Kassis, Timothy; Weiler, Michael J.; Dixon, J. Brandon

2012-03-01

All dietary lipids are transported to venous circulation through the lymphatic system, yet the underlying mechanisms that regulate this process remain unclear. Understanding how the lymphatics functionally respond to changes in lipid load is important in the diagnosis and treatment of lipid and lymphatic related diseases such as obesity, hypercholesterolemia, and lymphedema. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. A custom-built optical set-up provides us with the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. This is achieved by dividing the light path into two optical bands. Utilizing high-speed and back-illuminated CCD cameras and post-acquisition image processing algorithms, we have the potential quantify correlations between vessel contraction, lymph flow and lipid concentration of mesenteric lymphatic vessels in situ. Local flow velocity is measured through lymphocyte tracking, vessel contraction through measurements of the vessel walls and lipid uptake through fluorescence intensity tracking of a fluorescent long chain fatty acid analogue, Bodipy FL C16. This system will prove to be an invaluable tool for both scientists studying lymphatic function in health and disease, and those investigating strategies for targeting the lymphatic system with orally delivered drugs.

Ultrasound Mediated Microbubbles Destruction Augmented Sonolysis: An In Vitro and In Vivo Study.

PubMed

Cui, Hai; Zhu, Qiong; Gao, Yunhua; Xia, Hongmei; Tan, Kaibin; He, Ying; Liu, Zheng; Xu, Yali

2017-01-01

This study was aimed at exploring ultrasound mediated microbubbles destruction (UMMD) assisted sonolysis in both the in vitro and in vivo clots. Therapeutic ultrasound (TUS) and lipid microbubbles (MBs) were used in whole blood clots and divided into the control, TUS group, and TUS + MB group. Thrombolytic rates and microscopy were performed. Color Doppler flow imaging (CDFI) and angiography were performed to evaluate the recanalization rates and flow scores in femoral arterial thrombus (FAT) in rabbits. FAT were dyed with H&E. The average thrombolytic ratios of TUS + MB group were significantly higher than those of TUS group and the control group (both P < 0.05). Clots had different pathological changes. Recanalization rates and flow scores in TUS + MB group were significantly higher than the control and TUS group. Flow scores and recanalization ratios were grade 0 in 0% of the control group, grade I in 25% of TUS group, and grade II or higher in 87.5% of TUS + MB group after 30 min sonolysis. Both the in vitro and in vivo sonolysis can be significantly augmented by the introduction of MBs without thrombolytic agents, which might be induced by the enhanced cavitation via UMMD.

Polymeric and Lipid Membranes—From Spheres to Flat Membranes and vice versa

PubMed Central

Saveleva, Mariia S.; Gorin, Dmitry A.; Skirtach, Andre G.

2017-01-01

Membranes are important components in a number of systems, where separation and control of the flow of molecules is desirable. Controllable membranes represent an even more coveted and desirable entity and their development is considered to be the next step of development. Typically, membranes are considered on flat surfaces, but spherical capsules possess a perfect “infinite” or fully suspended membranes. Similarities and transitions between spherical and flat membranes are discussed, while applications of membranes are also emphasized. PMID:28809796

Polymeric and Lipid Membranes-From Spheres to Flat Membranes and vice versa.

PubMed

Saveleva, Mariia S; Lengert, Ekaterina V; Gorin, Dmitry A; Parakhonskiy, Bogdan V; Skirtach, Andre G

2017-08-15

Membranes are important components in a number of systems, where separation and control of the flow of molecules is desirable. Controllable membranes represent an even more coveted and desirable entity and their development is considered to be the next step of development. Typically, membranes are considered on flat surfaces, but spherical capsules possess a perfect "infinite" or fully suspended membranes. Similarities and transitions between spherical and flat membranes are discussed, while applications of membranes are also emphasized.

Ca-Mediated Electroformation of Cell-Sized Lipid Vesicles

PubMed Central

Tao, Fei; Yang, Peng

2015-01-01

Cell-sized lipid giant unilamellar vesicles (GUVs) are formed when lipid molecules self-assemble to construct a single bilayer compartment with similar morphology to living cells. The physics of self-assembly process is only generally understood and the size distribution of GUVs tends to be very polydisperse. Herein we report a strategy for the production of controlled size distributions of GUVs by a novel mechanism dissecting the mediation ability of calcium (Ca) on the conventional electroformation of GUVs. We finely construct both of the calcium ion (Ca2+) and calcium carbonate (CaCO3) mineral adsorption layers on a lipid film surface respectively during the electroformation of GUVs. It is found that Ca2+ Slip plane polarized by alternating electric field could induce a pattern of electroosmotic flow across the surface, and thus confine the fusion and growth of GUVs to facilitate the formation of uniform GUVs. The model is further improved by directly using CaCO3 that is in situ formed on a lipid film surface, providing a GUV population with narrow polydispersity. The two models deciphers the new biological function of calcium on the birth of cell-like lipid vesicles, and thus might be potentially relevant to the construction of new model to elucidate the cellular development process. PMID:25950604

Ca-mediated electroformation of cell-sized lipid vesicles.

PubMed

Tao, Fei; Yang, Peng

2015-05-07

Cell-sized lipid giant unilamellar vesicles (GUVs) are formed when lipid molecules self-assemble to construct a single bilayer compartment with similar morphology to living cells. The physics of self-assembly process is only generally understood and the size distribution of GUVs tends to be very polydisperse. Herein we report a strategy for the production of controlled size distributions of GUVs by a novel mechanism dissecting the mediation ability of calcium (Ca) on the conventional electroformation of GUVs. We finely construct both of the calcium ion (Ca(2+)) and calcium carbonate (CaCO3) mineral adsorption layers on a lipid film surface respectively during the electroformation of GUVs. It is found that Ca(2+) Slip plane polarized by alternating electric field could induce a pattern of electroosmotic flow across the surface, and thus confine the fusion and growth of GUVs to facilitate the formation of uniform GUVs. The model is further improved by directly using CaCO3 that is in situ formed on a lipid film surface, providing a GUV population with narrow polydispersity. The two models deciphers the new biological function of calcium on the birth of cell-like lipid vesicles, and thus might be potentially relevant to the construction of new model to elucidate the cellular development process.

Liposome retention in size exclusion chromatography

PubMed Central

Ruysschaert, Tristan; Marque, Audrey; Duteyrat, Jean-Luc; Lesieur, Sylviane; Winterhalter, Mathias; Fournier, Didier

2005-01-01

Background Size exclusion chromatography is the method of choice for separating free from liposome-encapsulated molecules. However, if the column is not presaturated with lipids this type of chromatography causes a significant loss of lipid material. To date, the mechanism of lipid retention is poorly understood. It has been speculated that lipid binds to the column material or the entire liposome is entrapped inside the void. Results Here we show that intact liposomes and their contents are retained in the exclusion gel. Retention depends on the pore size, the smaller the pores, the higher the retention. Retained liposomes are not tightly fixed to the beads and are slowly released from the gels upon direct or inverted eluent flow, long washing steps or column repacking. Further addition of free liposomes leads to the elution of part of the gel-trapped liposomes, showing that the retention is transitory. Trapping reversibility should be related to a mechanism of partitioning of the liposomes between the stationary phase, water-swelled polymeric gel, and the mobile aqueous phase. Conclusion Retention of liposomes by size exclusion gels is a dynamic and reversible process, which should be accounted for to control lipid loss and sample contamination during chromatography. PMID:15885140

Improved fatty acid analysis of conjugated linoleic acid rich egg yolk triacylglycerols and phospholipid species.

PubMed

Shinn, Sara; Liyanage, Rohana; Lay, Jack; Proctor, Andrew

2014-07-16

Reports from chicken conjugated linoleic acid (CLA) feeding trials are limited to yolk total fatty acid composition, which consistently described increased saturated fatty acids and decreased monounsaturated fatty acids. However, information on CLA triacylglycerol (TAG) and phospholipid (PL) species is limited. This study determined the fatty acid composition of total lipids in CLA-rich egg yolk produced with CLA-rich soy oil, relative to control yolks using gas chromatography with flame ionization detection (GC-FID), determined TAG and PL fatty acid compositions by thin-layer chromatography-GC-FID (TLC-GC-FID), identified intact PL and TAG species by TLC-matrix-assisted laser desorption/ionization mass spectrometry (TLC-MALDI-MS), and determined the composition of TAG and PL species in CLA and control yolks by direct flow infusion electrospray ionization MS (DFI ESI-MS). In total, 2 lyso-phosphatidyl choline (LPC) species, 1 sphingomyelin species, 17 phosphatidyl choline species, 19 TAG species, and 9 phosphatidyl ethanolamine species were identified. Fifty percent of CLA was found in TAG, occurring predominantly in C52:5 and C52:4 TAG species. CLA-rich yolks contained significantly more LPC than did control eggs. Comprehensive lipid profiling may provide insight on relationships between lipid composition and the functional properties of CLA-rich eggs.

Microalgae fractionation using steam explosion, dynamic and tangential cross-flow membrane filtration.

PubMed

Lorente, E; Hapońska, M; Clavero, E; Torras, C; Salvadó, J

2017-08-01

In this study, the microalga Nannochloropsis gaditana was subjected to acid catalysed steam explosion treatment and the resulting exploded material was subsequently fractionated to separate the different fractions (lipids, sugars and solids). Conventional and vibrational membrane setups were used with several polymeric commercial membranes. Two different routes were followed: 1) filtration+lipid solvent extraction and 2) lipid solvent extraction+filtration. Route 1 revealed to be much better since the used membrane for filtration was able to permeate the sugar aqueous phase and retained the fraction containing lipids; after this, an extraction required a much lower amount of solvent and a better recovering yield. Filtration allowed complete lipid rejection. Dynamic filtration improved permeability compared to the tangential cross-flow filtration. Best membrane performance was achieved using a 5000Da membrane with the dynamic system, obtaining a permeability of 6L/h/m 2 /bar. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential affinities of MinD and MinE to anionic phospholipid influence Min Patterning dynamics in vitro

PubMed Central

Vecchiarelli, Anthony G.; Li, Min; Mizuuchi, Michiyo; Mizuuchi, Kiyoshi

2014-01-01

The E. coli Min system forms a cell-pole-to-cell-pole oscillator that positions the divisome at mid-cell. The MinD ATPase binds the membrane and recruits the cell division inhibitor MinC. MinE interacts with and releases MinD (and MinC) from the membrane. The chase of MinD by MinE creates the in vivo oscillator that maintains a low level of the division inhibitor at mid-cell. In vitro reconstitution and visualization of Min proteins on a supported lipid bilayer has provided significant advances in understanding Min patterns in vivo. Here we studied the effects of flow, lipid composition, and salt concentration on Min patterning. Flow and no-flow conditions both supported Min protein patterns with somewhat different characteristics. Without flow, MinD and MinE formed spiraling waves. MinD and, to a greater extent MinE, have stronger affinities for anionic phospholipid. MinD-independent binding of MinE to anionic lipid resulted in slower and narrower waves. MinE binding to the bilayer was also more susceptible to changes in ionic strength than MinD. We find that modulating protein diffusion with flow, or membrane binding affinities with changes in lipid composition or salt concentration, can differentially affect the retention time of MinD and MinE, leading to spatiotemporal changes in Min patterning. PMID:24930948

Effects of flaxseed oil on anti-oxidative system and membrane deformation of human peripheral blood erythrocytes in high glucose level.

PubMed

Yang, Wei; Fu, Juan; Yu, Miao; Huang, Qingde; Wang, Di; Xu, Jiqu; Deng, Qianchun; Yao, Ping; Huang, Fenghong; Liu, Liegang

2012-07-08

The erythrocyte membrane lesion is a serious diabetic complication. A number of studies suggested that n-3 fatty acid could reduce lipid peroxidation and elevate α- or γ-tocopherol contents in membrane of erythrocytes. However, evidence regarding the protective effects of flaxseed oil, a natural product rich in n-3 fatty acid, on lipid peroxidation, antioxidative capacity and membrane deformation of erythrocytes exposed to high glucose is limited. Human peripheral blood erythrocytes were isolated and treated with 50 mM glucose to mimic hyperglycemia in the absence or presence of three different doses of flaxseed oil (50, 100 or 200 μM) in the culture medium for 24 h. The malondialdehyde (MDA) and L-glutathione (GSH) were measured by HPLC and LC/MS respectively. The phospholipids symmetry and membrane fatty acid composition of human erythrocytes were detected by flow cytometry and gas chromatograph (GC). The morphology of human erythrocyte was illuminated by ultra scanning electron microscopy. Flaxseed oil attenuated hyperglycemia-induced increase of MDA and decrease of GSH in human erythrocytes. Human erythrocytes treated with flaxseed oil contained higher C22:5 and C22:6 than those in the 50 mM glucose control group, indicating that flaxseed oil could reduce lipid asymmetric distribution and membrane perturbation. The ultra scanning electron microscopy and flow cytometer have also indicated that flaxseed oil could protect the membrane of human erythrocytes from deformation at high glucose level. The flaxseed oil supplementation may prevent lipid peroxidation and membrane dysfunction of human erythrocytes in hyperglycemia.

Influence of Algae Age and Population on the Response to TiO₂ Nanoparticles.

PubMed

Metzler, David M; Erdem, Ayca; Huang, Chin Pao

2018-03-25

This work shows the influence of algae age (at the time of the exposure) and the initial algae population on the response of green algae Raphidocelis subcapitata to titanium dioxide nanoparticles (TiO₂ NPs). The different algae age was obtained by changes in flow rate of continually stirred tank reactors prior to NP exposure. Increased algae age led to a decreased growth, variations in chlorophyll content, and an increased lipid peroxidation. Increased initial algae population (0.3-4.2 × 10⁶ cells/mL) at a constant NP concentration (100 mg/L) caused a decline in the growth of algae. With increased initial algae population, the lipid peroxidation and chlorophyll both initially decreased and then increased. Lipid peroxidation had 4× the amount of the control at high and low initial population but, at mid-ranged initial population, had approximately half the control value. Chlorophyll a results also showed a similar trend. These results indicate that the physiological state of the algae is important for the toxicological effect of TiO₂ NPs. The condition of algae and exposure regime must be considered in detail when assessing the toxicological response of NPs to algae.

Influence of Algae Age and Population on the Response to TiO2 Nanoparticles

PubMed Central

Metzler, David M.; Erdem, Ayca; Huang, Chin Pao

2018-01-01

This work shows the influence of algae age (at the time of the exposure) and the initial algae population on the response of green algae Raphidocelis subcapitata to titanium dioxide nanoparticles (TiO2 NPs). The different algae age was obtained by changes in flow rate of continually stirred tank reactors prior to NP exposure. Increased algae age led to a decreased growth, variations in chlorophyll content, and an increased lipid peroxidation. Increased initial algae population (0.3−4.2 × 106 cells/mL) at a constant NP concentration (100 mg/L) caused a decline in the growth of algae. With increased initial algae population, the lipid peroxidation and chlorophyll both initially decreased and then increased. Lipid peroxidation had 4× the amount of the control at high and low initial population but, at mid-ranged initial population, had approximately half the control value. Chlorophyll a results also showed a similar trend. These results indicate that the physiological state of the algae is important for the toxicological effect of TiO2 NPs. The condition of algae and exposure regime must be considered in detail when assessing the toxicological response of NPs to algae. PMID:29587381

Evaluation of the platelet counting by Abbott CELL-DYN SAPPHIRE haematology analyser compared with flow cytometry.

PubMed

Grimaldi, E; Del Vecchio, L; Scopacasa, F; Lo Pardo, C; Capone, F; Pariante, S; Scalia, G; De Caterina, M

2009-04-01

The Abbot Cell-Dyn Sapphire is a new generation haematology analyser. The system uses optical/fluorescence flow cytometry in combination with electronic impedance to produce a full blood count. Optical and impedance are the default methods for platelet counting while automated CD61-immunoplatelet analysis can be run as selectable test. The aim of this study was to determine the platelet count performance of the three counting methods available on the instrument and to compare the results with those provided by Becton Dickinson FACSCalibur flow cytometer used as reference method. A lipid interference experiment was also performed. Linearity, carryover and precision were good, and satisfactory agreement with reference method was found for the impedance, optical and CD61-immunoplatelet analysis, although this latter provided the closest results in comparison with flow cytometry. In the lipid interference experiment, a moderate inaccuracy of optical and immunoplatelet counts was observed starting from a very high lipid value.

The alteration of lipid bilayer dynamics by phloretin and 6-ketocholestanol.

PubMed

Przybylo, M; Procek, J; Hof, M; Langner, M

2014-02-01

Lipid bilayer properties are quantified with a variety of arbitrary selected parameters such as molecular packing and dynamics, electrostatic potentials or permeability. In the paper we determined the effect of phloretin and 6-ketocholestanol (dipole potential modifying agents) on the membrane hydration and efficiency of the trans-membrane water flow. The dynamics of water molecules within the lipid bilayer interface was evaluated using solvent relaxation method, whereas the osmotically induced trans-membrane water flux was estimated with the stopped-flow method using the liposome shrinkage kinetics. The presence of phloretin or 6-ketocholestanol resulted in a change of both, the interfacial hydration level and osmotically driven water fluxes. Specifically, the presence of 6-ketocholestanol reduced the amount and mobility of water in the membrane interface. It also slows the osmotically induced water flow. The interfacial hydration change caused by phloretin was much smaller and the effect on osmotically induced water flow was opposite to that of 6-ketocholestanol. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Clustering T cell GM1 Lipid Rafts Increases Cellular Resistance to Shear on Fibronectin through Changes in Integrin Affinity and Cytoskeletal Dynamics

PubMed Central

Mitchell, Jason S.; Brown, Wells S.; Woodside, Darren G.; Vanderslice, Peter; McIntyre, Bradley W.

2008-01-01

Lipid rafts are small laterally mobile microdomains that are highly enriched in lymphocyte signaling molecules. GM1 gangliosides are a common lipid raft component and have been shown to be important in many T cell functions. The aggregation of specific GM1 lipid rafts can control many T cell activation events, including their novel association with T cell integrins. We found that clustering GM1 lipid rafts can regulate β1 integrin function. This was apparent through increased resistance to shear flow dependent detachment of T cells adherent to the α4β1 and α5β1 integrin ligand fibronectin (FN). Adhesion strengthening as a result of clustering GM1 enriched lipid rafts correlated with increased cellular rigidity and morphology through the localization of cortical F-actin, the resistance to shear induced cell stretching, and an increase in the surface area and symmetry of the contact area between the cell surface and adhesive substrate. Furthermore, clustering GM1 lipid rafts could initiate integrin “inside-out” signaling mechanisms. This was seen through increased integrin-cytoskeleton associations and enhanced soluble binding of FN and VCAM-1 suggesting the induction of high affinity integrin conformations. The activation of these adhesion strengthening characteristics appear to be specific for the aggregation of GM1 lipid rafts as the aggregation of the heterogeneous raft associated molecule CD59 failed to activate these functions. These findings indicate a novel mechanism to signal to β1 integrins and to activate adhesion strengthening processes. PMID:19139760

The augmented lipid productivity in an emerging oleaginous model alga Coccomyxa subellipsoidea by nitrogen manipulation strategy.

PubMed

Wang, Chao; Wang, Zhenyao; Luo, Fei; Li, Yuqin

2017-08-01

The lipid productivity controlled by both of biomass and lipid content was really crucial for economic-feasibility of microalgae-based biofuels production. This study attempted at augmenting lipid productivity in an emerging oleaginous model alga Coccomyxa subellipsoidea by different nitrogen manipulation including one-stage continuous N-sufficiency (OCNS), N-deprivation (OCND), N-limitation (OCNL), and also two-stage batch N-starvation (TBNS). Amongst four tested nitrogen manipulation strategies, OCNS performed remarkable promoting effect on cell metabolic growth and the maximum biomass was achieved by 7.39 g/L. Whereas TBNS regime induced the highest lipid content (over 50.5%). Only OCNL treatment augmented the lipid productivity by 232.37 mg/L/day, representing 1.25-fold more than TBNS and even as much as 5.06-fold more than that of OCND strategy. OCNL also strengthened the proportions of saturated (C16:0 and C18:0) and monounsaturated fatty acid (C18:1) which were inclined to high-quality biofuels-making. This might be due to that most part of energy and metabolic flux (e.g. acetyl-CoA) derived from TCA cycle and glycolysis flowed into fatty acids biosynthesis pathway (especially C18:1) response to OCNL manipulation. This study represented a pioneering work of utilizing OCNL for lipids production by C. subellipsoidea and clearly implied that OCNL might be a feasible way for algal lipid production on a commercial scale and also promoted the potential of C. subellipsoidea as an ideal biodiesel feedstock.

Electronic control of H+ current in a bioprotonic device with Gramicidin A and Alamethicin

NASA Astrophysics Data System (ADS)

Hemmatian, Zahra; Keene, Scott; Josberger, Erik; Miyake, Takeo; Arboleda, Carina; Soto-Rodríguez, Jessica; Baneyx, François; Rolandi, Marco

2016-10-01

In biological systems, intercellular communication is mediated by membrane proteins and ion channels that regulate traffic of ions and small molecules across cell membranes. A bioelectronic device with ion channels that control ionic flow across a supported lipid bilayer (SLB) should therefore be ideal for interfacing with biological systems. Here, we demonstrate a biotic-abiotic bioprotonic device with Pd contacts that regulates proton (H+) flow across an SLB incorporating the ion channels Gramicidin A (gA) and Alamethicin (ALM). We model the device characteristics using the Goldman-Hodgkin-Katz (GHK) solution to the Nernst-Planck equation for transport across the membrane. We derive the permeability for an SLB integrating gA and ALM and demonstrate pH control as a function of applied voltage and membrane permeability. This work opens the door to integrating more complex H+ channels at the Pd contact interface to produce responsive biotic-abiotic devices with increased functionality.

Postprandial lymphatic pump function after a high-fat meal: a characterization of contractility, flow, and viscosity

PubMed Central

Kassis, Timothy; Yarlagadda, Sri Charan; Kohan, Alison B.; Tso, Patrick; Breedveld, Victor

2016-01-01

Dietary lipids are transported from the intestine through contractile lymphatics. Chronic lipid loads can adversely affect lymphatic function. However, the acute lymphatic pump response in the mesentery to a postprandial lipid meal has gone unexplored. In this study, we used the rat mesenteric collecting vessel as an in vivo model to quantify the effect of lipoproteins on vessel function. Lipid load was continuously monitored by using the intensity of a fluorescent fatty-acid analog, which we infused along with a fat emulsion through a duodenal cannula. The vessel contractility was simultaneously quantified. We demonstrated for the first time that collecting lymphatic vessels respond to an acute lipid load by reducing pump function. High lipid levels decreased contraction frequency and amplitude. We also showed a strong tonic response through a reduction in the end-diastolic and systolic diameters. We further characterized the changes in flow rate and viscosity and showed that both increase postprandially. In addition, shear-mediated Ca2+ signaling in lymphatic endothelial cells differed when cultured with lipoproteins. Together these results show that the in vivo response could be both shear and lipid mediated and provide the first evidence that high postprandial lipid has an immediate negative effect on lymphatic function even in the acute setting. PMID:26968208

Accounting for the effects of lipids in stable isotope (δ13C and δ15N values) analysis of skin and blubber of balaenopterid whales.

PubMed

Ryan, Conor; McHugh, Brendan; Trueman, Clive N; Harrod, Chris; Berrow, Simon D; O'Connor, Ian

2012-12-15

Stable isotope values (δ(13)C and δ(15)N) of darted skin and blubber biopsies can shed light on habitat use and diet of cetaceans, which are otherwise difficult to study. Non-dietary factors affect isotopic variability, chiefly the depletion of (13)C due to the presence of (12)C-rich lipids. The efficacy of post hoc lipid-correction models (normalization) must be tested. For tissues with high natural lipid content (e.g., whale skin and blubber), chemical lipid extraction or normalization is necessary. C:N ratios, δ(13)C values and δ(15)N values were determined for duplicate control and lipid-extracted skin and blubber of fin (Balaenoptera physalus), humpback (Megaptera novaeangliae) and minke whales (B. acutorostrata) by continuous-flow elemental analysis isotope ratio mass spectrometry (CF-EA-IRMS). Six different normalization models were tested to correct δ(13)C values for the presence of lipids. Following lipid extraction, significant increases in δ(13)C values were observed for both tissues in the three species. Significant increases were also found for δ(15)N values in minke whale skin and fin whale blubber. In fin whale skin, the δ(15)N values decreased, with no change observed in humpback whale skin. Non-linear models generally out-performed linear models and the suitability of models varied by species and tissue, indicating the need for high model specificity, even among these closely related taxa. Given the poor predictive power of the models to estimate lipid-free δ(13)C values, and the unpredictable changes in δ(15)N values due to lipid-extraction, we recommend against arithmetical normalization in accounting for lipid effects on δ(13)C values for balaenopterid skin or blubber samples. Rather, we recommend that duplicate analysis of lipid-extracted (δ(13)C values) and non-treated tissues (δ(15)N values) be used. Copyright © 2012 John Wiley & Sons, Ltd.

Stabilized filter-supported bilayer lipid membranes (BLMs) for automated flow monitoring of compounds of clinical, pharmaceutical, environmental and industrial interest

PubMed Central

Siontorou, Christina G.

1997-01-01

This paper describes the results of analytical applications of electrochemical biosensors based on bilayer lipid membranes (BLMs) for the automated rapid and sensitive flow monitoring of substrates of hydrolytic enzymes, antigens and triazine herbicides. BLMs, composed of mixtures of egg phosphatidylcholine (egg PC) and dipalmitoylphosphatidic acid (DPPA), were supported on ultrafiltration membranes (glass microfibre or polycarbonate filters) which were found to enhance their stability for flow experiments. The proteins (enzymes, antibodies) were incorporated into a floating lipid matrix at an air-electrolyte interface, and then a casting procedure was used to deliver the lipid onto the filter supports for BLM formation. Injections of the analyte were made into flowing streams of the carrier electrolyte solution and a current transient signal was obtained with a magnitude related to the analyte concentration. Substrates of hydrolytic enzyme reactions (acetylcholine, urea and penicillin) could be determined at the micromolar level with a maximum rate of 220 samples/h, whereas antigens (thyroxin) and triazine herbicides (simazine, atrazine and propazine) could be monitored at the nanomolar level in less than 2 min. The time of appearance of the transient response obtained for herbicides was increased to the order of simazine, atrazine and propazine which has permitted analysis of these triazines in mixtures. PMID:18924789

Cutaneous blood flow in psoriasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klemp, P.; Staberg, B.

1983-12-01

The disappearance rate of /sup 133/Xe was studied in 20 patients with psoriasis vulgaris, using an epicutaneous labeling technique in involved skin lesions or normal-appearing skin of the proximal extensor site of the forearm. Control experiments were performed in 10 normal subjects. Calculations of the cutaneous blood flow (CBF) in psoriatic skin lesions were performed using a tissue-to-blood partition coefficient for /sup 133/Xe, lambda c,pso, of 1.2 ml/100 g/min. lambda c,pso was estimated after the relative content of water, lipids, and proteins had been analyzed in psoriatic skin biopsies of 6 patients with untreated psoriasis. The mean relative content ofmore » water was markedly reduced to 23.5 +/- 1.5% (SEM), and lipids and proteins were markedly increased to 2.5 +/- 0.7% and 74.0 +/- 2.2, respectively, compared to previously published data for normal skin (water 72.5%, lipids 1%, proteins 26.5%). Mean CBF in untreated psoriatic skin was 63.5 +/- 9.0 ml/100 g/min. This was significantly higher than the mean CBF in 10 normal subjects, 6.3 +/- 0.5 ml/100 g/min (p much less than 0.0001). Mean CBF in normal-appearing skin in patients with psoriasis was 11.0 +/- 1.3 ml/100 g/min. This was significantly higher than CBF in normal subjects (p less than 0.0002).« less

The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients.

PubMed

Coimbra, S R; Lage, S H; Brandizzi, L; Yoshida, V; da Luz, P L

2005-09-01

Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic individuals (8 men and 8 women; mean age 51.6 +/- 8.1 years) without other risk factors. Twenty-four normal subjects were used as controls for vascular reactivity. Subjects randomly received RW, 250 ml/day, or purple grape juice (GJ), 500 ml/day, for 14 days with an equal wash-out period. At baseline, all 16 subjects were hypercholesterolemic (mean LDL = 181.0 +/- 28.7 mg/dl) but HDL, triglycerides, glucose, adhesion molecules, and platelet function were within normal limits. Brachial artery flow-mediated dilation was significantly decreased compared to controls (9.0 +/- 7.1 vs 12.1 +/- 4.5%; P < 0.05) and increased with both GJ (10.1 +/- 7.1 before vs 16.9 +/- 6.7% after: P < 0.05) and RW (10.1 +/- 6.4 before vs 15.6 +/- 4.6% after; P < 0.05). RW, but not GJ, also significantly increased endothelium-independent vasodilation (17.0 +/- 8.6 before vs 23.0 +/- 12.0% after; P < 0.01). GJ reduced ICAM-1 but not VCAM and RW had no effect on either molecule. No significant alterations were observed in plasma lipids, glucose or platelet aggregability with RW or GJ. Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced endothelium-independent vasodilation in hypercholesterolemic patients despite the increased plasma cholesterol. Thus, we conclude that GJ may protect against coronary artery disease without the additional negative effects of alcohol despite the gender.

Enhanced cavitation and heating of flowing polymer- and lipid-shelled microbubbles and phase-shift nanodroplets during focused ultrasound exposures

NASA Astrophysics Data System (ADS)

Zhang, Siyuan; Cui, Zhiwei; Li, Chong; Zhou, Fanyu; Zong, Yujin; Wang, Supin; Wan, Mingxi

2017-03-01

Cavitation and heating are the primary mechanisms of numerous therapeutic applications of ultrasound. Various encapsulated microbubbles (MBs) and phase-shift nanodroplets (NDs) have been used to enhance local cavitation and heating, creating interests in developing ultrasound therapy using these encapsulated MBs and NDs. This work compared the efficiency of flowing polymer- and lipid-shelled MBs and phase-shift NDs in cavitation and heating during focused ultrasound (FUS) exposures. Cavitation activity and temperature were investigated when the solution of polymer- and lipid-shelled MBs and NDs flowed through the vessel in a tissue-mimicking phantom with varying flow velocities when exposed to FUS at various acoustic power levels. The inertial cavitation dose (ICD) for the encapsulated MBs and NDs were higher than those for the saline. Temperature initially increased with increasing flow velocities of the encapsulated MBs, followed by a decrease of the temperature with increasing flow velocities when the velocity was much higher. Meanwhile, ICD showed a trend of increases with increasing flow velocity. For the phase-shift NDs, ICD after the first FUS exposure was lower than those after the second FUS exposure. For the encapsulated MBs, ICD after the first FUS exposure was higher than those after the second FUS exposure. Further studies are necessary to investigate the treatment efficiency of different encapsulated MBs and phase-shift NDs in cavitation and heating.

Salivary matrix metalloproteinase (MMP-8) levels and gelatinase (MMP-9) activities in patients with type 2 diabetes mellitus.

PubMed

Collin, H L; Sorsa, T; Meurman, J H; Niskanen, L; Salo, T; Rönkä, H; Konttinen, Y T; Koivisto, A M; Uusitupa, M

2000-10-01

We studied the salivary levels and activities of the matrix metalloproteinases (MMP) -8 and -9 in 45 type 2 diabetic patients and 77 control subjects. The patients' mean glycosylated haemoglobin (HbA1c) was 8.7%, indicating an unsatisfactory metabolic control of the disease. The MMP levels were further related to the clinical and microbiological periodontal findings as well as to salivary flow rate and other factors. The salivary flow rate, albumin and amylase concentrations were similar in type 2 diabetic patients to those in the control group. The mean gingival and periodontal pocket indexes were higher in the diabetes group. The number of potential periodontopathogenic bacteria was lower, however, in the diabetic than in the control group. Zymography and immunoblotting revealed that the major MMPs in the type 2 diabetic patients' saliva were MMP-8 and MMP-9. Salivary MMP levels and activities in type 2 diabetic patients were in general similar to those in the control group. However, the correlation coefficients using multiple regression analysis revealed that gingival bleeding, pocket depths and HbA1c were associated with increased MMP-8 levels which, in turn, were negatively predicted by elevated plasma lipid peroxide levels in the diabetic group. Our data on salivary MMP-8 and -9 do not support the concept of generalized neutrophil dysfunction in unbalanced diabetes. Moreover, plasma lipid peroxidation levels reflecting the increased oxidative burden, which is generated mainly by triggered neutrophils, do not indicate neutrophil dysfunction due to diabetes, but may rather be related to the increased tissue damage in an uncontrolled disease. However. advanced periodontitis in type 2 diabetes seems to be related to elevated salivary MMP-8 levels which might be useful in monitoring periodontal disease in diabetes.

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

PubMed Central

Spiller, R C; Trotman, I F; Adrian, T E; Bloom, S R; Misiewicz, J J; Silk, D B

1988-01-01

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions. PMID:3410330

Elevated CO2 improves lipid accumulation by increasing carbon metabolism in Chlorella sorokiniana.

PubMed

Sun, Zhilan; Chen, Yi-Feng; Du, Jianchang

2016-02-01

Supplying microalgae with extra CO2 is a promising means for improving lipid production. The molecular mechanisms involved in lipid accumulation under conditions of elevated CO2, however, remain to be fully elucidated. To understand how elevated CO2 improves lipid production, we performed sequencing of Chlorella sorokiniana LS-2 cellular transcripts during growth and compared transcriptional dynamics of genes involved in carbon flow from CO2 to triacylglycerol. These analyses identified the majority genes of carbohydrate metabolism and lipid biosynthesis pathways in C. sorokiniana LS-2. Under high doses of CO2 , despite down-regulation of most de novo fatty acid biosynthesis genes, genes involved in carbohydrate metabolic pathways including carbon fixation, chloroplastic glycolysis, components of the pyruvate dehydrogenase complex (PDHC) and chloroplastic membrane transporters were upexpressed at the prolonged lipid accumulation phase. The data indicate that lipid production is largely independent of de novo fatty acid synthesis. Elevated CO2 might push cells to channel photosynthetic carbon precursors into fatty acid synthesis pathways, resulting in an increase of overall triacylglycerol generation. In support of this notion, genes involved in triacylglycerol biosynthesis were substantially up-regulated. Thus, elevated CO2 may influence regulatory dynamics and result in increased carbon flow to triacylglycerol, thereby providing a feasible approach to increase lipid production in microalgae. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Effects of flaxseed oil on anti-oxidative system and membrane deformation of human peripheral blood erythrocytes in high glucose level

PubMed Central

2012-01-01

Background The erythrocyte membrane lesion is a serious diabetic complication. A number of studies suggested that n-3 fatty acid could reduce lipid peroxidation and elevate α- or γ-tocopherol contents in membrane of erythrocytes. However, evidence regarding the protective effects of flaxseed oil, a natural product rich in n-3 fatty acid, on lipid peroxidation, antioxidative capacity and membrane deformation of erythrocytes exposed to high glucose is limited. Methods Human peripheral blood erythrocytes were isolated and treated with 50 mM glucose to mimic hyperglycemia in the absence or presence of three different doses of flaxseed oil (50, 100 or 200 μM) in the culture medium for 24 h. The malondialdehyde (MDA) and L-glutathione (GSH) were measured by HPLC and LC/MS respectively. The phospholipids symmetry and membrane fatty acid composition of human erythrocytes were detected by flow cytometry and gas chromatograph (GC). The morphology of human erythrocyte was illuminated by ultra scanning electron microscopy. Results Flaxseed oil attenuated hyperglycemia-induced increase of MDA and decrease of GSH in human erythrocytes. Human erythrocytes treated with flaxseed oil contained higher C22:5 and C22:6 than those in the 50 mM glucose control group, indicating that flaxseed oil could reduce lipid asymmetric distribution and membrane perturbation. The ultra scanning electron microscopy and flow cytometer have also indicated that flaxseed oil could protect the membrane of human erythrocytes from deformation at high glucose level. Conclusion The flaxseed oil supplementation may prevent lipid peroxidation and membrane dysfunction of human erythrocytes in hyperglycemia. PMID:22768971

Three-compartment model for contaminant accumulation by semipermeable membrane devices

USGS Publications Warehouse

Gale, Robert W.

1998-01-01

Passive sampling of dissolved hydrophobic contaminants with lipid (triolein)-containing semipermeable membrane devices (SPMDs) has been gaining acceptance for environmental monitoring. Understanding of the accumulation process has employed a simple polymer film-control model of uptake by the polymer-enclosed lipid, while aqueous film control has been only briefly discussed. A more complete three-compartment model incorporating both aqueous film (turbulent-diffusive) and polymer film (diffusive) mass transfer is developed here and is fit to data from accumulation studies conducted in constant-concentration, flow-through dilutors. This model predicts aqueous film control of the whole device for moderate to high Kow compounds, rather than polymer film control. Uptake rates for phenanthrene and 2,2‘,5,5‘-tetrachlorobiphenyl were about 4.8 and 4.2 L/day/standard SPMD, respectively. Maximum 28 day SPMD concentration factors of 30 000 are predicted for solutes with log Kow values of >5.5. Effects of varying aqueous and polymer film thicknesses and solute diffusivities in the polymer film are modeled, and overall accumulation by the whole device is predicted to remain under aqueous film control, although accumulation in the triolein may be subject to polymer film control. The predicted half-life and integrative response of SPMDs to pulsed concentration events is proportional to log KSPMD.

Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

NASA Astrophysics Data System (ADS)

Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

2017-06-01

Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

Enzyme-aided extraction of lycopene from high-pigment tomato cultivars by supercritical carbon dioxide.

PubMed

Lenucci, Marcello Salvatore; De Caroli, Monica; Marrese, Pier Paolo; Iurlaro, Andrea; Rescio, Leonardo; Böhm, Volker; Dalessandro, Giuseppe; Piro, Gabriella

2015-03-01

This work reports a novel enzyme-assisted process for lycopene concentration into a freeze-dried tomato matrix and describes the results of laboratory scale lycopene supercritical CO2 (SC-CO2) extractions carried out with untreated (control) and enzyme-digested matrices. The combined use of food-grade commercial plant cell-wall glycosidases (Celluclast/Novozyme plus Viscozyme) allows to increase lycopene (∼153%) and lipid (∼137%) concentration in the matrix and rises substrate load onto the extraction vessel (∼46%) compared to the control. The addition of an oleaginous co-matrix (hazelnut seeds) to the tomato matrix (1:1 by weight) increases CO2 diffusion through the highly dense enzyme-treated matrix bed and provides lipids that are co-extracted increasing lycopene yield. Under the same operative conditions (50 MPa, 86 °C, 4 mL min(-1) SC-CO2 flow) extraction yield from control and Celluclast/Novozyme+Viscozyme-treated tomato matrix/co-matrix mixtures was similar, exceeding 75% after 4.5h of extraction. However, the total extracted lycopene was ∼3 times higher in enzyme-treated matrix than control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Glucagon-Like Peptide 1 Recruits Muscle Microvasculature and Improves Insulin’s Metabolic Action in the Presence of Insulin Resistance

PubMed Central

Chai, Weidong; Zhang, Xingxing; Barrett, Eugene J.

2014-01-01

Glucagon-like peptide 1 (GLP-1) acutely recruits muscle microvasculature, increases muscle delivery of insulin, and enhances muscle use of glucose, independent of its effect on insulin secretion. To examine whether GLP-1 modulates muscle microvascular and metabolic insulin responses in the setting of insulin resistance, we assessed muscle microvascular blood volume (MBV), flow velocity, and blood flow in control insulin-sensitive rats and rats made insulin-resistant acutely (systemic lipid infusion) or chronically (high-fat diet [HFD]) before and after a euglycemic-hyperinsulinemic clamp (3 mU/kg/min) with or without superimposed systemic GLP-1 infusion. Insulin significantly recruited muscle microvasculature and addition of GLP-1 further expanded muscle MBV and increased insulin-mediated glucose disposal. GLP-1 infusion potently recruited muscle microvasculature in the presence of either acute or chronic insulin resistance by increasing muscle MBV. This was associated with an increased muscle delivery of insulin and muscle interstitial oxygen saturation. Muscle insulin sensitivity was completely restored in the presence of systemic lipid infusion and significantly improved in rats fed an HFD. We conclude that GLP-1 infusion potently expands muscle microvascular surface area and improves insulin’s metabolic action in the insulin-resistant states. This may contribute to improved glycemic control seen in diabetic patients receiving incretin-based therapy. PMID:24658303

In-situ temperature-controllable shear flow device for neutron scattering measurement--an example of aligned bicellar mixtures.

PubMed

Xia, Yan; Li, Ming; Kučerka, Norbert; Li, Shutao; Nieh, Mu-Ping

2015-02-01

We have designed and constructed a temperature-controllable shear flow cell for in-situ study on flow alignable systems. The device has been tested in the neutron diffraction and has the potential to be applied in the small angle neutron scattering configuration to characterize the nanostructures of the materials under flow. The required sample amount is as small as 1 ml. The shear rate on the sample is controlled by the flow rate produced by an external pump and can potentially vary from 0.11 to 3.8 × 10(5) s(-1). Both unidirectional and oscillational flows are achievable by the setting of the pump. The instrument is validated by using a lipid bicellar mixture, which yields non-alignable nanodisc-like bicelles at low T and shear-alignable membranes at high T. Using the shear cell, the bicellar membranes can be aligned at 31 °C under the flow with a shear rate of 11.11 s(-1). Multiple high-order Bragg peaks are observed and the full width at half maximum of the "rocking curve" around the Bragg's condition is found to be 3.5°-4.1°. It is noteworthy that a portion of the membranes remains aligned even after the flow stops. Detailed and comprehensive intensity correction for the rocking curve has been derived based on the finite rectangular sample geometry and the absorption of the neutrons as a function of sample angle [See supplementary material at http://dx.doi.org/10.1063/1.4908165 for the detailed derivation of the absorption correction]. The device offers a new capability to study the conformational or orientational anisotropy of the solvated macromolecules or aggregates induced by the hydrodynamic interaction in a flow field.

Coffee Consumption Increases the Antioxidant Capacity of Plasma and Has No Effect on the Lipid Profile or Vascular Function in Healthy Adults in a Randomized Controlled Trial.

PubMed

Agudelo-Ochoa, Gloria M; Pulgarín-Zapata, Isabel C; Velásquez-Rodriguez, Claudia M; Duque-Ramírez, Mauricio; Naranjo-Cano, Mauricio; Quintero-Ortiz, Mónica M; Lara-Guzmán, Oscar J; Muñoz-Durango, Katalina

2016-03-01

Coffee, a source of antioxidants, has controversial effects on cardiovascular health. We evaluated the bioavailability of chlorogenic acids (CGAs) in 2 coffees and the effects of their consumption on the plasma antioxidant capacity (AC), the serum lipid profile, and the vascular function in healthy adults. Thirty-eight men and 37 women with a mean ± SD age of 38.5 ± 9 y and body mass index of 24.1 ± 2.6 kg/m(2) were randomly assigned to 3 groups: a control group that did not consume coffee or a placebo and 2 groups that consumed 400 mL coffee/d for 8 wk containing a medium (MCCGA; 420 mg) or high (HCCGA; 780 mg) CGA content. Both were low in diterpenes (0.83 mg/d) and caffeine (193 mg/d). Plasma caffeic and ferulic acid concentrations were measured by GC, and the plasma AC was evaluated with use of the ferric-reducing antioxidant power method. The serum lipid profile, nitric oxide (NO) plasma metabolites, vascular endothelial function (flow-mediated dilation; FMD), and blood pressure (BP) were evaluated. After coffee consumption (1 h and 8 wk), caffeic and ferulic acid concentrations increased in the coffee-drinking groups, although the values of the 2 groups were significantly different (P < 0.001); caffeic and ferulic acid concentrations were undetectable in the control group. At 1 h after consumption, the plasma AC in the control group was significantly lower than the baseline value (-2%) and significantly increased in the MCCGA (6%) and HCCGA (5%) groups (P < 0.05). After 8 wk, no significant differences in the lipid, FMD, BP, or NO plasma metabolite values were observed between the groups. Both coffees, which contained CGAs and were low in diterpenes and caffeine, provided bioavailable CGAs and had a positive acute effect on the plasma AC in healthy adults and no effect on blood lipids or vascular function. The group that did not drink coffee showed no improvement in serum lipid profile, FMD, BP, or NO plasma metabolites. This trial was registered at registroclinico.sld.cu as RPCEC00000168. © 2016 American Society for Nutrition.

Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency.

PubMed

van Rijn, Jorik M; Chandra Ardy, Rico; Kuloğlu, Zarife; Härter, Bettina; van Haaften-Visser, Désirée Y; van der Doef, Hubert P J; van Hoesel, Marliek; Kansu, Aydan; van Vugt, Anke H M; Ng, Marini; Kokke, Freddy T M; Krolo, Ana; Başaran, Meryem Keçeli; Kaya, Neslihan Gurcan; Aksu, Aysel Ünlüsoy; Dalgıç, Buket; Ozcay, Figen; Baris, Zeren; Kain, Renate; Stigter, Edwin C A; Lichtenbelt, Klaske D; Massink, Maarten P G; Duran, Karen J; Verheij, Joke B G M; Lugtenberg, Dorien; Nikkels, Peter G J; Brouwer, Henricus G F; Verkade, Henkjan J; Scheenstra, Rene; Spee, Bart; Nieuwenhuis, Edward E S; Coffer, Paul J; Janecke, Andreas R; van Haaften, Gijs; Houwen, Roderick H J; Müller, Thomas; Middendorp, Sabine; Boztug, Kaan

2018-03-29

Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids. We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequence analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for activities of caspases 3 and 7. In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids. We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Malathion-induced granulosa cell apoptosis in caprine antral follicles: an ultrastructural and flow cytometric analysis.

PubMed

Bhardwaj, Jitender K; Saraf, Priyanka

2014-12-01

Organophosphate pesticides (OPs) like malathion interfere with normal ovarian function resulting in an increased incidence of atresia and granulosa cell apoptosis that plays a consequential role in the loss of ovarian follicles or follicular atresia. The aim of present study was to assess malathion-induced (100 nM) reproductive stress, ultrastructural damage and changes in apoptosis frequency in ovarian granulosa cells of antral follicles. Transmission electron microscopy (TEM) was employed for ultrastructural characterization, oxidative stress was evaluated using thiobarbituric acid reactive substances (TBARS) assay to measure lipid peroxidation, and apoptosis was quantified via flow cytometry. By TEM, apoptosis was identified by the presence of an indented nuclear membrane with blebbing, pyknotic crescent-shaped fragmented nuclei, increased vacuolization, degenerating mitochondria, and lipid droplets. The results indicate a significant increase in malondialdehyde (MDA) level (nmols/g wet tissue) at a 100 nM dose of malathion i.e. 7.57±0.033*, 8.53±0.12*, and 12.87±0.78** at 4, 6, or 8 h, respectively, as compared with controls (6.07±0.033, p<0.01*, p<0.05**) showing a positive correlation between malathion-induced lipid peroxidation and percentage of granulosa cell apoptosis (r=1; p<0.01). The parallel use of these three methods enabled us to determine the role of malathion in inducing apoptosis as a consequence of cytogenetic damage and oxidative stress generated in granulosa cells of antral follicles.

Electronic control of H+ current in a bioprotonic device with Gramicidin A and Alamethicin

PubMed Central

Hemmatian, Zahra; Keene, Scott; Josberger, Erik; Miyake, Takeo; Arboleda, Carina; Soto-Rodríguez, Jessica; Baneyx, François; Rolandi, Marco

2016-01-01

In biological systems, intercellular communication is mediated by membrane proteins and ion channels that regulate traffic of ions and small molecules across cell membranes. A bioelectronic device with ion channels that control ionic flow across a supported lipid bilayer (SLB) should therefore be ideal for interfacing with biological systems. Here, we demonstrate a biotic–abiotic bioprotonic device with Pd contacts that regulates proton (H+) flow across an SLB incorporating the ion channels Gramicidin A (gA) and Alamethicin (ALM). We model the device characteristics using the Goldman–Hodgkin–Katz (GHK) solution to the Nernst–Planck equation for transport across the membrane. We derive the permeability for an SLB integrating gA and ALM and demonstrate pH control as a function of applied voltage and membrane permeability. This work opens the door to integrating more complex H+ channels at the Pd contact interface to produce responsive biotic–abiotic devices with increased functionality. PMID:27713411

Determining Double Bond Position in Lipids Using Online Ozonolysis Coupled to Liquid Chromatography and Ion Mobility-Mass Spectrometry.

PubMed

Harris, Rachel A; May, Jody C; Stinson, Craig A; Xia, Yu; McLean, John A

2018-02-06

The increasing focus on lipid metabolism has revealed a need for analytical techniques capable of structurally characterizing lipids with a high degree of specificity. Lipids can exist as any one of a large number of double bond positional isomers, which are indistinguishable by single-stage mass spectrometry alone. Ozonolysis reactions coupled to mass spectrometry have previously been demonstrated as a means for localizing double bonds in unsaturated lipids. Here we describe an online, solution-phase reactor using ozone produced via a low-pressure mercury lamp, which generates aldehyde products diagnostic of cleavage at a particular double bond position. This flow-cell device is utilized in conjunction with structurally selective ion mobility-mass spectrometry. The lamp-mediated reaction was found to be effective for multiple lipid species in both positive and negative ionization modes, and the conversion efficiency from precursor to product ions was tunable across a wide range (20-95%) by varying the flow rate through the ozonolysis device. Ion mobility separation of the ozonolysis products generated additional structural information and revealed the presence of saturated species in a complex mixture. The method presented here is simple, robust, and readily coupled to existing instrument platforms with minimal modifications necessary. For these reasons, application to standard lipidomic workflows is possible and aids in more comprehensive structural characterization of a myriad of lipid species.

Cell-sized asymmetric lipid vesicles facilitate the investigation of asymmetric membranes

NASA Astrophysics Data System (ADS)

Kamiya, Koki; Kawano, Ryuji; Osaki, Toshihisa; Akiyoshi, Kazunari; Takeuchi, Shoji

2016-09-01

Asymmetric lipid giant vesicles have been used to model the biochemical reactions in cell membranes. However, methods for producing asymmetric giant vesicles lead to the inclusion of an organic solvent layer that affects the mechanical and physical characteristics of the membrane. Here we describe the formation of asymmetric giant vesicles that include little organic solvent, and use them to investigate the dynamic responses of lipid molecules in the vesicle membrane. We formed the giant vesicles via the inhomogeneous break-up of a lipid microtube generated by applying a jet flow to an asymmetric planar lipid bilayer. The asymmetric giant vesicles showed a lipid flip-flop behaviour in the membrane, superficially similar to the lipid flip-flop activity observed in apoptotic cells. In vitro synthesis of membrane proteins into the asymmetric giant vesicles revealed that the lipid asymmetry in bilayer membranes improves the reconstitution ratio of membrane proteins. Our asymmetric giant vesicles will be useful in elucidating lipid-lipid and lipid-membrane protein interactions involved in the regulation of cellular functions.

Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

PubMed Central

Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

2016-01-01

Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production

PubMed Central

Talebi, Ahmad Farhad; Tohidfar, Masoud; Mousavi Derazmahalleh, Seyedeh Mahsa; Sulaiman, Alawi; Baharuddin, Azhari Samsu; Tabatabaei, Meisam

2015-01-01

Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L−1 myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L−1 myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that “there is a there there” for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality. PMID:26146623

Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production.

PubMed

Talebi, Ahmad Farhad; Tohidfar, Masoud; Mousavi Derazmahalleh, Seyedeh Mahsa; Sulaiman, Alawi; Baharuddin, Azhari Samsu; Tabatabaei, Meisam

2015-01-01

Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L(-1) myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L(-1) myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that "there is a there there" for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality.

Combination of Oxaliplatin and Vit.E-TPGS in Lipid Nanosystem for Enhanced Therapeutic Efficacy in Colon Cancers.

PubMed

Wang, Yanlei; Zhang, Xiang; Zhang, Wenqiang; Dong, Hao; Zhang, Wenjie; Mao, Jiajia; Dai, Yong

2018-01-08

The main aim of present study was to prepare the oxaliplatin (OXL)-loaded D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS)-based lipid nanoparticles to enhance the anticancer effect in colon cancer cells. The nanoparticles were nanosized and spherical shaped and exhibited controlled release kinetics. Flow cytometer and confocal laser scanning microscopy (CLSM) showed a remarkable uptake of nanoparticles in cancer cells in a time-dependent manner. The presence of TPGS remarkably increased the anticancer effect of OXL in HT-29 colon cancer cells. The IC50 value of free OXL was 4.25 μg/ml whereas IC50 value of OXL-loaded TPGS-based lipid nanoparticles (OXL/TLNP) was 1.12 μg/ml. The 3-fold lower IC50 value of OXL/TLNP indicates the superior anticancer effect of nanoparticle-based OXL. Consistently, OXL/TLNP induced a remarkable apoptosis of cancer cells. Approximately, ~52% of cells were in early apoptosis phase and ~13% of cells were in late apoptosis phase indicating the potent anticancer effect of the formulations. The findings from this study provide novel insights into the use of TPGS and lipid nanoparticle together for the better antitumor effect in colon cancers. Future studies will involve the detailed in vitro and in vivo studies on clinically relevant animals.

NBD-labelled phospholipid accelerates apolipoprotein C-II amyloid fibril formation but is not incorporated into mature fibrils

PubMed Central

Ryan, Timothy M.; Griffin, Michael D. W.; Bailey, Michael F.; Schuck, Peter; Howlett, Geoffrey J.

2014-01-01

Human apolipoprotein (apo) C-II is one of several lipid-binding proteins that self-assemble into fibrils and accumulate in disease-related amyloid deposits. A general characteristic of these amyloid deposits is the presence of lipids, known to modulate individual steps in amyloid fibril formation. ApoC-II fibril formation is activated by sub-micellar phospholipids but inhibited by micellar lipids. We examined the mechanism for the activation by sub-micellar lipids using the fluorescently-labelled, short-chain phospholipid, 1-dodecyl-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]-2-hydroxy-glycero-3-phosphocholine (NBD-lyso-12-PC). Addition of submicellar NBD-lyso-12-PC increased the rate of fibril formation by apoC-II approximately two-fold. Stopped flow kinetic analysis using fluorescence detection and low, non-fibril forming concentrations of apoC-II indicated NBD-Lyso-12-PC binds rapidly, in the millisecond timescale, followed by the slower formation of discrete apoC-II tetramers. Sedimentation velocity analysis showed NBD-Lyso-12-PC binds to both apoC-II monomers and tetramers at approximately 5 sites per monomer with an average dissociation constant of approximately 10 μM. Mature apoC-II fibrils formed in the presence of NBD-Lyso-12-PC were devoid of lipid indicating a purely catalytic role for sub-micellar lipids in the activation of apoC-II fibril formation. These studies demonstrate the catalytic potential of small amphiphilic molecules to control protein folding and fibril assembly pathways. PMID:21985034

Atorvastatin Restores Endothelial Function in Normocholesterolemic Smokers Independent of Changes in Low-Density Lipoprotein

PubMed Central

Beckman, Joshua A.; Liao, James K.; Hurley, Shauna; Garrett, Leslie A.; Chui, Daoshan; Mitra, Debi; Creager, Mark A.

2009-01-01

Cigarette smoking impairs endothelial function. Hydroxymethylglutaryl (HMG) CoA reductase inhibitors (statins) may favorably affect endothelial function via nonlipid mechanisms. We tested the hypothesis that statins would improve endothelial function independent of changes in lipids in cigarette smokers. Twenty normocholesterolemic cigarette smokers and 20 matched healthy control subjects were randomized to atorvastatin 40 mg daily or placebo for 4 weeks, washed out for 4 weeks, and then crossed-over to the other treatment. Baseline low-density lipoprotein (LDL) levels were similar in smokers and healthy subjects, 103±22 versus 95±27 mg/dL, respectively (P=NS) and were reduced similarly in smokers and control subjects by atorvastatin, to 55±30 and 58±20 mg/dL, respectively (P=NS). Vascular ultrasonography was used to determine brachial artery, flow-mediated, endothelium-dependent, and nitroglycerin-mediated, endothelium-independent vasodilation. To elucidate potential molecular mechanisms that may account for changes in endothelial function, skin biopsy specimens were assayed for eNOS mRNA, eNOS activity, and nitrotyrosine. Endothelium-dependent vasodilation was less in smokers than nonsmoking control subjects during placebo treatment, 8.0±0.6% versus 12.1±1.1%, (P=0.003). Atorvastatin increased endothelium-dependent vasodilation in smokers to 10.5±1.3% (P=0.017 versus placebo) but did not change endothelium-dependent vasodilation in control subjects (to 11.0±0.8%, P=NS). Endothelium-independent vasodilation did not differ between groups during placebo treatment and was not significantly affected by atorvastatin. Multivariate analysis did not demonstrate any association between baseline lipid levels or the change in lipid levels and endothelium-dependent vasodilation. Cutaneous nitrotyrosine levels and skin microvessel eNOS mRNA, but not ENOS activity, were increased in smokers compared with controls but unaffected by atorvastatin treatment. Atorvastatin restores endothelium-dependent vasodilation in normocholesterolemic cigarette smokers independent of changes in lipids. These results are consistent with a lipid-independent vascular benefit of statins but could not be explained by changes in eNOS message and tissue oxidative stress. These findings implicate a potential role for statin therapy to restore endothelial function and thereby investigate vascular disease in cigarette smokers. PMID:15178637

Selective and context-dependent effects of chemical stress across trophic levels at the basis of marine food webs.

PubMed

Mensens, Christoph; De Laender, Frederik; Janssen, Colin R; Rivera, Frances Camille; Sabbe, Koen; De Troch, Marleen

2018-04-26

Human activities increasingly impact the functioning of marine food webs, but anthropogenic stressors are seldom included in ecological study designs. Diet quality, as distinct from just diet quantity, has moreover rarely been highlighted in food web studies in a stress context. We measured the effects of metal and pesticide stress (copper and atrazine) on the contribution of a benthic intertidal diatom community to two processes that are key to the functioning of intertidal systems: biomass (diet quantity) and lipid (diet quality) production. We then examined if stressors affected diatom functioning by selectively targeting the species contributing most to functioning (selective stress effects) or by changing the species' functional contribution (context-dependent effects). Finally, we tested if stress-induced changes in diet quality altered the energy flow to the diatoms' main grazers (harpacticoid copepods). Diatom diet quantity was reduced by metal stress but not by low pesticide levels due to the presence of an atrazine-tolerant, mixotrophic species. Selective effects of the pesticide reduced diatom diet quality by 60% and 75% at low and high pesticide levels respectively, by shifting diatom community structure from dominance by lipid-rich species toward dominance by an atrazine-tolerant, but lipid-poor, species. Context-dependent effects did not affect individual diatom lipid content at low levels of both stressors, but caused diatoms to lose 40% of their lipids at high copper stress. Stress-induced changes in diet quality predicted the energy flow from the diatoms to their copepod consumers, which lost half of their lipids when feeding on diatoms grown under low and high pesticide and high metal stress. Selective pesticide effects were a more important threat for trophic energy transfer than context-dependent effects of both stressors, with shifts in diatom community structure affecting the energy flow to their copepod grazers at stress levels where no changes in diatom lipid content were detected. © 2018 by the Ecological Society of America.

Intermonolayer Friction and Surface Shear Viscosity of Lipid Bilayer Membranes

PubMed Central

den Otter, W. K.; Shkulipa, S. A.

2007-01-01

The flow behavior of lipid bilayer membranes is characterized by a surface viscosity for in-plane shear deformations, and an intermonolayer friction coefficient for slip between the two leaflets of the bilayer. Both properties have been studied for a variety of coarse-grained double-tailed model lipids, using equilibrium and nonequilibrium molecular dynamics simulations. For lipids with two identical tails, the surface shear viscosity rises rapidly with tail length, while the intermonolayer friction coefficient is less sensitive to the tail length. Interdigitation of lipid tails across the bilayer midsurface, as observed for lipids with two distinct tails, strongly enhances the intermonolayer friction coefficient, but hardly affects the surface shear viscosity. The simulation results are compared against the available experimental data. PMID:17468168

An Experimental Model to Study the Impact of Lipid Oxidation on Contact Lens Deposition In Vitro.

PubMed

Schuett, Burkhardt S; Millar, Thomas J

2017-09-01

This study was to establish a controlled in vitro test system to study the effect of lipid oxidation on lipid deposition on contact lenses. Fatty acids with varying degree of unsaturation were oxidized using the Fenton reaction. The degree of lipid oxidation and the lipid moieties formed during the oxidation were identified and estimated by various lipid staining techniques following separation with thin-layer chromatography, and by measuring thiobarbituric acid reactive substances or peroxides in solution. Two different silicone hydrogel-based contact lenses (Balafilcon A and Senofilcon A) were incubated with fatty acids laced with radioactive tracer oxidized to varying degrees, and the amount of lipid deposition was measured using unoxidized lipid samples as controls. The Fenton reaction together with the analytical methods to analyze the lipid oxidation can be used to control oxidation of lipids to a desired amount. In general, saturated fatty acids are not oxidized, the monounsaturated oleic acid produced peroxides while poly-unsaturated lipids initially produced peroxides and then fragmented into reactive aldehydes. Incubation with mildly oxidized lipids (most likely lipid peroxides) resulted in increased lipid deposition on Balafilcon A lenses compared to unoxidized lipids, but this was not observed for Senofilcon A lenses. Further oxidation of the lipids (carbon chain breakup) on the other hand resulted in diminished lipid deposition for both contact lens types. This study provides a method for inducing and controlling lipid oxidation so that the effect of lipid oxidation on contact lens binding can be compared. It could be shown that the degree of lipid oxidation has different effects on the lipid deposition on different contact lens types.

Lipidomic analysis of plasma in patients with lacunar infarction using normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry.

PubMed

Yang, Li; Lv, Pu; Ai, Wanpeng; Li, Linnan; Shen, Sensen; Nie, Honggang; Shan, Yabing; Bai, Yu; Huang, Yining; Liu, Huwei

2017-05-01

Stroke is a major cause of mortality and long-term disability worldwide. The study of biomarkers and pathogenesis is vital for early diagnosis and treatment of stroke. In the present study, a continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF/MS) method was employed to measure lipid species in human plasma, including healthy controls and lacunar infarction (LI) patients. As a result, 13 lipid species were demonstrated with significant difference between the two groups, and a "plasma biomarker model" including glucosylceramide (38:2), phosphatidylethanolamine (35:2), free fatty acid (16:1), and triacylglycerol (56:5) was finally established. This model was evaluated as an effective tool in that area under the receiver operating characteristic curve reached 1.000 in the discovery set and 0.947 in the validation set for diagnosing LI patients from healthy controls. Besides, the sensitivity and specificity of disease diagnosis in validation set were 93.3% and 96.6% at the best cutoff value, respectively. This study demonstrates the promising potential of NP/RP 2D LC-QToF/MS-based lipidomics approach in finding bio-markers for disease diagnosis and providing special insights into the metabolism of stroke induced by small vessel disease. Graphical abstract Flow-chart of the plasma biomarker model establishment through biomarker screening and validation.

Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells.

PubMed

Lopes da Silva, Mafalda; O'Connor, Marie N; Kriston-Vizi, Janos; White, Ian J; Al-Shawi, Raya; Simons, J Paul; Mössinger, Julia; Haucke, Volker; Cutler, Daniel F

2016-05-15

Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function. © 2016. Published by The Company of Biologists Ltd.

PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity

PubMed Central

Deckert, Valérie; Daien, Claire I.; Che, Hélène; Elhmioui, Jamila; Lemaire, Stéphanie; Pais de Barros, Jean-Paul; Desrumaux, Catherine; Combe, Bernard; Hahne, Michael; Lagrost, Laurent; Morel, Jacques

2018-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with modification of lipids profile and an increased risk of cardiovascular events related to inflammation. Plasma phospholipid transfer protein (PLTP) exerts a lipid transfer activity through its active form. PLTP can also bind to receptors such as ATP-binding cassette transporter A1 (ABCA1). In addition to its role in lipoprotein metabolism and atherosclerosis, the latest advances came in support of a complex role of PLTP in the regulation of the inflammatory response, both with pro-inflammatory or anti-inflammatory properties. The aim of the present study was to decipher the role of PLTP in joint inflammation and to assess its relevance in the context of RA. PLTP expression was examined by western-blot and by immunochemistry. ABCA1 expression was analyzed by flow cytometry. Lipid transfer activity of PLTP and pro-inflammatory cytokines were measured in sera and synovial fluid (SF) from RA patients and controls (healthy subjects or osteoarthritis patients [OA]). FLS were treated with both lipid-transfer active form and inactive form of recombinant human PLTP. IL-8, IL-6, VEGF and MMP3 produced by FLS were assessed by ELISA, and proliferation by measuring 3H-Thymidine incorporation. RA synovial tissues showed higher PLTP staining than OA and PLTP protein levels were also significantly higher in RA-FLS. In addition, RA, unlike OA patients, displayed elevated levels of PLTP activity in SF, which correlated with pro-inflammatory cytokines. Both lipid-transfer active and inactive forms of PLTP significantly increased the production of cytokines and proliferation of FLS. ABCA1 was expressed on RAFLS and PLTP activated STAT3 pathway. To conclude, PLTP is highly expressed in the joints of RA patients and may directly trigger inflammation and FLS proliferation, independently of its lipid transfer activity. These results suggest a pro-inflammatory role for PLTP in RA. PMID:29565987

Harnessing the Effect of pH on Lipid Production in Batch Cultures of Yarrowia lipolytica SKY7.

PubMed

Kuttiraja, Mathiazhakan; Dhouha, Ayed; Tyagi, Rajeshwar Dayal

2018-04-01

The objective of this research was to investigate the kinetics of lipid production by Yarrowia lipolytica SKY7 in the crude glycerol-supplemented media with and without the control of pH. Lipid and citric acid production were improved with the pH control condition. There was no significant difference observed in the biomass concentration with or without the pH control. In the pH-controlled experiments, the biomass and lipid concentration reached 18 and 7.78 g/L, (45.5% w/w), respectively, with lipid yield (Yp/s) of 0.179 g/g at 60 h of fermentation. The lipid production was directly correlated with growth and the process was defined as growth associated. After 60 h of fermentation, the lipid degradation was noticed in the pH-controlled reactor whereas it occurred after 84 h in the pH-uncontrolled reactor. Apart from lipid, citric acid was produced as the major extracellular product in both fermentations but the much lower concentration in uncontrolled pH. Based on the experimental results, it is evident that controlling the pH will enhance the lipid production by 15% compared to pH-uncontrolled fermentation.

Equilibrium and rate data for the extraction of lipids using compressed carbon dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, M.B.; Bott, T.R.; Barr, M.J.

1987-01-01

Equilibrium data are given for the solubilities in compressed CO2 of the lipid components in freshly ground rape seed and of glycerol trioleate (a typical constituent of rape oil) at pressures up to 200 bar and temperatures 25 to 75C. Continuous flow tests in which a bed of ground rape seed was contacted with a stream of liquid CO2 at 25C and varied flow conditions are also reported. The results are collated in terms of an empirical mass transfer coefficient. A sharp change took place in the lipid concentration in the extractant stream leaving the bed when about 65% ofmore » the available oil had been extracted. This, and changes in the composition of the extract, are discussed, together with the use of this type of data for design purposes.« less

Energy flow and trophic partitioning of contrasting Cold Water Coral ecosystems of the NE Atlantic.

NASA Astrophysics Data System (ADS)

Kiriakoulakis, K.; Smith, E. L.; Dempster, N. M.; Roberts, M.; Hennige, S. J.; Wolff, G. A.

2016-02-01

This study investigates the energy flow, trophic positioning and nutritional quality of suspended particulate organic matter (sPOM) that reaches cold-water coral (CWC) ecosystems from two contrasting oceanographic settings of the N. E. Atlantic using molecular (lipid) and stable isotopic analysis. Study sites are the shallow ( 150m) Mingulay Reef on the NW Scotland shelf vs the deeper ( 700m) Logachev Mounds on the eastern slope of the Rockall Bank. Cold water corals are now being realised as abundant, cosmopolitan and biodiverse hotspots of the global ocean. Recent research has shown links between high levels of surface primary productivity and sPOM flux; which when combined with hydrodynamic processes facilitates an almost continuous supply of nutrient rich sPOM to these deep-ocean ecosystems. However, little is understood regarding the exact nutritional requirements of these ecosystems. Fresh marine sPOM is usually rich in proteins and lipids; however during transport into the ocean interior its chemical composition is influenced by a variety of complex transformation, remineralisation and repackaging processes; thus altering its `freshness' and nutritional quality. The study of the bioavailable and nutritional fractions of sPOM in relation to specific oceanographic transport regimes can help further understand the processes, nutritional requirements and energy flow of these ecosystems. Isotopic ratios of carbon and nitrogen were analysed using EA-IR-MS and lipids via GC-MS. Initial results show significant differences in δ15N and δ13C values of sPOM between the two areas, indicating differences in trophic dynamics and sPOM re-working between locations. In addition lipid results highlight differences in trophic contributions to the energy flows of the two locations, yet similarities in molecular nutritional component contributions; thus supporting previous studies regarding the importance of certain lipid classes in the development of these deep and fragile ecosystems. This multi-disciplinary approach to biogeochemical analysis may also be used to detect chemosynthetic energy pathway contributions to sPOM.

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE-/- Mice With Unilateral Renal Artery Stenosis.

PubMed

Pathak, Alokkumar S; Huang, Jianhua; Rojas, Mauricio; Bazemore, Taylor C; Zhou, Ruihai; Stouffer, George A

2016-04-03

Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown. Male ApoE(-/-) mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic RAS resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P<0.05) and descending thoracic aorta (10.2% [6.4, 25.9] vs 4.9% [2.8, 7.8]; P<0.05), compared to sham surgery. There was an increased amount of aortic arch lipid staining in the D8LR group (22.7% [22.1, 32.7]), compared to sham-surgery, but less than observed with chronic RAS. Lipid staining in the aortic arch was not increased in the D4LR group, and lipid staining in the descending aorta was not increased in either the D8LR or D4LR groups. There was less macrophage expression in infrarenal aortic atheroma in the D4LR and D8LR groups compared to the chronic RAS group. Restoration of renal blood flow at either 4 or 8 days after unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Impaired postprandial tissue regulation of blood flow in insulin resistance: a determinant of cardiovascular risk?

PubMed

Summers, L K; Samra, J S; Frayn, K N

1999-11-01

The insulin resistant state is a major risk factor for coronary artery disease. This increased risk is likely to be due to associated lipid and coagulation abnormalities rather than just abnormalities in glucose metabolism or hyperinsulinaemia alone. Exaggerated postprandial lipaemia is a well-recognised associate of insulin resistance and postprandial hypertriglyceridaemia is particularly important in the development of coronary atheroma. It seems likely that insulin is one of the hormonal regulators of adipose tissue and skeletal muscle blood flow. The reduced blood flow and blunting of the postprandial rise of peripheral blood flow in insulin resistance may decrease chylomicron-triglyceride delivery to muscle in subjects with insulin resistance. This, in turn, will lead to increased production of atherogenic particles. We propose that impaired postprandial vasodilation, already recognised as a key feature of glucose intolerance, is also the cause of impaired lipid metabolism in insulin resistant subjects and predisposes them to cardiovascular disease.

Endothelial Microparticles (EMP) for the Assessment of Endothelial Function: An In Vitro and In Vivo Study on Possible Interference of Plasma Lipids

PubMed Central

van Ierssel, Sabrina H.; Hoymans, Vicky Y.; Van Craenenbroeck, Emeline M.; Van Tendeloo, Viggo F.; Vrints, Christiaan J.; Jorens, Philippe G.; Conraads, Viviane M.

2012-01-01

Background Circulating endothelial microparticles (EMP) reflect the condition of the endothelium and are of increasing interest in cardiovascular and inflammatory diseases. Recently, increased numbers of EMP following oral fat intake, possibly due to acute endothelial injury, have been reported. On the other hand, the direct interference of lipids with the detection of EMP has been suggested. This study aimed to investigate the effect of lipid-rich solutions, commonly administered in clinical practice, on the detection, both in vitro and in vivo, of EMP. Methods For the in vitro assessment, several lipid-rich solutions were added to whole blood of healthy subjects (n = 8) and patients with coronary heart disease (n = 5). EMP (CD31+/CD42b−) were detected in platelet poor plasma by flow cytometry. For the in vivo study, healthy volunteers were evaluated on 3 different study-days: baseline evaluation, following lipid infusion and after a NaCl infusion. EMP quantification, lipid measurements and peripheral arterial tonometry were performed on each day. Results Both in vitro addition and in vivo administration of lipids significantly decreased EMP (from 198.6 to 53.0 and from 272.6 to 90.6/µl PPP, respectively, p = 0.001 and p = 0.012). The EMP number correlated inversely with the concentration of triglycerides, both in vitro and in vivo (r = −0.707 and −0.589, p<0.001 and p = 0.021, respectively). The validity of EMP as a marker of endothelial function is supported by their inverse relationship with the reactive hyperemia index (r = −0.758, p = 0.011). This inverse relation was confounded by the intravenous administration of lipids. Conclusion The confounding effect of high circulating levels of lipids, commonly found in patients that receive intravenous lipid-based solutions, should be taken into account when flow cytometry is used to quantify EMP. PMID:22359595

Endothelial microparticles (EMP) for the assessment of endothelial function: an in vitro and in vivo study on possible interference of plasma lipids.

PubMed

van Ierssel, Sabrina H; Hoymans, Vicky Y; Van Craenenbroeck, Emeline M; Van Tendeloo, Viggo F; Vrints, Christiaan J; Jorens, Philippe G; Conraads, Viviane M

2012-01-01

Circulating endothelial microparticles (EMP) reflect the condition of the endothelium and are of increasing interest in cardiovascular and inflammatory diseases. Recently, increased numbers of EMP following oral fat intake, possibly due to acute endothelial injury, have been reported. On the other hand, the direct interference of lipids with the detection of EMP has been suggested. This study aimed to investigate the effect of lipid-rich solutions, commonly administered in clinical practice, on the detection, both in vitro and in vivo, of EMP. For the in vitro assessment, several lipid-rich solutions were added to whole blood of healthy subjects (n = 8) and patients with coronary heart disease (n = 5). EMP (CD31+/CD42b-) were detected in platelet poor plasma by flow cytometry. For the in vivo study, healthy volunteers were evaluated on 3 different study-days: baseline evaluation, following lipid infusion and after a NaCl infusion. EMP quantification, lipid measurements and peripheral arterial tonometry were performed on each day. Both in vitro addition and in vivo administration of lipids significantly decreased EMP (from 198.6 to 53.0 and from 272.6 to 90.6/µl PPP, respectively, p = 0.001 and p = 0.012). The EMP number correlated inversely with the concentration of triglycerides, both in vitro and in vivo (r = -0.707 and -0.589, p<0.001 and p = 0.021, respectively). The validity of EMP as a marker of endothelial function is supported by their inverse relationship with the reactive hyperemia index (r = -0.758, p = 0.011). This inverse relation was confounded by the intravenous administration of lipids. The confounding effect of high circulating levels of lipids, commonly found in patients that receive intravenous lipid-based solutions, should be taken into account when flow cytometry is used to quantify EMP.

Thermal conductivity and rectification in asymmetric archaeal lipid membranes

NASA Astrophysics Data System (ADS)

Youssefian, Sina; Rahbar, Nima; Van Dessel, Steven

2018-05-01

Nature employs lipids to construct nanostructured membranes that self-assemble in an aqueous environment to separate the cell interior from the exterior environment. Membrane composition changes among species and according to environmental conditions, which allows organisms to occupy a wide variety of different habitats. Lipid bilayers are phase-change materials that exhibit strong thermotropic and lyotropic phase behavior in an aqueous environment, which may also cause thermal rectification. Among different types of lipids, archaeal lipids are of great interest due to their ability to withstand extreme conditions. In this paper, nonequilibrium molecular dynamics simulations were employed to study the nanostructures and thermal properties of different archaeols and to investigate thermal rectification effects in asymmetric archaeal membranes. In particular, we are interested in understanding the role of bridged phytanyl chains and cyclopentane groups in controlling the phase transition temperature and heat flow across the membrane. Our results indicate that the bridged phytanyl chains decrease the molecular packing of lipids, whereas the existence of cyclopentane rings on the tail groups increases the molecular packing by enhancing the interactions between isoprenoid chains. We found that macrocyclic archaeols have the highest thermal conductivity, whereas macrocyclic archaeols with two cyclopentane rings have the lowest. The effect of the temperature on the variation of thermal conductivity was found to be progressive. Our results further indicate that small thermal rectification effects occur in asymmetric archaeol bilayer membranes at around 25 K temperature gradient. The calculated thermal rectification factor was around 0.09 which is in the range of rectification factor obtained experimentally for nanostructures such as carbon nanotubes (0.07). Such phenomena may be of biological significance and could also be optimized for use in various engineering applications.

Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study.

PubMed

Vafeiadou, Katerina; Weech, Michelle; Altowaijri, Hana; Todd, Susan; Yaqoob, Parveen; Jackson, Kim G; Lovegrove, Julie A

2015-07-01

Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. We investigated the substitution of 9.5-9.6%TE dietary SFAs with either monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on vascular function and other CVD risk factors. In a randomized, controlled, single-blind, parallel-group dietary intervention, 195 men and women aged 21-60 y from the United Kingdom with moderate CVD risk (≥50% above the population mean) followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA) that were rich in SFAs (36:17:11:4, n = 65), MUFAs (36:9:19:4, n = 64), or n-6 PUFAs (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation; secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation, and endothelial activation. Replacing SFAs with MUFAs or n-6 PUFAs did not affect the percentage of flow-mediated dilatation (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFAs with MUFAs attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFAs or n-6 PUFAs lowered fasting serum total cholesterol (-8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%), and total cholesterol to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. Substitution of 9.5-9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure, and E-selectin offer a potential public health strategy for CVD risk reduction. This trial was registered at www.clinicaltrials.gov as NCT01478958. © 2015 American Society for Nutrition.

Optimal control of nutrition restricted dynamics model of Microalgae biomass growth model

NASA Astrophysics Data System (ADS)

Ratianingsih, R.; Azim; Nacong, N.; Resnawati; Mardlijah; Widodo, B.

2017-12-01

The biomass of the microalgae is very potential to be proposed as an alternative renewable energy resources because it could be extracted into lipid. Afterward, the lipid could be processed to get the biodiesel or bioethanol. The extraction of the biomass on lipid synthesis process is very important to be studied because the process just gives some amount of lipid. A mathematical model of restricted microalgae biomass growth just gives 1/3 proportion of lipid with respect to the biomass in the synthesis process. An optimal control is designed to raise the ratio between the number of lipid formation and the microalgae biomass to be used in synthesis process. The minimum/ Pontryagin maximum principle is used to get the optimal lipid production. The simulation shows that the optimal lipid formation could be reach by simultaneously controlling the carbon dioxide, in the respiration and photosynthesis the process, and intake nutrition rates of liquid waste and urea substrate. The production of controlled microalgae lipid could be increase 6.5 times comparing to the uncontrolled one.

Biliary sphincterotomy does not relate to diarrhoea or major changes in bile acid synthesis or plasma lipids.

PubMed

Ung, Kjell-Arne; Mottacki, Nima; Rudling, Mats; Bajor, Antal

2009-01-01

Bile acid (BA) malabsorption may occur after cholecystectomy. Bile may flow more freely into the duodenum after endoscopic sphincterotomy (EST), in part resembling the situation after cholecystectomy. The (75)SeCHAT test used to diagnose BA malabsorption correlates inversely with synthesis and faecal excretion of BAs. The BA intermediate 7alpha-hydroxy-4-cholesten-3-one (C4) mirrors BA and lathosterol cholesterol synthesis. The aim was to study whether EST causes BA diarrhoea and alterations in BA synthesis or lipid profiles. Twelve patients underwent the (75)SeHCAT test prior to and 3 months after undergoing EST and a further 22 only after EST. The Gastrointestinal Symptom Rating Scale (GSRS), 1 week daily stool frequency and consistency, C4, lathosterol, cholesterol and triglycerides were investigated. The (75)SeHCAT values of 29 healthy subjects served as controls. Stool frequency (median 1/day, IQR (interquartile range): 0.7) and consistency (median: 3, IQR: 0.65) were normal and none reported diarrhoea after EST (n=34). The GSRS scores were normal. There was no significant change in (75)SeHCAT (median 22%, IQR 29% versus 19.5%, IQR 25, n=12). There was a trend towards lower (75)SeHCAT after EST compared with the controls (median 26%, IQR 32, n=34 versus median 38%, IQR 19.5, n=29, p=0.075) and higher lathosterol (median 47.1 mg/mole, IQR 32.7 versus median 52.5 mg/mole, IQR 35.6, n=14, p=0.055). The C4 and lipids did not change significantly. EST did not induce diarrhoea and in line with this BA synthesis and serum lipids are unaltered.

In-situ temperature-controllable shear flow device for neutron scattering measurement—An example of aligned bicellar mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Yan; Li, Ming; Kučerka, Norbert

We have designed and constructed a temperature-controllable shear flow cell for in-situ study on flow alignable systems. The device has been tested in the neutron diffraction and has the potential to be applied in the small angle neutron scattering configuration to characterize the nanostructures of the materials under flow. The required sample amount is as small as 1 ml. The shear rate on the sample is controlled by the flow rate produced by an external pump and can potentially vary from 0.11 to 3.8 × 10{sup 5} s{sup −1}. Both unidirectional and oscillational flows are achievable by the setting ofmore » the pump. The instrument is validated by using a lipid bicellar mixture, which yields non-alignable nanodisc-like bicelles at low T and shear-alignable membranes at high T. Using the shear cell, the bicellar membranes can be aligned at 31 °C under the flow with a shear rate of 11.11 s{sup −1}. Multiple high-order Bragg peaks are observed and the full width at half maximum of the “rocking curve” around the Bragg’s condition is found to be 3.5°–4.1°. It is noteworthy that a portion of the membranes remains aligned even after the flow stops. Detailed and comprehensive intensity correction for the rocking curve has been derived based on the finite rectangular sample geometry and the absorption of the neutrons as a function of sample angle [See supplementary material at http://dx.doi.org/10.1063/1.4908165 for the detailed derivation of the absorption correction]. The device offers a new capability to study the conformational or orientational anisotropy of the solvated macromolecules or aggregates induced by the hydrodynamic interaction in a flow field.« less

Ca(2+)-regulated cyclic electron flow supplies ATP for nitrogen starvation-induced lipid biosynthesis in green alga.

PubMed

Chen, Hui; Hu, Jinlu; Qiao, Yaqin; Chen, Weixian; Rong, Junfeng; Zhang, Yunming; He, Chenliu; Wang, Qiang

2015-10-09

We previously showed that both the linear photosynthetic electron transportation rate and the respiration rate dropped significantly during N starvation-induced neutral lipid accumulation in an oil-producing microalga, Chlorella sorokiniana, and proposed a possible role for cyclic electron flow (CEF) in ATP supply. In this study, we further exploited this hypothesis in both Chlorella sorokiniana C3 and the model green alga Chlamydomonas. We found that both the rate of CEF around photosystem I and the activity of thylakoid membrane-located ATP synthetase increased significantly during N starvation to drive ATP production. Furthermore, we demonstrated that the Chlamydomonas mutant pgrl1, which is deficient in PGRL1-mediated CEF, accumulated less neutral lipids and had reduced rates of CEF under N starvation. Further analysis revealed that Ca(2+) signaling regulates N starvation-induced neutral lipid biosynthesis in Chlamydomonas by increasing calmodulin activity and boosting the expression of the calcium sensor protein that regulates Pgrl1-mediated CEF. Thus, Ca(2+)-regulated CEF supplies ATP for N starvation-induced lipid biosynthesis in green alga. The increased CEF may re-equilibrate the ATP/NADPH balance and recycle excess light energy in photosystems to prevent photooxidative damage, suggesting Ca(2+)-regulated CEF also played a key role in protecting and sustaining photosystems.

Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

NASA Astrophysics Data System (ADS)

Evani, Shankar J.; Ramasubramanian, Anand K.

2016-01-01

Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

Changes in plasma membrane lipids, aquaporins and proton pump of broccoli roots, as an adaptation mechanism to salinity.

PubMed

López-Pérez, Luis; Martínez-Ballesta, María Del Carmen; Maurel, Christophe; Carvajal, Micaela

2009-03-01

Salinity stress is known to modify the plasma membrane lipid and protein composition of plant cells. In this work, we determined the effects of salt stress on the lipid composition of broccoli root plasma membrane vesicles and investigated how these changes could affect water transport via aquaporins. Brassica oleracea L. var. Italica plants treated with different levels of NaCl (0, 40 or 80mM) showed significant differences in sterol and fatty acid levels. Salinity increased linoleic (18:2) and linolenic (18:3) acids and stigmasterol, but decreased palmitoleic (16:1) and oleic (18:1) acids and sitosterol. Also, the unsaturation index increased with salinity. Salinity increased the expression of aquaporins of the PIP1 and PIP2 subfamilies and the activity of the plasma membrane H(+)-ATPase. However, there was no effect of NaCl on water permeability (P(f)) values of root plasma membrane vesicles, as determined by stopped-flow light scattering. The counteracting changes in lipid composition and aquaporin expression observed in NaCl-treated plants could allow to maintain the membrane permeability to water and a higher H(+)-ATPase activity, thereby helping to reduce partially the Na(+) concentration in the cytoplasm of the cell while maintaining water uptake via cell-to-cell pathways. We propose that the modification of lipid composition could affect membrane stability and the abundance or activity of plasma membrane proteins such as aquaporins or H(+)-ATPase. This would provide a mechanism for controlling water permeability and for acclimation to salinity stress.

Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes.

PubMed

Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel

2009-11-01

Ultrasound is used in many medical applications, such as imaging, blood flow analysis, dentistry, liposuction, tumor and fibroid ablation, and kidney stone disruption. In the past, low frequency ultrasound (LFUS) was the main method to downsize multilamellar (micron range) vesicles into small (nano scale) unilamellar vesicles. Recently, the ability of ultrasound to induce localized and controlled drug release from liposomes, utilizing thermal and/or mechanical effects, has been shown. This review, deals with the interaction of ultrasound with liposomes, focusing mainly on the mechanical mechanism of drug release from liposomes using LFUS. The effects of liposome lipid composition and physicochemical properties, on one hand, and of LFUS parameters, on the other, on liposomal drug release, are addressed. Acoustic cavitation, in which gas bubbles oscillate and collapse in the medium, thereby introducing intense mechanical strains, increases release substantially. We suggest that the mechanism of release may involve formation and collapse of small gas nuclei in the hydrophobic region of the lipid bilayer during exposure to LFUS, thereby inducing the formation of transient pores through which drugs are released. Introducing PEG-lipopolymers to the liposome bilayer enhances responsivity to LFUS, most likely due to absorption of ultrasonic energy by the highly hydrated PEG headgroups. The presence of amphiphiles, such as phospholipids with unsaturated acyl chains, which destabilize the lipid bilayer, also increases liposome susceptibility to LFUS. Application of these principles to design highly LFUS-responsive liposomes is discussed.

Controlling Styrene Maleic Acid Lipid Particles through RAFT.

PubMed

Smith, Anton A A; Autzen, Henriette E; Laursen, Tomas; Wu, Vincent; Yen, Max; Hall, Aaron; Hansen, Scott D; Cheng, Yifan; Xu, Ting

2017-11-13

The ability of styrene maleic acid copolymers to dissolve lipid membranes into nanosized lipid particles is a facile method of obtaining membrane proteins in solubilized lipid discs while conserving part of their native lipid environment. While the currently used copolymers can readily extract membrane proteins in native nanodiscs, their highly disperse composition is likely to influence the dispersity of the discs as well as the extraction efficiency. In this study, reversible addition-fragmentation chain transfer was used to control the polymer architecture and dispersity of molecular weights with a high-precision. Based on Monte Carlo simulations of the polymerizations, the monomer composition was predicted and allowed a structure-function analysis of the polymer architecture, in relation to their ability to assemble into lipid nanoparticles. We show that a higher degree of control of the polymer architecture generates more homogeneous samples. We hypothesize that low dispersity copolymers, with control of polymer architecture are an ideal framework for the rational design of polymers for customized isolation and characterization of integral membrane proteins in native lipid bilayer systems.

Assessing the In Vitro Drug Release from Lipid-Core Nanocapsules: a New Strategy Combining Dialysis Sac and a Continuous-Flow System.

PubMed

de Andrade, Diego Fontana; Zuglianello, Carine; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver

2015-12-01

The in vitro assessment of drug release from polymeric nanocapsules suspensions is one of the most studied parameters in the development of drug-loaded nanoparticles. Nevertheless, official methods for the evaluation of drug release from submicrometric carriers are not available. In this work, a new approach to assess the in vitro drug release profile from drug-loaded lipid-core nanocapsules (LNC) was proposed. A continuous-flow system (open system) was designed to evaluate the in vitro drug release profiles from different LNC formulations containing prednisolone or clobetasol propionate (LNC-CP) as drug model (LNC-PD) using a homemade apparatus. The release medium was constantly renewed throughout the experiment. A dialysis bag containing 5 mL of formulation (0.5 mg mL(-1)) was maintained inside the apparatus, under magnetic stirring and controlled temperature (37°C). In parallel, studies based on the conventional dialysis sac technique (closed system) were performed. It was possible to discriminate the in vitro drug release profile of different formulations using the open system. The proposed strategy improved the sink condition, by constantly renewing the release medium, thus maintaining the drug concentration farther from the saturated concentration in the release medium. Moreover, problems due to sampling errors can be easily overcome using this semi-automated system, since the collection is done automatically without interference from the analyst. The system proposed in this paper brings important methodological and analytical advantages, becoming a promising prototype semi-automated apparatus for performing in vitro drug release studies from drug-loaded lipid-core nanocapsules and other related nanoparticle drug delivery systems.

Lipid-Polymer Nanoparticles for Folate-Receptor Targeting Delivery of Doxorubicin.

PubMed

Zheng, Mingbin; Gong, Ping; Zheng, Cuifang; Zhao, Pengfei; Luo, Zhenyu; Ma, Yifan; Cai, Lintao

2015-07-01

A biocompatible PLGA-lipid hybrid nanoparticles (NPs) was developed for targeted delivery of anticancer drugs with doxorubicin (DOX). The hydrodynamic diameter and zeta potential of DOX-loaded PLGA-lipid NPs (DNPs) were affected by the mass ratio of Lipid/PLGA or DSPE-PEG-COOH/Lecithin. At the 1:20 drug/polymer mass ratio, the mean hydrodynamic diameter of DNPs was the lowest (99.2 1.83 nm) and the NPs presented the encapsulation efficiency of DOX with 42.69 1.30%. Due to the folate-receptor mediated endocytosis, the PLGA-lipid NPs with folic acid (FA) targeting ligand showed significant higher uptake by folate-receptor-positive MCF-7 cells as compared to PLGA-lipid NPs without folate. Confocal microscopic observation and flow cytometry analysis also supported the enhanced cellular uptake of the FA-targeted NPs. The results indicated that the FA-targeted DNPs exhibited higher cytotoxicity in MCF-7 cells compared with non-targeted NPs. The lipid-polymer nanoparticles provide a solution of biocompatible nanocarrier for cancer targeting therapy.

[Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

PubMed

Tian, Lei; Li, Yuanjing; Tian, Chunjie

2016-01-04

Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem.

SNARE-mediated Fusion of Single Proteoliposomes with Tethered Supported Bilayers in a Microfluidic Flow Cell Monitored by Polarized TIRF Microscopy

PubMed Central

Nikolaus, Joerg; Karatekin, Erdem

2016-01-01

In the ubiquitous process of membrane fusion the opening of a fusion pore establishes the first connection between two formerly separate compartments. During neurotransmitter or hormone release via exocytosis, the fusion pore can transiently open and close repeatedly, regulating cargo release kinetics. Pore dynamics also determine the mode of vesicle recycling; irreversible resealing results in transient, "kiss-and-run" fusion, whereas dilation leads to full fusion. To better understand what factors govern pore dynamics, we developed an assay to monitor membrane fusion using polarized total internal reflection fluorescence (TIRF) microscopy with single molecule sensitivity and ~15 msec time resolution in a biochemically well-defined in vitro system. Fusion of fluorescently labeled small unilamellar vesicles containing v-SNARE proteins (v-SUVs) with a planar bilayer bearing t-SNAREs, supported on a soft polymer cushion (t-SBL, t-supported bilayer), is monitored. The assay uses microfluidic flow channels that ensure minimal sample consumption while supplying a constant density of SUVs. Exploiting the rapid signal enhancement upon transfer of lipid labels from the SUV to the SBL during fusion, kinetics of lipid dye transfer is monitored. The sensitivity of TIRF microscopy allows tracking single fluorescent lipid labels, from which lipid diffusivity and SUV size can be deduced for every fusion event. Lipid dye release times can be much longer than expected for unimpeded passage through permanently open pores. Using a model that assumes retardation of lipid release is due to pore flickering, a pore "openness", the fraction of time the pore remains open during fusion, can be estimated. A soluble marker can be encapsulated in the SUVs for simultaneous monitoring of lipid and soluble cargo release. Such measurements indicate some pores may reseal after losing a fraction of the soluble cargo. PMID:27585113

Culture and Sampling of Primary Adipose Tissue in Practical Microfluidic Systems.

PubMed

Brooks, Jessica C; Judd, Robert L; Easley, Christopher J

2017-01-01

Microfluidic culture of primary adipose tissue allows for reduced sample and reagent volumes as well as constant media perfusion of the cells. By continuously flowing media over the tissue, microfluidic sampling systems can more accurately mimic vascular flow in vivo. Quantitative measurements can be performed on or off chip to provide time-resolved secretion data, furthering insight into the dynamics of the function of adipose tissue. Buoyancy resulting from the large lipid storage capacity in this tissue presents a unique challenge for culture, and it is important to account for this buoyancy during microdevice design. Herein, we describe approaches for microfluidic device fabrication that utilize 3D-printed interface templating to help counteract cell buoyancy. We apply such methods to the culture of both isolated, dispersed primary adipocytes and epididymal adipose explants. To facilitate more widespread adoption of the methodology, the devices presented here are designed for user-friendly operation. Only handheld syringes are needed to control flow, and devices are inexpensive and disposable.

Improved cardiac management with a disease management program incorporating comprehensive lipid profiling.

PubMed

McAna, John F; Goldfarb, Neil I; Couto, Joseph; Henry, Michelle A; Piefer, Gary; Rapier, George M

2012-02-01

The objective of this study was to evaluate the improved effectiveness of a disease management treatment protocol incorporating comprehensive lipid profiling and targeted lipid care based on lipid profile findings in patients with ischemic heart disease (IHD) or congestive heart failure (CHF) enrolled in a managed care plan. This retrospective cohort study, conducted over a 2-year period, compared outcomes between patients with a standard lipid profile to those evaluated with a comprehensive lipid profile. All adult members of the WellMed Medical Management, Inc. managed care health plan diagnosed with IHD or CHF, and continuously enrolled between July 1, 2006 and June 30, 2008, were included in the study. Cases were defined as those who had at least 1 comprehensive lipid test (the VAP [vertical auto profile] ultracentrifuge test) during this period (n=1767); they were compared to those who had no lipid testing or traditional standard lipid testing only (controls, n=289). Univariate statistics were analyzed to describe the groups, and bivariate t tests or chi-squares examined differences between the 2 cohorts. Multivariate regression analyses were performed to control for potential confounders. The results show that the case group had lower total costs ($4852.62 vs. $7413.18; P=0.0255), fewer inpatient stays (13.1% vs. 18.3% of controls; P=0.0175) and emergency department visits (11.9% vs. 15.6% of controls; P=0.0832). Prescription use and frequency of lipid measurement suggested improved control resulting from a targeted approach to managing specific dyslipidemias. A treatment protocol incorporating a comprehensive lipid profile appears to improve care and reduce utilization and costs in a disease management program for cardiac patients.

Studies on the regulation of lipid biosynthesis in plants: application of control analysis to soybean.

PubMed

Guschina, Irina A; Everard, John D; Kinney, Anthony J; Quant, Patti A; Harwood, John L

2014-06-01

Although there is much knowledge of the enzymology (and genes coding the proteins) of lipid biosynthesis in higher plants, relatively little attention has been paid to regulation. We have demonstrated the important role for cholinephosphate cytidylyltransferase in the biosynthesis of the major extra-plastidic membrane lipid, phosphatidylcholine. We followed this work by applying control analysis to light-induced fatty acid synthesis. This was the first such application to lipid synthesis in any organism. The data showed that acetyl-CoA carboxylase was very important, exerting about half of the total control. We then applied metabolic control analysis to lipid accumulation in important oil crops - oilpalm, olive, and rapeseed. Recent data with soybean show that the block of fatty acid biosynthesis reactions exerts somewhat more control (63%) than lipid assembly although both are clearly very important. These results suggest that gene stacks, targeting both parts of the overall lipid synthesis pathway will be needed to increase significantly oil yields in soybean. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of free-flowing peppermint essential oil-loaded hollow solid lipid micro- and nanoparticles via atomization with carbon dioxide.

PubMed

Yang, Junsi; Ciftci, Ozan Nazim

2016-09-01

The main objective of this study was to overcome the issues related to the volatility and strong smell that limit the efficient utilization of essential oils as "natural" antimicrobials in the food industry. Peppermint essential oil-loaded hollow solid lipid micro- and nanoparticles were successfully formed using a novel "green" method based on atomization of CO 2 -expanded lipid mixture. The highest essential oil loading efficiency (47.5%) was achieved at 50% initial essential oil concentration at 200bar expansion pressure and 50μm nozzle diameter, whereas there was no significant difference between the loading efficiencies (35%-39%) at 5%, 7%, 10%, and 20% initial essential oil concentrations (p>0.05). Particles generated at all initial essential oil concentrations were spherical but increasing the initial essential oil concentration to 20% and 50% generated a less smooth particle surface. After 4weeks of storage, 61.2%, 42.5%, 0.2%, and 2.0% of the loaded essential oil was released from the particles formed at 5%, 10%, 20%, and 50% initial essential oil concentrations, respectively. This innovative simple and clean process is able to form spherical hollow micro- and nanoparticles loaded with essential oil that can be used as food grade antimicrobials. These novel hollow solid lipid micro- and nanoparticles are alternatives to the solid lipid nanoparticles, and overcome the issues associated with the solid lipid nanoparticles. The dry free-flowing products make the handling and storage more convenient, and the simple and clean process makes the scaling up more feasible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of combined metformin and oral contraceptive on metabolic factors and endothelial function in overweight and obese women with polycystic ovary syndrome

PubMed Central

Essah, Paulina A; Arrowood, James A; Cheang, Kai I; Adawadkar, Swati S; Stovall, Dale W.; Nestler, John E.

2011-01-01

In this randomized, double-blind, placebo controlled study, 19 overweight women with PCOS were randomized to a 3-month course of either metformin plus combined hormonal oral contraceptive (OC) (n=9) or OC and matched placebo (n=10). After 3 months, both treatments had similar effects on androgen levels, lipid profile, insulin sensitivity and serum inflammatory markers, but flow-mediated dilatation increased by 69.0% in the metformin-OC group (p=0.01) while it remained unchanged in the OC group. PMID:21733508

Structure and Function of Skin: The Application of THz Radiation in Dermatology

NASA Astrophysics Data System (ADS)

Jo, Seong Jin; Kwon, Oh Sang

Skin, the largest organ of human being, is a soft membrane covering the exterior of the body. It protects the host from mechanical injuries, toxic materials, pathogenic organisms, and so on. Although its basic function is protection from the environment like this, it is not a simple and static shield but a complex and dynamic organ which performs important roles in maintaining the homeostasis of the body. Skin controls evaporation to prevent massive water loss, and regulates body temperature by controlling the blood flow of skin and perspiration [1]. It is responsible for the synthesis of vitamin D and a storage center for lipid and water. In addition, skin contains nerve endings and provides sensation for temperature, touch, pressure, and vibration.

Veganism Is a Viable Alternative to Conventional Diet Therapy for Improving Blood Lipids and Glycemic Control.

PubMed

Trepanowski, John F; Varady, Krista A

2015-01-01

The American Diabetes Association (ADA) and the National Cholesterol Education Program (NCEP) have each outlined a set of dietary recommendations aimed at improving glycemic control and blood lipids, respectively. However, traditional vegan diets (low-fat diets that proscribe animal product consumption) are also effective at improving glycemic control, and dietary portfolios (vegan diets that contain prescribed amounts of plant sterols, viscous fibers, soy protein, and nuts) are also effective at improving blood lipids. The purpose of this review was to compare the effects of traditional vegan diets and dietary portfolios with ADA and NCEP diets on body weight, blood lipids, blood pressure, and glycemic control. The main findings are that traditional vegan diets appear to improve glycemic control better than ADA diets in individuals with type 2 diabetes mellitus (T2DM), while dietary portfolios have been consistently shown to improve blood lipids better than NCEP diets in hypercholesterolemic individuals.

Effect of cinnamon on glucose control and lipid parameters.

PubMed

Baker, William L; Gutierrez-Williams, Gabriela; White, C Michael; Kluger, Jeffrey; Coleman, Craig I

2008-01-01

To perform a meta-analysis of randomized controlled trials of cinnamon to better characterize its impact on glucose and plasma lipids. A systematic literature search through July 2007 was conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters. The mean change in each study end point from baseline was treated as a continuous variable, and the weighted mean difference was calculated as the difference between the mean value in the treatment and control groups. A random-effects model was used. Five prospective randomized controlled trials (n = 282) were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, FBG, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results. Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.

Peroxidised dietary lipids impair intestinal function and morphology of the small intestine villi of nursery pigs in a dose-dependent manner.

PubMed

Rosero, David S; Odle, Jack; Moeser, Adam J; Boyd, R Dean; van Heugten, Eric

2015-12-28

The objective of this study was to investigate the effect of increasing degrees of lipid peroxidation on structure and function of the small intestine of nursery pigs. A total of 216 pigs (mean body weight was 6·5 kg) were randomly allotted within weight blocks and sex and fed one of five experimental diets for 35 d (eleven pens per treatment with three to four pigs per pen). Treatments included a control diet without added lipid, and diets supplemented with 6 % soyabean oil that was exposed to heat (80°C) and constant oxygen flow (1 litre/min) for 0, 6, 9 and 12 d. Increasing lipid peroxidation linearly reduced feed intake (P<0·001) and weight gain (P=0·024). Apparent faecal digestibility of gross energy (P=0·001) and fat (P<0·001) decreased linearly as the degree of peroxidation increased. Absorption of mannitol (linear, P=0·097) and d-xylose (linear, P=0·089), measured in serum 2 h post gavage with a solution containing 0·2 g/ml of d-xylose and 0·3 g/ml of mannitol, tended to decrease progressively as the peroxidation level increased. Increasing peroxidation also resulted in increased villi height (linear, P<0·001) and crypt depth (quadratic, P=0·005) in the jejunum. Increasing peroxidation increased malondialdehyde concentrations (quadratic, P=0·035) and reduced the total antioxidant capacity (linear, P=0·044) in the jejunal mucosa. In conclusion, lipid peroxidation progressively diminished animal performance and modified the function and morphology of the small intestine of nursery pigs. Detrimental effects were related with the disruption of redox environment of the intestinal mucosa.

Synthesis and validation of novel cholesterol-based fluorescent lipids designed to observe the cellular trafficking of cationic liposomes.

PubMed

Kim, Bieong-Kil; Seu, Young-Bae; Choi, Jong-Soo; Park, Jong-Won; Doh, Kyung-Oh

2015-09-15

Cholesterol-based fluorescent lipids with ether linker were synthesized using NBD (Chol-E-NBD) or Rhodamine B (Chol-E-Rh), and the usefulnesses as fluorescent probes for tracing cholesterol-based liposomes were validated. The fluorescent intensities of liposomes containing these modified lipids were measured and observed under a microscope. Neither compound interfered with the expression of GFP plasmid, and live cell images were obtained without interferences. Changes in the fluorescent intensity of liposomes containing Chol-E-NBD were followed by flow cytometry for up to 24h. These fluorescent lipids could be useful probes for trafficking of cationic liposome-mediated gene delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of statistical methods for detection of serum lipid biomarkers for mesothelioma and asbestos exposure.

PubMed

Xu, Rengyi; Mesaros, Clementina; Weng, Liwei; Snyder, Nathaniel W; Vachani, Anil; Blair, Ian A; Hwang, Wei-Ting

2017-07-01

We compared three statistical methods in selecting a panel of serum lipid biomarkers for mesothelioma and asbestos exposure. Serum samples from mesothelioma, asbestos-exposed subjects and controls (40 per group) were analyzed. Three variable selection methods were considered: top-ranked predictors from univariate model, stepwise and least absolute shrinkage and selection operator. Crossed-validated area under the receiver operating characteristic curve was used to compare the prediction performance. Lipids with high crossed-validated area under the curve were identified. Lipid with mass-to-charge ratio of 372.31 was selected by all three methods comparing mesothelioma versus control. Lipids with mass-to-charge ratio of 1464.80 and 329.21 were selected by two models for asbestos exposure versus control. Different methods selected a similar set of serum lipids. Combining candidate biomarkers can improve prediction.

Maximization of cell growth and lipid production of freshwater microalga Chlorella vulgaris by enrichment technique for biodiesel production.

PubMed

Wong, Y K; Ho, Y H; Ho, K C; Leung, H M; Yung, K K L

2017-04-01

Chlorella vulgaris was cultivated under limitation and starvation and under controlled conditions using different concentrations of nitrate (NaNO 3 ) and phosphate (K 2 HPO 4 and KH 2 PO 4 ) chemicals in modified Bold basal medium (BBM). The biomass and lipid production responses to different media were examined in terms of optical density, cell density, dry biomass, and lipid productivity. In the 12-day batch culture period, the highest biomass productivity obtained was 72.083 mg L -1  day -1 under BBM - N control P limited condition. The highest lipid content, lipid concentration, and lipid productivity obtained were 53.202 %, 287.291 mg/L, and 23.449 mg L -1  day -1 under BBM - N Control P Deprivation condition, respectively. Nitrogen had a major effect in the biomass concentration of C. vulgaris, while no significant effect was found for phosphorus. Nitrogen and phosphorus starvation was found to be the strategy affecting the lipid accumulation and affected the lipid composition of C. vulgaris cultures.

Regulation of Lipid Droplet Size in Mammary Epithelial Cells by Remodeling of Membrane Lipid Composition—A Potential Mechanism

PubMed Central

Cohen, Bat-Chen; Shamay, Avi; Argov-Argaman, Nurit

2015-01-01

Milk fat globule size is determined by the size of its precursors—intracellular lipid droplets—and is tightly associated with its composition. We examined the relationship between phospholipid composition of mammary epithelial cells and the size of both intracellular and secreted milk fat globules. Primary culture of mammary epithelial cells was cultured in medium without free fatty acids (control) or with 0.1 mM free capric, palmitic or oleic acid for 24 h. The amount and composition of the cellular lipids and the size of the lipid droplets were determined in the cells and medium. Mitochondrial quantity and expression levels of genes associated with mitochondrial biogenesis and polar lipid composition were determined. Cells cultured with oleic and palmitic acids contained similar quantities of triglycerides, 3.1- and 3.8-fold higher than in controls, respectively (P < 0.0001). When cultured with oleic acid, 22% of the cells contained large lipid droplets (>3 μm) and phosphatidylethanolamine concentration was higher by 23 and 63% compared with that in the control and palmitic acid treatments, respectively (P < 0.0001). In the presence of palmitic acid, only 4% of the cells contained large lipid droplets and the membrane phosphatidylcholine concentration was 22% and 16% higher than that in the control and oleic acid treatments, respectively (P < 0.0001). In the oleic acid treatment, approximately 40% of the lipid droplets were larger than 5 μm whereas in that of the palmitic acid treatment, only 16% of the droplets were in this size range. Triglyceride secretion in the oleic acid treatment was 2- and 12-fold higher compared with that in the palmitic acid and control treatments, respectively. Results imply that membrane composition of bovine mammary epithelial cells plays a role in controlling intracellular and secreted lipid droplets size, and that this process is not associated with cellular triglyceride content. PMID:25756421

High-rate anaerobic treatment system for solid/lipid-rich wastewater using anaerobic baffled reactor with scum recovery.

PubMed

Fujihira, Takuya; Seo, Shogo; Yamaguchi, Takashi; Hatamoto, Masashi; Tanikawa, Daisuke

2018-04-27

A laboratory scale experiment was conducted to investigate the treatment of solid/lipid-rich wastewater with an anaerobic baffled reactor (ABR) and a down-flow hanging sponge (DHS) reactor. In this study, experimental periods were divided into three phases to explore efficient treatment of solids and lipids in wastewater. In ABR, >90% of the influent chemical oxygen demand (COD) was removed and >70% of the removed COD was converted to methane under steady-state conditions during each phase. During this period, >4.5 kg COD m -3  d -1 was achieved on an average in Phases 1 and 3. Biogas contributed to scum formation, and the scum was categorized into lipid-rich and sludge-containing types, which have energy potentials of 53.4 and 212 kcal/kg-wet weight, respectively. Therefore, by recovering solids and lipids, which formed persistent scum, ABR can be applied as a high-rate treatment for solid/lipid-rich wastewater. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dynamic interfacial properties of human tear-lipid films and their interactions with model-tear proteins in vitro.

PubMed

Svitova, Tatyana F; Lin, Meng C

2016-07-01

This review summarizes the current state of knowledge regarding interfacial properties of very complex biological colloids, specifically, human meibum and tear lipids, and their interactions with proteins similar to the proteins found in aqueous part of human tears. Tear lipids spread as thin films over the surface of tear-film aqueous and play crucial roles in tear-film stability and overall ocular-surface health. The vast majority of papers published to date report interfacial properties of meibum-lipid monolayers spread on various aqueous sub-phases, often containing model proteins, in Langmuir trough. However, it is well established that natural human ocular tear lipids exist as multilayered films with a thickness between 30 and 100nm, that is very much disparate from 1 to 2nm thick meibum monolayers. We employed sessile-bubble tensiometry to study the dynamic interfacial and rheological properties of reconstituted multilayered human tear-lipid films. Small amounts (0.5-1μg) of human tear lipids were deposited on an air-bubble surface to produce tear-lipid films in thickness range 30-100nm corresponding to ocular lipid films. Thus, we were able to overcome major Langmuir-trough method limitations because ocular tear lipids can be safely harvested only in minute, sub-milligram quantities, insufficient for Langmuir through studies. Sessile-bubble method is demonstrated to be a versatile tool for assessing conventional synthetic surfactants adsorption/desorption dynamics at an air-aqueous solution interface. (Svitova T., Weatherbee M., Radke C.J. Dynamics of surfactant sorption at the air/water interface: continuous-flow tensiometry. J. Colloid Interf. Sci. 2003;261:1170-179). The augmented flow-sessile-bubble setup, with step-strain relaxation module for dynamic interfacial rheological properties and high-precision syringe pump to generate larger and slow interfacial area expansions-contractions, was developed and employed in our studies. We established that this method is uniquely suitable for examination of multilayered lipid-film interfacial properties. Recently it was compellingly proven that chemical composition of human tear lipids extracted from whole tears is substantially different from that of meibum lipids. To be exact, healthy human tear lipids contain 8-16% of polar lipids, similar to lung lipids, and they are mostly double-tailed phospholipids, with C16 and longer alkyl chains. Rationally, one would assume that the results obtained for meibum lipids, devoid of surface-active components such as phospholipids, and, above all, in a form of monolayers, are not pertinent or useful for elucidating behavior and stability of an averaged 60-nm thick ocular tear-lipid films in vivo. The advantage of sessile-bubble technique, specifically, using a small amount of lipids required to attain multilayered films, unlocks the prospect of evaluating and comparing the interfacial properties of human tear lipids collected from a single individual, typically 100-150μg. This is in sharp contrast with several milligrams of lipids that would be required to build equally thick films for Langmuir-trough experiments. The results of our studies provided in-depth understanding of the mechanisms responsible for properties and stability of human tear-lipid films in vivo. Here we summarize recent publications and our latest findings regarding human tear-lipid interfacial properties, their chemical composition, and their interaction with model proteins mimicking the proteins found in human tear-aqueous phase. Published by Elsevier B.V.

The use of Design of Experiments and Response Surface Methodology to optimize biomass and lipid production by the oleaginous marine green alga, Nannochloropsis gaditana in response to light intensity, inoculum size and CO2.

PubMed

Hallenbeck, Patrick C; Grogger, Melanie; Mraz, Megan; Veverka, Donald

2015-05-01

Biodiesel produced from microalgal lipids is being considered as a potential source of renewable energy. However, a number of hurdles will have to be overcome if such a process is to become practical. One important factor is the volumetric production of biomass and lipid that can be achieved. The marine alga Nannochloropsis gaditana is under study since it is known to be highly oleaginous and has a number of other attractive properties. Factors that might be important in biomass and lipid production by this alga are light intensity, inoculum size and CO2. Here we have carried out for the first time a RSM-DOE study of the influence of these important culture variables and define conditions that maximize biomass production, lipid content (BODIPY® fluorescence) and total lipid production. Moreover, flow cytometry allowed the examination on a cellular level of changes that occur in cellular populations as they age and accumulate lipids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of feeding outer bran fraction of rice on lipid accumulation and fecal excretion in rats.

PubMed

Ijiri, Daichi; Nojima, Tsutomu; Kawaguchi, Mana; Yamauchi, Yoko; Fujita, Yoshikazu; Ijiri, Satoru; Ohtsuka, Akira

2015-01-01

Outer bran fraction of rice (OBFR) contains higher concentrations of crude fiber, γ-oryzanol, and phytic acid compared to whole rice bran (WRB). In this study, we examined the effects of feeding OBFR on lipid accumulation and fecal excretion in rats. Twenty-one male rats at seven-week-old were divided into a control group and two treatment groups. The control group was fed a control diet, and the treatment groups were fed OBFR- or WRB-containing diet for 21 days. There was no significant difference in growth performance. Feeding OBFR diet increased fecal number and weight accompanied by increased fecal lipid content, while it did not affect mRNA expressions encoding lipid metabolism-related protein in liver. In addition, feeding OBFR-diet decreased the abdominal fat tissue weight and improved plasma lipid profiles, while WRB-containing diet did not affect them. These results suggested that feeding OBFR-diet might prevent lipid accumulation via enhancing fecal lipid excretion in rats.

NMR spectroscopy for evaluation of lipid oxidation

USDA-ARS?s Scientific Manuscript database

During storage and use of edible oils and other lipid-containing foods, reactions between lipids and oxygen occur, resulting in lipid oxidation and the subsequent development of off-flavors and odors. Accurate and timely assessment of lipid oxidation is critical for effective quality control of food...

Multiple sclerosis: Presence of serum antibodies to lipids and predominance of cholesterol recognition.

PubMed

Jurewicz, Anna; Domowicz, Malgorzata; Galazka, Grazyna; Raine, Cedric S; Selmaj, Krzysztof

2017-10-01

A lot of available data on lipid immunology in multiple sclerosis (MS) have been derived from studies using synthetic lipids, therefore the role of lipids in the immunopathogenesis of MS remains poorly defined. The present study on the lipid response in MS was performed on native lipids from autopsied brain tissue. For this, lipid fractions (n = 9) were prepared from MS (n = 3) and control (n = 2) white matter according to the Folch procedure and were characterized depending on their solubility in chloroform/methanol. TLC showed that, in brain from MS cases, neutral lipids were rich in cholesterol and cholesterol esters while lipids from control brains displayed a predominance of phospholipids. MS serum IgG and IgM were found to bind to MS brain lipid fractions with a higher efficacy (p < 0.05) than the control serum. F(ab) 2 fractionation revealed that MS serum IgG binding depended on a specific antibody-type of recognition. Pre-adsorption of serum with cholesterol, galactocerebrosides, sulfitides, and phosphatidylinositol prior to ELISA with MS brain lipids, showed that cholesterol diminished IgG and IgM binding up to 70%. Experiments with synthetic lipids confirmed the predominance of cholesterol binding by MS serum. Our results demonstrate that IgG and IgM fractions from MS serum specifically and predominantly recognize native cholesterol and cholesterol esters isolated from the brain tissue of patients with MS. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The effect of temperature on apoptosis and adipogenesis on skeletal muscle satellite cells derived from different muscle types

PubMed Central

Harding, Rachel L; Clark, Daniel L; Halevy, Orna; Coy, Cynthia S; Yahav, Shlomo; Velleman, Sandra G

2015-01-01

Satellite cells are multipotential stem cells that mediate postnatal muscle growth and respond differently to temperature based upon aerobic versus anaerobic fiber-type origin. The objective of this study was to determine how temperatures below and above the control, 38°C, affect the fate of satellite cells isolated from the anaerobic pectoralis major (p. major) or mixed fiber biceps femoris (b. femoris). At all sampling times, p. major and b. femoris cells accumulated less lipid when incubated at low temperatures and more lipid at elevated temperatures compared to the control. Satellite cells isolated from the p. major were more sensitive to temperature as they accumulated more lipid at elevated temperatures compared to b. femoris cells. Expression of adipogenic genes, CCAAT/enhancer-binding protein β (C/EBPβ) and proliferator-activated receptor gamma (PPARγ) were different within satellite cells isolated from the p. major or b. femoris. At 72 h of proliferation, C/EBPβ expression increased with increasing temperature in both cell types, while PPARγ expression decreased with increasing temperature in p. major satellite cells. At 48 h of differentiation, both C/EBPβ and PPARγ expression increased in the p. major and decreased in the b. femoris, with increasing temperature. Flow cytometry measured apoptotic markers for early apoptosis (Annexin-V-PE) or late apoptosis (7-AAD), showing less than 1% of apoptotic satellite cells throughout all experimental conditions, therefore, apoptosis was considered biologically not significant. The results support that anaerobic p. major satellite cells are more predisposed to adipogenic conversion than aerobic b. femoris cells when thermally challenged. PMID:26341996

Microbial Diversity and Lipid Abundance in Microbial Mats from a Sulfidic, Saline, Warm Spring in Utah, USA

NASA Astrophysics Data System (ADS)

Gong, J.; Edwardson, C.; Mackey, T. J.; Dzaugis, M.; Ibarra, Y.; Course 2012, G.; Frantz, C. M.; Osburn, M. R.; Hirst, M.; Williamson, C.; Hanselmann, K.; Caporaso, J.; Sessions, A. L.; Spear, J. R.

2012-12-01

The microbial diversity of Stinking Springs, a sulfidic, saline, warm spring northeast of the Great Salt Lake was investigated. The measured pH, temperature, salinity, and sulfide concentration along the flow path ranged from 6.64-7.77, 40-28° C, 2.9-2.2%, and 250 μM to negligible, respectively. Five sites were selected along the flow path and within each site microbial mats were dissected into depth profiles based on the color and texture of the mat layers. Genomic DNA was extracted from each layer, and the 16S rRNA gene was amplified and sequenced on the Roche 454 Titanium platform. Fatty acids were also extracted from the mat layers and analyzed by liquid chromatography and mass spectrometry. The mats at Stinking Springs were classified into roughly two morphologies with respect to their spatial distribution: loose, sometimes floating mats proximal to the spring source; and thicker, well-laminated mats distal to the spring source. Loosely-laminated mats were found in turbulent stream flow environments, whereas well-laminated mats were common in less turbulent sheet flows. Phototrophs, sulfur oxidizers, sulfate reducers, methanogens, other bacteria and archaea were identified by 16S rRNA gene sequences. Diatoms, identified by microscopy and lipid analysis were found to increase in abundance with distance from the source. Methanogens were generally more abundant in deeper mat laminae. Photoheterotrophs were found in all mat layers. Microbial diversity increased significantly with depth at most sites. In addition, two distinct microbial streamers were identified and characterized at the two fast flowing sites. These two streamer varieties were dominated by either cyanobacteria or flavobacteria. Overall, our genomic and lipid analysis suggest that the physical and chemical environment is more predictive of the community composition than mat morphology. Site Map

Control analysis of lipid biosynthesis in tissue cultures from oil crops shows that flux control is shared between fatty acid synthesis and lipid assembly.

PubMed Central

Ramli, Umi S; Baker, Darren S; Quant, Patti A; Harwood, John L

2002-01-01

Top-Down (Metabolic) Control Analysis (TDCA) was used to examine, quantitatively, lipid biosynthesis in tissue cultures from two commercially important oil crops, olive (Olea europaea L.) and oil palm (Elaeis guineensis Jacq.). A conceptually simplified system was defined comprising two blocks of reactions: fatty acid synthesis (Block A) and lipid assembly (Block B), which produced and consumed, respectively, a common and unique system intermediate, cytosolic acyl-CoA. We manipulated the steady-state levels of the system intermediate by adding exogenous oleic acid and, using two independent assays, measured the effect of the addition on the system fluxes (J(A) and J(B)). These were the rate of incorporation of radioactivity: (i) through Block A from [1-(14)C]acetate into fatty acids and (ii) via Block B from [U-(14)C]glycerol into complex lipids respectively. The data showed that fatty acid formation (Block A) exerted higher control than lipid assembly (Block B) in both tissues with the following group flux control coefficients (C):(i) Oil palm: *C(J(TL))(BlkA)=0.64+/-0.05 and *C(J(TL))(BlkB)=0.36+/-0.05(ii) Olive: *C(J(TL))(BlkA)=0.57+/-0.10 and *C(J(TL))(BlkB)=0.43+/-0.10where *C indicates the group flux control coefficient over the lipid biosynthesis flux (J(TL)) and the subscripts BlkA and BlkB refer to defined blocks of the system, Block A and Block B. Nevertheless, because both parts of the lipid biosynthetic pathway exert significant flux control, we suggest strongly that manipulation of single enzyme steps will not affect product yield appreciably. The present study represents the first use of TDCA to examine the overall lipid biosynthetic pathway in any tissue, and its findings are of immediate academic and economic relevance to the yield and nutritional quality of oil crops. PMID:12023882

Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver.

PubMed

Airanthi, M K Widjaja-Adhi; Sasaki, Naoya; Iwasaki, Sayaka; Baba, Nobuko; Abe, Masayuki; Hosokawa, Masashi; Miyashita, Kazuo

2011-04-27

Brown seaweed lipids from Undaria pinnatifida (Wakame), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) contained several bioactive compounds, namely, fucoxanthin, polyphenols, and omega-3 polyunsaturated fatty acids (PUFA). Fucoxanthin and polyphenol contents of Akamoku and Uganomoku lipids were higher than those of Wakame lipids, while Wakame lipids showed higher total omega-3 PUFA content than Akamoku and Uganomoku lipids. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in liver lipids of KK-A(y) mouse significantly increased by Akamoku and Uganomoku lipid feeding as compared with the control, but not by Wakame lipid feeding. Fucoxanthin has been reported to accelerate the bioconversion of omega-3 PUFA and omega-6 PUFA to DHA and AA, respectively. The higher hepatic DHA and AA level of mice fed Akamoku and Uganomoku lipids would be attributed to the higher content of fucoxanthin of Akamoku and Uganomoku lipids. The lipid hydroperoxide levels of the liver of mice fed brown seaweed lipids were significantly lower than those of control mice, even though total PUFA content was higher in the liver of mice fed brown seaweed lipids. This would be, at least in part, due to the antioxidant activity of fucoxanthin metabolites in the liver.

Protection against early intestinal compromise by lipid-rich enteral nutrition through cholecystokinin receptors.

PubMed

de Haan, Jacco J; Thuijls, Geertje; Lubbers, Tim; Hadfoune, M'hamed; Reisinger, Kostan; Heineman, Erik; Greve, Jan-Willem M; Buurman, Wim A

2010-07-01

Early gut wall integrity loss and local intestinal inflammation are associated with the development of inflammatory complications in surgical and trauma patients. Prevention of these intestinal events is a potential target for therapies aimed to control systemic inflammation. Previously, we demonstrated in a rodent shock model that lipid-rich enteral nutrition attenuated systemic inflammation and prevented organ damage through a cholecystokinin receptor-dependent vagal pathway. The influence of lipid-rich nutrition on very early intestinal compromise as seen after shock is investigated. Next, the involvement of cholecystokinin receptors on the nutritional modulation of immediate gut integrity loss and intestinal inflammation is studied. Randomized controlled in vivo study. University research unit. Male Sprague-Dawley rats. Liquid lipid-rich nutrition or control low-lipid feeding was administered per gavage before hemorrhagic shock. Cholecystokinin receptor antagonists were used to investigate involvement of the vagal antiinflammatory pathway. Gut permeability to horseradish peroxidase increased as soon as 30 mins postshock and was prevented by lipid-rich nutrition compared with low-lipid (p<.01) and fasted controls (p<.001). Furthermore, lipid-rich nutrition reduced plasma levels of enterocyte damage marker ileal lipid binding protein at 60 mins (p<.05). Early gut barrier dysfunction correlated with rat mast cell protease plasma concentrations at 30 mins (rs=0.67; p<.001) and intestinal myeloperoxidase levels at 60 mins (rs=0.58; p<.05). Lipid-rich nutrition significantly reduced plasma rat mast cell protease (p<.01) and myeloperoxidase (p<.05) before systemic inflammation was detectable. Protective effects of lipid-rich nutrition were abrogated by cholecystokinin receptor antagonists (horseradish peroxidase; p<.05 and rat mast cell protease; p<.05). Lipid-rich enteral nutrition prevents early gut barrier loss, enterocyte damage, and local intestinal inflammation before systemic inflammation develops in a cholecystokinin receptor-dependent manner. This study identifies activation of the vagal antiinflammatory pathway with lipid-rich nutrition as a potential therapy in patients prone to develop a compromised gut.

The Impact of Bubbles on Measurement of Drug Release from Echogenic Liposomes

PubMed Central

Kopechek, Jonathan A.; Haworth, Kevin J.; Radhakrishnan, Kirthi; Huang, Shaoling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

2013-01-01

Echogenic liposomes (ELIP) encapsulate gas bubbles and drugs within lipid vesicles, but the mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures above and below the inertial and stable cavitation thresholds. Control samples were exposed to a surfactant, Triton X-100 (positive control), or to flow alone (negative control). Fluorescence techniques were used to detect release. Encapsulated microbubbles reduced the measured fluorescence intensity and this effect should be considered when assessing drug release from ELIP. The origin of this effect is not specific to ELIP. Release of rosiglitazone or calcein compared to the negative control was only observed with detergent treatment, but not with ultrasound exposure, despite the presence of stable and inertial cavitation activity. Release of rosiglitazone or calcein from ELIP exposed to diagnostic ultrasound was not observed, even in the presence of cavitation activity. Ultrasound-mediated drug delivery strategies with ELIP will thus rely on passage of the drug-loaded liposomes to target tissues. PMID:23357288

Control of lipid oxidation in extruded salmon jerky snacks.

PubMed

Kong, Jian; Perkins, L Brian; Dougherty, Michael P; Camire, Mary Ellen

2011-01-01

A shelf-life study was conducted to evaluate the effect of antioxidants on oxidative stability of extruded jerky-style salmon snacks. Deterioration of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) due to lipid oxidation is a major concern for this healthy snack. A control jerky with no added antioxidants and 4 jerkies with antioxidants (rosemary, mixed tocopherols, tertiary butylhydroquinone, and ascorbyl palmitate) added as 0.02% of the lipid content were extruded in duplicate in a Coperion ZSK-25 twin screw extruder. Salmon jerkies from each formulation were placed in 3 mil barrier pouches, flushed with nitrogen, and stored at 35 °C and 75% relative humidity. Lipid oxidation was evaluated as by peroxide value and malonaldehyde content. Other chemical analyses included total fatty acid composition, lipid content, moisture, water activity, pH, and salt. Astaxanthin and CIE L*, a*, b* color were also analyzed at 4-wk intervals. Rosemary inhibited peroxide formation better than did other antioxidants at week 8; no treatment inhibited malonaldehyde levels. All jerkies had lower astaxanthin levels after 8 wk, but rosemary-treated jerky had higher pigment concentrations than did the control at weeks 4 and 8. Protection of omega-3 lipids in these extruded jerkies must be improved to offer consumers a convenient source of these healthful lipids. Practical Application: Salmon flesh can be extruded to produce a jerky that provides 410 mg of omega-3 lipids per serving. Natural antioxidants such as rosemary should be added at levels over 0.02% of the lipid content to help control lipid oxidation. Astaxanthin and CIE a* values correlated well with lipid stability and could be used to monitor quality during storage if initial values are known.

Identification of aquaporin-5 and lipid rafts in human resting saliva and their release into cevimeline-stimulated saliva.

PubMed

Pan, Yan; Iwata, Fusako; Wang, Di; Muraguchi, Masahiro; Ooga, Keiko; Ohmoto, Yasukazu; Takai, Masaaki; Cho, Gota; Kang, Jinsen; Shono, Masayuki; Li, Xue-jun; Okamura, Ko; Mori, Toyoki; Ishikawa, Yasuko

2009-01-01

It is unknown whether AQP5 and lipid rafts are released into human unstimulated (resting) saliva and saliva in response to secretagogues. In order to quantitate the salivary concentration of AQP5, we produced a polyclonal antibody for human AQP5 and developed an enzyme-like immunosorbent assay (ELISA). AQP5 and lipid rafts were identified in human resting saliva. The amount of AQP5 in resting saliva showed a diurnal variation with high levels during waking hours, and an age-related decrease in AQP5 was coincident with the volume of resting saliva. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, induced the release of AQP5 with lipid rafts, amylase, mucin, and lysozyme. Changes in saliva AQP5 levels after cevimeline administration occurred simultaneously with changes in saliva flow rates. Confocal microscopy revealed that AQP5 was located in the apical plasma membrane and showed a diffuse pattern in parotid glands under resting conditions. Following cevimeline administration, AQP5 was predominantly associated with the APM and was localized in the lumen. AQP5 and lipid rafts were released with salivary proteins from human salivary glands by the stimulation of M3 mAChRs, and that changes in saliva AQP5 levels can be used as an indicator of salivary flow rate and also as a useful index of M3 mAChR agonist's action on human salivary glands.

Optimization of the C11-BODIPY(581/591) dye for the determination of lipid oxidation in Chlamydomonas reinhardtii by flow cytometry.

PubMed

Cheloni, Giulia; Slaveykova, Vera I

2013-10-01

Lipid oxidation is a recognized end point for the study of oxidative stress and is an important parameter to describe the mode of micropollutant action on aquatic microorganisms. Therefore, the development of quick and reliable methodologies probing the oxidative stress and damage in living cells is highly sought. In the present proof-of-concept work, we examined the potential of the fluorescent dye C11-BODIPY(591/581) to probe lipid oxidation in the green microalga Chlamydomonas reinhardtii. C11-BODIPY(591/581) staining was combined with flow cytometry measurements to obtain multiparameter information on cellular features and oxidative stress damage within single cells. First, staining conditions were optimized by exploring the capability of the dye to stain algal cells under increasing cell and dye concentrations and different staining procedures. Then lipid oxidation in algae induced by short- and long-term exposures to the three metallic micropollutants, copper, mercury, and nanoparticulate copper oxide, and the two organic contaminants, diethyldithiocarbamate (DDC) and diuron was determined. In this work we pointed out C11-BODIPY(591/581) applicability in a wide range of exposure conditions, including studies of oxidation as a function of time and that it is suitable for in vivo measurements of lipid oxidation due to its high permeation and stability in cells and its low interference with algal autofluorescence. © 2013 International Society for Advancement of Cytometry. Copyright © 2013 International Society for Advancement of Cytometry.

Dynamic patterns in a supported lipid bilayer driven by standing surface acoustic waves.

PubMed

Hennig, Martin; Neumann, Jürgen; Wixforth, Achim; Rädler, Joachim O; Schneider, Matthias F

2009-11-07

In the past decades supported lipid bilayers (SLBs) have been an important tool in order to study the physical properties of biological membranes and cells. So far, controlled manipulation of SLBs is very limited. Here we present a new technology to create lateral patterns in lipid membranes controllable in both space and time. Surface acoustic waves (SAWs) are used to generate lateral standing waves on a piezoelectric substrate which create local "traps" in the lipid bilayer and lead to a lateral modulation in lipid concentration. We demonstrate that pattern formation is reversible and does not affect the integrity of the lipid bilayer as shown by extracting the diffusion constant of fluid membranes. The described method could possibly be used to design switchable interfaces for the lateral transport and organization of membrane bound macromolecules to create dynamic bioarrays and control biofilm formation.

Ternary liquid mixtures control the multiplicity, shape and internal structure of emulsion droplets

NASA Astrophysics Data System (ADS)

Haase, Martin F.; Brujic, Jasna

2014-03-01

It is important to control the shape, internal structure and stability of emulsion droplets for drug delivery, biochemical assays, and the design of materials with novel physical properties. Successful methods involve the mechanical manipulation of the flow of oil in water using complex microfluidic devices to make multiple emulsions with a sequential introduction of specific reactants. Instead, here we show how the thermodynamics of immiscible liquid mixtures tailor emulsions using a single dripping instability. For example, the initial composition and choice of surfactant govern the multiplicity of concentric alternating oil and water layers inside the droplets. Stabilizing ternary droplets using nanoparticles gives rise to a plethora of shapes whose geometry is defined by the deformability of the shell and the flow rate. Another option is to incorporate lipids to the multiple emulsion droplet, which form vesicles upon expulsion of the inner water droplets. Depending on the number of initial water droplets, these vesicles eventually form complex hollow topologies, which can be used as junctions or scaffolds for the self-assembly of colloidal particles in the future.

Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function.

PubMed

Robinson, George A; Waddington, Kirsty E; Pineda-Torra, Ines; Jury, Elizabeth C

2017-01-01

It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed.

Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function

PubMed Central

Robinson, George A.; Waddington, Kirsty E.; Pineda-Torra, Ines; Jury, Elizabeth C.

2017-01-01

It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed. PMID:29225604

Apparatus and method for controlling autotroph cultivation

DOEpatents

Fuxman, Adrian M; Tixier, Sebastien; Stewart, Gregory E; Haran, Frank M; Backstrom, Johan U; Gerbrandt, Kelsey

2013-07-02

A method includes receiving at least one measurement of a dissolved carbon dioxide concentration of a mixture of fluid containing an autotrophic organism. The method also includes determining an adjustment to one or more manipulated variables using the at least one measurement. The method further includes generating one or more signals to modify the one or more manipulated variables based on the determined adjustment. The one or more manipulated variables could include a carbon dioxide flow rate, an air flow rate, a water temperature, and an agitation level for the mixture. At least one model relates the dissolved carbon dioxide concentration to one or more manipulated variables, and the adjustment could be determined by using the at least one model to drive the dissolved carbon dioxide concentration to at least one target that optimize a goal function. The goal function could be to optimize biomass growth rate, nutrient removal and/or lipid production.

Dietary Lipid Levels Influence Lipid Deposition in the Liver of Large Yellow Croaker (Larimichthys crocea) by Regulating Lipoprotein Receptors, Fatty Acid Uptake and Triacylglycerol Synthesis and Catabolism at the Transcriptional Level.

PubMed

Yan, Jing; Liao, Kai; Wang, Tianjiao; Mai, Kangsen; Xu, Wei; Ai, Qinghui

2015-01-01

Ectopic lipid accumulation has been observed in fish fed a high-lipid diet. However, no information is available on the mechanism by which dietary lipid levels comprehensively regulate lipid transport, uptake, synthesis and catabolism in fish. Therefore, the present study aimed to gain further insight into how dietary lipids affect lipid deposition in the liver of large yellow croaker(Larimichthys crocea). Fish (150.00±4.95 g) were fed a diet with a low (6%), moderate (12%, the control diet) or high (18%) crude lipid content for 10 weeks. Growth performance, plasma biochemical indexes, lipid contents and gene expression related to lipid deposition, including lipoprotein assembly and clearance, fatty acid uptake and triacylglycerol synthesis and catabolism, were assessed. Growth performance was not significantly affected. However, the hepato-somatic and viscera-somatic indexes as well as plasma triacylglycerol, non-esterified fatty acids and LDL-cholesterol levels were significantly increased in fish fed the high-lipid diet. In the livers of fish fed the high-lipid diet, the expression of genes related to lipoprotein clearance (LDLR) and fatty acid uptake (FABP11) was significantly up-regulated, whereas the expression of genes involved in lipoprotein assembly (apoB100), triacylglycerol synthesis and catabolism (DGAT2, CPT I) was significantly down-regulated compared with fish fed the control diet, and hepatic lipid deposition increased. In fish fed the low-lipid diet, the expression of genes associated with lipoprotein assembly and clearance (apoB100, LDLR, LRP-1), fatty acid uptake (CD36, FATP1, FABP3) and triacylglycerol synthesis (FAS) was significantly increased, whereas the expression of triacylglycerol catabolism related genes (ATGL, CPT I) was reduced compared with fish fed the control diet. However, hepatic lipid content in fish fed the low-lipid diet decreased mainly due to low dietary lipid intake. In summary, findings of this study provide molecular insight into the role of lipid deposition in the liver in response to different dietary lipid contents.

Dietary Lipid Levels Influence Lipid Deposition in the Liver of Large Yellow Croaker (Larimichthys crocea) by Regulating Lipoprotein Receptors, Fatty Acid Uptake and Triacylglycerol Synthesis and Catabolism at the Transcriptional Level

PubMed Central

Yan, Jing; Liao, Kai; Wang, Tianjiao; Mai, Kangsen; Xu, Wei; Ai, Qinghui

2015-01-01

Ectopic lipid accumulation has been observed in fish fed a high-lipid diet. However, no information is available on the mechanism by which dietary lipid levels comprehensively regulate lipid transport, uptake, synthesis and catabolism in fish. Therefore, the present study aimed to gain further insight into how dietary lipids affect lipid deposition in the liver of large yellow croaker(Larimichthys crocea). Fish (150.00±4.95 g) were fed a diet with a low (6%), moderate (12%, the control diet) or high (18%) crude lipid content for 10 weeks. Growth performance, plasma biochemical indexes, lipid contents and gene expression related to lipid deposition, including lipoprotein assembly and clearance, fatty acid uptake and triacylglycerol synthesis and catabolism, were assessed. Growth performance was not significantly affected. However, the hepato-somatic and viscera-somatic indexes as well as plasma triacylglycerol, non-esterified fatty acids and LDL-cholesterol levels were significantly increased in fish fed the high-lipid diet. In the livers of fish fed the high-lipid diet, the expression of genes related to lipoprotein clearance (LDLR) and fatty acid uptake (FABP11) was significantly up-regulated, whereas the expression of genes involved in lipoprotein assembly (apoB100), triacylglycerol synthesis and catabolism (DGAT2, CPT I) was significantly down-regulated compared with fish fed the control diet, and hepatic lipid deposition increased. In fish fed the low-lipid diet, the expression of genes associated with lipoprotein assembly and clearance (apoB100, LDLR, LRP-1), fatty acid uptake (CD36, FATP1, FABP3) and triacylglycerol synthesis (FAS) was significantly increased, whereas the expression of triacylglycerol catabolism related genes (ATGL, CPT I) was reduced compared with fish fed the control diet. However, hepatic lipid content in fish fed the low-lipid diet decreased mainly due to low dietary lipid intake. In summary, findings of this study provide molecular insight into the role of lipid deposition in the liver in response to different dietary lipid contents. PMID:26114429

Control mechanisms operating for lipid biosynthesis differ in oil-palm (Elaeis guineensis Jacq.) and olive (Olea europaea L.) callus cultures.

PubMed Central

Ramli, Umi S; Baker, Darren S; Quant, Patti A; Harwood, John L

2002-01-01

As a prelude to detailed flux control analysis of lipid synthesis in plants, we have examined the latter in tissue cultures from two important oil crops, olive (Olea europaea L.) and oil palm (Elaeis guineensis Jacq.). Temperature was used to manipulate the overall rate of lipid formation in order to characterize and validate the system to be used for analysis. With [1-14C]acetate as a precursor, an increase in temperature from 20 to 30 degrees C produced nearly a doubling of total lipid labelling. This increase in total lipids did not change the radioactivity in the intermediate acyl-(acyl carrier protein) or acyl-CoA pools, indicating that metabolism of these pools did not exert any significant constraint for overall synthesis. In contrast, there were some differences in the proportional labelling of fatty acids and of lipid classes at the two temperatures. The higher temperature caused a decrease in polyunsaturated fatty acid labelling and an increase in the proportion of triacylglycerol labelling in both calli. The intermediate diacylglycerol was increased in olive, but not in oil palm. Overall the data indicate the suitability of olive and oil-palm cultures for the study of lipid synthesis and indicate that de novo fatty acid synthesis may exert more flux control than complex lipid assembly. In olive, diacylglycerol acyltransferase may exert significant flux control when lipid synthesis is rapid. PMID:12023881

Digestion of fatty acids in ruminants: a meta-analysis of flows and variation factors: 2. C18 fatty acids.

PubMed

Glasser, F; Schmidely, P; Sauvant, D; Doreau, M

2008-05-01

In ruminants, dietary lipids are extensively hydrogenated by rumen micro-organisms, and the extent of this biohydrogenation is a major determinant of long-chain fatty acid profiles of animal products (milk, meat). This paper reports on the duodenal flows of C18 fatty acids and their absorption in the small intestine, using a meta-analysis of a database of 77 experiments (294 treatments). We established equations for the prediction of duodenal flows of various 18-carbon (C18) fatty acids as a function of the intakes of their precursors and other dietary factors (source and/or technological treatment of dietary lipids). We also quantified the influence of several factors modifying rumen metabolism (pH, forage : concentrate ratio, level of intake, fish oil supplementation). We established equations for the apparent absorption of these fatty acids in the small intestine as a function of their duodenal flows. For all C18 unsaturated fatty acids, apparent absorption was a linear function of duodenal flow. For 18:0, apparent absorption levelled off for high duodenal flows. From this database, with fatty acid flows expressed in g/kg dry matter intake, we could not find any significant differences between animal categories (lactating cows, other cattle or sheep) in terms of rumen metabolism or intestinal absorption of C18 fatty acids.

Metabolic control analysis of developing oilseed rape (Brassica napus cv Westar) embryos shows that lipid assembly exerts significant control over oil accumulation.

PubMed

Tang, Mingguo; Guschina, Irina A; O'Hara, Paul; Slabas, Antoni R; Quant, Patti A; Fawcett, Tony; Harwood, John L

2012-10-01

Metabolic control analysis allows the study of metabolic regulation. We applied both single- and double-manipulation top-down control analysis to examine the control of lipid accumulation in developing oilseed rape (Brassica napus) embryos. The biosynthetic pathway was conceptually divided into two blocks of reactions (fatty acid biosynthesis (Block A), lipid assembly (Block B)) connected by a single system intermediate, the acyl-coenzyme A (acyl-CoA) pool. Single manipulation used exogenous oleate. Triclosan was used to inhibit specifically Block A, whereas diazepam selectively manipulated flux through Block B. Exogenous oleate inhibited the radiolabelling of fatty acids from [1-(14)C]acetate, but stimulated that from [U-14C]glycerol into acyl lipids. The calculation of group flux control coefficients showed that c. 70% of the metabolic control was in the lipid assembly block of reactions. Monte Carlo simulations gave an estimation of the error of the resulting group flux control coefficients as 0.27±0.06 for Block A and 0.73±0.06 for Block B. The two methods of control analysis gave very similar results and showed that Block B reactions were more important under our conditions. This contrasts notably with data from oil palm or olive fruit cultures and is important for efforts to increase oilseed rape lipid yields. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Controlling Two-dimensional Tethered Vesicle Motion Using an Electric Field

PubMed Central

Yoshina-Ishii, Chiaki; Boxer, Steven G.

2008-01-01

We recently introduced methods to tether phospholipid vesicles or proteoliposomes onto a fluid supported lipid bilayer using DNA hybridization. These intact tethered vesicles diffuse in two dimensions parallel to the supporting membrane surface. In this paper, we report the dynamic response of individual tethered vesicles to an electric field applied parallel to the bilayer surface. Vesicles respond to the field by moving in the direction of electro-osmotic flow, and this can be used to reversibly concentrate tethered vesicles against a barrier. By adding increasing amounts of negatively charged phosphatidylserine to the supporting bilayer to increase electro-osmosis, the electrophoretic mobility of the tethered vesicles can be increased. The electro-osmotic contribution can be modeled well by a sphere connected to a cylindrical anchor in a viscous membrane with charged head groups. The electrophoretic force on the negatively charged tethered vesicles opposes the electro-osmotic force. By increasing the amount of negative charge on the tethered vesicle, drift in the direction of electro-osmotic flow can be slowed; at high negative charge on the tethered vesicle, motion can be forced in the direction of electrophoresis. The balance between these forces can be visualized on a patterned supporting bilayer containing negatively charged lipids which themselves reorganize in an externally applied electric field to create a gradient of charge within a corralled region. The charge gradient at the surface creates a gradient of electro-osmotic flow, and vesicles carrying similar amounts of negative charge can be focused to a region perpendicular to the applied field where electrophoresis is balanced by electro-osmosis, away from the corral boundary. Electric fields are effective tools to direct tethered vesicles, concentrate them and to measure the tethered vesicle’s electrostatic properties. PMID:16489833

The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet.

PubMed

Kim, Min Hee; Lee, Jongsung; Jung, Sehyun; Kim, Joo Wan; Shin, Jae-Ho; Lee, Hae-Jeung

2017-04-01

The present study investigated the effect of ginseng berry hot water extract (GBx) on blood flow via the regulation of lipid metabolites and blood coagulation in rats fed a high-fat diet (HFD). Sixty rats were divided into five groups in descending order of body weight. Except for the control group, the other four groups were fed a HFD containing 45% kcal from fat for 11 wk without GBx. GBx groups were then additionally treated by gastric gavage with GBx dissolved in distilled water at 50 (GBx 50) mg/kg, 100 (GBx 100) mg/kg, or 150 (GBx 150) mg/kg body weight for 6 wk along with the HFD. To investigate the effects of GBx on rats fed a HFD, biochemical metabolite, blood coagulation assay, and histological analysis were performed. In the experiments to measure the serum levels of leptin and apolipoprotein B/A, GBx treatment attenuated the HFD-induced increases in these metabolites ( p  < 0.05). Adiponectin and apolipoprotein E levels in GBx-treated groups were significantly higher than the HFD group. Prothrombin time and activated partial thromboplastin time were increased in all GBx-treated groups. In the GBx-treated groups, the serum levels of thromboxane A 2 and serotonin were decreased and concentrations of serum fibrinogen degradation products were increased ( p  < 0.05). Moreover, histomorphometric dyslipidemia-related atherosclerotic changes were significantly improved by treatment with GBx. These results suggest the possibility that GBx can ameliorate blood flow by decreasing intima-media thickness via the regulation of blood coagulation factors related to lipid metabolites in rats fed a HFD.

Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome.

PubMed

Lavrencic, A; Salobir, B G; Keber, I

2000-02-01

Endothelial dysfunction that can be detected as impaired flow-mediated dilation by ultrasonography is an early event in atherogenesis and has been demonstrated in healthy subjects with risk factors for atherosclerosis many years before the appearance of atheromatous plaques. We examined the influence of physical training on flow-mediated dilation in patients with the polymetabolic syndrome. Twenty-nine asymptomatic men aged 40 to 60 years with the polymetabolic syndrome were randomly divided between the control group and the training group, which trained 3 times a week for 12 weeks. On high-resolution ultrasound images, the diameter of the brachial artery was measured at rest, after reactive hyperemia (causing flow-mediated, endothelium-dependent dilation), and after sublingual glyceryltrinitrate (causing endothelium-independent vasodilation) in all subjects before and after the training period. The training program induced an increase of 18% in physical fitness. Flow-mediated dilation increased from 5.3+/-2.8% to 7.3+/-2.7% (P<0. 05). There was no change in body mass index, blood pressure, insulin resistance, lipids, and big endothelin-1 in either group. Flow-mediated dilation measured before training was negatively correlated with resting heart rate, waist-to-hip ratio, and insulin resistance. Resting heart rate emerged as the only independent determinant, which explained 22% of the variation in flow-mediated dilation. In conclusion, our findings suggest that a 3-month physical training program, which improved maximal exercise capacity, enhances flow-mediated dilation in patients with the polymetabolic syndrome.

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

PubMed

Ahmed, A K; Goodwin, C R; Sarabia-Estrada, R; Lay, F; Ansari, A M; Steenbergen, C; Pang, C; Cohen, R; Born, L J; Matsangos, A E; Ng, C; Marti, G P; Abu-Bonsrah, N; Phillips, N A; Suk, I; Sciubba, D M; Harmon, J W

2016-12-01

Experimental study. The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Smoking habits and plasma lipid peroxide and vitamin E levels in never-treated first-episode patients with schizophrenia.

PubMed

2000-03-01

Lipid peroxidation may be increased in schizophrenia, due to the illness, lifestyle or medication. To determine plasma lipid peroxide levels and serum vitamin E and A levels in first-episode never-treated people with schizophrenia and in controls. Thirty in-patients with a first episode of schizophrenia or schizophreniform psychosis were recruited, as were controls matched for gender, age, smoking and dietary status. Blood samples were taken, smoking status was recorded and body mass index measured. There were no significant differences between patients and controls in plasma peroxide levels. Seventy-three per cent of the patients smoked. Patients who smoked had a higher mean lipid peroxide level than non-smokers. Seventy-seven per cent of patients and 70% of controls had a ratio of vitamin E to cholesterol of less than 5. Body mass index was lower in patients than in controls. As a result of the high prevalence of smoking this group shows increased lipid peroxidation. Low serum ratios of vitamin E to cholesterol in both patients and controls suggest an unsatisfactory diet.

Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

DTIC Science & Technology

2014-11-01

ORIGINAL CONTRIBUTION Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant...and chronic pain. Intravenous lipid emulsion (ILE) is a recent antidote for lipophilic drug overdose with unclear effectiveness. ILE has been studied in...Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled

Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

PubMed

Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong; Liu, Wei

2017-03-01

Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. Copyright © 2017 by the Endocrine Society

Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

PubMed Central

Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong

2017-01-01

Abstract Context: Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. Objective: This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Design and Setting: Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Main Outcome Measures: Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography–mass spectrometry (MS) and liquid chromatography–MS. Results: Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Conclusions: Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. PMID:27886515

Ultra-large scale AFM of lipid droplet arrays: investigating the ink transfer volume in dip pen nanolithography.

PubMed

Förste, Alexander; Pfirrmann, Marco; Sachs, Johannes; Gröger, Roland; Walheim, Stefan; Brinkmann, Falko; Hirtz, Michael; Fuchs, Harald; Schimmel, Thomas

2015-05-01

There are only few quantitative studies commenting on the writing process in dip-pen nanolithography with lipids. Lipids are important carrier ink molecules for the delivery of bio-functional patters in bio-nanotechnology. In order to better understand and control the writing process, more information on the transfer of lipid material from the tip to the substrate is needed. The dependence of the transferred ink volume on the dwell time of the tip on the substrate was investigated by topography measurements with an atomic force microscope (AFM) that is characterized by an ultra-large scan range of 800 × 800 μm(2). For this purpose arrays of dots of the phospholipid1,2-dioleoyl-sn-glycero-3-phosphocholine were written onto planar glass substrates and the resulting pattern was imaged by large scan area AFM. Two writing regimes were identified, characterized of either a steady decline or a constant ink volume transfer per dot feature. For the steady state ink transfer, a linear relationship between the dwell time and the dot volume was determined, which is characterized by a flow rate of about 16 femtoliters per second. A dependence of the ink transport from the length of pauses before and in between writing the structures was observed and should be taken into account during pattern design when aiming at best writing homogeneity. The ultra-large scan range of the utilized AFM allowed for a simultaneous study of the entire preparation area of almost 1 mm(2), yielding good statistic results.

Ultra-large scale AFM of lipid droplet arrays: investigating the ink transfer volume in dip pen nanolithography

NASA Astrophysics Data System (ADS)

Förste, Alexander; Pfirrmann, Marco; Sachs, Johannes; Gröger, Roland; Walheim, Stefan; Brinkmann, Falko; Hirtz, Michael; Fuchs, Harald; Schimmel, Thomas

2015-05-01

There are only few quantitative studies commenting on the writing process in dip-pen nanolithography with lipids. Lipids are important carrier ink molecules for the delivery of bio-functional patters in bio-nanotechnology. In order to better understand and control the writing process, more information on the transfer of lipid material from the tip to the substrate is needed. The dependence of the transferred ink volume on the dwell time of the tip on the substrate was investigated by topography measurements with an atomic force microscope (AFM) that is characterized by an ultra-large scan range of 800 × 800 μm2. For this purpose arrays of dots of the phospholipid1,2-dioleoyl-sn-glycero-3-phosphocholine were written onto planar glass substrates and the resulting pattern was imaged by large scan area AFM. Two writing regimes were identified, characterized of either a steady decline or a constant ink volume transfer per dot feature. For the steady state ink transfer, a linear relationship between the dwell time and the dot volume was determined, which is characterized by a flow rate of about 16 femtoliters per second. A dependence of the ink transport from the length of pauses before and in between writing the structures was observed and should be taken into account during pattern design when aiming at best writing homogeneity. The ultra-large scan range of the utilized AFM allowed for a simultaneous study of the entire preparation area of almost 1 mm2, yielding good statistic results.

Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.

PubMed

Wu, Bo; Yu, Ping; Cui, Can; Wu, Ming; Zhang, Yang; Liu, Lei; Wang, Cai-Xia; Zhuo, Ren-Xi; Huang, Shi-Wen

2015-04-01

The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.

Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions.

PubMed

Patel, P S; Shah, M H; Jha, F P; Raval, G N; Rawal, R M; Patel, M M; Patel, J B; Patel, D D

2004-01-01

The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC) and its association with habit of tobacco consumption. This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) and (v) triglycerides were analysed by spectrophotometric kits. Student's t-test was performed to compare mean values of the parameters. A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively) as well as in patients with OPC (P=0.014 and P=0.000, respectively) as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04) and controls (P=0.059). The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.

Effect of thyroid function on LDL oxidation.

PubMed

Costantini, F; Pierdomenico, S D; De Cesare, D; De Remigis, P; Bucciarelli, T; Bittolo-Bon, G; Cazzolato, G; Nubile, G; Guagnano, M T; Sensi, S; Cuccurullo, F; Mezzetti, A

1998-05-01

In this study, the effect of different levels of thyroid hormone and metabolic activity on low density lipoprotein (LDL) oxidation was investigated. Thus, in 16 patients with hyperthyroidism, 16 with hypothyroidism, and 16 age- and sex-matched healthy normolipidemic control subjects, the native LDL content in lipid peroxides, vitamin E, beta-carotene, and lycopene, as well as the susceptibility of these particles to undergo lipid peroxidation, was assessed. Hyperthyroidism was associated with significantly higher lipid peroxidation, as characterized by a higher native LDL content in lipid peroxides, a lower lag phase, and a higher oxidation rate than in the other two groups. This elevated lipid peroxidation was associated with a lower LDL antioxidant concentration. Interestingly, hypothyroid patients showed an intermediate behavior. In fact, in hypothyroidism, LDL oxidation was significantly lower than in hyperthyroidism but higher than in the control group. Hypothyroidism was also characterized by the highest beta-carotene LDL content, whereas vitamin E was significantly lower than in control subjects. In hyperthyroidism but not in the other two groups, LDL oxidation was strongly influenced by free thyroxine blood content. In fact in this group, the native LDL lipid peroxide content and the lag phase were directly and indirectly, respectively, related to free thyroxine blood levels. On the contrary, in hypothyroidism LDL oxidation was strongly and significantly related to serum lipids. In conclusion, both hypothyroidism and hyperthyroidism are characterized by higher levels of LDL oxidation when compared with normolipidemic control subjects. In hyperthyroid patients, the increased lipid peroxidation was strictly related to free thyroxine levels, whereas in hypothyroidism it was strongly influenced by serum lipids.

Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers.

PubMed

Skotland, Tore; Ekroos, Kim; Kauhanen, Dimple; Simolin, Helena; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2017-01-01

Exosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. We have here investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers. A high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls. Control samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes and exosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed. This study shows for the first time the potential use of exosomal lipid species in urine as prostate cancer biomarkers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay.

PubMed

Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Bauer-Brandl, Annette; Brandl, Martin

2016-06-28

Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated with liposome bilayers even upon extensive dilution. Upon i.v. injection, in contrast, rapid drug loss often occurs due to drug transfer from the liposomal carriers to endogenous lipophilic sinks such as lipoproteins, plasma proteins or membranes of red blood cells and endothelial cells. Here we report on the application of a recently introduced in vitro predictive drug transfer assay based on incubation of the liposomal drug carrier with large multilamellar liposomes, the latter serving as a biomimetic model sink, using flow field-flow fractionation as a tool to separate the two types of liposomes. By quantifying the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, both the kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)21H,23H-porphine). p-THPP is structurally similar to temoporfin, a photosensitizer which is under clinical evaluation in a liposomal formulation. Mechanistic insights were gained by varying the donor-to-acceptor lipid mass ratio, size and lamellarity of the liposomes. Drug transfer kinetics from one liposome to another was found rate determining as compared to redistribution from the outermost to the inner concentric bilayers, such that the overall process could be adequately described by a single 1st order kinetic model. By varying the donor-to-acceptor lipid mass ratio in the range 1:1 to 1:10, a correlation was established between donor-to-acceptor-lipid mass ratio and transfer kinetics, which is regarded essential for scaling to physiological lipid mass ratios. By applying the assay to a series of structurally related model compounds of different bilayer affinity, transfer and release kinetics were established over the whole expected range of liposome bilayer associated drugs in terms of water solubility and lipophilicity. A very rapid transfer and considerable release from liposomes to the water phase was observed for the more water-soluble compounds Sudan II (clogP 5.45) and Sudan III (clogP 6.83). For the more lipophilic compounds, the rate of transfer from the donor liposomes followed the rank order Sudan IV (fastest)>Oil Red O>Sudan Black>p-THPP (slowest). For an equimolar donor-to-acceptor lipid mass ratio, half-lifes of transfer in the range of 12min (Sudan IV) up to 1.5h (p-THPP) were determined. In essence, the results presented here allow for both, mechanistic insights and predictions of drug loss from liposomal carriers upon exposure to biological sinks, which appear more realistic than the commonly employed in vitro release tests. Copyright © 2016 Elsevier B.V. All rights reserved.

Marine microalgae Nannochloropsis oculata biomass harvesting using ultrafiltration in cross-flow mode

NASA Astrophysics Data System (ADS)

Devianto, L. A.; Aprilia, D. N.; Indriani, D. W.; Sukarni, S.; Sumarlan, S. H.; Wibisono, Y.

2018-03-01

Microalgae is a potential bioenergy source. It can grows rapidly, even it could be harvested within 7 days. Harvesting is an important part of microalgae cultivation due to the method used. It should be undamaging toward essential content of microalgae and should produces high yields of biomass. In this study, the harvesting of Nannochloropsis oculata was carried out using capillary ultrafiltration in cross flow mode. This study aims to test ultrafiltration membrane performance in Nannochloropsis oculata harvesting accompanied by Backwash and Non-Backwash modes and to analyse its total lipid content. The harvest was done under 1; 1.5; and 2 bar of trans membrane pressure. Some observed parameters were permeate flux, cell density, biomass recovery, microalgae’s dry weight, yield, and total lipid content. The application of high pressure and backwashed treatment have boosted slurry production time which lead to microalgae’s biomass abundance. The result showed that the best treatment of Nannochloropsis oculata harvesting using capillary ultrafiltration membrane in cross flow mode is under 2 bar of pressure with backwashed treatment. This is the fastest condition to produce slurry within 1800 s with the highest recovery percentage 79.50%, 16.05 × 106 cell/ml of post-treatment cell density, 6.8 grams of biomass’ dry weight, 22.66 % of yield, and 2.52 % of total lipid content.

Effect of Medium pH on Rhodosporidium toruloides NCYC 921 Carotenoid and Lipid Production Evaluated by Flow Cytometry.

PubMed

Dias, Carla; Silva, Corália; Freitas, Claudia; Reis, Alberto; da Silva, Teresa Lopes

2016-07-01

The effect of the culture medium pH (3.5-6.0) on the carotenoid and lipid (as fatty acids) production by the yeast Rhodosporidium toruloides NCYC 921 was studied. Flow cytometry was used to evaluate the yeast's physiological response to different culture medium pH values. The yeast biomass concentration and lipid content were maxima at pH 4.0 (5.90 g/L and 21.85 % w/w, respectively), while the maximum carotenoid content (63.37 μg/g) was obtained at pH 5.0. At the exponential phase, the yeast cell size and internal complexity were similar, at different medium pH. At the stationary phase, the yeast cell size and internal complexity decreased as the medium pH increased. At the exponential phase, the proportion of cells with polarized membranes was always high (>80 %) but at the stationary phase, the proportion of yeast cells with depolarized membranes was dominant (>65 %) and increased with the medium pH increase. The results here reported may contribute for yeast bioprocesses optimization. For the first time, multiparameter flow cytometry was used to evaluate the impact of medium pH changes on the yeast cell physiological status, specifically on the yeast membrane potential, membrane integrity, cell size and internal complexity.

Chemotherapy drugs form ion pores in membranes due to physical interactions with lipids.

PubMed

Ashrafuzzaman, Mohammad; Tseng, Chih-Yuan; Duszyk, Marek; Tuszynski, Jack A

2012-12-01

We demonstrate the effects on membrane of the tubulin-binding chemotherapy drugs: thiocolchicoside and taxol. Electrophysiology recordings across lipid membranes in aqueous phases containing drugs were used to investigate the drug effects on membrane conductance. Molecular dynamics simulation of the chemotherapy drug-lipid complexes was used to elucidate the mechanism at an atomistic level. Both drugs are observed to induce stable ion-flowing pores across membranes. Discrete pore current-time plots exhibit triangular conductance events in contrast to rectangular ones found for ion channels. Molecular dynamics simulations indicate that drugs and lipids experience electrostatic and van der Waals interactions for short periods of time when found within each other's proximity. The energies from these two interactions are found to be similar to the energies derived theoretically using the screened Coulomb and the van der Waals interactions between peptides and lipids due to mainly their charge properties while forming peptide-induced ion channels in lipid bilayers. Experimental and in silico studies together suggest that the chemotherapy drugs induce ion pores inside lipid membranes due to drug-lipid physical interactions. The findings reveal cytotoxic effects of drugs on the cell membrane, which may aid in novel drug development for treatment of cancer and other diseases. © 2012 John Wiley & Sons A/S.

Estimating 10-year cardiovascular disease risk in Asian patients with schizophrenia.

PubMed

Rekhi, Gurpreet; Khyne, Toe Toe; Lee, Jimmy

This study aims to describe the cardiovascular risk profile of Asian patients with schizophrenia. Data was extracted from the databases of 139 patients with schizophrenia and 206 controls from two previous studies conducted at the Institute for Mental Health (IMH), Singapore. Their medical and smoking histories were obtained, and anthropometric parameters measured. Framingham risk score (FRS) calculator using body mass index was used to compute the 10-year cardiovascular disease risk (FRS BMI ) and the vascular age (VA BMI ) for each participant. Data on fasting lipids were available for 80 patients and all the controls; hence the FRS for lipids (FRS lipids ) and VA (VA lipids ) were also computed. The difference between VA and actual age was computed as VA diff . The 10-year CVD risk and VA diff based on lipids as well as BMI were significantly higher for patients compared to controls (all p<0.01). There was a strong correlation between FRS lipids and FRS BMI (r=0.97, p<0.001). Significantly higher numbers of patients than controls were smokers and obese; and reported having dyslipidaemia. We found a high risk of CVD in patients with schizophrenia as compared to controls; and conclude that patients with schizophrenia need regular physical health monitoring, especially for cardiovascular risk factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrated analysis of transcriptome and lipid profiling reveals the co-influences of inositol-choline and Snf1 in controlling lipid biosynthesis in yeast.

PubMed

Chumnanpuen, Pramote; Zhang, Jie; Nookaew, Intawat; Nielsen, Jens

2012-07-01

In the yeast Saccharomyces cerevisiae many genes involved in lipid biosynthesis are transcriptionally controlled by inositol-choline and the protein kinase Snf1. Here we undertook a global study on how inositol-choline and Snf1 interact in controlling lipid metabolism in yeast. Using both a reference strain (CEN.PK113-7D) and a snf1Δ strain cultured at different nutrient limitations (carbon and nitrogen), at a fixed specific growth rate of 0.1 h(-1), and at different inositol choline concentrations, we quantified the expression of genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through integrated analysis of the transcriptome, the lipid profiling and the fluxome, it was possible to obtain a high quality, large-scale dataset that could be used to identify correlations and associations between the different components. At the transcription level, Snf1 and inositol-choline interact either directly through the main phospholipid-involving transcription factors (i.e. Ino2, Ino4, and Opi1) or through other transcription factors e.g. Gis1, Mga2, and Hac1. However, there seems to be flux regulation at the enzyme levels of several lipid involving enzymes. The analysis showed the strength of using both transcriptome and lipid profiling analysis for mapping the co-influence of inositol-choline and Snf1 on phospholipid metabolism.

Golgi Membrane Dynamics Viewed Through a Lens of Lipids

PubMed Central

Bankaitis, Vytas A.; Garcia-Mata, Rafael; Mousley, Carl J.

2012-01-01

Summary The striking morphology of the Golgi complex has fascinated cell biologists since its discovery over 100 years ago. Yet, despite intense efforts to understand how membrane flow relates to Golgi form and function, this organelle continues to baffle cell biologists and biochemists alike. Fundamental questions regarding Golgi function, while hotly debated, remain unresolved. While Golgi function is historically described from a protein-centric point of view, we now appreciate that conceptual frameworks for how lipid metabolism is integrated with Golgi biogenesis and function are essential for a mechanistic understanding of this fascinating organelle. It is from a lipid-centric perspective that we discuss the larger question of Golgi dynamics and membrane trafficking. We review the growing body of evidence for how lipid metabolism is integrally written into the engineering of the Golgi system, and highlight questions for future study. PMID:22625862

Lipid profile in oral submucous fibrosis.

PubMed

Mehrotra, Ravi; Pandya, Shruti; Chaudhary, Ajay Kumar; Singh, Himanshu Pratap; Jaiswal, Ritesh Kumar; Singh, Mangal; Gupta, S C; Singh, Mamta

2009-07-24

Changes in lipid profile have long been associated with malignancies as lipids play a key role in maintenance of cell integrity. This study evaluated the alterations in extended lipid profile in untreated patients of oral submucous fibrosis (OSMF) and studied the correlation between lipid levels with tobacco consumption. In this hospital-based study, 65 clinically diagnosed and histopathologically proven patients of OSMF and 42 age and sex matched controls were studied. In these samples serum lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) (v) triglycerides (vi) Apo-A1 (viii) Apo-B and (viii) LPa were analyzed. A significant decrease in plasma total cholesterol, HDLC and Apo-A1 was observed in patients with OSMF as compared to the controls. Thus an inverse relationship between plasma lipid levels and patients was found in OSMF. The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in patients with oral precancerous conditions.

Skin lipid structure controls water permeability in snake molts.

PubMed

Torri, Cristian; Mangoni, Alfonso; Teta, Roberta; Fattorusso, Ernesto; Alibardi, Lorenzo; Fermani, Simona; Bonacini, Irene; Gazzano, Massimo; Burghammer, Manfred; Fabbri, Daniele; Falini, Giuseppe

2014-01-01

The role of lipids in controlling water exchange is fundamentally a matter of molecular organization. In the present study we have observed that in snake molt the water permeability drastically varies among species living in different climates and habitats. The analysis of molts from four snake species: tiger snake, Notechis scutatus, gabon viper, Bitis gabonica, rattle snake, Crotalus atrox, and grass snake, Natrix natrix, revealed correlations between the molecular composition and the structural organization of the lipid-rich mesos layer with control in water exchange as a function of temperature. It was discovered, merging data from micro-diffraction and micro-spectroscopy with those from thermal, NMR and chromatographic analyses, that this control is generated from a sophisticated structural organization that changes size and phase distribution of crystalline domains of specific lipid molecules as a function of temperature. Thus, the results of this research on four snake species suggest that in snake skins different structured lipid layers have evolved and adapted to different climates. Moreover, these lipid structures can protect, "safety", the snakes from water lost even at temperatures higher than those of their usual habitat. Copyright © 2013 Elsevier Inc. All rights reserved.

Compatibility of phospholipid liposomal spray with silicone hydrogel contact lens wear.

PubMed

Wang, Michael T M; Ganesalingam, Kalaivarny; Loh, Chee Seang; Alberquerque, Trisha; Al-Kanani, Suhaila; Misra, Stuti L; Craig, Jennifer P

2017-02-01

To assess the effects of two weeks of regular phospholipid liposomal spray application on lipid layer grade, tear film stability, subjective comfort, visual acuity, and lipid deposition in silicone hydrogel contact lens wearers. Thirty-one existing contact lens wearers were enrolled and fitted with two week planned replacement silicone hydrogel contact lenses (Acuvue ® Oasys ® ) in a prospective, randomized, paired-eye, investigator-masked trial. A phospholipid liposomal spray (Tears Again ® ) was applied to one eye (randomized) four times daily for two weeks. LogMAR high contrast visual acuity (VA), low contrast glare acuity (LCGA), non-invasive tear film break-up time (NIBUT), and lipid layer grade (LLG) were measured at baseline and day 14, in both treated and control eyes. Subjective comfort relative to baseline, and spectrofluorophotometric assessment of contact lens surface lipid deposition were also assessed on day 14. All measurements did not differ at baseline between treated and control eyes. Lipid layer thickness and tear film stability were increased on day 14 in treated eyes (all p<0.05), but not in control eyes (all p>0.05). A greater proportion of participants reported improved comfort in the treated eye relative to the control eye (p=0.002). There were no significant differences in visual acuity or in contact lens surface lipid deposition, between treated and control eyes, on day 14 (all p>0.05). The phospholipid liposomal spray increased tear film stability, lipid layer thickness and subjective comfort in silicone hydrogel contact lens wearers, without adversely affecting visual acuity or contact lens surface lipid deposition. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Chemical characterization of milk after treatment with thermal (HTST and UHT) and nonthermal (turbulent flow ultraviolet) processing technologies.

PubMed

Cappozzo, Jack C; Koutchma, Tatiana; Barnes, Gail

2015-08-01

As a result of growing interest to nonthermal processing of milk, the purpose of this study was to characterize the chemical changes in raw milk composition after exposure to a new nonthermal turbulent flow UV process, conventional thermal pasteurization process (high-temperature, short-time; HTST), and their combinations, and compare those changes with commercially UHT-treated milk. Raw milk was exposed to UV light in turbulent flow at a flow rate of 4,000L/h and applied doses of 1,045 and 2,090 J/L, HTST pasteurization, and HTST in combination with UV (before or after the UV). Unprocessed raw milk, HTST-treated milk, and UHT-treated milk were the control to the milk processed with the continuous turbulent flow UV treatment. The chemical characterization included component analysis and fatty acid composition (with emphasis on conjugated linoleic acid) and analysis for vitamin D and A and volatile components. Lipid oxidation, which is an indicator to oxidative rancidity, was evaluated by free fatty acid analysis, and the volatile components (extracted organic fraction) by gas chromatography-mass spectrometry to obtain mass spectral profile. These analyses were done over a 14-d period (initially after treatment and at 7 and 14 d) because of the extended shelf-life requirement for milk. The effect of UV light on proteins (i.e., casein or lactalbumin) was evaluated qualitatively by sodium dodecyl sulfate-PAGE. The milk or liquid soluble fraction was analyzed by sodium dodecyl sulfate-PAGE for changes in the protein profile. From this study, it appears that continuous turbulent flow UV processing, whether used as a single process or in combination with HTST did not cause any statistically significant chemical changes when compared with raw milk with regard to the proximate analysis (total fat, protein, moisture, or ash), the fatty acid profile, lipid oxidation with respect to volatile analysis, or protein profile. A 56% loss of vitamin D and a 95% loss of vitamin A content was noted after 7 d from the continuous turbulent flow UV processing, but this loss was equally comparable to that found with traditional thermal processing, such as HTST and UHT. Chemical characterization of milk showed that turbulent flow UV light technology can be considered as alternative nonthermal treatment of pasteurized milk and raw milk to extend shelf life. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reversed phase HPLC analysis of stability and microstructural effects on degradation kinetics of β-carotene encapsulated in freeze-dried maltodextrin-emulsion systems.

PubMed

Harnkarnsujarit, Nathdanai; Charoenrein, Sanguansri; Roos, Yrjö H

2012-09-26

Degradation of dispersed lipophilic compounds in hydrophilic solids depends upon matrix stability and lipid physicochemical properties. This study investigated effects of solid microstructure and size of lipid droplets on the stability of dispersed β-carotene in freeze-dried systems. Emulsions of β-carotene in sunflower oil were dispersed in maltodextrin systems (M040/DE6, M100/DE11, and M250/DE25.5) (8% w/w oil) and prefrozen at various freezing conditions prior to freeze-drying to control nucleation and subsequent pore size and structural collapse of freeze-dried solids. The particle size, physical state, and β-carotene contents of freeze-dried emulsions were measured during storage at various water activity (a(w)) using a laser particle size analyzer, differential scanning calorimeter, and high performance liquid chromatography (HPLC), respectively. The results showed that M040 stabilized emulsions in low temperature freezing exhibited lipid crystallization. Collapse of solids in storage at a(w) which plasticized systems to the rubbery state led to flow and increased the size of oil droplets. Degradation of β-carotene analyzed using a reversed-phase C(30) column followed first-order kinetics. Porosity of solids had a major effect on β-carotene stability; however, the highest stability was found in fully plasticized and collapsed solids.

Interaction of S-layer proteins of Lactobacillus kefir with model membranes and cells.

PubMed

Hollmann, Axel; Delfederico, Lucrecia; Santos, Nuno C; Disalvo, E Anibal; Semorile, Liliana

2018-06-01

In previous works, it was shown that S-layer proteins from Lactobacillus kefir were able to recrystallize and stabilize liposomes, this feature reveling a great potential for developing liposomal-based carriers. Despite previous studies on this subject are important milestones, a number of questions remain unanswered. In this context, the feasibility of S-layer proteins as a biomaterial for drug delivery was evaluated in this work. First, S-layer proteins were fully characterized by electron microscopy, 2D-electrophoresis, and anionic exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD). Afterward, interactions of S-layer proteins with model lipid membranes were evaluated, showing that proteins adsorb to the lipid surface following a non-fickean or anomalous diffusion, when positively charged lipid were employed, suggesting that electrostatic interaction is a key factor in the recrystallization process on these proteins. Finally, the interaction of S-layer coated liposomes with Caco-2 cell line was assessed: First, cytotoxicity of formulations was tested showing no cytotoxic effects in S-layer coated vesicles. Second, by flow cytometry, it was observed an increased ability to transfer cargo molecules into Caco-2 cells from S-layer coated liposomes in comparison to control ones. All data put together, supports the idea that a combination of adhesive properties of S-layer proteins concomitant with higher stability of S-layer coated liposomes represents an exciting starting point in the development of new drug carriers.

Carotid duplex ultrasound and transcranial Doppler findings in commercial divers and pilots.

PubMed

Dormanesh, Banafshe; Vosoughi, Kia; Akhoundi, Fahimeh H; Mehrpour, Masoud; Fereshtehnejad, Seyed-Mohammad; Esmaeili, Setareh; Sabet, Azin Shafiee

2016-12-01

The risky working environments of divers and pilots, and the possible role of extreme ambient pressure in carotid stenosis, make ischemic stroke an important occupational concern among these professionals. In this study, we aimed to evaluate the association of being exposed to hyperbaric or hypobaric conditions with carotid artery stenosis by comparing common carotid intima-media thickness (CCIMT) and blood flow velocities of cerebral arteries in divers and pilots using carotid duplex ultrasound (CDUS) and transcranial Doppler (TCD). CDUS and transtemporal TCD were performed in 29 divers, 36 pilots and 30 control participants. Medical history, blood pressure, lipid profile and blood sugar were recorded to control the previously well-known risk factors of atherosclerosis. Findings of the CDUS and TCD [including: CCIMT and blood flow velocities of internal carotid artery (ICA), common carotid artery (CCA), and middle cerebral artery (MCA)] of divers and pilots were compared with those of the control group using regression analysis models. Both right and left side CCIMT were significantly higher in divers (P < 0.05) and pilots (P < 0.05) in comparison with the control group. Carotid index [peak systolic velocity (PSV) of ICA/PSV of CCA) of divers and pilots were also higher than the control group. TCD findings were not significantly different between divers, pilots, and the control group. Increased CCIMT and carotid index in diver and pilot groups appear to be suggestive of accelerated atherosclerosis of carotid artery in these occupational groups.

The effect of temperature on apoptosis and adipogenesis on skeletal muscle satellite cells derived from different muscle types.

PubMed

Harding, Rachel L; Clark, Daniel L; Halevy, Orna; Coy, Cynthia S; Yahav, Shlomo; Velleman, Sandra G

2015-09-01

Satellite cells are multipotential stem cells that mediate postnatal muscle growth and respond differently to temperature based upon aerobic versus anaerobic fiber-type origin. The objective of this study was to determine how temperatures below and above the control, 38°C, affect the fate of satellite cells isolated from the anaerobic pectoralis major (p. major) or mixed fiber biceps femoris (b. femoris). At all sampling times, p. major and b. femoris cells accumulated less lipid when incubated at low temperatures and more lipid at elevated temperatures compared to the control. Satellite cells isolated from the p. major were more sensitive to temperature as they accumulated more lipid at elevated temperatures compared to b. femoris cells. Expression of adipogenic genes, CCAAT/enhancer-binding protein β (C/EBPβ) and proliferator-activated receptor gamma (PPARγ) were different within satellite cells isolated from the p. major or b. femoris. At 72 h of proliferation, C/EBPβ expression increased with increasing temperature in both cell types, while PPARγ expression decreased with increasing temperature in p. major satellite cells. At 48 h of differentiation, both C/EBPβ and PPARγ expression increased in the p. major and decreased in the b. femoris, with increasing temperature. Flow cytometry measured apoptotic markers for early apoptosis (Annexin-V-PE) or late apoptosis (7-AAD), showing less than 1% of apoptotic satellite cells throughout all experimental conditions, therefore, apoptosis was considered biologically not significant. The results support that anaerobic p. major satellite cells are more predisposed to adipogenic conversion than aerobic b. femoris cells when thermally challenged. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Over-expression of AtPAP2 in Camelina sativa leads to faster plant growth and higher seed yield

PubMed Central

2012-01-01

Background Lipids extracted from seeds of Camelina sativa have been successfully used as a reliable source of aviation biofuels. This biofuel is environmentally friendly because the drought resistance, frost tolerance and low fertilizer requirement of Camelina sativa allow it to grow on marginal lands. Improving the species growth and seed yield by genetic engineering is therefore a target for the biofuels industry. In Arabidopsis, overexpression of purple acid phosphatase 2 encoded by Arabidopsis (AtPAP2) promotes plant growth by modulating carbon metabolism. Overexpression lines bolt earlier and produce 50% more seeds per plant than wild type. In this study, we explored the effects of overexpressing AtPAP2 in Camelina sativa. Results Under controlled environmental conditions, overexpression of AtPAP2 in Camelina sativa resulted in longer hypocotyls, earlier flowering, faster growth rate, higher photosynthetic rate and stomatal conductance, increased seed yield and seed size in comparison with the wild-type line and null-lines. Similar to transgenic Arabidopsis, activity of sucrose phosphate synthase in leaves of transgenic Camelina was also significantly up-regulated. Sucrose produced in photosynthetic tissues supplies the building blocks for cellulose, starch and lipids for growth and fuel for anabolic metabolism. Changes in carbon flow and sink/source activities in transgenic lines may affect floral, architectural, and reproductive traits of plants. Conclusions Lipids extracted from the seeds of Camelina sativa have been used as a major constituent of aviation biofuels. The improved growth rate and seed yield of transgenic Camelina under controlled environmental conditions have the potential to boost oil yield on an area basis in field conditions and thus make Camelina-based biofuels more environmentally friendly and economically attractive. PMID:22472516

Dietary inclusion of fish oil changes the semen lipid composition but does not improve the post-thaw semen quality of ram spermatozoa.

PubMed

Díaz, Rommy; Torres, Mariana A; Paz, Erwin; Quiñones, John; Bravo, Silvana; Farías, Jorge G; Sepúlveda, Néstor

2017-08-01

The aim of this study was to investigate the effects of dietary fish oil (FO) time-response on the fatty acid profile, cholesterol levels and sperm cryosurvival in ram semen. Criollo Araucano rams were randomly assigned to two groups (n=4) according to the type of supplementation: a control group without FO and a supplemented group fed a diet with 3% FO for 8 weeks. The semen lipid profile and post-thaw sperm quality were analyzed at weeks 0 (pre-supplementation), 4, 8, 12 and 16 (post-supplementation) to evaluate the effects of FO supplementation by time interaction. Post-thaw sperm quality was determined by CASA and flow cytometry. In spermatozoa, the supplemented group increased the linoleic acid (C18:2n6c) and docosahexaenoic acid (DHA; C22:6n3) with levels higher at week 16 (P<0.05). The effect of FO on cholesterol concentration in sperm was significant at the end of the experiment (week 16). In seminal plasma, statistical differences of butyric acid (C4:0), palmitic acid (C16:0), stearic acid (C18:0), eicosatrienoic acid (C20:3n3) and DHA were observed at week 12. The cholesterol concentration was not affected by dietary treatments (P>0.05). However, the post-thaw sperm quality of the FO treatment group decreased. Motility percentage decreased 50% and spermatozoa with permeable plasma membrane and reacted acrosome were higher (63%) at week 16 than the control group. These results showed that DHA was effectively incorporated into semen through dietary supplementation with FO, but evaluations of post-thaw sperm quality confirm alteration specificity related to the structure of the lipid bilayer. Copyright © 2017 Elsevier B.V. All rights reserved.

Model for the dynamic responses of taste receptor cells to salty stimuli. I. Function of lipid bilayer membranes.

PubMed Central

Naito, M; Fuchikami, N; Sasaki, N; Kambara, T

1991-01-01

The dynamic response of the lipid bilayer membrane is studied theoretically using a microscopic model of the membrane. The time courses of membrane potential variations due to monovalent salt stimulation are calculated explicitly under various conditions. A set of equations describing the time evolution of membrane surface potential and diffusion potential is derived and solved numerically. It is shown that a rather simple membrane such as lipid bilayer has functions capable of reproducing the following properties of dynamic response observed in gustatory receptor potential. Initial transient depolarization does not occur under Ringer adaptation but does under water. It appears only for comparatively rapid flows of stimuli, the peak height of transient response is expressed by a power function of the flow rate, and the membrane potential gradually decreases after reaching its peak under long and strong stimulation. The dynamic responses in the present model arise from the differences between the time dependences in the surface potential phi s and the diffusion potential phi d across a membrane. Under salt stimulation phi d cannot immediately follow the variation in phi s because of the delay due to the charging up of membrane capacitance. It is suggested that lipid bilayer in the apical membrane is the most probable agency producing the initial phasic response to the stimulation. PMID:1873461

Extensive sphingolipid depletion does not affect lipid raft integrity or lipid raft localization and efflux function of the ABC transporter MRP1.

PubMed

Klappe, Karin; Dijkhuis, Anne-Jan; Hummel, Ina; van Dam, Annie; Ivanova, Pavlina T; Milne, Stephen B; Myers, David S; Brown, H Alex; Permentier, Hjalmar; Kok, Jan W

2010-09-15

We show that highly efficient depletion of sphingolipids in two different cell lines does not abrogate the ability to isolate Lubrol-based DRMs (detergent-resistant membranes) or detergent-free lipid rafts from these cells. Compared with control, DRM/detergent-free lipid raft fractions contain equal amounts of protein, cholesterol and phospholipid, whereas the classical DRM/lipid raft markers Src, caveolin-1 and flotillin display the same gradient distribution. DRMs/detergent-free lipid rafts themselves are severely depleted of sphingolipids. The fatty acid profile of the remaining sphingolipids as well as that of the glycerophospholipids shows several differences compared with control, most prominently an increase in highly saturated C(16) species. The glycerophospholipid headgroup composition is unchanged in sphingolipid-depleted cells and cell-derived detergent-free lipid rafts. Sphingolipid depletion does not alter the localization of MRP1 (multidrug-resistance-related protein 1) in DRMs/detergent-free lipid rafts or MRP1-mediated efflux of carboxyfluorescein. We conclude that extensive sphingolipid depletion does not affect lipid raft integrity in two cell lines and does not affect the function of the lipid-raft-associated protein MRP1.

Extensive sphingolipid depletion does not affect lipid raft integrity or lipid raft localization and efflux function of the ABC transporter MRP1

PubMed Central

Klappe, Karin; Dijkhuis, Anne-Jan; Hummel, Ina; vanDam, Annie; Ivanova, Pavlina T.; Milne, Stephen B.; Myers, David S.; Brown, H. Alex; Permentier, Hjalmar; Kok, Jan W.

2013-01-01

We show that highly efficient depletion of sphingolipids in two different cell lines does not abrogate the ability to isolate Lubrol-based DRMs (detergent-resistant membranes) or detergent-free lipid rafts from these cells. Compared with control, DRM/detergent-free lipid raft fractions contain equal amounts of protein, cholesterol and phospholipid, whereas the classical DRM/lipid raft markers Src, caveolin-1 and flotillin display the same gradient distribution. DRMs/detergent-free lipid rafts themselves are severely depleted of sphingolipids. The fatty acid profile of the remaining sphingolipids as well as that of the glycerophospholipids shows several differences compared with control, most prominently an increase in highly saturated C16 species. The glycerophospholipid headgroup composition is unchanged in sphingolipid-depleted cells and cell-derived detergent-free lipid rafts. Sphingolipid depletion does not alter the localization of MRP1 (multidrug-resistance-related protein 1) in DRMs/detergent-free lipid rafts or MRP1-mediated efflux of carboxyfluorescein. We conclude that extensive sphingolipid depletion does not affect lipid raft integrity in two cell lines and does not affect the function of the lipid-raft-associated protein MRP1. PMID:20604746

Advanced Atherogenic Index for the Assessment of Consolidated Lipid Risk in Premature Coronary Artery Disease Patients in India.

PubMed

Bansal, Sanjiv Kumar; Agarwal, Sarita; Daga, Mridul Kumar

2016-01-01

The high prevalence, severity, and prematurity of coronary artery disease (CAD) in the Indian population cannot be completely explained by the conventional lipid parameters and the existing lipid indices. To calculate newly defined advanced atherogenic index (AAI) in premature CAD patients and compare it between cases and controls and Correlate its values with the existing indices. One hundred and twenty premature CAD patients and an equal number of age and sex matched healthy individuals were included in this study. Lipid profile and nonconventional lipid parameters like oxidized Low density lipoprotein (OX LDL), small dense LDL (SD LDL), lipoprotein (a) apolipoprotein B (Apo B), and apolipoprotein A1 (Apo A1) were estimated and their values were used to define AAI and existing lipid indices like AI, lipid tetrad index (LTI) and lipid pentad index (LPI). The mean age of cases and controls was 37.29 + 4.50 and 36.13 + 3.53 years, respectively. The value of AAI was highly significant in cases (3461.22 ± 45.20) as compared to controls (305.84 ± 21.80). AAI has shown better statistical significance and correlation (P < 0.0001, r = 0.737) as compared to the earlier indices such as AI (P < 0.01, r = 0.52), LTI (P < 0.001, r = 0.677) and LPI (P < 0.001, r = 0.622) in premature CAD. Kolmogorov D statistic and cumulative distribution function plot has shown that AAI can discriminate cases and controls more accurately as compared to the earlier indices. Statistically AAI appears to be a better marker of consolidated lipid risk in premature CAD patients as compared to the earlier indices.

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

PubMed

Aye, Myint Myint; Kilpatrick, Eric S; Aburima, Ahmed; Wraith, Katie S; Magwenzi, Simbarashe; Spurgeon, B; Rigby, Alan S; Sandeman, Derek; Naseem, Khalid M; Atkin, Stephen L

2014-02-28

Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814.

[Research of Hippophae rhamnoides fruits on serum lipids and liver protection effects in high-fat-diet rats].

PubMed

Song, Chunmei; Du, Juan; Ge, Hongjuan

2015-07-01

To study the effects o Hippophae rhamnoides fruits on serum lipids and liver protection in high-fat-diet rats. Wistar rats were divided into 5 groups,including control group, high lipid model group and Hippophae rhamnoides low-, medium- and high- dose groups,every group wastaken high-fat diet except control group. The rats in control group and high lipid group were lavaged with physiological saline. The doses of Hippophae rhamnoides in low, middle and high groups were determined based on the 1x, 5x, and 10x standard human doses (50 g/60 kg BW), respectively. The rat were orally given test sample respectively for 28 days, once a day. Observed the changes of serum lipids and hepatic tissues pathology. Compared with the control group, the serum levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) were increased significantly (P < 0.05) in high-fat-diet rats. Compared with the high lipid group, Hippophae rhamnoides of different doses could significantly reduce the content of TG (P < 0.01). Hippophae rhamnoides reduced the tendency of TC and LDL-C in serum and reduced the fatty degeneration of liver cells. The Hippophae rhamnoides fruits can reduce the level of serum lipids and prevent the occurrence of fatty liver, can be used for the prevention of hyperlipidemia.

Oxalomalate, a competitive inhibitor of NADP+ -dependent isocitrate dehydrogenase, regulates lipid peroxidation-mediated apoptosis in U937 cells.

PubMed

Yang, Eun Sun; Yang, Joon-Hyuck; Park, Ji Eun; Park, Jeen-Woo

2005-01-01

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Recently, we demonstrated that the control of cytosolic redox balance and the cellular defense against oxidative damage is one of the primary functions of cytosolic NADP+ -dependent isocitrate dehydrogenase (IDPc) through to supply NADPH for antioxidant systems. The protective role of IDPc against lipid peroxidation-mediated apoptosis in U937 cells was investigated in control and cells pre-treated with oxlalomalate, a competitive inhibitor of IDPc. Upon exposure to 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the susceptibility to apoptosis was higher in oxalomalate-treated cells as compared to control cells. The results suggest that IDPc plays an important protective role in apoptosis of U937 cells induced by lipid peroxidation-mediated oxidative stress.

Job characteristics and serum lipid profile in Japanese rural workers: the Jichi Medical School Cohort Study.

PubMed

Tsutsumi, Akizumi; Kayaba, Kazunori; Ishikawa, Shizukiyo; Gotoh, Tadao; Nago, Naoki; Yamada, Seishi; Mizooka, Masafumi; Sakai, Kenichiro; Hayasaka, Shinya

2003-03-01

To observe the association between adverse psychosocial job characteristics, measured by the Karasek job demand-control questionnaire, and a lipid profile, cross-sectional analyses were performed for a Japanese rural working population. The study population comprised 3,333 male and 3,596 female actively employed workers, aged 65 years and under. Among men, higher psychological demands were associated with high total cholesterol levels, with an adjusted difference from the top to bottom tertiles of 3.3 mg/dl (F = 3.03; p = 0.048). High demands were also positively associated with the total/HDL cholesterol ratio (F = 3.94; p = 0.020). Neither job control nor job strain (the ratio of demands to control) was associated with any of the lipid levels in either gender. A psychologically demanding job may be associated with an unfavorable lipid profile, but the impact of job strain on atherogenic lipids is negligible.

Modeling and design of light powered biomimicry micropump utilizing transporter proteins

NASA Astrophysics Data System (ADS)

Liu, Jin; Sze, Tsun-Kay Jackie; Dutta, Prashanta

2014-11-01

The creation of compact micropumps to provide steady flow has been an on-going challenge in the field of microfluidics. We present a mathematical model for a micropump utilizing Bacteriorhodopsin and sugar transporter proteins. This micropump utilizes transporter proteins as method to drive fluid flow by converting light energy into chemical potential. The fluid flow through a microchannel is simulated using the Nernst-Planck, Navier-Stokes, and continuity equations. Numerical results show that the micropump is capable of generating usable pressure. Designing parameters influencing the performance of the micropump are investigated including membrane fraction, lipid proton permeability, illumination, and channel height. The results show that there is a substantial membrane fraction region at which fluid flow is maximized. The use of lipids with low membrane proton permeability allows illumination to be used as a method to turn the pump on and off. This capability allows the micropump to be activated and shut off remotely without bulky support equipment. This modeling work provides new insights on mechanisms potentially useful for fluidic pumping in self-sustained bio-mimic microfluidic pumps. This work is supported in part by the National Science Fundation Grant CBET-1250107.

Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes.

PubMed

Kim, Jeong Tae; Barua, Sonia; Kim, Hyeongmin; Hong, Seong-Chul; Yoo, Seung-Yup; Jeon, Hyojin; Cho, Yeongjin; Gil, Sangwon; Oh, Kyungsoo; Lee, Jaehwi

2017-07-01

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation.

PubMed

Belcik, J Todd; Mott, Brian H; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J; Ammi, Azzdine; Linden, Joel M; Lindner, Jonathan R

2015-04-01

Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10(8) IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (P<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively; P<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase attenuated flow augmentation produced by ultrasound and microbubbles by 70% (P<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase. © 2015 American Heart Association, Inc.

AUGMENTATION OF LIMB PERFUSION AND REVERSAL OF TISSUE ISCHEMIA PRODUCED BY ULTRASOUND-MEDIATED MICROBUBBLE CAVITATION

PubMed Central

Belcik, J. Todd; Mott, Brian H.; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J.; Ammi, Azzdine; Linden, Joel M.; Lindner, Jonathan R.

2015-01-01

Background Ultrasound can increase tissue blood flow in part through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation, and sought to characterize the biologic mediators. Methods and Results Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in non-ischemic mice after unilateral 10 min exposure to intermittent ultrasound alone (mechanical index [MI] 0.6 or 1.3) or ultrasound with lipid microbubbles (2×108 I.V.). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (p<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3-fold and 10-fold higher than control for MI 0.6 and 1.3, respectively; p<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase (eNOS) attenuated flow augmentation produced by ultrasound and microbubbles by 70% (p<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide (NO) production and muscle phospho-eNOS increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40–50% reduction in flow), ultrasound (MI 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control non-ischemic limb. Conclusions Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of eNOS. PMID:25834183

Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein particles as a function of particle size in one workflow integrating asymmetric flow field-flow fractionation and liquid chromatography-tandem mass spectrometry

PubMed Central

Jones, Jeffery I.; Gardner, Michael S.; Schieltz, David M.; Parks, Bryan A.; Toth, Christopher A.; Rees, Jon C.; Andrews, Michael L.; Carter, Kayla; Lehtikoski, Antony K.; McWilliams, Lisa G.; Williamson, Yulanda M.; Bierbaum, Kevin P.; Pirkle, James L.; Barr, John R.

2018-01-01

Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples. PMID:29634782

Lipid class and depth-specific thermal properties in the blubber of the short-finned pilot whale and the pygmy sperm whale.

PubMed

Bagge, Laura E; Koopman, Heather N; Rommel, Sentiel A; McLellan, William A; Pabst, D A

2012-12-15

Blubber, the specialized hypodermis of cetaceans, provides thermal insulation through the quantity and quality of lipids it contains. Quality refers to percent lipid content; however, not all lipids are the same. Certain deep-diving cetacean groups possess blubber with lipids - wax esters (WE) - that are not typically found in mammals, and the insulative quality of 'waxy' blubber is unknown. Our study explored the influence of lipid storage class - specifically WE in pygmy sperm whales (Kogia breviceps; N=7) and typical mammalian triacylglycerols in short-finned pilot whales (Globicephala macrorhynchus; N=7) - on blubber's thermal properties. Although the blubber of both species had similar total lipid contents, the thermal conductivity of G. macrorhynchus blubber (0.20±0.01 W m(-1) °C(-1)) was significantly higher than that of K. breviceps (0.15±0.01 W m(-1) °C(-1); P=0.0006). These results suggest that lipid class significantly influences the ability of blubber to resist heat flow. In addition, because the lipid content of blubber is known to be stratified, we measured its depth-specific thermal conductivities. In K. breviceps blubber, the depth-specific conductivity values tended to vary inversely with lipid content. In contrast, G. macrorhynchus blubber displayed unexpected depth-specific relationships between lipid content and conductivity, which suggests that temperature-dependent effects, such as melting, may be occurring. Differences in heat flux measurements across the depth of the blubber samples provide evidence that both species are capable of storing heat in their blubber. The function of blubber as an insulator is complex and may rely upon its lipid class, stratified composition and dynamic heat storage capabilities.

Quantifying lipid changes in various membrane compartments using lipid binding protein domains.

PubMed

Várnai, Péter; Gulyás, Gergő; Tóth, Dániel J; Sohn, Mira; Sengupta, Nivedita; Balla, Tamas

2017-06-01

One of the largest challenges in cell biology is to map the lipid composition of the membranes of various organelles and define the exact location of processes that control the synthesis and distribution of lipids between cellular compartments. The critical role of phosphoinositides, low-abundant lipids with rapid metabolism and exceptional regulatory importance in the control of almost all aspects of cellular functions created the need for tools to visualize their localizations and dynamics at the single cell level. However, there is also an increasing need for methods to determine the cellular distribution of other lipids regulatory or structural, such as diacylglycerol, phosphatidic acid, or other phospholipids and cholesterol. This review will summarize recent advances in this research field focusing on the means by which changes can be described in more quantitative terms. Published by Elsevier Ltd.

Lipid peroxidation in sarcoplasmic reticulum membranes: effect on functional and biophysical properties.

PubMed

Dinis, T C; Almeida, L M; Madeira, V M

1993-03-01

The fluorescent polyunsaturated parinaric acid (PnA) incorporated in sarcoplasmic reticulum membranes (SR) was used to probe the initial stages of membrane lipid peroxidation. The experimental set up of the PnA assay was investigated by means of several peroxidation initiators to ascertain peroxidation conditions. This assay in SR is particularly useful to evaluate the membrane susceptibility to peroxidation and to ascertain suitable conditions (concentration of initiators and cofactors) to challenge peroxidation in each preparation under study. On the basis of the PnA assay, Fe2+/ascorbate was selected among the different initiator systems to assess the effect of lipid peroxidation upon biochemical and biophysical parameters of SR membranes. Under mildly controlled conditions at 25 degrees C, the lipid degradative process, as detected by fatty acid analysis, decreases the Ca2+ uptake (up to about 50% of control) and reduces the Ca2+ pump efficiency (Ca2+/ATP ratio) up to about 58% of control, without inactivation the ATPase enzyme turnover. The effect of lipid peroxidation on the SR bilayer organization is dependent either on the extent of lipid peroxidation or on the depth of the bilayer as probed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene and by intramolecular excimerization of 1,3-di(1-pyrenyl)propane. It is concluded that the effect of mild lipid peroxidation on Ca2+ pump activity is partially exerted through the alteration of physical properties in the lipid phase or lipid-protein interfaces.

Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells.

PubMed

Zeng, Juan; Zhang, Heying; Tan, Yonggang; Sun, Cheng; Liang, Yusi; Yu, Jinyang; Zou, Huawei

2018-05-30

Activation of c-Met, a receptor tyrosine kinase, induces radiation therapy resistance in non-small cell lung cancer (NSCLC). The activated residual of c-Met is located in lipid rafts (Duhon et al. Mol Carcinog 49:739-49, 2010). Therefore, we hypothesized that disturbing the integrity of lipid rafts would restrain the activation of the c-Met protein and reverse radiation resistance in NSCLC. In this study, a series of experiments was performed to test this hypothesis. NSCLC A549 and H1993 cells were incubated with methyl-β-cyclodextrin (MβCD), a lipid raft inhibitor, at different concentrations for 1 h before the cells were X-ray irradiated. The following methods were used: clonogenic (colony-forming) survival assays, flow cytometry (for cell cycle and apoptosis analyses), immunofluorescence microscopy (to show the distribution of proteins in lipid rafts), Western blotting, and biochemical lipid raft isolation (purifying lipid rafts to show the distribution of proteins in lipid rafts). Our results showed that X-ray irradiation induced the aggregation of lipid rafts in A549 cells, activated c-Met and c-Src, and induced c-Met and c-Src clustering to lipid rafts. More importantly, MβCD suppressed the proliferation of A549 and H1993 cells, and the combination of MβCD and radiation resulted in additive increases in A549 and H1993 cell apoptosis. Destroying the integrity of lipid rafts inhibited the aggregation of c-Met and c-Src to lipid rafts and reduced the expression of phosphorylated c-Met and phosphorylated c-Src in lipid rafts. X-ray irradiation induced the aggregation of lipid rafts and the clustering of c-Met and c-Src to lipid rafts through both lipid raft-dependent and lipid raft-independent mechanisms. The lipid raft-dependent activation of c-Met and its downstream pathways played an important role in the development of radiation resistance in NSCLC cells mediated by c-Met. Further studies are still required to explore the molecular mechanisms of the activation of c-Met and c-Src in lipid rafts induced by radiation.

Effects of host nutrition on virulence and fitness of entomopathogenic nematodes: Lipid- and protein-based supplements in Tenebrio molitor diets

PubMed Central

Shapiro-Ilan, David; Rojas, M. Guadalupe; Morales-Ramos, Juan A.; Lewis, Edwin E.; Tedders, W. Louis

2008-01-01

Entomopathogenic nematodes, Heterorhabditis indica and Steinernema riobrave, were tested for virulence and reproductive yield in Tenebrio molitor that were fed wheat bran diets with varying lipid- and protein-based supplements. Lipid supplements were based on 20% canola oil, peanut, pork or salmon, or a low lipid control (5% canola). Protein treatments consisted of basic supplement ingredients plus 0, 10, or 20% egg white; a bran-only control was also included. Some diet supplements had positive effects on nematode quality, whereas others had negative or neutral effects. All supplements with 20% lipids except canola oil caused increased T. molitor susceptibility to H. indica, whereas susceptibility to S. riobrave was not affected. Protein supplements did not affect host susceptibility, and neither lipid nor protein diet supplements affected reproductive capacity of either nematode species. Subsequently, we determined the pest control efficacy of progeny of nematodes that had been reared through T. molitor from different diets against Diaprepes abbreviatus and Otiorhynchus sulcatus. All nematode treatments reduced insect survival relative to the control (water only). Nematodes originating from T. molitor diets with the 0% or 20% protein exhibited lower efficacy versus D. abbreviatus than the intermediate level of protein (10%) or bran-only treatments. Nematodes originating from T. molitor lipid or control diets did not differ in virulence. Our research indicates that nutritional content of an insect host diet can affect host susceptibility to entomopathogenic nematodes and nematode fitness; therefore, host media could conceivably be optimized to increase in vivo nematode production efficiency. PMID:19259513

Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction.

PubMed

Kjellqvist, Sanela; Klose, Christian; Surma, Michal A; Hindy, George; Mollet, Inês G; Johansson, Anna; Chavaux, Patrick; Gottfries, Johan; Simons, Kai; Melander, Olle; Fernandez, Céline

2016-11-29

Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmö Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI. Fatty acid desaturases (FADS) and elongation of very long chain fatty acid protein 5 (ELOVL5) activities were estimated by calculating product to precursor ratios of polyunsaturated fatty acids in complex lipids. FADS genotypes encoding these desaturases were then tested for association with lipid levels and ratios. Differences in the levels of lipids belonging to the phosphatidylcholine and triacylglyceride (TAG) classes contributed the most to separating DM from controls. TAGs also played a dominating role in discriminating MI from controls. Levels of C18:2 fatty acids in complex lipids were lower both in DM and MI versus controls (DM, P=0.004; MI, P=6.0E-06) at least due to an acceleration in the metabolic flux from C18:2 to C20:4 (eg, increased estimated ELOVL5: DM, P=0.02; MI, P=0.04, and combined elongase-desaturase activities: DM, P=3.0E-06; MI, P=2.0E-06). Minor allele carriers of FADS genotypes were associated with increased levels of C18:2 (P≤0.007) and lower desaturase activity (P≤0.002). We demonstrate a possible relationship between decreased levels of C18:2 in complex lipids and DM or MI. We thereby highlight the importance of molecular lipids in the pathogenesis of both diseases. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The plasma membrane of Saccharomyces cerevisiae: structure, function, and biogenesis.

PubMed Central

van der Rest, M E; Kamminga, A H; Nakano, A; Anraku, Y; Poolman, B; Konings, W N

1995-01-01

The composition of phospholipids, sphingolipids, and sterols in the plasma membrane has a strong influence on the activity of the proteins associated or embedded in the lipid bilayer. Since most lipid-synthesizing enzymes in Saccharomyces cerevisiae are located in intracellular organelles, an extensive flux of lipids from these organelles to the plasma membrane is required. Although the pathway of protein traffic to the plasma membrane is similar to that of most of the lipids, the bulk flow of lipids is separate from vesicle-mediated protein transport. Recent advances in the analysis of membrane budding and membrane fusion indicate that the mechanisms of protein transport from the endoplasmic reticulum to the Golgi and from the Golgi to plasma membrane are similar. The majority of plasma membrane proteins transport solutes across the membrane. A number of ATP-dependent export systems have been detected that couple the hydrolysis of ATP to transport of molecules out of the cell. The hydrolysis of ATP by the plasma membrane H(+)-ATPase generates a proton motive force which is used to drive secondary transport processes. In S. cerevisiae, many substrates are transported by more than one system. Transport of monosaccharide is catalyzed by uniport systems, while transport of disaccharides, amino acids, and nucleosides is mediated by proton symport systems. Transport activity can be regulated at the level of transcription, e.g., induction and (catabolite) repression, but transport proteins can also be affected posttranslationally by a process termed catabolite inactivation. Catabolite inactivation is triggered by the addition of fermentable sugars, intracellular acidification, stress conditions, and/or nitrogen starvation. Phosphorylation and/or ubiquitination of the transport proteins has been proposed as an initial step in the controlled inactivation and degradation of the target enzyme. The use of artificial membranes, like secretory vesicles and plasma membranes fused with proteoliposomes, as model systems for studies on the mechanism and regulation of transport is evaluated. PMID:7603412

Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates.

PubMed

Deushi, Michiyo; Osaka, Mizuko; Nakano, Kaku; Osada, Kyoichi; Egashira, Kensuke; Yoshida, Masayuki

2016-10-01

Oxidized cholesterol (oxysterols) plays an important and multifaceted role in lipid metabolism. Here we examined whether dietary oxysterols accelerate hepatic lipid accumulation and inflammation in nonhuman primates. We also examined the effect of the Niemann-Pick C1-like1 inhibitor, ezetimibe (Ez). Macaca fascicularis (5-year-old males) were fed either regular cholesterol + high-fat diet (control-HFD) or oxysterols + high-fat diet (ox-HFD; with 0.015% of oxysterols cholesterol) for 24 weeks. Compared with control-HFD, ox-HFD did not affect plasma lipid levels, but it did affect hepatic lipid levels [total cholesterol, 40.9 mg·g -1 (ox-HFD) versus 3.2 (control-HFD) mg·g -1 ; triglycerides, 28.0 (ox-HFD) versus 5.7 (control-HFD) mg·g -1 ]. Ox-HFD increased lipid accumulation as well as recruitment of inflammatory cells when compared to control-HFD. We then examined the effects of Ez, 0.2 mg·kg -1 ·day -1 for 12 weeks. In addition to a significant reduction in dyslipidemia, Ez alleviated biochemical and pathological aspects of steatosis. Dietary oxysterols aggravate steatosis in nonhuman primates. Treatment with Ez may be a novel therapeutic approach to NAFLD by alleviating dyslipidemia.

Biodiesel production from microbial oil derived from wood isolate Trichoderma reesei.

PubMed

Bharathiraja, B; Sowmya, V; Sridharan, Sridevi; Yuvaraj, D; Jayamuthunagai, J; Praveenkumar, R

2017-09-01

In the present study Trichoderma reesei, a wood isolate can yield high biomass quantities up to 30g/L, yielding 32.4% of lipids of dry cell weight (DCW). Biodiesel production from Trichoderma reesei involved simple unit operations like filtration and ultrasonication, yet giving good lipid yield with desirable bio-diesel properties. Optimization of ultrasonication conditions was done to ensure maximum lipid extraction. SEM analysis of ultrasonicated samples showed distinct breakage of fungal hyphae. The lipids were found to contain 49.7% saturated fatty acids. Transesterification using chemical and biological catalysts were compared and 96.09% efficiency was observed for lipase-catalyzed transesterification. The bio-diesel properties satisfied ASTM and EN specifications with cetane number: 53.1, iodine value: 63.34g, saponification value: 235.07mg KOH/g, cold flow plugging point: 9.13°C. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rigid aromatic linking moiety in cationic lipids for enhanced gene transfection efficiency.

PubMed

Wang, Bing; Zhao, Rui-Mo; Zhang, Ji; Liu, Yan-Hong; Huang, Zheng; Yu, Qing-Ying; Yu, Xiao-Qi

2017-08-18

Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines. Moreover, the rigid aromatic linkage also affords the material higher serum tolerance ability. Flow cytometry assay revealed that the target lipids have good cellular uptake, while confocal microscopy observation showed weaker endosome escape than Lipofectamine 2000. To solve such problem and further increase the transfection efficiency, some lysosomotropic reagents were used to improve the endosome escape of lipoplex. As expected, higher transfection efficiency than Lipofectamine 2000 could be obtained via this strategy. Cytotoxicity assay showed that these lipids have lower toxicity in various cell lines than Lipofectamine 2000, suggesting their potential for further application. This work demonstrates that a rigid aromatic linkage might distinctly improve the gene transfection abilities of cationic lipids and affords information to construct safe and efficient gene vector towards practical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Enhanced bioavailability of tripterine through lipid nanoparticles using broccoli-derived lipids as a carrier material.

PubMed

Li, Wan; Zhang, Tianpeng; Ye, Yanghuan; Zhang, Xingwang; Wu, Baojian

2015-11-30

Chemotherapy via the oral route remains a considerable challenge due to poor water-solubility and permeability of anticancer agents. This study aimed to construct lipid nanoparticles using broccoli-derived lipids for oral delivery of tripterine (Tri), a natural anticancer candidate, and to enhance its oral bioavailability. Tri-loaded broccoli lipid nanoparticles (Tri-BLNs) were prepared by a solvent-diffusion method. The resulting Tri-BLNs were 75±10 nm in particle size with entrapment efficiency over 98%. In vitro release study indicated that Tri was almost not released from Tri-BLNs (<2%), whereas the lipolytic experiment showed that Tri-BLNs possessed a relatively strong anti-enzymatic degradation ability to Tri-CLNs (Tri-loaded common lipid nanoparticles). In situ single-pass intestinal perfusion manifested that the effective permeability of Tri-BLNs were significantly higher than that of Tri-CLNs. Further, Tri-BLNs exhibited more efficient cellular uptake in MDCK-II cells as evidenced by flow cytometry and confocal microscopy. The relative bioavailability of Tri-BLNs and Tri-CLNs was 494.13% and 281.95% compared with Tri suspensions, respectively. Depending on the ability in enhancement of biomembrane permeability, broccoli-derived lipids as an alternative source should be useful to construct lipid nanoparticles for bettering oral delivery of drugs with low bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.

Liver Disease, Systemic Inflammation, and Growth Using a Mixed Parenteral Lipid Emulsion, Containing Soybean Oil, Fish Oil, and Medium Chain Triglycerides, Compared With Soybean Oil in Parenteral Nutrition-Fed Neonatal Piglets.

PubMed

Turner, Justine M; Josephson, Jessica; Field, Catherine J; Wizzard, Pamela R; Ball, Ronald O; Pencharz, Paul B; Wales, Paul W

2016-09-01

The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure-associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω-6 and ω-3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil-based emulsion (ω-6:ω-3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (ω-6:ω-3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Neonatal piglets, 3-6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C-reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Compared with the IL group, ML-treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω-6 long-chain PUFA content was lower in plasma and brain for the ML group. The key ω-3 long-chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. The mixed lipid, having less ω-6 PUFA and more ω-3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN-fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes. © 2015 American Society for Parenteral and Enteral Nutrition.

A method of coupling the Paternò-Büchi reaction with direct infusion ESI-MS/MS for locating the C[double bond, length as m-dash]C bond in glycerophospholipids.

PubMed

Stinson, Craig A; Xia, Yu

2016-06-21

Tandem mass spectrometry (MS/MS) coupled with soft ionization is established as an essential platform for lipid analysis; however, determining high order structural information, such as the carbon-carbon double bond (C[double bond, length as m-dash]C) location, remains challenging. Recently, our group demonstrated a method for sensitive and confident lipid C[double bond, length as m-dash]C location determination by coupling online the Paternò-Büchi (PB) reaction with nanoelectrospray ionization (nanoESI) and MS/MS. Herein, we aimed to expand the scope of the PB reaction for lipid analysis by enabling the reaction with infusion ESI-MS/MS at much higher flow rates than demonstrated in the nanoESI setup (∼20 nL min(-1)). In the new design, the PB reaction was effected in a fused silica capillary solution transfer line, which also served as a microflow UV reactor, prior to ESI. This setup allowed PB reaction optimization and kinetics studies. Under optimized conditions, a maximum of 50% PB reaction yield could be achieved for a standard glycerophosphocholine (PC) within 6 s of UV exposure over a wide flow rate range (0.1-10 μL min(-1)). A solvent composition of 7 : 3 acetone : H2O (with 1% acid or base modifier) allowed the highest PB yields and good lipid ionization, while lower yields were obtained with an addition of a variety of organic solvents. Radical induced lipid peroxidation was identified to induce undesirable side reactions, which could be effectively suppressed by eliminating trace oxygen in the solution via N2 purge. Finally, the utility of coupling the PB reaction with infusion ESI-MS/MS was demonstrated by analyzing a yeast polar lipid extract where C[double bond, length as m-dash]C bond locations were revealed for 35 glycerophospholipids (GPs).

Lipid droplets form from distinct regions of the cell in the fission yeast Schizosaccharomyces pombe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyers, Alex; del Rio, Zuania P.; Beaver, Rachael A.

Eukaryotic cells store cholesterol/sterol esters (SEs) and triacylglycerols (TAGs) in lipid droplets, which form from the contiguous endoplasmic reticulum (ER) network. However, it is not known if droplets preferentially form from certain regions of the ER over others. Here, we used fission yeast Schizosaccharomyces pombe cells where the nuclear and cortical/peripheral ER domains are distinguishable by light microscopy to show that SE-enriched lipid droplets form away from the nucleus at the cell tips, whereas TAG-enriched lipid droplets form around the nucleus. Sterols localize to the regions of the cells where droplets enriched in SEs are observed. TAG droplet formation aroundmore » the nucleus appears to be a strong function of diacylglycerol (DAG) homeostasis with Cpt1p, which coverts DAG into phosphatidylcholine and phosphatidylethanolamine localized exclusively to the nuclear ER. Also, Dgk1p, which converts DAG into phosphatidic acid localized strongly to the nuclear ER over the cortical/peripheral ER. We also show that TAG more readily translocates from the ER to lipid droplets than do SEs. Lastly, the results augment the standard lipid droplet formation model, which has SEs and TAGs flowing into the same nascent lipid droplet regardless of its biogenesis point in the cell.« less

Lipid droplets form from distinct regions of the cell in the fission yeast Schizosaccharomyces pombe

DOE PAGES

Meyers, Alex; del Rio, Zuania P.; Beaver, Rachael A.; ...

2016-04-29

Eukaryotic cells store cholesterol/sterol esters (SEs) and triacylglycerols (TAGs) in lipid droplets, which form from the contiguous endoplasmic reticulum (ER) network. However, it is not known if droplets preferentially form from certain regions of the ER over others. Here, we used fission yeast Schizosaccharomyces pombe cells where the nuclear and cortical/peripheral ER domains are distinguishable by light microscopy to show that SE-enriched lipid droplets form away from the nucleus at the cell tips, whereas TAG-enriched lipid droplets form around the nucleus. Sterols localize to the regions of the cells where droplets enriched in SEs are observed. TAG droplet formation aroundmore » the nucleus appears to be a strong function of diacylglycerol (DAG) homeostasis with Cpt1p, which coverts DAG into phosphatidylcholine and phosphatidylethanolamine localized exclusively to the nuclear ER. Also, Dgk1p, which converts DAG into phosphatidic acid localized strongly to the nuclear ER over the cortical/peripheral ER. We also show that TAG more readily translocates from the ER to lipid droplets than do SEs. Lastly, the results augment the standard lipid droplet formation model, which has SEs and TAGs flowing into the same nascent lipid droplet regardless of its biogenesis point in the cell.« less

Impact of dietary dairy polar lipids on lipid metabolism of mice fed a high-fat diet.

PubMed

Reis, Mariza G; Roy, Nicole C; Bermingham, Emma N; Ryan, Leigh; Bibiloni, Rodrigo; Young, Wayne; Krause, Lutz; Berger, Bernard; North, Mike; Stelwagen, Kerst; Reis, Marlon M

2013-03-20

The effect of milk polar lipids on lipid metabolism of liver, adipose tissue, and brain and on composition of intestinal microbiota was investigated. C57BL/6J mice were fed a high-fat diet (HFD) for 5 weeks, followed by 5 weeks with HFD without (control) or supplemented with total polar lipids (TPL), phospholipids (PL), or sphingolipids (SPL). Animals fed SPL showed a tendency for lower triglyceride synthesis (P = 0.058) in the liver, but not in adipose tissue. PL and TPL reduced de novo hepatic fatty acid biosynthesis. The ratio of palmitoleic to palmitic acid in the liver was lower for animals fed SPL or TPL compared to control. There was little effect of the supplementation on the cecal microbiota composition. In the brain, DHA (C22:6) content correlated negatively with tetracosanoic acid (C24:0) after TPL supplementation (-0.71, P = 0.02) but not in control (0.26, P = 0.44). Arachidonic acid (C20:4) was negatively correlated with C24:0 in both groups (TPL, -0.77, P = 0.008; control, -0.81, P = 0.003).

The Effects of Body Acupuncture on Obesity: Anthropometric Parameters, Lipid Profile, and Inflammatory and Immunologic Markers

PubMed Central

Abdi, Hamid; Zhao, Baixiao; Darbandi, Mahsa; Ghayour-Mobarhan, Majid; Tavallaie, Shima; Rahsepar, Amir Ali; Parizadeh, Seyyed Mohammad Reza; Safariyan, Mohammad; Nemati, Mohsen; Mohammadi, Maryam; Abbasi-Parizad, Parisa; Darbandi, Sara; Akhlaghi, Saeed; Ferns, Gordon A. A.

2012-01-01

A randomized controlled clinical trial in 196 obese subjects was performed to examine the effectiveness of body acupuncture on body weight loss, lipid profile and immunogenic and inflammatory markers. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Subjects were assessed at the beginning, 6 and 12 weeks later. Heat shock protein (Hsps)-27, 60, 65, 70 antibody titers and high sensitivity C-reactive protein (hs-CRP) levels were also assessed. A significant reduction in measures of adiposity and improvement in lipid profile were observed in both groups, but the levels of anti-Hsp-antibodies decreased in cases only. A reduction in anthropometric and lipid profile in cases were sustained in the second period, however, only changes in lipid profile were observed in the control group. Anti-Hsp-antibodies and hs-CRP levels continued to be reduced in cases but in controls only the reduction in hs-CRP remained. Changes in anthropometric parameters, lipid profile, and anti-Hsp-antibodies were more evident in cases. Body acupuncture in combination with diet restriction was effective in enhancing weight loss and improving dyslipidemia. PMID:22649299

Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis.

PubMed

Iswanto, Arya Bagus Boedi; Kim, Jae-Yean

2017-04-03

A bstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD), which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs) is highly controlled by plasmodesmata callose (PDC), which is synthesized by callose synthases (CalS) and degraded by β-1,3-glucanases (BGs). In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft-processed PDC.

Design and modeling of a light powered biomimicry micropump

NASA Astrophysics Data System (ADS)

Sze, Tsun-kay Jackie; Liu, Jin; Dutta, Prashanta

2015-06-01

The design of compact micropumps to provide steady flow has been an on-going challenge in the field of microfluidics. In this work, a novel micropump concept is introduced utilizing bacteriorhodopsin and sugar transporter proteins. The micropump utilizes light energy to activate the transporter proteins, which create an osmotic pressure gradient and drive the fluid flow. The capability of the bio inspired micropump is demonstrated using a quasi 1D numerical model, where the contributions of bacteriorhodopsin and sugar transporter proteins are taken care of by appropriate flux boundary conditions in the flow channel. Proton flux created by the bacteriorhodopsin proteins is compared with experimental results to obtain the appropriate working conditions of the proteins. To identify the pumping capability, we also investigate the influences of several key parameters, such as the membrane fraction of transporter proteins, membrane proton permeability and the presence of light. Our results show that there is a wide bacteriorhodopsin membrane fraction range (from 0.2 to 10%) at which fluid flow stays nearly at its maximum value. Numerical results also indicate that lipid membranes with low proton permeability can effectively control the light source as a method to turn on/off fluid flow. This capability allows the micropump to be activated and shut off remotely without bulky support equipment. In comparison with existing micropumps, this pump generates higher pressures than mechanical pumps. It can produce peak fluid flow and shutoff head comparable to other non-mechanical pumps.

Biomimetic engineering of a generic cell-on-membrane architecture by microfluidic engraving for on-chip bioassays.

PubMed

Lee, Sang-Wook; Noh, Ji-Yoon; Park, Seung Chul; Chung, Jin-Ho; Lee, Byoungho; Lee, Sin-Doo

2012-05-22

We develop a biomimetic cell-on-membrane architecture in close-volume format which allows the interfacial biocompatibility and the reagent delivery capability for on-chip bioassays. The key concept lies in the microfluidic engraving of lipid membranes together with biological cells on a supported substrate with topographic patterns. The simultaneous engraving process of a different class of fluids is promoted by the front propagation of an air-water interface inside a flow-cell. This highly parallel, microfluidic cell-on-membrane approach opens a door to the natural biocompatibility in mimicking cellular stimuli-response behavior essential for diverse on-chip bioassays that can be precisely controlled in the spatial and temporal manner.

Effect of combined metformin and oral contraceptive therapy on metabolic factors and endothelial function in overweight and obese women with polycystic ovary syndrome.

PubMed

Essah, Paulina A; Arrowood, James A; Cheang, Kai I; Adawadkar, Swati S; Stovall, Dale W; Nestler, John E

2011-08-01

In this randomized, double-blind, placebo-controlled study, 19 overweight women with polycystic ovary syndrome were randomized to a 3-month course of either metformin plus combined hormonal oral contraceptive (OC) (n = 9) or OC plus matched placebo (n = 10). After 3 months, both treatments had similar effects on androgen levels, lipid profile, insulin sensitivity, and serum inflammatory markers, but flow-mediated dilatation increased by 69.0% in the metformin plus OC group while it remained unchanged in the OC group. CLINICAL TRIAL REGISTRATION NO: NCT00682890. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Stepwise Synthesis of Giant Unilamellar Vesicles on a Microfluidic Assembly Line

PubMed Central

2011-01-01

Among the molecular milieu of the cell, the membrane bilayer stands out as a complex and elusive synthetic target. We report a microfluidic assembly line that produces uniform cellular compartments from droplet, lipid, and oil/water interface starting materials. Droplets form in a lipid-containing oil flow and travel to a junction where the confluence of oil and extracellular aqueous media establishes a flow-patterned interface that is both stable and reproducible. A triangular post mediates phase transfer bilayer assembly by deflecting droplets from oil, through the interface, and into the extracellular aqueous phase to yield a continuous stream of unilamellar phospholipid vesicles with uniform and tunable size. The size of the droplet precursor dictates vesicle size, encapsulation of small-molecule cargo is highly efficient, and the single bilayer promotes functional insertion of a bacterial transmembrane pore. PMID:21309555

Maternal early pregnancy lipid profile and offspring's lipids and glycaemic control at age 5-6 years: The ABCD study.

PubMed

van Lieshout, Noekie; Oostvogels, Adriëtte J J M; Gademan, Maaike G J; Vrijkotte, Tanja G M

2017-12-01

Maternal early pregnancy lipid profile might influence offspring's lipids and glycaemic control, through an increased offspring's fat percentage. This explorative study investigates whether maternal early pregnancy lipid profile is associated with offspring's lipids and glycaemic control independently of offspring's fat percentage and if these associations are mediated by offspring's fat percentage. Possible sex differences in these associations are also examined. 1133 mother-child pairs of the prospective ABCD-study were included. Maternal non-fasting lipids were collected in early pregnancy: triglycerides, total cholesterol (TC), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and free fatty acids (FFA). Fasting triglycerides, TC, high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and C-peptide were assessed in offspring aged 5-6 years and HOMA2-IR was calculated. After adjustment for covariates, strongest associations were found between maternal TC and offspring's TC (boys β(95%CI) = 0.141 (0.074-0.207); girls β(95%CI) = 0.268 (0.200; 0.336)) and LDL (boys β(95%CI) = 0.114 (0.052; 0.176); girls β(95%CI) = 0.247 (0.181-0.312)), maternal ApoB and offspring's TC (boys β(95%CI) = 0.638 (0.311-0.965); girls β(95%CI) = 1.121 (0.766-1.475)) and LDL (boys β(95%CI) = 0.699 (0.393-1.005); girls β(95%CI) = 1.198 (0.868-1.529)), and maternal ApoA1 and offspring's HDL (only boys β(95%CI) = 0.221 (0.101-0.341)). No significant association was found between maternal lipids and offspring's glycaemic control, and offspring's fat percentage played no mediating role. Maternal early pregnancy lipid profile is associated with offspring's lipid profile in childhood, with overall stronger associations in girls. This study provides further evidence that lowering lipid levels during pregnancy might be beneficial for the long term health of the offspring. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Lipid nanoparticle interactions and assemblies

NASA Astrophysics Data System (ADS)

Preiss, Matthew Ryan

Novel liposome-nanoparticle assemblies (LNAs) provide a biologically inspired route for designing multifunctional bionanotheranostics. LNAs combine the benefits of lipids and liposomes to encapsulate, transport, and protect hydrophilic and hydrophobic therapeutics with functional nanoparticles. Functional nanoparticles endow LNAs with additional capabilities, including the ability to target diseases, triggered drug release, controlled therapeutic output, and diagnostic capabilities to produce a drug delivery system that can effectively and efficiently deliver therapeutics while reducing side effects. Not only could LNAs make existing drugs better, they could also provide an avenue to allow once promising non-approved drugs (rejected due to harmful side effects, inadequate pharmacokinetics, and poor efficacy) to be safely used through targeted and controlled delivery directly to the diseased site. LNAs have the potential to be stimuli responsive, delivering drugs on command by external (ultrasound, RF heating, etc.) or internal (pH, blood sugar, heart rate, etc.) stimuli. Individually, lipids and nanoparticles have been clinically approved for therapy, such as Doxil (a liposomal doxorubicin for cancer treatment), and diagnosis, such as Feridex (an iron oxide nanoparticle an MRI contrast enhancement agent for liver tumors). In order to engineer these multifunctional LNAs for theranostic applications, the interactions between nanoparticles and lipids must be better understood. This research sought to explore the formation, design, structures, characteristics, and functions of LNAs. To achieve this goal, different types of LNAs were formed, specifically magnetoliposomes, bilayer decorated LNAs (DLNAs), and lipid-coated magnetic nanoparticles (LMNPs). A fluorescent probe was embedded in the lipid bilayer of magnetoliposomes allowing the local temperature and membrane fluidity to be observed. When subjected to an electromagnetic field that heated the encapsulated iron oxide nanoparticles encapsulated in the lipid bilayer, the local temperature and membrane fluidity could be observed. DLNAs were encapsulated with different sized nanoparticles and concentrations in order to observe the effect of the bilayer nanoparticles on the lipid bilayer's phase behavior and leakage. Two different sized nanoparticles were used, a 2 nm gold nanoparticle (GNP) much smaller than the thickness of the bilayer and a 4 nm GNP near the thickness of the lipid bilayer. The 2 nm GNPs were shown to affect the lipid bilayer differently than the 4 nm GNP. Specifically, the two nanoparticles altered the phase behavior and leakage differently in a temperature dependent fashion, demonstrating that embedded nanoparticle size can be used induce or inhibit bilayer leakage. A dual solvent exchange method was used to control the lipid surface composition of an iron oxide nanoparticle with a cationic lipid and a polyethylene glycol (PEG) lipid to produce lipid coated magnetic nanoparticles (LMNPs). PEG is well known for its ability to enhance the pharmacokinetics of nanostructures by preventing uptake by the immune system. By controlling the lipid surface composition, the surface charge and PEG conformation can be controlled which allowed the LMNPs to be used as an MRI contrast agent and a delivery system for siRNA that could be triggered with temperature.

The Relationship between Serum Lipids and Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis

PubMed Central

Chang, I Jen; Kang, Chung Jan; Yueh, Chen Yu; Fang, Ku Hao; Yeh, Re Ming; Tsai, Yao Te

2015-01-01

Background Sudden sensorineural hearing loss (SSNHL) is a relatively common condition that is usually of unknown etiology. A number of individual studies have investigated the association between various serum lipids and SSNHL; however, the findings have been inconsistent. In an attempt to obtain more definitive information on the relationship between serum lipids and SSNHL, we carried out a systematic review and meta-analysis. Methods Medline, the Cochrane Library, and EMBASE were searched using the following key words: lipid, cholesterol, triglyceride, fat, serum, blood, sudden hearing loss, hearing loss, hearing disorders. Randomized controlled trials, prospective cohort studies, and retrospective case-control studies involving patients with SSNHL and healthy controls that examined the relationship (reported as odds ratios [OR]) between lipid profiles and SSNHL were included. Primary outcomes were total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations. Secondary outcomes were triglyceride, high-density lipoprotein cholesterol, and lipoprotein(a) concentrations. Results A total of 6 case-control studies were included in this systematic review/meta-analysis. The total number of participants ranged from 30 to 250 in the case group and from 43 to 271 in the control group. Meta-analysis revealed no significant difference in total cholesterol levels between the case and control groups (pooled OR = 1.79, 95% confidence interval [CI] = 0.98 to 3.26, P = 0.057). Likewise, meta-analysis revealed no significant difference in LDL-C concentrations between the case and control groups (pooled OR = 1.15, 95% CI = 0.64 to 2.07, P = 0.639). Since there were an insufficient number of studies reporting data for the secondary outcomes, meta-analysis was not possible. Conclusions Our results do not provide evidence for serum lipids being associated with SSNHL, nor do they definitively rule out such an association. Additional studies are needed to ascertain the relationship, or lack thereof, between serum lipids and SSNHL. PMID:25866869

Lipid antigens in immunity

PubMed Central

Dowds, C. Marie; Kornell, Sabin-Christin

2014-01-01

Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity. PMID:23999493

Synthetic ion channels via self-assembly: a route for embedding porous polyoxometalate nanocapsules in lipid bilayer membranes.

PubMed

Carr, Rogan; Weinstock, Ira A; Sivaprasadarao, Asipu; Müller, Achim; Aksimentiev, Aleksei

2008-11-01

Porous polyoxometalate nanocapsules of Keplerate type are known to exhibit the functionality of biological ion channels; however, their use as an artificial ion channel is tempered by the high negative charge of the capsules, which renders their spontaneous incorporation into a lipid bilayer membrane unlikely. In this Letter we report coarse-grained molecular dynamics simulations that demonstrate a route for embedding negatively charged nanocapsules into lipid bilayer membranes via self-assembly. A homogeneous mixture of water, cationic detergent, and phospholipid was observed to spontaneously self-assemble around the nanocapsule into a layered, liposome-like structure, where the nanocapsule was enveloped by a layer of cationic detergent followed by a layer of phospholipid. Fusion of such a layered liposome with a lipid bilayer membrane was observed to embed the nanocapsule into the lipid bilayer. The resulting assembly was found to remain stable even after the surface of the capsule was exposed to electrolyte. In the latter conformation, water was observed to flow into and out of the capsule as Na(+) cations entered, suggesting that a polyoxometalate nanocapsule can form a functional synthetic ion channel in a lipid bilayer membrane.

Synthetic Ion Channels via Self-Assembly: a Route for Embedding Porous Polyoxometalate Nanocapsules in Lipid Bilayer Membranes

PubMed Central

Carr, Rogan; Weinstock, Ira A.; Sivaprasadarao, Asipu; Müller, Achim; Aksimentiev, Aleksei

2010-01-01

Porous polyoxometalate nanocapsules of Keplerate type are known to exhibit the functionality of biological ion channels, however, their use as artificial ion channel is tempered by the high negative charge of the capsules, which renders their spontaneous incorporation into a lipid bilayer membrane unlikely. In this letter we report coarse-grained molecular dynamics simulations that demonstrate a route for embedding negatively charged nanocapsules into lipid bilayer membranes via self-assembly. A homogeneous mixture of water, cationic detergent, and phospholipid was observed to spontaneously self-assemble around the nanocapsule into a layered, liposome-like structure, where the nanocapsule was enveloped by a layer of cationic detergent followed by a layer of phospholipid. Fusion of such a layered liposome with a lipid bilayer membrane was observed to embed the nanocapsule into the lipid bilayer. The resulting assembly was found to remain stable even after the surface of the capsule was exposed to electrolyte. In the latter conformation, water was observed to flow into and out of the capsule as Na+ cations entered, suggesting that a polyoxometalate nanocapsule can form a functional synthetic ion channel in a lipid bilayer membrane. PMID:18844424

Commentary: why don't plant leaves get fat?

PubMed

Chapman, Kent D; Dyer, John M; Mullen, Robert T

2013-06-01

Recent pressures to obtain energy from plant biomass have encouraged new metabolic engineering strategies that focus on accumulating lipids in vegetative tissues at the expense of lignin, cellulose and/or carbohydrates. There are at least three important factors that support this rationale. (i) Lipids are more reduced than carbohydrates and so they have more energy per unit of mass. (ii) Lipids are hydrophobic and thus take up less volume than hydrated carbohydrates on a mass basis for storage in tissues. (iii) Lipids are more easily extracted and converted into useable biofuels than cellulosic-derived fuels, which require extensive fractionation, degradation of lignocellulose and fermentation of plant tissues. However, while vegetative organs such as leaves are the majority of harvestable biomass and would be ideal for accumulation of lipids, they have evolved as "source" tissues that are highly specialized for carbohydrate synthesis and export and do not have a propensity to accumulate lipid. Metabolism in leaves is directed mostly toward the synthesis and export of sucrose, and engineering strategies have been devised to divert the flow of photosynthetic carbon from sucrose, starch, lignocellulose, etc. toward the accumulation of triacylglycerols in non-seed, vegetative tissues for bioenergy applications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Composition Based Strategies for Controlling Radii in Lipid Nanotubes

PubMed Central

Kurczy, Michael E.; Mellander, Lisa J.; Najafinobar, Neda; Cans, Ann-Sofie

2014-01-01

Nature routinely carries out small-scale chemistry within lipid bound cells and organelles. Liposome–lipid nanotube networks are being developed by many researchers in attempt to imitate these membrane enclosed environments, with the goal to perform small-scale chemical studies. These systems are well characterized in terms of the diameter of the giant unilamellar vesicles they are constructed from and the length of the nanotubes connecting them. Here we evaluate two methods based on intrinsic curvature for adjusting the diameter of the nanotube, an aspect of the network that has not previously been controllable. This was done by altering the lipid composition of the network membrane with two different approaches. In the first, the composition of the membrane was altered via lipid incubation of exogenous lipids; either with the addition of the low intrinsic curvature lipid soy phosphatidylcholine (soy-PC) or the high intrinsic curvature lipid soy phosphatidylethanolamine (soy-PE). In the second approach, exogenous lipids were added to the total lipid composition during liposome formation. Here we show that for both lipid augmentation methods, we observed a decrease in nanotube diameter following soy-PE additions but no significant change in size following the addition of soy-PC. Our results demonstrate that the effect of soy-PE on nanotube diameter is independent of the method of addition and suggests that high curvature soy-PE molecules facilitate tube membrane curvature. PMID:24392077

Effects of SNPs at newly identified lipids loci on blood lipid levels and risk of coronary heart disease in Chinese Han population: a case control study.

PubMed

Zhuang, Ke; Zhang, Wencai; Zhang, Xiaobo; Wu, Fangqin; Cheng, Longxian

2011-08-01

Associations between "lipid-related" candidate genes, blood lipid concentrations and coronary artery disease (CHD) risk are not clear. We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population. The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age- and sex-frequency matched controls from an unrelated Chinese Han population. Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio (OR) being 0.64 (95% CI 0.50 to 0.81), after adjusting for conventional risk factors and was associated with a 33% decreased CHD risk (P<0.01) comparing with the major allele G. Individuals with GT genotype had the lowest CHD risk. No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population. SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population. However, it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.

Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients

PubMed Central

Taha, Ameer Y.; Cheon, Yewon; Ma, Kaizong; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Background Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in schizophrenic (SCZ) patients, often as percent of total lipid concentration or incomplete lipid profile. In this study, we quantified absolute concentrations (nmol/g wet weight) of several lipid classes and their constituent fatty acids in postmortem prefrontal cortex of SCZ patients (n = 10) and age-matched controls (n = 10). Methods Lipids were extracted, fractionated with thin layer chromatography and assayed. Results Mean total lipid, phospholipid, individual phospholipids, plasmalogen, triglyceride and cholesteryl ester concentrations did not differ significantly between the groups. Compared to controls, SCZ brains showed significant increases in several monounsaturated and polyunsaturated fatty acids in cholesteryl ester. Significant increases or decreases occurred in palmitoleic, linoleic, γ-linolenic and n-3 docosapentaenoic acid in total lipids, triglycerides or phospholipids. Conclusion These changes suggest disturbed prefrontal cortex fatty acid concentrations, particularly within cholesteryl esters, as a pathological aspect of schizophrenia. PMID:23428160

Effects of lipid emulsion particle size on satiety and energy intake: a randomised cross-over trial.

PubMed

Poppitt, Sally D; Budgett, Stephanie C; MacGibbon, Alastair K; Quek, Siew-Young; Kindleysides, Sophie; Wiessing, Katy R

2018-03-01

Emulsified lipids, with central lipid core surrounded by polar lipid 'protective coat', have been proposed to stimulate the ileal brake, alter appetite, food intake and aid weight control. In addition to lipid composition, emulsion particle size may contribute to efficacy with small droplets providing a larger surface area for gastrointestinal (GI) lipase action and larger droplets prolonging and delaying digestion in the GI tract. Tube feeding studies delivering emulsions directly into the small intestine show clear effects of smaller particle size on appetite and food intake, but evidence from oral feeding studies is sparse. The objective of this study was to determine the effects of lipid emulsion particle size on appetite response and food intake. In a three-arm randomised cross-over, high-phospholipid (PL) dairy lipid emulsions or matched control were consumed at breakfast within a yoghurt smoothie: (i) large-particle size emulsion, LPE (diameter 0.759 µm, 10 g lipid emulsion, 190 g yoghurt), (ii) small-particle size emulsion, SPE (diameter 0.290 µm, 10 g lipid emulsion, 190 g yoghurt), (iii) control non-emulsion, NE (10 g non-emulsion lipid, 190 g yoghurt). Twenty male participants completed the study, where postprandial appetite response was rated using visual analogue scales (VAS) and ad libitum energy intake at a lunch meal measured 3 h later. There was a trend for LPE to suppress hunger (P = 0.08) and enhance fullness (P = 0.24) relative to both SPE and NE but not statistically significant, and no significant effect of either emulsion on food intake at the lunch meal (P > 0.05). Altering particle size of a high-PL emulsion did not enhance satiety or alter eating behaviour in a group of lean men.

The dynamic behavior of chemically "stiffened" red blood cells in microchannel flows.

PubMed

Forsyth, Alison M; Wan, Jiandi; Ristenpart, William D; Stone, Howard A

2010-07-01

The rigidity of red blood cells (RBCs) plays an important role in whole blood viscosity and is correlated with several cardiovascular diseases. Two chemical agents that are commonly used to study cell deformation are diamide and glutaraldehyde. Despite diamide's common usage, there are discrepancies in the literature surrounding diamide's effect on the deformation of RBCs in shear and pressure-driven flows; in particular, shear flow experiments have shown that diamide stiffens cells, while pressure-driven flow in capillaries did not give this result. We performed pressure-driven flow experiments with RBCs in a microfluidic constriction and quantified the cell dynamics using high-speed imaging. Diamide, which affects RBCs by cross-linking spectrin skeletal membrane proteins, did not reduce deformation and showed an unchanged effective strain rate when compared to healthy cells. In contrast, glutaraldehyde, which is a non-specific fixative that acts on all components of the cell, did reduce deformation and showed increased instances of tumbling, both of which are characteristic features of stiffened, or rigidified, cells. Because glutaraldehyde increases the effective viscosity of the cytoplasm and lipid membrane while diamide does not, one possible explanation for our results is that viscous effects in the cytoplasm and/or lipid membrane are a dominant factor in dictating dynamic responses of RBCs in pressure-driven flows. Finally, literature on the use of diamide as a stiffening agent is summarized, and provides supporting evidence for our conclusions. Copyright 2010 Elsevier Inc. All rights reserved.

A Novel Macroscale Acoustic Device for Blood Filtration.

PubMed

Dutra, Brian; Carmen Mora, Maria; Gerhardson, Tyler I; Sporbert, Brianna; Dufresne, Alexandre; Bittner, Katharine R; Lovewell, Carolanne; Rust, Michael J; Tirabassi, Michael V; Masi, Louis; Lipkens, Bart; Kennedy, Daniel R

2018-03-01

Retransfusion of a patient's own shed blood during cardiac surgery is attractive since it reduces the need for allogeneic transfusion, minimizes cost, and decreases transfusion related morbidity. Evidence suggests that lipid micro-emboli associated with the retransfusion of the shed blood are the predominant causes of the neurocognitive disorders. We have developed a novel acoustophoretic filtration system that can remove lipids from blood at clinically relevant flow rates. Unlike other acoustophoretic separation systems, this ultrasound technology works at the macroscale, and is therefore able to process larger flow rates than typical micro-electromechanical system (MEMS) scale acoustophoretic separation devices. In this work, we have first demonstrated the systematic design of the acoustic device and its optimization, followed by examining the feasibility of the device to filter lipids from the system. Then, we demonstrate the effects of the acoustic waves on the shed blood; examining hemolysis using both haptoglobin formation and lactate dehydrogenase release, as well as the potential of platelet aggregation or inflammatory cascade activation. Finally, in a porcine surgical model, we determined the potential viability of acoustic trapping as a blood filtration technology, as the animal responded to redelivered blood by increasing both systemic and mean arterial blood pressure.

Influence of thermally oxidized vegetable oils and animal fats on intestinal barrier function and immune variables in young pigs.

PubMed

Liu, P; Kerr, B J; Weber, T E; Chen, C; Johnston, L J; Shurson, G C

2014-07-01

To evaluate the effect of feeding thermally oxidized lipids on metabolic oxidative status, gut barrier function, and immune response of young pigs, 108 barrows (6.67 ± 0.03 kg BW) were assigned to 12 dietary treatments in a 4 × 3 factorial arrangement in addition to a corn-soybean meal control diet. Main effects were 4 lipid sources (corn oil [CN], canola oil [CA], poultry fat [PF], and tallow [TL]) and 3 oxidation levels (original lipids [OL], slow oxidation [SO] of lipids heated for 72 h at 95°C, or rapid oxidation [RO] of lipids heated for 7 h at 185°C). Pigs were provided ad libitum access to diets for 28 d followed by controlled feed intake for 10 d. After a 24-h fast on d 38, serum was collected and analyzed for α-tocopherol (α-T), thiobarbituric acid reactive substances (TBARS), endotoxin, haptoglobin, IgA, and IgG. On the same day following serum collection, lactulose and mannitol were fed and subsequently measured in the urine to evaluate gut permeability. There was a source × peroxidation interaction for serum α-T concentration where pigs fed SO or RO had decreased (P < 0.05) serum α-T concentration compared with pigs fed OL in CA and CN diets but not in pigs fed PF and TL diets. There was no source × peroxidation interaction for serum TBARS, but among all lipid sources, pigs fed SO or RO lipids had increased (P < 0.05) serum TBARS compared with pigs fed OL. In addition, pigs fed CN or CA had greater (P < 0.05) serum TBARS compared with pigs fed PF or TL diets. There were no lipid source × peroxidation level interaction or lipid source or peroxidation level effects on serum endotoxin, haptoglobin, IgA, or IgG. Pigs fed lipid supplemented diets tended to have increased serum endotoxin (P = 0.06), IgA (P = 0.10), and IgG (P = 0.09) compared with pigs fed the control diet. There were no lipid source × peroxidation level interaction or lipid source or peroxidation level effects on urinary TBARS and lactulose to mannitol ratio. Compared with pigs fed the control diet, pigs fed diets containing lipids had a lower lactulose to mannitol ratio (P < 0.01). In conclusion, feeding weaning pigs diets containing 10% thermally oxidized lipids for 38 d, especially vegetable oils containing greater concentrations of PUFA, appeared to impair oxidative status but had little influence on gut barrier function or serum immunity parameters.

Effect of dietary protein and lipid levels on growth, nutrient utilization and whole-body composition of blue gourami, Trichogaster trichopterus fingerlings.

PubMed

Mohanta, K N; Subramanian, S; Korikanthimath, V S

2013-02-01

Nine semi-purified diets were prepared with three levels each of protein (300, 350 and 400 g/kg) and lipid (60, 80 and 100 g/kg) and fed ad libitum to Trichogaster trichopterus fingerlings (0.61 ± 0.03 g) in triplicate groups (10 fish/replicate) for 90 days to determine optimum dietary protein and lipid levels. Twenty-seven flow-through fibre-reinforced plastic tanks (200 l capacity each with 100 l of water) were used for rearing the fish. The dietary protein, lipid and their interactions had significant effects (p < 0.05) on weight gain, feed conversion ratio, specific growth rate, nutrient retention and digestibility, but not on hepato- and viscerosomatic indexes (p > 0.05). Dietary protein and the interaction of protein with lipid had significant effect (p < 0.05) on whole-body dry matter, lipid and energy contents, but not on protein and ash contents (p > 0.05). But, the dietary lipid had significant (p < 0.05) effect on whole-body dry matter, protein, lipid and energy contents except the ash contents (p > 0.05). For each level of dietary protein, the increase in dietary lipid resulted significant increase (p < 0.05) in whole-body lipid contents without affecting the protein and ash contents (p > 0.05). Based on better growth and dietary performances, the optimum dietary protein and lipid levels of blue gourami fingerling are 350 and 80 g/kg diet respectively. © 2011 Blackwell Verlag GmbH.

Microfluidics for producing poly (lactic-co-glycolic acid)-based pharmaceutical nanoparticles.

PubMed

Li, Xuanyu; Jiang, Xingyu

2017-12-24

Microfluidic chips allow the rapid production of a library of nanoparticles (NPs) with distinct properties by changing the precursors and the flow rates, significantly decreasing the time for screening optimal formulation as carriers for drug delivery compared to conventional methods. The batch-to-batch reproducibility which is essential for clinical translation is achieved by precisely controlling the precursors and the flow rate, regardless of operators. Poly (lactic-co-glycolic acid) (PLGA) is the most widely used Food and Drug Administration (FDA)-approved biodegradable polymers. Researchers often combine PLGA with lipids or amphiphilic molecules to assemble into a core/shell structure to exploit the potential of PLGA-based NPs as powerful carriers for cancer-related drug delivery. In this review, we discuss the advantages associated with microfluidic chips for producing PLGA-based functional nanocomplexes for drug delivery. These laboratory-based methods can readily scale up to provide sufficient amount of PLGA-based NPs in microfluidic chips for clinical studies and industrial-scale production. Copyright © 2017. Published by Elsevier B.V.

On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging

PubMed Central

Hettiarachchi, Kanaka; Talu, Esra; Longo, Marjorie L.; Dayton, Paul A.; Lee, Abraham P.

2007-01-01

This paper presents a new manufacturing method to generate monodisperse microbubble contrast agents with polydispersity index (σ) values of <2% through microfluidic flow-focusing. Micron-sized lipid shell-based perfluorocarbon (PFC) gas microbubbles for use as ultrasound contrast agents were produced using this method. The poly(dimethylsiloxane) (PDMS)-based devices feature expanding nozzle geometry with a 7 μm orifice width, and are robust enough for consistent production of microbubbles with runtimes lasting several hours. With high-speed imaging, we characterized relationships between channel geometry, liquid flow rate Q, and gas pressure P in controlling bubble sizes. By a simple optimization of the channel geometry and Q and P, bubbles with a mean diameter of <5 μm can be obtained, ideal for various ultrasonic imaging applications. This method demonstrates the potential of microfluidics as an efficient means for custom-designing ultrasound contrast agents with precise size distributions, different gas compositions and new shell materials for stabilization, and for future targeted imaging and therapeutic applications. PMID:17389962

Liver, pancreas and biliary tract enhanced lipoperoxidation products in pure pancreatic juice: evidence for organ-specific oxidative stress in chronic pancreatitis.

PubMed

Santini, S A; Spada, C; Bononi, F; Foschia, F; Mutignani, M; Perri, V; Giardina, B; Silveri, N Gentiloni; Costamagna, G

2003-12-01

Oxygen-free radicalscan play a role in the development of chronic pancreatitis, altering the redox state with damage of cell constituents and decrease in antioxidant defences. To measure levels of lipoperoxidation products, conjugated dienes and lipid hydroperoxides, in pure pancreatic juice and serum of chronic pancreatitis patients and compare them to that in controls. To investigate a possible correlation with serum indexes of pancreatic inflammation (amylase and lipase). Pancreatic juice was collected during ERCP, after secretin stimulation, in 20 patients with chronic pancreatitis and 11 controls with biliary diseases. Lipid hydroperoxide levels were determined with FOX2 method and measured as absorbance at 560 nm. Conjugated diene levels were measured using second-derivative spectroscopy. No substantial difference was present in serum levels of lipid hydroperoxides, conjugated dienes (in both isomeric forms) and isomer-ratio values between those of patients with chronic pancreatitis and controls. In pancreatic juice, there was a significant increase in lipid hydroperoxides and conjugated dienes levels (especially trans-trans isomers) in chronic pancreatitis patients compared with controls, with a decrease in cis-trans isomers and a significant difference in isomer-ratio values. Increased levels of lipid hydroperoxides and conjugated dienes in the pancreatic juice of chronic pancreatitis patients is indicative of an enhanced lipoperoxidation and antioxidants consumption in pancreatic tissue, confirmed by the decreased isomer-ratio values as an indirect index of decreased antioxidant capacity. The lack of significant difference in conjugated diene and lipid hydroperoxide levels in the serum of chronic pancreatitis patients versus that of controls suggests an oxidative stress limited to pancreatic tissue and indicative of an organ-specific pathology, confirmed by the parallel behaviour of oxidative parameters (lipid hydroperoxides and conjugated dienes) and indexes of pancreatic inflammation (amylase and lipase).

Investigation on Large Molecule Permeation through Liposome Lipid Bilayer Induced by Microplasma Irradiation

NASA Astrophysics Data System (ADS)

Nagaiwa, Hidenori; Aibara, Daijiro; Ikeda, Yoshihisa; Motomura, Hideki; Kido, Yugo; Satoh, Susumu; Tachibana, Kunihide; Jinno, Masahumi

2015-09-01

The authors have been developing a novel gene transfection method using microplasma irradiation. In order to clarify the mechanism of large molecule permeation process through the lipid bilayer, plasma induced outflow of hydrophilic fluorescent dye molecules, which were encapsulated in the liposome, was observed. By microplasma irradiation on the liposome suspension, the dyes flowed out from the inside of the liposomes. The outflow of the dyes was enhanced by longer plasma irradiation time. Investigation of the outflow mechanism, i.e. permeation enhancement of the lipid bilayer or burst of the liposome, is under progress. This work was partly supported by JSPS KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Number 25108509,15H00896) and a grant from Ehime University.

[The use of white and yellow turpentine baths with diabetic patients].

PubMed

Davydova, O B; Turova, E A; Golovach, A V

1998-01-01

In patients with insulin-dependent diabetes mellitus while and yellow turpentine baths produced a positive effect on carbohydrate metabolism. White baths were more effective in respect to lipid metabolism, blood viscosity, produced a good effect on plasmic hemocoagulation factors. Both while and yellow turpentine baths were beneficial for capillary blood flow: initially high distal blood flow in patients with prevailing distal polyneuropathy decreased while in patients with macroangiopathy initially subnormal blood flow increased. Both white and yellow turpentine baths promoted better pulse blood filling of the lower limbs and weaker peripheral resistance of large vessels. In patients with non-insulin-dependent diabetes mellitus white and yellow turpentine baths contributed to normalization of carbohydrate metabolism. Yellow baths were more effective in lowering lipids. White baths induced inhibition of platelet aggregation but had no effect on coagulation, yellow baths promoted a reduction of fibrinogen but had no effect on platelet aggregation. Yellow baths produced more pronounced effect than white ones on blood viscosity and microcirculation. Both yellow and white baths stimulated pulse blood filling, corrected peripheral resistance of large and small vessels of the lower limbs.

Bioremediation of Cephalexin with non-living Chlorella sp., biomass after lipid extraction.

PubMed

Angulo, E; Bula, L; Mercado, I; Montaño, A; Cubillán, N

2018-06-01

In this work, the removal of the Cephalexin by Chlorella sp., nonliving modified by extraction of lipids was evaluated. First, the microalga was grown to completing 20 days and later, the biomass of crop was centrifuged and the extraction of lipids was performed. Two adsorption experiments were performed: (1) with nonliving Chlorella sp. (control), and (2) the obtained biomass after lipid extraction. The high antibiotic removal, 71.19% and 82.77% (control), were obtained at the lowest initial concentration. The contact time between the biosorbent and the antibiotic was 2 h. The adsorption isotherm follows the Freundlich model and the obtained maximum absorption capacity was 63.29 mg of antibiotic/g of biosorbent for lipid-extracted biomass, while the control follows best to the Langmuir model with 129.87 mg/g in maximum absorption capacity. In summary, this biosorbent provides a potential alternative in the removal of Cephalexin. Copyright © 2018 Elsevier Ltd. All rights reserved.

Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion, and degranulation.

PubMed

Wanten, G J; Geijtenbeek, T B; Raymakers, R A; van Kooyk, Y; Roos, D; Jansen, J B; Naber, A H

2000-01-01

To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.

Plasma lipids, lipoprotein metabolism and HDL lipid transfers are equally altered in metabolic syndrome and in type 2 diabetes.

PubMed

Silva, Vanessa M; Vinagre, Carmen G C; Dallan, Luis A O; Chacra, Ana P M; Maranhão, Raul C

2014-07-01

Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40-70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [(3)H]-triolein ([(3)H]-TAG) and [(14)C]-cholesteryl esters ([(14)C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p < 0.05). Fractional clearance rate (FCR, in min(1)) of [(3)H]-TAG and [(14)C]-CE were equal in T2DM (0.008 ± 0.018; 0.005 ± 0.024) and MetS (0.010 ± 0.016; 0.006 ± 0.013), and both were reduced compared to controls. The transfer of non-esterified cholesterol, phospholipids and triacylglycerols to HDL was higher in MetS and T2DM than in controls (p < 0.01). Cholesteryl ester transfer and HDL size were equal in all groups. Results imply that MetS is equal to poorly controlled T2DM concerning the disturbances of plasma lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases.

Analyzing and Understanding Lipids of Yeast: A Challenging Endeavor.

PubMed

Kohlwein, Sepp D

2017-05-01

Lipids are essential biomolecules with diverse biological functions, ranging from building blocks for all biological membranes to energy substrates, signaling molecules, and protein modifiers. Despite advances in lipid analytics by mass spectrometry, the extraction and quantitative analysis of the diverse classes of lipids are still an experimental challenge. Yeast is a model organism that provides several advantages for studying lipid metabolism, because most biosynthetic pathways are well described and a great deal of information is available on the regulatory mechanisms that control lipid homeostasis. In addition, the composition of yeast lipids is much less complex than that of mammalian lipids, making yeast an excellent reference system for studying lipid-associated cell functions. © 2017 Cold Spring Harbor Laboratory Press.

Diffusion in Single Supported Lipid Bilayers

NASA Astrophysics Data System (ADS)

Armstrong, C. L.; Trapp, M.; Rheinstädter, M. C.

2011-03-01

Despite their potential relevance for the development of functionalized surfaces and biosensors, the study of single supported membranes using neutron scattering has been limited by the challenge of obtaining relevant dynamic information from a sample with minimal material. Using state of the art neutron instrumentation we have, for the first time, modeled lipid diffusion in single supported lipid bilayers. While we find that the diffusion coefficient for the single bilayer system is comparable to a multi-lamellar lipid system, the molecular mechanism for lipid motion in the single bilayer is a continuous diffusion process with no sign of the flow-like ballistic motion reported in the stacked membrane system. In the future, these membranes will be used to hold and align proteins, mimicking physiological conditions enabling the study of protein structure, function and interactions in relevant and highly topical membrane/protein systems with minimal sample material. C.L. Armstrong, M.D. Kaye, M. Zamponi, E. Mamontov, M. Tyagi, T. Jenkins and M.C. Rheinstädter, Soft Matter Communication, 2010, Advance Article, DOI: 10.1039/C0SM00637H

Remote Control of Tissue Interactions via Engineered Photo-switchable Cell Surfaces

NASA Astrophysics Data System (ADS)

Luo, Wei; Pulsipher, Abigail; Dutta, Debjit; Lamb, Brian M.; Yousaf, Muhammad N.

2014-09-01

We report a general cell surface molecular engineering strategy via liposome fusion delivery to create a dual photo-active and bio-orthogonal cell surface for remote controlled spatial and temporal manipulation of microtissue assembly and disassembly. Cell surface tailoring of chemoselective functional groups was achieved by a liposome fusion delivery method and quantified by flow cytometry and characterized by a new cell surface lipid pull down mass spectrometry strategy. Dynamic co-culture spheroid tissue assembly in solution and co-culture tissue multilayer assembly on materials was demonstrated by an intercellular photo-oxime ligation that could be remotely cleaved and disassembled on demand. Spatial and temporal control of microtissue structures containing multiple cell types was demonstrated by the generation of patterned multilayers for controlling stem cell differentiation. Remote control of cell interactions via cell surface engineering that allows for real-time manipulation of tissue dynamics may provide tools with the scope to answer fundamental questions of cell communication and initiate new biotechnologies ranging from imaging probes to drug delivery vehicles to regenerative medicine, inexpensive bioreactor technology and tissue engineering therapies.

Increased Flow of Fatty Acids toward β-Oxidation in Developing Seeds of Arabidopsis Deficient in Diacylglycerol Acyltransferase Activity or Synthesizing Medium-Chain-Length Fatty Acids1

PubMed Central

Poirier, Yves; Ventre, Giovanni; Caldelari, Daniela

1999-01-01

Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid β-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0.06 mg g−1 dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward β-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via β-oxidation and that a considerable flow toward β-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids. PMID:10594123

Increased flow of fatty acids toward beta-oxidation in developing seeds of Arabidopsis deficient in diacylglycerol acyltransferase activity or synthesizing medium-chain-length fatty acids.

PubMed

Poirier, Y; Ventre, G; Caldelari, D

1999-12-01

Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid beta-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0. 06 mg g(-1) dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward beta-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via beta-oxidation and that a considerable flow toward beta-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids.

Parenteral lipid administration to very-low-birth-weight infants--early introduction of lipids and use of new lipid emulsions: a systematic review and meta-analysis.

PubMed

Vlaardingerbroek, Hester; Veldhorst, Margriet A B; Spronk, Sandra; van den Akker, Chris H P; van Goudoever, Johannes B

2012-08-01

The use of intravenous lipid emulsions in preterm infants has been limited by concerns regarding impaired lipid tolerance. As a result, the time of initiation of parenteral lipid infusion to very-low-birth-weight (VLBW) infants varies widely among different neonatal intensive care units. However, lipids provide energy for protein synthesis and supply essential fatty acids that are necessary for central nervous system development. The objective was to summarize the effects of initiation of lipids within the first 2 d of life and the effects of different lipid compositions on growth and morbidities in VLBW infants. A systematic review and meta-analysis of publications identified in a search of PubMed, EMBASE, and Cochrane databases was undertaken. Randomized controlled studies were eligible if information on growth was available. The search yielded 14 studies. No differences were observed in growth or morbidity with early lipid initiation. We found a weak favorable association of non-purely soybean-based emulsions with the incidence of sepsis (RR: 0.75; 95% CI: 0.56, 1.00). The initiation of lipids within the first 2 d of life in VLBW infants appears to be safe and well tolerated; however, beneficial effects on growth could not be shown for this treatment nor for the type of lipid emulsion. Emulsions that are not purely soybean oil-based might be associated with a lower incidence of sepsis. Large-scale randomized controlled trials in preterm infants are warranted to determine whether early initiation of lipids and lipid emulsions that are not purely soybean oil-based results in improved long-term outcomes.

Adipose differentiation-related protein regulates lipids and insulin in pancreatic islets

PubMed Central

Faleck, D. M.; Ali, K.; Roat, R.; Graham, M. J.; Crooke, R. M.; Battisti, R.; Garcia, E.; Ahima, R. S.

2010-01-01

The excess accumulation of lipids in islets is thought to contribute to the development of diabetes in obesity by impairing β-cell function. However, lipids also serve a nutrient function in islets, and fatty acids acutely increase insulin secretion. A better understanding of lipid metabolism in islets will shed light on complex effects of lipids on β-cells. Adipose differentiation-related protein (ADFP) is localized on the surface of lipid droplets in a wide range of cells and plays an important role in intracellular lipid metabolism. We found that ADFP was highly expressed in murine β-cells. Moreover, islet ADFP was increased in mice on a high-fat diet (3.5-fold of control) and after fasting (2.5-fold of control), revealing dynamic changes in ADFP in response to metabolic cues. ADFP expression was also increased by addition of fatty acids in human islets. The downregulation of ADFP in MIN6 cells by antisense oligonucleotide (ASO) suppressed the accumulation of triglycerides upon fatty acid loading (56% of control) along with a reduction in the mRNA levels of lipogenic genes such as diacylglycerol O-acyltransferase-2 and fatty acid synthase. Fatty acid uptake, oxidation, and lipolysis were also reduced by downregulation of ADFP. Moreover, the reduction of ADFP impaired the ability of palmitate to increase insulin secretion. These findings demonstrate that ADFP is important in regulation of lipid metabolism and insulin secretion in β-cells. PMID:20484013

Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently

PubMed Central

Koynova, Rumiana; MacDonald, Robert C.

2007-01-01

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30 min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserine or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/ phosphatidylserine/cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, ∼40-45°C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer “frustration” which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored curvature elastic energy in a “frustrated” bilayer seems to be comparable to the binding energy between cationic lipid and DNA, the balance between these two energies could play a significant role in the lipoplex-membrane interactions and DNA release energetics. PMID:17559800

Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koynova, Rumiana; MacDonald, Robert C.

2010-01-18

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30-min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserinemore » or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine /cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, {approx} 40-45 C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer 'frustration' which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored curvature elastic energy in a 'frustrated' bilayer seems to be comparable to the binding energy between cationic lipid and DNA, the balance between these two energies could play a significant role in the lipoplex-membrane interactions and DNA release energetics.« less

Effect of health information technology interventions on lipid management in clinical practice: a systematic review of randomized controlled trials.

PubMed

Aspry, Karen E; Furman, Roy; Karalis, Dean G; Jacobson, Terry A; Zhang, Audrey M; Liptak, Gregory S; Cohen, Jerome D

2013-01-01

Large gaps in lipid treatment and medication adherence persist in high-risk outpatients in the United States. Health information technology (HIT) is being applied to close quality gaps in chronic illness care, but its utility for lipid management has not been widely studied. To perform a qualitative review of the impact of HIT interventions on lipid management processes of care (screening or testing; drug initiation, titration or adherence; or referrals) or clinical outcomes (percent at low density lipoprotein cholesterol goal; absolute lipid levels; absolute risk scores; or cardiac hospitalizations) in outpatients with coronary heart disease or at increased risk. PubMed and Google Scholar databases were searched using Medical Subject Headings related to clinical informatics and cholesterol or lipid management. English language articles that described a randomized controlled design, tested at least one HIT tool in high risk outpatients, and reported at least 1 lipid management process measure or clinical outcome, were included. Thirty-four studies that enrolled 87,874 persons were identified. Study ratings, outcomes, and magnitude of effects varied widely. Twenty-three trials reported a significant positive effect from a HIT tool on lipid management, but only 14 showed evidence that HIT interventions improve clinical outcomes. There was mixed evidence that provider-level computerized decision support improves outcomes. There was more evidence in support of patient-level tools that provide connectivity to the healthcare system, as well as system-level interventions that involve database monitoring and outreach by centralized care teams. Randomized controlled trials show wide variability in the effects of HIT on lipid management outcomes. Evidence suggests that multilevel HIT approaches that target not only providers but include patients and systems approaches will be needed to improve lipid treatment, adherence and quality. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the Endocytosis Pathway Analysis and Intracellular Localization

PubMed Central

Wang, Zhao; Luo, Ting; Cao, Amin; Sun, Jingjing

2018-01-01

Using renewable and biocompatible natural-based resources to construct functional biomaterials has attracted great attention in recent years. In this work, we successfully prepared a series of steroid-based cationic lipids by integrating various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile and efficient synthetic approach. The plasmid DNA (pDNA) binding affinity of the steroid-based cationic lipids, average particle sizes, surface potentials, morphologies and stability of the steroid-based cationic lipids/pDNA lipoplexes were disclosed to depend largely on the steroid skeletons. Cellular evaluation results revealed that cytotoxicity and gene transfection efficiency of the steroid-based cationic lipids in H1299 and HeLa cells strongly relied on the steroid hydrophobes. Interestingly, the steroid lipids/pDNA lipoplexes inclined to enter H1299 cells mainly through caveolae and lipid-raft mediated endocytosis pathways, and an intracellular trafficking route of “lipid-raft-mediated endocytosis→lysosome→cell nucleic localization” was accordingly proposed. The study provided possible approach for developing high-performance steroid-based lipid gene carriers, in which the cytotoxicity, gene transfection capability, endocytosis pathways, and intracellular trafficking/localization manners could be tuned/controlled by introducing proper steroid skeletons/hydrophobes. Noteworthy, among the lipids, Cho-Arg showed remarkably high gene transfection efficacy, even under high serum concentration (50% fetal bovine serum), making it an efficient gene transfection agent for practical application. PMID:29373505

Lipid partitioning at the nuclear envelope controls membrane biogenesis

PubMed Central

Barbosa, Antonio Daniel; Sembongi, Hiroshi; Su, Wen-Min; Abreu, Susana; Reggiori, Fulvio; Carman, George M.; Siniossoglou, Symeon

2015-01-01

Partitioning of lipid precursors between membranes and storage is crucial for cell growth, and its disruption underlies pathologies such as cancer, obesity, and type 2 diabetes. However, the mechanisms and signals that regulate this process are largely unknown. In yeast, lipid precursors are mainly used for phospholipid synthesis in nutrient-rich conditions in order to sustain rapid proliferation but are redirected to triacylglycerol (TAG) stored in lipid droplets during starvation. Here we investigate how cells reprogram lipid metabolism in the endoplasmic reticulum. We show that the conserved phosphatidate (PA) phosphatase Pah1, which generates diacylglycerol from PA, targets a nuclear membrane subdomain that is in contact with growing lipid droplets and mediates TAG synthesis. We find that cytosol acidification activates the master regulator of Pah1, the Nem1-Spo7 complex, thus linking Pah1 activity to cellular metabolic status. In the absence of TAG storage capacity, Pah1 still binds the nuclear membrane, but lipid precursors are redirected toward phospholipids, resulting in nuclear deformation and a proliferation of endoplasmic reticulum membrane. We propose that, in response to growth signals, activation of Pah1 at the nuclear envelope acts as a switch to control the balance between membrane biogenesis and lipid storage. PMID:26269581

Observation of non-linear biomass-capacitance correlations: reasons and implications for bioprocess control.

PubMed

Maskow, Thomas; Röllich, Anita; Fetzer, Ingo; Yao, Jun; Harms, Hauke

2008-09-15

Electrical capacitance has been discussed as a real time measure for living biomass concentration in technical bioreactors such as brewery (fermentation) tanks. Commonly, a linear correlation between biomass concentration and capacitance is assumed. While following the growth and subsequent lipid formation of the yeast Arxula adeninivorans we observed non-linearity between biomass concentration and capacitance. Capacitance deviation from linearity coincided with incipient lipid formation and depended on the intracellular lipid content. As the extent of deviation between capacitance and biomass concentration was proportional to the lipid concentration, it was considered as a quantitative measure of intracellular product formation. The correlation between shifts in dielectric relaxation (summarized as characteristic frequency of the Cole-Cole equation) and lipid content could not be explained by interfacial polarization on the lipid droplets alone. However, the parameters of the Cole-Cole equation were found to be a clear indicator for different phases of growth and lipid production. Integrating all results in a redundancy analysis (RDA), we were able to accurately describe the formation of cellular lipid inclusions. Our measurements are thus potentially valuable as components of future bioprocess control strategies targeting intracellular products such as proteins or biopolyesters.

Lipids in RA: What do they mean?

PubMed Central

Plutzky, Jorge; Liao, Katherine P.

2018-01-01

In rheumatoid arthritis (RA), lipid levels are dynamic and can fluctuate along with changes in inflammation. A reduction in inflammation, most commonly as a result of disease modifying anti-rheumatic drug (DMARD) therapy, is associated with increases in total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). A similar pattern of increased lipids is observed across biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs), suggesting that the main driver of changes in lipids is inflammation rather than individual treatments. In this review, we discuss new evidence shedding light on the potential mechanism underlying changes in lipid levels observed with changes in inflammation. Measured lipid levels in the blood are a result of a balance between synthesis and catabolism or absorption. Recent human studies in active RA show that the catabolic rates of lipids are higher than expected compared to expected rates in the general population. DMARD therapy appears to allow a return to baseline lower catabolic rates, resulting in an apparent increase in lipids. Additionally, we discuss findings from the recently published randomized controlled clinical trial, Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS). Findings from CANTOS provide further evidence for tighter control of inflammation to reduce cardiovascular risk in RA. PMID:29464513

Geochemical Influence on Microbial Diversity in the Warm, Salty, Stinking Spring, Utah, USA

NASA Astrophysics Data System (ADS)

Spear, J. R.

2012-12-01

Little is known of the geochemistry and microbiology in the Stinking Springs, a sulfidic, saline, warm spring northeast of the Great Salt Lake, Utah. The International Geobiology Course of 2012 investigated the geochemistry, lipid abundances, dissolved inorganic carbon (DIC) uptake rates and microbial diversity on different kinds of samples from a number of locations in the spring. The measured pH, temperature, salinity, and sulfide concentration along the 100 m flow path ranged from 6.64-7.77, 40-28° C, 2.9-2.2%, and 250 μM - negligible, respectively. Five sites were selected along the flow path and within each site microbial mats were sub-sampled according to their morphological characteristics; a range from floating to streamer-style in zones of higher flow rates to highly-layered mats in low- or sheet-flow zones. Geochemical characterization of the above plus metals, anions and cations were conducted at each site. Genomic DNA was extracted from each microbial sample / layer, and 16S rRNA genes were amplified and subjected to pyrosequencing. Fatty acids and pigments were extracted from the mat samples / layers and analyzed by liquid chromatography and mass spectrometry for lipid / pigment composition. Bicarbonate uptake rates for mat samples / layers were determined with 24 hour light and dark incubations of 13HCO3-spiked spring water. Microbial diversity varied by site and was generally high in all three domains of life with phototrophs, sulfur oxidizers, sulfate reducers, methanogens, and other bacteria / archaea identified by 16S rRNA gene sequence. Diatoms, identified by both microscopy and lipid analyses were found to increase in abundance with distance from the source. Methanogens were generally more abundant in deeper mat laminae and underlying sediments. Photoheterotrophs were found in all mat layers. Microbial diversity increased significantly with depth at most sites. In addition, two distinct microbial streamers were also identified and characterized at the two fast flowing sites. These two streamer varieties were dominated by either cyanobacteria or flavobacteria. Bicarbonate uptake in the light ranged from 0-2.1%/day with maximum rates found in floating, surface mats. Uptake in the dark ranged from 0-0.3%/day and was higher in lower layers. Both 16S rRNA analysis and pigment extractions showed no correlation between high autotrophic rates and presence of cyanobacteria or chlorophyll A. Lipid analysis showed no correlation between bicarbonate uptake and diatom abundance. The results suggest that carbon cycling in the various kinds of mats sampled is dominated by heterotrophs and anaerobic phototrophs despite abundant cyanobacteria and diatoms. A large depletion in sulfate from 16 mM to almost zero combined with low concentrations of measured sulfide and presence of elemental sulfur crystals in most mat samples indicate that the mats are a major sink of S in the system. Overall, our geochemical, genetic, lipid and bicarbonate analysis suggests that the physical and geochemical environment was more predictive of the community composition than mat morphology.

Screening of aphrodisiac property in sea slug, Aplysia dactylomela.

PubMed

Hashim, Ridzwan; Roslan, Noor Atika Elliyana Mohd; Zulkipli, Farah Hanis; Daud, Jamaluddin Mohd

2014-09-01

To evaluate the aphrodisiac property of Aplysia dactylomela (A. dactylomelan), locally known as 'dugu-dugu', which is one of the sea slug species. Two types of extractions were used; aqueous and lipid. Three doses of each A. dactylomelan extract, respectively; 50, 100, 200 mg/kg were administered (i.p.) to male mice for mounting behavior test. Sildenafil citrate or Viagra® (5 mg/kg) being positive control while negative control received saline solution. The animals treated with lipid extract at the respective dose exhibited mounting behavior, but the mounting frequency decreased at higher doses (100 and 200 mg/kg). However, all doses of aqueous extract did not show any mounting behavior. Meanwhile, in all doses of lipid extracts administered displayed significant difference (P<0.05) from the positive control. Despite this, only the lipid extract of 50 mg/kg showed significant difference (P<0.05) with negative control. This signifies that lipid extracts especially in dose 50 mg/kg have a substantial effect of aphrodisiac property. In addition, the presence of steroids was detected in the phytochemical screening of lipid extract. The findings from this study provides preliminary scientific evidence that A. dactylomela could be used as an alternative medication of natural product for promoting sexual activity in men. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Small particle size lipid emulsions, satiety and energy intake in lean men.

PubMed

Chan, Y K; Budgett, S C; MacGibbon, A K; Quek, S Y; Kindleysides, S; Poppitt, S D

2017-02-01

Lipid emulsions have been proposed to suppress hunger and food intake. Whilst there is no consensus on optimal structural properties or mechanism of action, small particle size (small-PS) stable emulsions may have greatest efficacy. Fabuless®, a commercial lipid emulsion reported in some studies to decrease energy intake (EI), is a small-PS, 'hard' fat emulsion comprising highly saturated palm oil base (PS, 82nm). To determine whether small-PS dairy lipid emulsions can enhance satiety, firstly, we investigated 2 'soft' fat dairy emulsions generated using dairy and soy emulsifying agents (PS, 114nm and 121nm) and a non-emulsified dairy control. Secondly, we investigated a small-PS palmolein based 'hard' fat emulsion (fractionated palm oil, PS, 104nm) and non-emulsified control. This was a 6 arm, randomized, cross-over study in 18 lean men, with test lipids delivered in a breakfast meal: (i) Fabuless® emulsion (F EM ); (ii) dairy emulsion with dairy emulsifier (DE DE ); (iii) dairy emulsion with soy lecithin emulsifier (DE SE ); (iv) dairy control (DC ON ); (v) palmolein emulsion with dairy emulsifier (PE DE ); (vi) palmolein control (PC ON ). Participants rated postprandial appetite sensations using visual analogue scales (VAS), and ad libitum energy intake (EI) was measured at a lunch meal 3.5h later. Dairy lipid emulsions did not significantly alter satiety ratings or change EI relative to dairy control (DE DE , 4035kJ; DE SE , 3904kJ; DC ON , 3985kJ; P>0.05) nor did palm oil based emulsion relative to non-emulsified control (PE DE, 3902 kJ; PC ON, 3973kJ; P>0.05). There was no evidence that small-PS dairy lipid emulsions or commercial Fabuless altered short-term appetite or food intake in lean adults. Copyright © 2016. Published by Elsevier Inc.

Comparative effects of intraduodenal protein and lipid on ghrelin, peptide YY, and leptin release in healthy men.

PubMed

Ullrich, Sina S; Otto, Bärbel; Hutchison, Amy T; Luscombe-Marsh, Natalie D; Horowitz, Michael; Feinle-Bisset, Christine

2015-02-15

Intraduodenal infusion of lipid or protein potently reduces subsequent energy intake. There is evidence that the underlying mechanisms differ significantly between the two nutrients. While intraduodenal lipid stimulates glucagon-like peptide-1 and CCK much more than protein, the release of insulin and glucagon is substantially greater in response to protein. Ghrelin and PYY are both involved in short-term regulation, while leptin is a long-term regulator, of energy balance; the acute effects of nutrients on leptin release are unclear. We investigated the comparative effects of intraduodenal lipid and protein on plasma ghrelin, PYY, and leptin concentrations. Thirteen lean, young men received 90-min intraduodenal infusions of protein (whey hydrolysate) or lipid (long-chain triglyceride emulsion) at a rate of 3 kcal/min, or saline control, on three separate days. Blood samples were collected at baseline and regularly during infusions. Both lipid and protein potently suppressed plasma ghrelin compared with control (both P < 0.001), with no difference between them. While both lipid and protein stimulated plasma PYY (P < 0.001), the effect of lipid was substantially greater than that of protein (P < 0.001). Neither intraduodenal lipid nor protein affected plasma leptin. In conclusion, intraduodenal lipid and protein have discrepant effects on the release of PYY, but not ghrelin. When considered with our previous findings, it appears that, with the exception of ghrelin, the energy intake-suppressant effects of lipid and protein are mediated by different mechanisms. Copyright © 2015 the American Physiological Society.

Experimental analysis of behavior in nanobubbles using echograms under ultrasound exposure

NASA Astrophysics Data System (ADS)

Wada, Hikaru; Koido, Jun; Miyazawa, Shinya; Mochizuki, Takashi; Masuda, Kohji; Unga, Johan; Oda, Yusuke; Suzuki, Ryo; Maruyama, Kazuo

2016-07-01

Although we have reported our attempts to actively control microbubbles in flow using acoustic radiation force for future drug delivery systems, the microbubbles we used are not applicable for in vivo experiments. Thus, we examined two types of nanobubble with a drug-retaining function. Because the nanobubbles are invisible in a conventional optical observation, we observed the behavior of nanobubbles using ultrasound images (echograms). First, we found the optimal settings of echography to guarantee the relationship between the brightness variation and lipid concentration of nanobubbles. Then, we derived the destructive coefficient using two types of path under continuous ultrasound exposure of 5 MHz. Results indicate that the controllability is related to the construction of nanobubbles and the spatial distribution of the ultrasound field. We realized that the design of the ultrasound field is important with Bubble A, whereas the frequency of ultrasound emission needs to be discussed with Bubble B.

Implications of lipid raft disintegration: enhanced anti-inflammatory macrophage phenotype.

PubMed

Cuschieri, Joseph

2004-08-01

Lipid rafts are membrane microdomains characterized by an enriched cholesterol environment and appear to serve as a platform for signaling. Their role within the macrophage during endotoxin exposure is unknown. THP-1 cells were subjected to lipopolysaccharide stimulation with or without methyl-beta-cyclodextrin (MbetaCD) pretreatment, a cholesterol depleting agent. Cell surface expression of toll-like receptor-4 (TLR4) and platelet-activating factor receptor (PAFr) was determined by flow cytometry. Membrane receptor components and activation of the mitogen-activated protein kinases (MAPK) was determined from lipid raft and cellular protein by immunoblot. Inflammatory mediator production was determined from harvested supernatants by enzyme-linked immunosorbent assay. Surface expression of TLR4 and PAFr was not affected by MbetaCD. Lipopolysaccharide stimulation led to TLR4 mobilization to lipid rafts, MAPK activation, and inflammatory mediator production. Pretreatment with MbetaCD did not affect TLR4 mobilization to lipid rafts, but did result in lost lipid raft expression of the PAFr coupled G-protein, Galpha1. MbetaCD treatment led to selective attenuation of MAPK activation through ERK 1/2. This dysregulated signaling was associated with attenuated production of tumor necrosis factor-alpha, but increased production of interleukin-10. Lipid raft disintegration results in lost expression of Galpha1, dysregulated MAPK signaling, and selective anti-inflammatory mediator production. Therefore, modulation of lipid raft cholesterol content may represent a potential mechanism for regulation of macrophage phenotypic differentiation. Copyright 2004 Elsevier Inc.

Enhancement of neutral lipid productivity in the microalga Isochrysis affinis Galbana (T-Iso) by a mutation-selection procedure.

PubMed

Bougaran, Gaël; Rouxel, Catherine; Dubois, Nolwenn; Kaas, Raymond; Grouas, Sophie; Lukomska, Ewa; Le Coz, Jean-René; Cadoret, Jean-Paul

2012-11-01

Microalgae offer a high potential for energetic lipid storage as well as high growth rates. They are therefore considered promising candidates for biofuel production, with the selection of high lipid-producing strains a major objective in projects on the development of this technology. We developed a mutation-selection method aimed at increasing microalgae neutral lipid productivity. A two step method, based on UVc irradiation followed by flow cytometry selection, was applied to a set of strains that had an initial high lipid content and improvement was assessed by means of Nile-red fluorescence measurements. The method was first tested on Isochrysis affinis galbana (T-Iso). Following a first round of mutation-selection, the total fatty acid content had not increased significantly, being 262 ± 21 mgTFA (gC)-1 for the wild type (WT) and 269 ± 49 mgTFA (gC)-1 for the selected population (S1M1). Conversely, fatty acid distribution among the lipid classes was affected by the process, resulting in a 20% increase for the fatty acids in the neutral lipids and a 40% decrease in the phospholipids. After a second mutation-selection step (S2M2), the total fatty acid content reached 409 ± 64 mgTFA (gC)-1 with a fatty acid distribution similar to the S1M1 population. Growth rate remained unaffected by the process, resulting in a 80% increase for neutral lipid productivity. Copyright © 2012 Wiley Periodicals, Inc.

SH2 Domains Serve as Lipid-Binding Modules for pTyr-Signaling Proteins.

PubMed

Park, Mi-Jeong; Sheng, Ren; Silkov, Antonina; Jung, Da-Jung; Wang, Zhi-Gang; Xin, Yao; Kim, Hyunjin; Thiagarajan-Rosenkranz, Pallavi; Song, Seohyeon; Yoon, Youngdae; Nam, Wonhee; Kim, Ilshin; Kim, Eui; Lee, Dong-Gyu; Chen, Yong; Singaram, Indira; Wang, Li; Jang, Myoung Ho; Hwang, Cheol-Sang; Honig, Barry; Ryu, Sungho; Lorieau, Justin; Kim, You-Me; Cho, Wonhwa

2016-04-07

The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that ∼90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Bioactive Structure of Membrane Lipids and Natural Products Elucidated by a Chemistry-Based Approach.

PubMed

Murata, Michio; Sugiyama, Shigeru; Matsuoka, Shigeru; Matsumori, Nobuaki

2015-08-01

Determining the bioactive structure of membrane lipids is a new concept, which aims to examine the functions of lipids with respect to their three-dimensional structures. As lipids are dynamic by nature, their "structure" does not refer solely to a static picture but also to the local and global motions of the lipid molecules. We consider that interactions with lipids, which are completely defined by their structures, are controlled by the chemical, functional, and conformational matching between lipids and between lipid and protein. In this review, we describe recent advances in understanding the bioactive structures of membrane lipids bound to proteins and related molecules, including some of our recent results. By examining recent works on lipid-raft-related molecules, lipid-protein interactions, and membrane-active natural products, we discuss current perspectives on membrane structural biology. © 2015 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Membrane Lipid Replacement for chronic illnesses, aging and cancer using oral glycerolphospholipid formulations with fructooligosaccharides to restore phospholipid function in cellular membranes, organelles, cells and tissues.

PubMed

Nicolson, Garth L; Ash, Michael E

2017-09-01

Membrane Lipid Replacement is the use of functional, oral supplements containing mixtures of cell membrane glycerolphospholipids, plus fructooligosaccharides (for protection against oxidative, bile acid and enzymatic damage) and antioxidants, in order to safely replace damaged, oxidized, membrane phospholipids and restore membrane, organelle, cellular and organ function. Defects in cellular and intracellular membranes are characteristic of all chronic medical conditions, including cancer, and normal processes, such as aging. Once the replacement glycerolphospholipids have been ingested, dispersed, complexed and transported, while being protected by fructooligosaccharides and several natural mechanisms, they can be inserted into cell membranes, lipoproteins, lipid globules, lipid droplets, liposomes and other carriers. They are conveyed by the lymphatics and blood circulation to cellular sites where they are endocytosed or incorporated into or transported by cell membranes. Inside cells the glycerolphospholipids can be transferred to various intracellular membranes by lipid globules, liposomes, membrane-membrane contact or by lipid carrier transfer. Eventually they arrive at their membrane destinations due to 'bulk flow' principles, and there they can stimulate the natural removal and replacement of damaged membrane lipids while undergoing further enzymatic alterations. Clinical trials have shown the benefits of Membrane Lipid Replacement in restoring mitochondrial function and reducing fatigue in aged subjects and chronically ill patients. Recently Membrane Lipid Replacement has been used to reduce pain and other symptoms as well as removing hydrophobic chemical contaminants, suggesting that there are additional new uses for this safe, natural medicine supplement. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen.

PubMed

Abos Gracia, Beatriz; López Relaño, Juan; Revilla, Ana; Castro, Lourdes; Villalba, Mayte; Martín Adrados, Beatriz; Regueiro, Jose Ramon; Fernández-Malavé, Edgar; Martínez Naves, Eduardo; Gómez Del Moral, Manuel

2017-01-01

Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study was to analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA. Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ. Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses. © 2017 S. Karger AG, Basel.

Deleterious effects of increased body weight associated with intensive insulin therapy for type 1 diabetes: increased blood pressure and worsened lipid profile partially negate improvements in life expectancy.

PubMed

Palmer, Andrew J; Roze, Stéphane; Valentine, William J; Minshall, Michael E; Lammert, Morten; Nicklasson, Lars; Spinas, Giatgen A

2004-08-01

Weight gain is an unwanted side effect of improved glycaemic control in type 1 diabetes, associated with increased blood pressure (BP) and worsening lipid profiles. While improved glycaemic control per se should improve long-term patient outcomes, increases in BP and worsening lipid profiles may counteract these benefits. The aim of this modelling study was to assess whether the increased body weight and associated worsening of lipid profile and blood pressure would negate the improvements in glycaemic control seen with intensive therapy in patients with type 1 diabetes. A validated diabetes model projected life expectancy (LE), quality-adjusted LE (QALE) and total lifetime costs of complications in type 1 diabetes cohorts with the characteristics of patients from the Diabetes Control and Complications Trial (DCCT). The following four cohorts (A-D) were created based on increased body weight under either conventional or intensive therapy: A) conventional glycaemic control in the subgroup with lowest weight-gain quartile after 6.5 years (HbA1c increased by 11% from baseline); B) conventional control in the highest weight-gain quartile (no change in HbA1c from baseline); C) intensive control in the lowest quartile of weight gain (with 16.1% decrease in HbA1c, but no increase in weight or associated BP, and improved lipid profile); D) intensive control in the highest quartile of weight gain (with 21% decrease in HbA1c, increased systolic BP of 6 mmHg, and worsened lipid profile). Data were derived from DCCT and other published sources. Intensive control, even with weight gain, led to major improvements in LE and QALE, and reduction in costs of complications versus conventional therapy. Intensive therapy with no weight increase led to a higher LE (increased by 0.57 years) and higher QALE (increased by 0.28 years) and lower costs of complications (reduced by 523 dollars/patient), compared to intensive therapy with the highest quartile of weight gain. Concerns about weight gain should not deter intensive insulin therapy. However, the value of improving glycaemic control without increasing body weight (and associated increased BP and worsening of lipid profile) has been confirmed.

Light-activated control of protein channel assembly mediated by membrane mechanics

NASA Astrophysics Data System (ADS)

Miller, David M.; Findlay, Heather E.; Ces, Oscar; Templer, Richard H.; Booth, Paula J.

2016-12-01

Photochemical processes provide versatile triggers of chemical reactions. Here, we use a photoactivated lipid switch to modulate the folding and assembly of a protein channel within a model biological membrane. In contrast to the information rich field of water-soluble protein folding, there is only a limited understanding of the assembly of proteins that are integral to biological membranes. It is however possible to exploit the foreboding hydrophobic lipid environment and control membrane protein folding via lipid bilayer mechanics. Mechanical properties such as lipid chain lateral pressure influence the insertion and folding of proteins in membranes, with different stages of folding having contrasting sensitivities to the bilayer properties. Studies to date have relied on altering bilayer properties through lipid compositional changes made at equilibrium, and thus can only be made before or after folding. We show that light-activation of photoisomerisable di-(5-[[4-(4-butylphenyl)azo]phenoxy]pentyl)phosphate (4-Azo-5P) lipids influences the folding and assembly of the pentameric bacterial mechanosensitive channel MscL. The use of a photochemical reaction enables the bilayer properties to be altered during folding, which is unprecedented. This mechanical manipulation during folding, allows for optimisation of different stages of the component insertion, folding and assembly steps within the same lipid system. The photochemical approach offers the potential to control channel assembly when generating synthetic devices that exploit the mechanosensitive protein as a nanovalve.

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer.

PubMed

Liang, Yan; Tian, Baocheng; Zhang, Jing; Li, Keke; Wang, Lele; Han, Jingtian; Wu, Zimei

2017-01-01

Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N -acetyl-d-glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6- O -methacryloyl-d-galactopyranose)-GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.

A Postnatal Diet Containing Phospholipids, Processed to Yield Large, Phospholipid-Coated Lipid Droplets, Affects Specific Cognitive Behaviors in Healthy Male Mice.

PubMed

Schipper, Lidewij; van Dijk, Gertjan; Broersen, Laus M; Loos, Maarten; Bartke, Nana; Scheurink, Anton Jw; van der Beek, Eline M

2016-06-01

Infant cognitive development can be positively influenced by breastfeeding rather than formula feeding. The composition of breast milk, especially lipid quality, and the duration of breastfeeding have been linked to this effect. We investigated whether the physical properties and composition of lipid droplets in milk may contribute to cognitive development. From postnatal day (P) 16 to P44, healthy male C57BL/6JOlaHsd mice were fed either a control or a concept rodent diet, in which the dietary lipid droplets were large and coated with milk phospholipids, resembling more closely the physical properties and composition of breast milk lipids. Thereafter, all mice were fed an AIN-93M semisynthetic rodent diet. The mice were subjected to various cognitive tests during adolescence (P35-P44) and adulthood (P70-P101). On P102, mice were killed and brain phospholipids were analyzed. The concept diet improved performance in short-term memory tasks that rely on novelty exploration during adolescence (T-maze; spontaneous alternation 87% in concept-fed mice compared with 74% in mice fed control diet; P < 0.05) and adulthood (novel object recognition; preference index 0.48 in concept-fed mice compared with 0.05 in control-fed mice; P < 0.05). Cognitive performance in long-term memory tasks, however, was unaffected by diet. Brain phospholipid composition at P102 was not different between diet groups. Exposure to a diet with lipids mimicking more closely the structure and composition of lipids in breast milk improved specific cognitive behaviors in mice. These data suggest that lipid structure should be considered as a relevant target to improve dietary lipid quality in infant milk formulas. © 2016 American Society for Nutrition.

Comparison of Lipid Accumulation Product Index with Body Mass Index and Waist Circumference as a Predictor of Metabolic Syndrome in Indian Population.

PubMed

Ray, Lopamudra; Ravichandran, Kandasamy; Nanda, Sunil Kumar

2018-06-01

Metabolic syndrome (MetS), which confers a high risk for cardiovascular diseases, needs early diagnosis and treatment to reduce morbidity and mortality. Lipid accumulation product index has been reported to be an inexpensive marker of visceral fat and metabolic syndrome. This study aimed to evaluate lipid accumulation product index as a marker for metabolic syndrome in the Indian population where the prevalence of the condition is steadily increasing. A hospital-based, case-control study was conducted with 72 diagnosed cases of metabolic syndrome and 79 control subjects. In all the participants, body mass index (BMI) and lipid accumulation product index were calculated. The difference between cases and controls in BMI, waist circumference (WC), and lipid accumulation product index was assessed by Mann-Whitney U test/unpaired t-test. Associations of BMI, WC, and lipid accumulation product index with metabolic syndrome were compared by multiple logistic regression analysis and receiver operating characteristic analysis. BMI, WC, and lipid accumulation product index were significantly higher in metabolic syndrome (P < 0.05). Although all were independently associated with metabolic syndrome, lipid accumulation product index had the highest prediction accuracy. The parameter also had a high area under curve of 0.901 (95% confidence interval 0.85-0.95) and a high sensitivity (76.4%), specificity (91.1%), positive predictive value (88.7%), and negative predictive value (80.9%) for detection of metabolic syndrome. In the Indian population, lipid accumulation product index is a better predictor of metabolic syndrome compared to BMI and WC and should be incorporated in laboratory reports as early, accurate, and inexpensive indicator of metabolic syndrome.

Proton MR spectroscopy in patients with acute temporal lobe seizures.

PubMed

Castillo, M; Smith, J K; Kwock, L

2001-01-01

Decreases in N-acetyl aspartate (NAA) as seen by proton MR spectroscopy are found in hippocampal sclerosis, and elevated levels of lipids/lactate have been observed after electroconvulsive therapy. Our purpose was to determine whether increased levels of lipids/lactate are found in patients with acute seizures of hippocampal origin. Seventeen patients with known temporal lobe epilepsy underwent proton MR spectroscopy of the mesial temporal lobes within 24 hours of their last seizure. Four of them were restudied when they were seizure-free. Five healthy individuals were used as control subjects. All MR spectroscopy studies were obtained using a single-voxel technique with TEs of 135 and 270. The relationship between the presence of lipids/lactate and seizures was tested using Fisher's exact test. Mean and standard deviations for NAA/creatine (Cr) were obtained in the hippocampi in patients with seizures on initial and follow-up studies and these values were compared with those in the control subjects. Seizure lateralization was obtained in 15 patients. Of the 17 seizure locations that involved hippocampi, 16 showed lipids/lactate by proton MR spectroscopy. Of the 13 hippocampi not directly affected by seizures, 10 showed no lipids/lactate and three showed lipids/lactate. The relationship between lipids/lactate and seizure location was confirmed. A comparison of NAA/Cr ratios for the involved hippocampi with those in control subjects showed significant differences on initial MR spectroscopy; however, no significant difference was found between acute and follow-up NAA/Cr ratios in hippocampi affected by seizures. Lipids/lactate were present in the hippocampi of patients with acute seizures and decreased when the patients were seizure-free. Thus, lipids/lactate may be a sensitive marker for acute temporal lobe seizures.

The effects of abscisic acid, salicylic acid and jasmonic acid on lipid accumulation in two freshwater Chlorella strains.

PubMed

Wu, Guanxun; Gao, Zhengquan; Du, Huanmin; Lin, Bin; Yan, Yuchen; Li, Guoqiang; Guo, Yanyun; Fu, Shenggui; Wei, Gongxiang; Wang, Miaomiao; Cui, Meng; Meng, Chunxiao

2018-03-27

Sustainable renewable energy is being hotly debated globally because the continued use of finite fossil fuels is now widely recognized as being unsustainable. Microalgae potentially offer great opportunities for resolving this challenge. Abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) are involved in regulating many physiological properties and have been widely used in higher plants. To test if phytohormones have an impact on accumulating lipid for microalgae, ABA, JA and SA were used to induce two Chlorella strains in the present study. The results showed 1.0 mg/L ABA, 10 mg/L SA, and 0.5 mg/L JA, led strain C. vulgaris ZF strain to produce a 45%, 42% and 49% lipid content that was 1.8-, 1.7- and 2.0-fold that of controls, respectively. For FACHB 31 (number 31 of the Freshwater Algae Culture Collection at the Institute of Hydrobiology, Chinese Academy of Sciences), the addition of 1.0 mg/L ABA, 10 mg/L SA, and 0.5 mg/L, JA produced 33%, 30% and 38% lipid content, which was 1.8-, 1.6- and 2.1-fold that of controls, respectively. As for lipid productivity, 1.0 mg/L ABA increased the lipid productivity of C. vulgaris ZF strain and FACHB-31 by 123% and 44%; 10 mg/L SA enhanced lipid productivity by 100% and 33%; the best elicitor, 0.5 mg/L JA, augmented lipid productivity by 127% and 75% compared to that of controls, respectively. The results above suggest that the three phytohormones at physiological concentrations play crucial roles in inducing lipid accumulation in Chlorella.

Breathable NIPAAm Network with Controllable Hydration Supports Model Lipid Membrane

NASA Astrophysics Data System (ADS)

Jablin, Michael; Smith, Hillary; Zhernenkov, Mikhail; Vidyasagar, Ajay; Toomey, Ryan; Saiz, Jessica; Toperverg, Boris; Watkins, Erik; Kuhl, Tonya; Hurd, Alan; Majewski, Jaroslaw

2009-03-01

The interaction of a model lipid bilayer composed of DPPC with a surface-tethered poly(N-isopropylacrylamide) (NIPAAm) was explored with neutron reflectometry (NR). The Langmuir-Blodgett / Langmuir-Schaeffer method was used to deposit a lipid bilayer onto the polymer. NR measurements were used to probe the in- and out-of-plane structure of the system as a function of temperature. NR with fluorescence microscopy show that the polymer supports a lipid bilayer, and hydration of the support can be controlled. At low temp. the membrane develops out-of-plane undulations visible in off-specular scattering. Analysis of the off-specular reveals in-plane correlation of the bilayer fluctuations. The separation of the lipid bilayer from the solid support of a substrate constitutes a significant step towards a more realistic model of biological membranes.

FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth

PubMed Central

Slebe, Felipe; Rojo, Federico; Vinaixa, Maria; García-Rocha, Mar; Testoni, Giorgia; Guiu, Marc; Planet, Evarist; Samino, Sara; Arenas, Enrique J.; Beltran, Antoni; Rovira, Ana; Lluch, Ana; Salvatella, Xavier; Yanes, Oscar; Albanell, Joan; Guinovart, Joan J.; Gomis, Roger R.

2016-01-01

The mechanisms that allow breast cancer (BCa) cells to metabolically sustain rapid growth are poorly understood. Here we report that BCa cells are dependent on a mechanism to supply precursors for intracellular lipid production derived from extracellular sources and that the endothelial lipase (LIPG) fulfils this function. LIPG expression allows the import of lipid precursors, thereby contributing to BCa proliferation. LIPG stands out as an essential component of the lipid metabolic adaptations that BCa cells, and not normal tissue, must undergo to support high proliferation rates. LIPG is ubiquitously and highly expressed under the control of FoxA1 or FoxA2 in all BCa subtypes. The downregulation of either LIPG or FoxA in transformed cells results in decreased proliferation and impaired synthesis of intracellular lipids. PMID:27045898

Liquid Crystal Droplet-Based Amplification of Microvesicles that are Shed by Mammalian Cells

PubMed Central

Tan, Lie Na; Wiepz, Gregory J.; Miller, Daniel S.; Shusta, Eric V.; Abbott, Nicholas L.

2014-01-01

Membrane-derived microvesicles (MVs) shed by cells are being investigated for their role in intercellular communication and as potential biomarkers of disease, but facile and sensitive methods for their analysis do not exist. Here we demonstrate new principles for analysis of MVs that use micrometer-sized droplets of liquid crystals (LCs) to amplify MVs that are selectively captured via antibody-mediated interactions. The influence of the MVs on the micrometer-sized LC droplets is shown to be readily quantified via use of flow cytometry. The methodology was developed using MVs shed by epidermoid carcinoma A431 cells that contain epidermal growth factor receptor (EGFR) as an important and representative example of MVs containing signaling proteins that play a central role in cancer. The LC droplets were found to be sensitive to 106 MVs containing EGFR (relative to controls using isotype control antibody) and to possess a dynamic range of response across several orders of magnitude. Because the 100 nm-sized MVs captured via EGFR generate an optical response in the micrometer-sized LC droplets that can be readily detected by flow cytometry in light scattering mode, the approach possesses significant advantages over direct detection of MVs by flow cytometry. The LC droplets are also substantially more sensitive than techniques such as immunoblotting because the lipid-component of the MVs serves to amplify the antibody-mediated capture of the target proteins in the MVs. Other merits of the approach are defined and discussed in the paper. PMID:24667742

Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals.

PubMed

Souza, D R S; Nakazone, M A; Pinhel, M A S; Alvares, R M; Monaco, A C; Pinheiro, A; Barros, C F D C; Cury, P M; Cunrath, G S; Netinho, J G

2009-05-01

We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the epsilon4/epsilon4 genotype (6%) was present only in controls. The patients had reduced levels (mean +/- SD) of total cholesterol and low-density lipoprotein cholesterol fraction (180.4 +/- 49.5 and 116.1 +/- 43.1 mg/dL, respectively) compared to controls (204.2 +/- 55.6, P = 0.135 and 134.7 +/- 50.8 mg/dL; P = 0.330, respectively) indicating that they were not statistically significant after the Bonferroni correction. The APOE*4 allele was associated with lower levels of total cholesterol, low- and high-density lipoprotein cholesterol fraction and increased levels of very low-density lipoprotein cholesterol fraction and triglycerides only among patients (P = 0.014). There was a positive correlation between the altered lipid profile and increased body mass indexes in both groups (P < 0.010). Moreover, a higher rate of hypertension and overweight was observed in controls (P < 0.002). In conclusion, the presence of the epsilon4/epsilon4 genotype only in controls may be due to a protective effect against CRC. Lower lipid profile values among patients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in CRC.

Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution.

PubMed

Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Kessoku, Takaomi; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi

2015-12-17

Although many factors and molecules that are closely associated with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported, the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in the pathogenesis of NAFLD/NASH remains unclear. We therefore investigated the role of eNOS-derived NO in NAFLD pathogenesis using systemic eNOS-knockout mice fed a high-fat diet. eNOS-knockout and wild-type mice were fed a basal diet or a high-fat diet for 12 weeks. Lipid accumulation and inflammation were evaluated in the liver, and various factors that are closely associated with NAFLD/NASH and hepatic tissue blood flow were analyzed. Lipid accumulation and inflammation were more extensive in the liver and lipid accumulation was less extensive in the visceral fat tissue in eNOS-knockout mice, compared with wild-type mice, after 12 weeks of being fed a high-fat diet. While systemic insulin resistance was comparable between the eNOS-knockout and wild-type mice fed a high-fat diet, hepatic tissue blood flow was significantly suppressed in the eNOS-knockout mice, compared with the wild-type mice, in mice fed a high-fat diet. The microsomal triglyceride transfer protein activity was down-regulated in eNOS-knockout mice, compared with wild-type mice, in mice fed a high-fat diet. A deficiency of eNOS-derived NO may exacerbate the early-stage of NASH pathogenesis by changing the fat distribution in a mouse model via the regulation of hepatic tissue blood flow.

Study of Valproic Acid-Enhanced Hepatocyte Steatosis

PubMed Central

Chang, Renin; Chou, Mei-Chia; Hung, Li-Ying; Wang, Mu-En; Hsu, Meng-Chieh; Chiu, Chih-Hsien

2016-01-01

Valproic acid (VPA) is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-based in vitro model. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG) synthesis, and lipid droplet formation. Real-time PCR results showed that, following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36), low-density lipoprotein receptor-related protein 1 (Lrp1), diacylglycerol acyltransferase 2 (Dgat2), and perilipin 2 (Plin2) were increased, that of carnitine palmitoyltransferase I a (Cpt1a) was not affected, and those of acetyl-Co A carboxylase α (Acca) and fatty acid synthase (Fasn) were decreased. Furthermore, using immunofluorescence staining and flow cytometry analyses, we found that VPA also induced peroxisome proliferator-activated receptor γ (PPARγ) nuclear translocation and increased levels of cell-surface CD36. Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation. PMID:27034954

Molecular Dynamics Simulations of KirBac1.1 Mutants Reveal Global Gating Changes of Kir Channels.

PubMed

Linder, Tobias; Wang, Shizhen; Zangerl-Plessl, Eva-Maria; Nichols, Colin G; Stary-Weinzinger, Anna

2015-04-27

Prokaryotic inwardly rectifying (KirBac) potassium channels are homologous to mammalian Kir channels. Their activity is controlled by dynamical conformational changes that regulate ion flow through a central pore. Understanding the dynamical rearrangements of Kir channels during gating requires high-resolution structure information from channels crystallized in different conformations and insight into the transition steps, which are difficult to access experimentally. In this study, we use MD simulations on wild type KirBac1.1 and an activatory mutant to investigate activation gating of KirBac channels. Full atomistic MD simulations revealed that introducing glutamate in position 143 causes significant widening at the helix bundle crossing gate, enabling water flux into the cavity. Further, global rearrangements including a twisting motion as well as local rearrangements at the subunit interface in the cytoplasmic domain were observed. These structural rearrangements are similar to recently reported KirBac3.1 crystal structures in closed and open conformation, suggesting that our simulations capture major conformational changes during KirBac1.1 opening. In addition, an important role of protein-lipid interactions during gating was observed. Slide-helix and C-linker interactions with lipids were strengthened during activation gating.

Status of serum magnesium in Egyptian children with type 1 diabetes and its correlation to glycemic control and lipid profile.

PubMed

Shahbah, Doaa; El Naga, Amr Abo; Hassan, Tamer; Zakaria, Marwa; Beshir, Mohamed; Al Morshedy, Salah; Abdalhady, Mohamed; Kamel, Ezzat; Rahman, Doaa Abdel; Kamel, Lamiaa; Abdelkader, May

2016-11-01

Diabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency, having 25% to 39% prevalence. This deficit could be associated with the development of late diabetic complications, especially macroangiopathy.We aimed to evaluate the status of serum Mg in children with type 1 diabetes and assess its relation to glycemic control and lipid profile.We included 71 Egyptian children with type 1diabetes having their follow-up at Pediatric Endocrinology outpatient clinic, Zagazig University Hospital and 71 age- and sex-matched control. We measured Serum magnesium, HbA1c, and lipid profile in all study subjects.Diabetic children had significantly lower serum magnesium level compared to control children (1.83 ± .27 mg/dL in diabetic children versus 2.00 ± .16 mg/dL in control children). Taking cut-off level of serum magnesium <1.7 mg/dL for definition of hypomagnesemia, hypomagnesemia was detected in 28.2% of diabetic children compared to 9.9% of control children. In diabetic patients, there was statistically significant difference in HbA1c between hypomagnesemic and normomagnesemic group being higher in the low magnesium group, as it is mean ± SD was 11.93 ± 3.17 mg/dL in group I versus 8.92 ± 0.93 mg/dL in the normomagnesemic group. Serum magnesium was found to be positively correlated with HDL (P < 0.001), and negatively correlated with age, HbA1c, triglycerides, total cholesterol, LDL, and duration of diabetes (P < 0.001).We concluded that total serum magnesium was frequently low in Egyptian children with type 1 diabetes and it is correlated with HbA1c and with lipid profile. Hypomagnesemia was more evident in patients with poor diabetic control and those with higher atherogenic lipid parameters. We suggest that low serum magnesium may be included in pathogenesis of poor glycemic control and abnormal lipid profile in children with type 1 diabetes. We need to perform further studies on giving magnesium supplements in diabetic children with hypomagnesemia to observe the effect of correction of serum magnesium on glycemic control, lipid profile, and the risk of diabetic complications.

Status of serum magnesium in Egyptian children with type 1 diabetes and its correlation to glycemic control and lipid profile

PubMed Central

Shahbah, Doaa; El Naga, Amr Abo; Hassan, Tamer; Zakaria, Marwa; Beshir, Mohamed; Al Morshedy, Salah; Abdalhady, Mohamed; Kamel, Ezzat; Rahman, Doaa Abdel; Kamel, Lamiaa; Abdelkader, May

2016-01-01

Abstract Diabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency, having 25% to 39% prevalence. This deficit could be associated with the development of late diabetic complications, especially macroangiopathy. We aimed to evaluate the status of serum Mg in children with type 1 diabetes and assess its relation to glycemic control and lipid profile. We included 71 Egyptian children with type 1diabetes having their follow-up at Pediatric Endocrinology outpatient clinic, Zagazig University Hospital and 71 age- and sex-matched control. We measured Serum magnesium, HbA1c, and lipid profile in all study subjects. Diabetic children had significantly lower serum magnesium level compared to control children (1.83 ± .27 mg/dL in diabetic children versus 2.00 ± .16 mg/dL in control children). Taking cut-off level of serum magnesium <1.7 mg/dL for definition of hypomagnesemia, hypomagnesemia was detected in 28.2% of diabetic children compared to 9.9% of control children. In diabetic patients, there was statistically significant difference in HbA1c between hypomagnesemic and normomagnesemic group being higher in the low magnesium group, as it is mean ± SD was 11.93 ± 3.17 mg/dL in group I versus 8.92 ± 0.93 mg/dL in the normomagnesemic group. Serum magnesium was found to be positively correlated with HDL (P < 0.001), and negatively correlated with age, HbA1c, triglycerides, total cholesterol, LDL, and duration of diabetes (P < 0.001). We concluded that total serum magnesium was frequently low in Egyptian children with type 1 diabetes and it is correlated with HbA1c and with lipid profile. Hypomagnesemia was more evident in patients with poor diabetic control and those with higher atherogenic lipid parameters. We suggest that low serum magnesium may be included in pathogenesis of poor glycemic control and abnormal lipid profile in children with type 1 diabetes. We need to perform further studies on giving magnesium supplements in diabetic children with hypomagnesemia to observe the effect of correction of serum magnesium on glycemic control, lipid profile, and the risk of diabetic complications. PMID:27893657

Magnesium aminoclay enhances lipid production of mixotrophic Chlorella sp. KR-1 while reducing bacterial populations.

PubMed

Kim, Bohwa; Praveenkumar, Ramasamy; Lee, Jiye; Nam, Bora; Kim, Dong-Myung; Lee, Kyubock; Lee, Young-Chul; Oh, You-Kwan

2016-11-01

Improving lipid productivity and preventing overgrowth of contaminating bacteria are critical issues relevant to the commercialization of the mixotrophic microalgae cultivation process. In this paper, we report the use of magnesium aminoclay (MgAC) nanoparticles for enhanced lipid production from oleaginous Chlorella sp. KR-1 with simultaneous control of KR-1-associated bacterial growth in mixotrophic cultures with glucose as the model substrate. Addition of 0.01-0.1g/L MgAC promoted microalgal biomass production better than the MgAC-less control, via differential biocidal effects on microalgal and bacterial cells (the latter being more sensitive to MgAC's bio-toxicity than the former). The inhibition effect of MgAC on co-existing bacteria was, as based on density-gradient-gel-electrophoresis (DGGE) analysis, largely dosage-dependent and species-specific. MgAC also, by inducing an oxidative stress environment, increased both the cell size and lipid content of KR-1, resulting in a considerable, ∼25% improvement of mixotrophic algal lipid productivity (to ∼410mgFAME/L/d) compared with the untreated control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apicobasal polarity of brain endothelial cells

PubMed Central

Worzfeld, Thomas

2015-01-01

Normal brain homeostasis depends on the integrity of the blood–brain barrier that controls the access of nutrients, humoral factors, and immune cells to the CNS. The blood–brain barrier is composed mainly of brain endothelial cells. Forming the interface between two compartments, they are highly polarized. Apical/luminal and basolateral/abluminal membranes differ in their lipid and (glyco-)protein composition, allowing brain endothelial cells to secrete or transport soluble factors in a polarized manner and to maintain blood flow. Here, we summarize the basic concepts of apicobasal cell polarity in brain endothelial cells. To address potential molecular mechanisms underlying apicobasal polarity in brain endothelial cells, we draw on investigations in epithelial cells and discuss how polarity may go awry in neurological diseases. PMID:26661193

CSF Flow in the Brain in the Context of Normal Pressure Hydrocephalus.

PubMed

Bradley, W G

2015-05-01

CSF normally flows back and forth through the aqueduct during the cardiac cycle. During systole, the brain and intracranial vasculature expand and compress the lateral and third ventricles, forcing CSF craniocaudad. During diastole, they contract and flow through the aqueduct reverses. Hyperdynamic CSF flow through the aqueduct is seen when there is ventricular enlargement without cerebral atrophy. Therefore, patients presenting with clinical normal pressure hydrocephalus who have hyperdynamic CSF flow have been found to respond better to ventriculoperitoneal shunting than those with normal or decreased CSF flow. Patients with normal pressure hydrocephalus have also been found to have larger intracranial volumes than sex-matched controls, suggesting that they may have had benign external hydrocephalus as infants. While their arachnoidal granulations clearly have decreased CSF resorptive capacity, it now appears that this is fixed and that the arachnoidal granulations are not merely immature. Such patients appear to develop a parallel pathway for CSF to exit the ventricles through the extracellular space of the brain and the venous side of the glymphatic system. This pathway remains functional until late adulthood when the patient develops deep white matter ischemia, which is characterized histologically by myelin pallor (ie, loss of lipid). The attraction between the bare myelin protein and the CSF increases resistance to the extracellular outflow of CSF, causing it to back up, resulting in hydrocephalus. Thus idiopathic normal pressure hydrocephalus appears to be a "2 hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood. © 2015 by American Journal of Neuroradiology.

Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High Cholesterol Diet.

PubMed

Guo, Wenxin; Shu, Yang; Yang, Xiaoping

2016-06-01

Tea dietary fiber (TDF) was prepared from tea residues and modified to get cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine grinding. The in vitro lipid-binding capacities of the three fibers and their effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet were evaluated. The results showed that the three fibers had excellent lipid-binding capacities, and the cholesterol- and sodium cholate-binding capacities of CTDF and MTDF were significantly higher than those of TDF. Animal studies showed that, compared to model control, the three fibers significantly decreased mice average daily gain, gain: feed, and liver index, reduced total cholesterol (TC), triglyceride, and low density lipoprotein-cholesterol of serum and liver, increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and promoted the excretion of fecal lipids, and they also significantly increased the activities of superoxide dismutase and glutathione peroxidase of serum and liver, and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were better than that of TDF. It was concluded that the three fibers could improve serum and hepatic lipid profiles in mice fed a high cholesterol diet and the mechanism of action might be due to the promotion of fecal excretion of lipids through their lipid-binding ability and the inhibition of lipid peroxidation. These findings suggest that tea dietary fiber has the potential to be used as a functional ingredient to control cardiovascular disease.

Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism

PubMed Central

Almatrafi, Manal Mused; Vergara-Jimenez, Marcela; Murillo, Ana Gabriela; Norris, Gregory H.; Blesso, Christopher N.; Fernandez, Maria Luz

2017-01-01

To investigate the mechanisms by which Moringa oleifera leaves (ML) modulate hepatic lipids, guinea pigs were allocated to either control (0% ML), 10% Low Moringa (LM) or 15% High Moringa (HM) diets with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, guinea pigs were sacrificed and liver and plasma were collected to determine plasma lipids, hepatic lipids, cytokines and the expression of genes involved in hepatic cholesterol (CH) and triglyceride (TG) metabolism. There were no differences in plasma lipids among groups. A dose-response effect of ML was observed in hepatic lipids (CH and TG) with the lowest concentrations in the HM group (p < 0.001), consistent with histological evaluation of lipid droplets. Hepatic gene expression of diglyceride acyltransferase-2 and peroxisome proliferator activated receptor-γ, as well as protein concentrations interleukin (IL)-1β and interferon-γ, were lowest in the HM group (p < 0.005). Hepatic gene expression of cluster of differentiation-68 and sterol regulatory element binding protein-1c were 60% lower in both the LM and HM groups compared to controls (p < 0.01). This study demonstrates that ML may prevent hepatic steatosis by affecting gene expression related to hepatic lipids synthesis resulting in lower concentrations of cholesterol and triglycerides and reduced inflammation in the liver. PMID:28640194

Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism.

PubMed

Almatrafi, Manal Mused; Vergara-Jimenez, Marcela; Murillo, Ana Gabriela; Norris, Gregory H; Blesso, Christopher N; Fernandez, Maria Luz

2017-06-22

To investigate the mechanisms by which Moringa oleifera leaves (ML) modulate hepatic lipids, guinea pigs were allocated to either control (0% ML), 10% Low Moringa (LM) or 15% High Moringa (HM) diets with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, guinea pigs were sacrificed and liver and plasma were collected to determine plasma lipids, hepatic lipids, cytokines and the expression of genes involved in hepatic cholesterol (CH) and triglyceride (TG) metabolism. There were no differences in plasma lipids among groups. A dose-response effect of ML was observed in hepatic lipids (CH and TG) with the lowest concentrations in the HM group ( p < 0.001), consistent with histological evaluation of lipid droplets. Hepatic gene expression of diglyceride acyltransferase-2 and peroxisome proliferator activated receptor-γ, as well as protein concentrations interleukin (IL)-1β and interferon-γ, were lowest in the HM group ( p < 0.005). Hepatic gene expression of cluster of differentiation-68 and sterol regulatory element binding protein-1c were 60% lower in both the LM and HM groups compared to controls ( p < 0.01). This study demonstrates that ML may prevent hepatic steatosis by affecting gene expression related to hepatic lipids synthesis resulting in lower concentrations of cholesterol and triglycerides and reduced inflammation in the liver.

Autonomous buckling of micrometer-sized lipid-protein membrane patches constructed by Dictyostelium discoideum.

PubMed

Takahashi, Kei; Toyota, Taro

2015-01-01

The cytosol of amoeba cells controls the membrane deformation during their motion in vivo. To investigate such ability of the cytosol of amoeba cell, Dictyostelium discoideum (Dictyostelium), in vitro, we used lipids extracted from Dictyostelium and commercially available phospholipids, and prepared substrate-supported lipid membrane patches on the micrometer scale by spin coating. We found that the spin coater holder, which has pores (pore size = 3.1 mm) of negative pressure to hold the cover glass induced the concave surface of the cover glass. The membrane lipid patches were formed at each position in the vicinity of the holder pores and their sizes were in the range of 2.7 to 3.2 × 10(4) μm(2). After addition of the cytosol extracted from Dictyostelium to the lipid membrane patches, through time-lapse observation with a confocal laser scanning fluorescence microscope, we observed an autonomous buckling of the Dictyostelium lipid patches and localized behaviours of proteins found within. The current method serves as the novel technique for the preparation of film patches in which the positions of patches are controlled by the holder pores without fabricating, modifying, and arranging the chemical properties of the solution components of lipids. The findings imply that lipid-binding proteins in the cytosol were adsorbed and accumulated within the Dictyostelium lipid patches, inducing the transformation of the cell-sized patch.

Effects of a Preconditioning Oral Nutritional Supplement on Pig Livers after Warm Ischemia

PubMed Central

Nickkholgh, Arash; Li, Zhanqing; Yi, Xue; Mohr, Elvira; Liang, Rui; Mikalauskas, Saulius; Gross, Marie-Luise; Zorn, Markus; Benzing, Steffen; Schneider, Heinz; Büchler, Markus W.; Schemmer, Peter

2012-01-01

Background. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS) containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods. pONS (70 g per serving, Fresenius Kabi, Germany) was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results. HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF-α, MPO, and cleaved caspase-3 (P < 0.001). Conclusion. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis. PMID:22791934

The level of serum lipids, vitamin E and low density lipoprotein oxidation in Wilson's disease patients.

PubMed

Rodo, M; Czonkowska, A; Pulawska, M; Swiderska, M; Tarnacka, B; Wehr, H

2000-09-01

The aim of this study was to estimate the level of lipids and of the main serum antioxidant, alpha-tocopherol (vitamin E), and to evaluate the susceptibility of low density lipoprotein (LDL) to oxidation in Wilson's disease patients. It was assumed that enhanced LDL peroxidation caused by high copper levels could contribute to the injury of liver and other tissues. The group investigated comprised 45 individuals with Wilson's disease treated with penicillamine or zinc salts and a control group of 36 healthy individuals. Lipids were determined by enzymatic methods, alpha-tocopherol by high performance liquid chromatography, the susceptibility of LDL to oxidation in vitro by absorption changes at 234 nm during 5 h and end-products of LDL lipid oxidation as thiobarbituric acid reacting substances. In Wilson's disease patients total cholesterol, LDL cholesterol and alpha-tocopherol levels were significantly lower compared with the control group. No difference in LDL oxidation in vitro between the patients and the controls was stated. enhanced susceptibility of isolated LDL for lipid peroxidation in vitro was not observed in Wilson's disease patients. One cannot exclude, however, that because of low alpha-tocopherol level lipid peroxidation in the tissues can play a role in the pathogenesis of tissue injury in this disease.

Influence of poloxamers on the dissolution performance and stability of controlled-release formulations containing Precirol ATO 5.

PubMed

Jannin, V; Pochard, E; Chambin, O

2006-02-17

Lipid excipients are usually used for the development of sustained-release formulations. When used in relatively high quantities, Precirol ATO 5 imparts sustained-release properties to solid oral dosage forms, by forming a lipid matrix. To control or adjust the drug release kinetics from such lipid matrix however, one must often resort to complementary ingredients or techniques. This study investigates the influence of poloxamers (Lutrol) included in lipid matrices composed of glyceryl palmitostearate (Precirol ATO 5) on their dissolution performance and their stability. The addition of these hydrophilic polymers in the lipid matrix increased the amount of theophylline released thanks to the swelling of the hydrophilic polymer and the creation of a porous network into the inert lipid matrix. The grade and the quantity of Lutrol could modulate the extent of drug release. Theophylline was released mainly by the matrix erosion but also by diffusion through the pores as suggested by the Peppas' model. Moreover, the addition of Lutrol enhanced the stability during storage. The theophylline release was quite steady after 6 months in different conditions (temperature and humidity). Thus, the mixture of glyceryl palmitostearate and poloxamers is an approach with many advantages for the development of controlled-release formulations by capsule molding.

Incorporation of mRNA in Lamellar Lipid Matrices for Parenteral Administration.

PubMed

Ziller, Antje; Nogueira, Sara S; Hühn, Eva; Funari, Sergio S; Brezesinski, Gerald; Hartmann, Hermann; Sahin, Ugur; Haas, Heinrich; Langguth, Peter

2018-02-05

Insertion of high molecular weight messenger RNA (mRNA) into lyotropic lipid phases as model systems for controlled release formulations for the mRNA was investigated. Low fractions of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as an anchor to load the mRNA into a lamellar lipid matrix. Dispersions of zwitterionic lipid in the aqueous phase in the presence of increasing fractions of mRNA and cationic lipid were prepared, and the molecular organization was investigated as a function of mRNA and cationic lipid fraction. Insertion of both cationic lipid and mRNA was clearly proven from the physicochemical characteristics. The d-spacing of the lipid bilayers, as determined by small-angle X-ray scattering (SAXS) measurements, responded sensitively to the amount of inserted DOTAP and mRNA. A concise model of the insertion of the mRNA in the lipid matrices was derived, indicating that the mRNA was accommodated in the aqueous slab between lipid bilayers. Depending on the DOTAP and mRNA fraction, a different excess of water was present in this slab. Results from further physicochemical characterization, including determination of free and bound mRNA, zeta potential, and calorimetry data, were in line with this assumption. The structure of these concentrated lipid/mRNA preparations was maintained upon dilution. The functionality of the inserted mRNA was proven by cell culture experiments using C2C12 murine myoblast cells with the luciferase-encoding mRNA. The described lipid phases as carriers for the mRNA may be applicable for different routes of local administration, where control of the release kinetics and the form of the released mRNA (bound or free) is required.

Effect of Selenium Supplementation on Glycemic Control and Lipid Profiles in Patients with Diabetic Nephropathy.

PubMed

Bahmani, Fereshteh; Kia, Mahsa; Soleimani, Alireza; Asemi, Zatollah; Esmaillzadeh, Ahmad

2016-08-01

To our knowledge, data on the effects of selenium supplementation on glycemic control and lipid concentrations in patients with diabetic nephropathy (DN) are scarce. The current study was done to determine the effects of selenium supplementation on glycemic control and lipid concentrations in patients with DN. This was a randomized double-blind placebo-controlled clinical trial in which 60 patients with DN were randomly allocated into two groups to receive either 200 μg of selenium supplements (n = 30) or placebo (n = 30) daily for 12 weeks. Blood sampling was performed for the quantification of glycemic indicators and lipid profiles at the onset of the study and after 12 weeks of intervention. Selenium supplementation for 12 weeks resulted in a significant decrease in serum insulin levels (P = 0.01), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), homeostasis model of assessment-estimated B cell function (HOMA-B) (P = 0.009) and a significant rise in plasma glutathione peroxidase (GPx) (P = 0.001) compared with the placebo. Taking selenium supplements had no significant effects on fasting plasma glucose (FPG), quantitative insulin sensitivity check index (QUICKI) and lipid profiles compared with the placebo. Overall, our study demonstrated that selenium supplementation for 12 weeks among patients with DN had beneficial effects on plasma GPx, serum insulin levels, HOMA-IR, and HOMA-B, while it did not affect FPG, QUICKI, and lipid profiles.

Molecular characterization of freshwater microalgae and nutritional exploration to enhance their lipid yield.

PubMed

Mandal, Madan Kumar; Chaurasia, Neha

2018-05-01

Biomass and lipid yield under nutrient depleted and supplemented conditions of N and Mg in two freshwater isolates, Chlorella sp. NC-MKM and Scenedesmus acutus NC-M2 from Meghalaya were investigated for biodiesel production. Both the strains, Chlorella sp. NC-MKM and Scenedesmus acutus NC-M2 are oleaginous in nature having lipid content of 40.2 ± 1.4 and 37.3 ± 2.6% DCW, respectively. The significant increase (92.8%) in lipid content was found in N-depleted condition while an increase (46.65%) in biomass yield was observed under Mg-supplemented condition in Chlorella sp. NC-MKM. Studying the interactive effects of nutrient depletion and supplementation, combination of N-depleted and Mg-supplemented condition was selected for further investigation to check enhanced lipid yield in Chlorella sp. NC-MKM. The results showed a significant increase in biomass yield, lipid yield and lipid content (30, 66.8, and 28.66%, respectively). Under this condition, accumulation of neutral lipid was also enhanced (47.17% M2 gated cells) compared to control (21.37% M2 gated cells). Further, FAMEs revealed that the relative percentage of saturated and mono-unsaturated fatty acids increased (66.16%) in Chlorella sp. NC-MKM compared to control that improves biodiesel properties.

Lipid profiling of parkin-mutant human skin fibroblasts.

PubMed

Lobasso, Simona; Tanzarella, Paola; Vergara, Daniele; Maffia, Michele; Cocco, Tiziana; Corcelli, Angela

2017-12-01

Parkin mutations are a major cause of early-onset Parkinson's disease (PD). The impairment of protein quality control system together with defects in mitochondria and autophagy process are consequences of the lack of parkin, which leads to neurodegeneration. Little is known about the role of lipids in these alterations of cell functions. In the present study, parkin-mutant human skin primary fibroblasts have been considered as cellular model of PD to investigate on possible lipid alterations associated with the lack of parkin protein. Dermal fibroblasts were obtained from two unrelated PD patients with different parkin mutations and their lipid compositions were compared with that of two control fibroblasts. The lipid extracts of fibroblasts have been analyzed by combined matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) and thin-layer chromatography (TLC). In parallel, we have performed direct MALDI-TOF/MS lipid analyses of intact fibroblasts by skipping lipid extraction steps. Results show that the proportions of some phospholipids and glycosphingolipids were altered in the lipid profiles of parkin-mutant fibroblasts. The detected higher level of gangliosides, phosphatidylinositol, and phosphatidylserine could be linked to dysfunction of autophagy and mitochondrial turnover; in addition, the lysophosphatidylcholine increase could represent the marker of neuroinflammatory state, a well-known component of PD. © 2017 Wiley Periodicals, Inc.

Autoxidation of unsaturated lipids in food emulsion.

PubMed

Sun, Yue-E; Wang, Wei-Dong; Chen, Hong-Wei; Li, Chao

2011-05-01

Unsaturated lipids having various physiological roles are of significance in biochemistry, nutrition, medicine, and food. However, the susceptibility of lipids to oxidation is a major cause of quality deterioration in food emulsions. The reaction mechanism and factors that influence oxidation are appreciably different for emulsified lipids and bulk lipids. This article gives a brief overview of the current knowledge on autoxidation of oil-in-water food emulsions, especially those that contain unsaturated lipids, which are important in the food industry. Autoxidation of unsaturated lipids in oil-in-water emulsion is discussed, and so also their oxidation mechanism, the major factors influencing oxidation, determination measures, research status, and the problems encountered in recent years. Some effective strategies for controlling lipid oxidation in food emulsion have been presented in this review.

A statistical and experimental approach for assessing the preservation of plant lipids in soil

NASA Astrophysics Data System (ADS)

Mueller, K. E.; Eissenstat, D. M.; Oleksyn, J.; Freeman, K. H.

2011-12-01

Plant-derived lipids contribute to stable soil organic matter, but further interpretations of their abundance in soils are limited because the factors that control lipid preservation are poorly understood. Using data from a long-term field experiment and simple statistical models, we provide novel constraints on several predictors of the concentration of hydrolyzable lipids in forest mineral soils. Focal lipids included common monomers of cutin, suberin, and plant waxes present in tree leaves and roots. Soil lipid concentrations were most strongly influenced by the concentrations of lipids in leaves and roots of the overlying trees, but were also affected by the type of lipid (e.g. alcohols vs. acids), lipid chain length, and whether lipids originated in leaves or roots. Collectively, these factors explained ~80% of the variation in soil lipid concentrations beneath 11 different tree species. In order to use soil lipid analyses to test and improve conceptual models of soil organic matter stabilization, additional studies that provide experimental and quantitative (i.e. statistical) constraints on plant lipid preservation are needed.

Lipid Microarray Biosensor for Biotoxin Detection.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Anup K.; Throckmorton, Daniel J.; Moran-Mirabal, Jose C.

2006-05-01

We present the use of micron-sized lipid domains, patterned onto planar substrates and within microfluidic channels, to assay the binding of bacterial toxins via total internal reflection fluorescence microscopy (TIRFM). The lipid domains were patterned using a polymer lift-off technique and consisted of ganglioside-populated DSPC:cholesterol supported lipid bilayers (SLBs). Lipid patterns were formed on the substrates by vesicle fusion followed by polymer lift-off, which revealed micron-sized SLBs containing either ganglioside GT1b or GM1. The ganglioside-populated SLB arrays were then exposed to either Cholera toxin subunit B (CTB) or Tetanus toxin fragment C (TTC). Binding was assayed on planar substrates bymore » TIRFM down to 1 nM concentration for CTB and 100 nM for TTC. Apparent binding constants extracted from three different models applied to the binding curves suggest that binding of a protein to a lipid-based receptor is strongly affected by the lipid composition of the SLB and by the substrate on which the bilayer is formed. Patterning of SLBs inside microfluidic channels also allowed the preparation of lipid domains with different compositions on a single device. Arrays within microfluidic channels were used to achieve segregation and selective binding from a binary mixture of the toxin fragments in one device. The binding and segregation within the microfluidic channels was assayed with epifluorescence as proof of concept. We propose that the method used for patterning the lipid microarrays on planar substrates and within microfluidic channels can be easily adapted to proteins or nucleic acids and can be used for biosensor applications and cell stimulation assays under different flow conditions. KEYWORDS. Microarray, ganglioside, polymer lift-off, cholera toxin, tetanus toxin, TIRFM, binding constant.4« less

Lipid transfer proteins do their thing anchored at membrane contact sites… but what is their thing?

PubMed

Wong, Louise H; Levine, Tim P

2016-04-15

Membrane contact sites are structures where two organelles come close together to regulate flow of material and information between them. One type of inter-organelle communication is lipid exchange, which must occur for membrane maintenance and in response to environmental and cellular stimuli. Soluble lipid transfer proteins have been extensively studied, but additional families of transfer proteins have been identified that are anchored into membranes by transmembrane helices so that they cannot diffuse through the cytosol to deliver lipids. If such proteins target membrane contact sites they may be major players in lipid metabolism. The eukaryotic family of so-called Lipid transfer proteins Anchored at Membrane contact sites (LAMs) all contain both a sterol-specific lipid transfer domain in the StARkin superfamily (related to StART/Bet_v1), and one or more transmembrane helices anchoring them in the endoplasmic reticulum (ER), making them interesting subjects for study in relation to sterol metabolism. They target a variety of membrane contact sites, including newly described contacts between organelles that were already known to make contact by other means. Lam1-4p target punctate ER-plasma membrane contacts. Lam5p and Lam6p target multiple contacts including a new category: vacuolar non-NVJ cytoplasmic ER (VancE) contacts. These developments confirm previous observations on tubular lipid-binding proteins (TULIPs) that established the importance of membrane anchored proteins for lipid traffic. However, the question remaining to be solved is the most difficult of all: are LAMs transporters, or alternately are they regulators that affect traffic more indirectly? © 2016 Authors; published by Portland Press Limited.

Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment.

PubMed

Cordeiro, Fernanda Bertuccez; Cataldi, Thaís Regiani; do Vale Teixeira da Costa, Lívia; de Lima, Camila Bruna; Stevanato, Juliana; Zylbersztejn, Daniel Suslik; Ferreira, Christina Ramires; Eberlin, Marcos Nogueira; Cedenho, Agnaldo Pereira; Turco, Edson Guimarães Lo

2015-01-01

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation. Follicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment. The lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR). These findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.

Evaluation of Lipid Profile in Patients with Cherry Angioma: A Case-Control Study in Guilan, Iran.

PubMed

Darjani, Abbas; Rafiei, Rana; Shafaei, Sareh; Rafiei, Elahe; Eftekhari, Hojat; Alizade, Narges; Gharaei Nejad, Kaveh; Rafiee, Behnam; Najirad, Sara

2018-01-01

Cherry angioma is the most common type of acquired cutaneous vascular proliferation which would increase with aging due to some angiogenic factors but the exact pathogenesis is unknown. Usually angiogenic factors are synthesized in human body to compensate occlusive effects of atherogenic agents such as serum lipids. Our hypothesis was that increased levels of these angiogenic factors could be a trigger for development of cherry angioma. This study has been designed to compare frequency of dyslipidemia in subjects with and without cutaneous cherry angioma. In this case-control study, 122 cases with cherry angioma and 122 control subjects without cherry angioma were enrolled. Demographic characteristics, number of the cherry angioma lesions, and serum lipid profile were collected for all subjects. The data was analyzed using SPSS 18 software. Mean levels of the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were higher in patients with cherry angioma compared to control subjects in which differences were significant for total cholesterol, low-density lipoprotein, and triglyceride ( P < 0.05) but not for high-density lipoprotein level. Serum lipids may have a role in producing angiogenic factors and development of cherry angioma and it seems logical to evaluate lipid profile in these cases.

Lipid emulsions differentially affect LPS-induced acute monocytes inflammation: in vitro effects on membrane remodeling and cell viability.

PubMed

Boisramé-Helms, Julie; Delabranche, Xavier; Klymchenko, Andrey; Drai, Jocelyne; Blond, Emilie; Zobairi, Fatiha; Mely, Yves; Hasselmann, Michel; Toti, Florence; Meziani, Ferhat

2014-11-01

The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)-induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell-growth medium was supplemented with three different industrial lipid emulsions: Intralipid(®), containing long-chain triglycerides (LCT--soybean oil); Medialipid(®), containing LCT (soybean oil) and medium-chain triglycerides (MCT--coconut oil); and SMOFlipid(®), containing LCT, MCT, omega-9 and -3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid(®) compared to Intralipid(®), SMOFlipid(®) and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid-treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n-3 and n-9 fatty acids have no effect on endotoxin-induced cell death and inflammation.

Engineering Lipid Bilayer Membranes for Protein Studies

PubMed Central

Khan, Muhammad Shuja; Dosoky, Noura Sayed; Williams, John Dalton

2013-01-01

Lipid membranes regulate the flow of nutrients and communication signaling between cells and protect the sub-cellular structures. Recent attempts to fabricate artificial systems using nanostructures that mimic the physiological properties of natural lipid bilayer membranes (LBM) fused with transmembrane proteins have helped demonstrate the importance of temperature, pH, ionic strength, adsorption behavior, conformational reorientation and surface density in cellular membranes which all affect the incorporation of proteins on solid surfaces. Much of this work is performed on artificial templates made of polymer sponges or porous materials based on alumina, mica, and porous silicon (PSi) surfaces. For example, porous silicon materials have high biocompatibility, biodegradability, and photoluminescence, which allow them to be used both as a support structure for lipid bilayers or a template to measure the electrochemical functionality of living cells grown over the surface as in vivo. The variety of these media, coupled with the complex physiological conditions present in living systems, warrant a summary and prospectus detailing which artificial systems provide the most promise for different biological conditions. This study summarizes the use of electrochemical impedance spectroscopy (EIS) data on artificial biological membranes that are closely matched with previously published biological systems using both black lipid membrane and patch clamp techniques. PMID:24185908

Lipid production in aquatic plant Azolla at vegetative and reproductive stages and in response to abiotic stress.

PubMed

Miranda, Ana F; Liu, Zhiqian; Rochfort, Simone; Mouradov, Aidyn

2018-03-01

The aquatic plant Azolla became increasingly popular as bioenergy feedstock because of its high growth rate, production of biomass with high levels of biofuel-producing molecules and ability to grow on marginal lands. In this study, we analysed the contribution of all organs of Azolla to the total yield of lipids at vegetative and reproductive stages and in response to stress. Triacylglycerol-containing lipid droplets were detected in all (vegetative and reproductive) organs with the highest level in the male microsporocarps and microspores. As a result, significantly higher total yields of lipids were detected in Azolla filiculoides and Azolla pinnata at the reproductive stage. Starving changed the yield and composition of the fatty acid as a result of re-direction of carbon flow from fatty acid to anthocyanin pathways. The composition of lipids, in regard the length and degree of unsaturation of fatty acids, in Azolla meets most of the important requirements for biodiesel standards. The ability of Azolla to grow on wastewaters, along with their high productivity rate, makes it an attractive feedstock for the production of biofuels. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effects of right ventricular hemodynamic burden on intraventricular flow in tetralogy of fallot: an echocardiographic contrast particle imaging velocimetry study.

PubMed

Kutty, Shelby; Li, Ling; Danford, David A; Houle, Helene; Datta, Saurabh; Mancina, Joel; Xiao, Yunbin; Pedrizzetti, Gianni; Porter, Thomas R

2014-12-01

The purpose of this investigation was to test the hypothesis that flow patterns in the right ventricle are abnormal in patients with repaired tetralogy of Fallot (TOF). High-resolution echocardiographic contrast particle imaging velocimetry was used to investigate rotation intensity and kinetic energy dissipation of right ventricular (RV) flow in patients with TOF compared with normal controls. Forty-one subjects (16 with repaired TOF and varying degrees of RV dilation and 25 normal controls) underwent prospective contrast imaging using the lipid-encapsulated microbubble (Definity) on Sequoia systems. A mechanical index of 0.4, three-beat high-frame rate (>60 Hz) captures, and harmonic frequencies were used. Rotation intensity and kinetic energy dissipation of flow in the right and left ventricles were studied (Hyperflow). Ventricular volumes and ejection fractions in all subjects were derived from same-day cardiac magnetic resonance (CMR). Measurable planar maps were obtained for the left ventricle in 14 patients and the right ventricle in 10 patients among those with TOF and for the left ventricle in 23 controls and the right ventricle in 21 controls. Compared with controls, the TOF group had higher RV indexed end-diastolic volumes (117.8 ± 25.5 vs 88 ± 15.4 mL/m(2), P < .001) and lower RV ejection fractions (44.6 ± 3.6% vs 51.8 ± 3.6%, P < .001). Steady-streaming (heartbeat-averaged) flow rotation intensities were higher in patients with TOF for the left ventricle (0.4 ± 0.13 vs 0.29 ± 0.08, P = .012) and the right ventricle (0.53 ± 0.15 vs 0.26 ± 0.12, P < .001), whereas kinetic energy dissipation in TOF ventricles was lower (for the left ventricle, 0.51 ± 0.29 vs 1.52 ± 0.69, P < .001; for the right ventricle, 0.4 ± 0.24 vs 1.65 ± 0.91, P < .001). It is feasible to characterize RV and left ventricular flow parameters and planar maps in adolescents and adults with repaired TOF using echocardiographic contrast particle imaging velocimetry. Intraventricular flow patterns in the abnormal and/or enlarged right ventricle in patients with TOF differ from those in normal young adults. The rotation intensity and energy dissipation trends in this investigation suggest that they may be quantitative markers of RV and left ventricular compliance abnormalities in patients with repaired TOF. This hypothesis merits further investigation. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

PubMed

Chia, L S; Thompson, J E; Moscarello, M A

1984-09-05

Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

[Peroxisome proliferator activated receptors PPARs: their role in carbohydrate and lipid metabolism].

PubMed

Andrééva-Gatéva, P

2003-01-01

Peroxisome proliferator activated receptors (PPAR) belong to a family of nuclear receptors broadly distributed in the organism. Their pleiotropic role has been recently proved as well as their pathogenic significance in diabetes, obesity, cell cycle controlling, carcinogenesis, inflammation and atherosclerosis. The three types of PPAR identified until today have different tissue localization. PPARgamma, primarily identified in macrophages and adipocytes, play an important role in the expression of proteins essential for lipid metabolism and adipogenesis. PPARalpha are localized predominantly in hepatocytes and have also an important role in lipid metabolism. PPAR are though to be lipid sensors in organism. Carbohydrate metabolism is also under the control of PPAR and their exogenous ligands, (ie: thiasolidinediones), are important antidiabetic drugs.

[Relationship between lipid alterations during pregnancy and adverse pregnancy outcomes].

PubMed

Ferriols, Elena; Rueda, Carolina; Gamero, Rocío; Vidal, Mar; Payá, Antonio; Carreras, Ramón; Flores-le Roux, Juana A; Pedro-Botet, Juan

Lipids play an important role during pregnancy, and in this period major changes occur in lipoprotein metabolism. During the third trimester plasma cholesterol and triglyceride levels are substantially increased, returning to normal after delivery. Described associations between increased morbidity during pregnancy and excessive increases in plasma cholesterol and triglycerides. For this reason we have reviewed the relationship between lipid alterations, preeclampsia, gestational diabetes and preterm birth. The overall metabolic control can improve pregnancy outcomes, and the assessment of supraphysiological changes in lipid profile will classify pregnancy risk at a higher level, which would entail a stricter control. Copyright © 2015 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Disruption of THY-1 signaling in alveolar lipofibroblasts in experimentally induced congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Hofmann, Alejandro Daniel; Takahashi, Hiromizu; Takahashi, Toshiaki; Gosemann, Jan-Hendrik; Puri, Prem

2014-02-01

Pulmonary hypoplasia (PH), characterized by alveolar immaturity, remains the main cause of neonatal mortality and long-term morbidity in infants with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) are critically important for normal alveolar development. Thymocyte antigen 1 (Thy-1) is a highly expressed cell-surface protein in this specific subset of lung fibroblasts, which plays a key role in fetal alveolarization by coordinating the differentiation and lipid homeostasis of alveolar LIFs. Thy-1 increases the lipid content of LIFs by upregulation of adipocyte differentiation-related protein (ADRP), a lipogenic molecular marker characterizing pulmonary LIFs. Thy-1 (-/-) mice further show impaired alveolar development with reduced proliferation of pulmonary LIFs, resulting in a PH-similar phenotype. We hypothesized that pulmonary Thy-1 signaling is disrupted in experimentally induced CDH, which may has an adverse effect on the lipid content of alveolar LIFs. Timed-pregnant Sprague-Dawley rats were treated with either 100 mg nitrofen or vehicle on embryonic day 9.5 (E9.5). Fetuses were killed on E21.5, and lungs were divided into controls (n = 14) and CDH-associated PH (n = 14). Pulmonary gene expression levels of Thy-1 and ADRP were assessed by quantitative real-time PCR. ADRP immunohistochemistry and oil-red-O staining were used to localize alveolar LIF expression and lipid droplets. Immunofluorescence double staining for Thy-1 and oil-red-O was performed to evaluate Thy-1 expression and lipid content in alveolar LIFs. Radial alveolar count was significantly reduced in CDH-associated PH with significant downregulation of pulmonary Thy-1 and ADRP mRNA expression compared to controls. ADRP immunoreactivity and lipid droplets were markedly diminished in alveolar interstitial cells, which coincided with decreased alveolar LIF expression in CDH-associated PH compared to controls. Confocal laser scanning microscopy confirmed markedly decreased Thy-1 expression and lipid content in alveolar LIFs of CDH-associated PH compared to controls. Our study provides strong evidence that disruption of pulmonary Thy-1 signaling results in reduced lipid droplets in alveolar LIFs and may thus contribute to PH in the nitrofen-induced CDH model. Treatment modalities aimed at increasing lipid content in alveolar LIFs may therefore have a therapeutic potential in attenuating CDH-associated PH.

Effects of diet, packaging, and irradiation on protein oxidation, lipid oxidation, and color of raw broiler thigh meat during refrigerated storage.

PubMed

Xiao, S; Zhang, W G; Lee, E J; Ma, C W; Ahn, D U

2011-06-01

This study was designed to evaluate the effects of dietary treatment, packaging, and irradiation singly or in combination on the oxidative stability of broiler chicken thigh meat. A total of 120 four-week-old chickens were divided into 12 pens (10 birds/pen), and 4 pens of broilers were randomly assigned to a control oxidized diet (5% oxidized oil) or an antioxidant-added diet [500 IU of vitamin E + 200 mg/kg of butylated hydroxyanisole (BHA)] and fed for 2 wk. After slaughter, thigh meats were separated, ground, packaged in either oxygen-permeable or oxygen-impermeable vacuum bags, and irradiated at 0 or 3 kGy. Lipid oxidation (TBA-reactive substances), protein oxidation (carbonyl), and color of the meat were measured at 1, 4, and 7 d of refrigerated storage. The lipid and protein oxidation of thigh meats from birds fed the diet supplemented with antioxidants (vitamin E + BHA) was significantly lower than the lipid and protein oxidation of birds fed the control diet, whereas the lipid and protein oxidation of broilers fed the oxidized oil diet was higher than that of birds fed the control diet. Vacuum packaging slowed, but irradiation accelerated, the lipid and protein oxidation of thigh meat during storage. Dietary antioxidants (vitamin E + BHA) and irradiation treatments showed a stronger effect on lipid oxidation than on protein oxidation. A significant correlation between lipid and protein oxidation in meat was found during storage. Dietary supplementation of vitamin E + BHA and the irradiation treatment increased the lightness and redness of thigh meat, respectively. It is suggested that appropriate use of dietary antioxidants in combination with packaging could be effective in minimizing oxidative changes in irradiated raw chicken thigh meat.

Acute β-Hydroxy-β-Methyl Butyrate Suppresses Regulators of Mitochondrial Biogenesis and Lipid Oxidation While Increasing Lipid Content in Myotubes.

PubMed

Schnuck, Jamie K; Johnson, Michele A; Gould, Lacey M; Gannon, Nicholas P; Vaughan, Roger A

2016-10-01

Leucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine-derived metabolite β-hydroxy-β-methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB-treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator-activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP-activated protein kinase. As a result, HMB-treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.

Saliva as a surrogate to explore the association between lipid profiles and chronic periodontitis: A case-control study

PubMed Central

Kalburgi, Veena; Leburu, Sravya; Warad, Shivaraj

2014-01-01

Background: There is abundance of literature delving into whether periodontal infection contributes to changes in serum lipid profiles. Whole saliva is an important physiologic fluid that contains a highly complex mixture of substances. Research on salivary lipid profiles and chronic periodontitis remains unexplored and limited. This study was designed with an aim to investigate the association between the chronic periodontitis and salivary lipid levels and to make use of saliva as a non-invasive diagnostic aid. Materials and Methods: This case-control study included 60 subjects of which, 40 were diagnosed as having chronic periodontitis based on the probing depth and clinical attachment levels and 20 healthy subjects as control group. Whole saliva was collected and lipid concentrations (total cholesterol (TC), triglycerides (TG), low density lipoprotein [LDL] and high density lipoprotein [HDL]) were assessed by enzymatic methods and the values were read in ultraviolet-Spectrophotometer. Data was analyzed using student's t test for equality of means. P < 0.05 was considered to be statistically significant. Results: The mean difference in the concentrations of TC and TG in saliva of chronic periodontitis patients were statistically significant (P = 0.02) when compared to the healthy. HDL and LDL concentrations were not statistically significant, but there was a difference in their means. LDL was higher in chronic periodontitis and HDL mean levels were high among the healthy. Conclusion: Increased salivary lipids in chronic periodontitis patients suggest an association between hyperlipidemia and periodontitis. The relatively easy and non-invasive nature of saliva can be used as a diagnostic tool to assess the lipid status. Further research is needed to determine its specificity as a surrogate to serum lipid profiles. PMID:25540654

Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans.

PubMed

Bernelot Moens, Sophie J; Verweij, Simone L; Schnitzler, Johan G; Stiekema, Lotte C A; Bos, Merijn; Langsted, Anne; Kuijk, Carlijn; Bekkering, Siroon; Voermans, Carlijn; Verberne, Hein J; Nordestgaard, Børge G; Stroes, Erik S G; Kroon, Jeffrey

2017-05-01

Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). Arterial wall inflammation and bone marrow activity were measured using 18 F-FDG PET/CT. Monocyte phenotype was assessed with flow cytometry. The correlation between remnant levels and hematopoietic activity was validated in the CGPS (Copenhagen General Population Study). We found a 1.2-fold increase of 18 F-FDG uptake in the arterial wall in patients with FD (n=17, age 60±8 years, remnant cholesterol: 3.26 [2.07-5.71]) compared with controls (n=17, age 61±8 years, remnant cholesterol 0.29 [0.27-0.40]; P <0.001). Monocytes from patients with FD showed increased lipid accumulation (lipid-positive monocytes: Patients with FD 92% [86-95], controls 76% [66-81], P =0.001, with an increase in lipid droplets per monocyte), and a higher expression of surface integrins (CD11b, CD11c, and CD18). Patients with FD also exhibited monocytosis and leukocytosis, accompanied by a 1.2-fold increase of 18 F-FDG uptake in bone marrow. In addition, we found a strong correlation between remnant levels and leukocyte counts in the CGPS (n=103 953, P for trend 5×10-276). In vitro experiments substantiated that remnant cholesterol accumulates in human hematopoietic stem and progenitor cells coinciding with myeloid skewing. Patients with FD have increased arterial wall and cellular inflammation. These findings imply an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to the increased cardiovascular disease risk in patients with FD. © 2017 American Heart Association, Inc.

Analysis and optimization of triacylglycerol synthesis in novel oleaginous Rhodococcus and Streptomyces strains isolated from desert soil.

PubMed

Röttig, Annika; Hauschild, Philippa; Madkour, Mohamed H; Al-Ansari, Ahmed M; Almakishah, Naief H; Steinbüchel, Alexander

2016-05-10

As oleaginous microorganisms represent an upcoming novel feedstock for the biotechnological production of lipids or lipid-derived biofuels, we searched for novel, lipid-producing strains in desert soil. This was encouraged by the hypothesis that neutral lipids represent an ideal storage compound, especially under arid conditions, as several animals are known to outlast long periods in absence of drinking water by metabolizing their body fat. Ten lipid-accumulating bacterial strains, affiliated to the genera Bacillus, Cupriavidus, Nocardia, Rhodococcus and Streptomyces, were isolated from arid desert soil due to their ability to synthesize poly(β-hydroxybutyrate), triacylglycerols or wax esters. Particularly two Streptomyces sp. strains and one Rhodococcus sp. strain accumulate significant amounts of TAG under storage conditions under optimized cultivation conditions. Rhodococcus sp. A27 and Streptomyces sp. G49 synthesized approx. 30% (w/w) fatty acids from fructose or cellobiose, respectively, while Streptomyces isolate G25 reached a cellular fatty acid content of nearly 50% (w/w) when cultivated with cellobiose. The stored triacylglycerols were composed of 30-40% branched fatty acids, such as anteiso-pentadecanoic or iso-hexadecanoic acid. To date, this represents by far the highest lipid content described for streptomycetes. A biotechnological production of such lipids using (hemi)cellulose-derived raw material could be used to obtain sustainable biodiesel with a high proportion of branched-chain fatty acids to improve its cold-flow properties and oxidative stability. Copyright © 2016 Elsevier B.V. All rights reserved.

76 FR 23324 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31, rm... Cardiovascular Risk in Diabetes-Lipid (ACCORD Lipid) trial as they relate to the efficacy and safety of the... cholesterol goal. The ACCORD Lipid study was a randomized, double-blind, placebo- controlled add-on trial...

Targeting SREBP-1-driven lipid metabolism to treat cancer

PubMed Central

Guo, Deliang; Bell, Erica Hlavin; Mischel, Paul; Chakravarti, Arnab

2014-01-01

Metabolic reprogramming is a hallmark of cancer. Oncogenic growth signaling regulates glucose, glutamine and lipid metabolism to meet the bioenergetics and biosynthetic demands of rapidly proliferating tumor cells. Emerging evidence indicates that sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that controls lipid metabolism, is a critical link between oncogenic signaling and tumor metabolism. We recently demonstrated that SREBP-1 is required for the survival of mutant EGFR-containing glioblastoma, and that this pro-survival metabolic pathway is mediated, in part, by SREBP-1-dependent upregulation of the fatty acid synthesis and low density lipoprotein (LDL) receptor (LDLR). These results have identified EGFR/PI3K/Akt/SREBP-1 signaling pathway that promotes growth and survival in glioblastoma, and potentially other cancer types. Here, we summarize recent insights in the understanding of cancer lipid metabolism, and discuss the evidence linking SREBP-1 with PI3K/Akt signaling-controlled glycolysis and with Myc-regulated glutaminolysis to lipid metabolism. We also discuss the development of potential drugs targeting the SREBP-1-driven lipid metabolism as anti-cancer agents. PMID:23859617

Electrostatic swelling of bicontinuous cubic lipid phases.

PubMed

Tyler, Arwen I I; Barriga, Hanna M G; Parsons, Edward S; McCarthy, Nicola L C; Ces, Oscar; Law, Robert V; Seddon, John M; Brooks, Nicholas J

2015-04-28

Lipid bicontinuous cubic phases have attracted enormous interest as bio-compatible scaffolds for use in a wide range of applications including membrane protein crystallisation, drug delivery and biosensing. One of the major bottlenecks that has hindered exploitation of these structures is an inability to create targeted highly swollen bicontinuous cubic structures with large and tunable pore sizes. In contrast, cubic structures found in vivo have periodicities approaching the micron scale. We have been able to engineer and control highly swollen bicontinuous cubic phases of spacegroup Im3m containing only lipids by (a) increasing the bilayer stiffness by adding cholesterol and (b) inducing electrostatic repulsion across the water channels by addition of anionic lipids to monoolein. By controlling the composition of the ternary mixtures we have been able to achieve lattice parameters up to 470 Å, which is 5 times that observed in pure monoolein and nearly twice the size of any lipidic cubic phase reported previously. These lattice parameters significantly exceed the predicted maximum swelling for bicontinuous cubic lipid structures, which suggest that thermal fluctuations should destroy such phases for lattice parameters larger than 300 Å.

Effective Brownian ratchet separation by a combination of molecular filtering and a self-spreading lipid bilayer system.

PubMed

Motegi, Toshinori; Nabika, Hideki; Fu, Yingqiang; Chen, Lili; Sun, Yinlu; Zhao, Jianwei; Murakoshi, Kei

2014-07-01

A new molecular manipulation method in the self-spreading lipid bilayer membrane by combining Brownian ratchet and molecular filtering effects is reported. The newly designed ratchet obstacle was developed to effectively separate dye-lipid molecules. The self-spreading lipid bilayer acted as both a molecular transport system and a manipulation medium. By controlling the size and shape of ratchet obstacles, we achieved a significant increase in the separation angle for dye-lipid molecules compared to that with the previous ratchet obstacle. A clear difference was observed between the experimental results and the simple random walk simulation that takes into consideration only the geometrical effect of the ratchet obstacles. This difference was explained by considering an obstacle-dependent local decrease in molecular diffusivity near the obstacles, known as the molecular filtering effect at nanospace. Our experimental findings open up a novel controlling factor in the Brownian ratchet manipulation that allow the efficient separation of molecules in the lipid bilayer based on the combination of Brownian ratchet and molecular filtering effects.

Climate change and cutaneous water loss of birds.

PubMed

Williams, Joseph B; Muñoz-Garcia, Agustí; Champagne, Alex

2012-04-01

There is a crucial need to understand how physiological systems of animals will respond to increases in global air temperature. Water conservation may become more important for some species of birds, especially those living in deserts. Lipids of the stratum corneum (SC), the outer layer of the epidermis, create the barrier to water vapor diffusion, and thus control cutaneous water loss (CWL). An appreciation of the ability of birds to change CWL by altering lipids of the skin will be important to predict responses of birds to global warming. The interactions of these lipids are fundamental to the modulation of water loss through skin. Cerebrosides, with their hexose sugar moiety, are a key component of the SC in birds, but how these lipids interact with other lipids of the SC, or how they form hydrogen bonds with water molecules, to form a barrier to water vapor diffusion remains unknown. An understanding of how cerebrosides interact with other lipids of the SC, and of how the hydroxyl groups of cerebrosides interact with water molecules, may be a key to elucidating the control of CWL by the SC.

Exploiting lipopolysaccharide-induced deformation of lipid bilayers to modify membrane composition and generate two-dimensional geometric membrane array patterns

DOE PAGES

Adams, Peter G.; Swingle, Kirstie L.; Paxton, Walter F.; ...

2015-05-27

Supported lipid bilayers have proven effective as model membranes for investigating biophysical processes and in development of sensor and array technologies. The ability to modify lipid bilayers after their formation and in situ could greatly advance membrane technologies, but is difficult via current state-of-the-art technologies. Here we demonstrate a novel method that allows the controlled post-formation processing and modification of complex supported lipid bilayer arrangements, under aqueous conditions. We exploit the destabilization effect of lipopolysaccharide, an amphiphilic biomolecule, interacting with lipid bilayers to generate voids that can be backfilled to introduce desired membrane components. We further demonstrate that when usedmore » in combination with a single, traditional soft lithography process, it is possible to generate hierarchically-organized membrane domains and microscale 2-D array patterns of domains. Significantly, this technique can be used to repeatedly modify membranes allowing iterative control over membrane composition. This approach expands our toolkit for functional membrane design, with potential applications for enhanced materials templating, biosensing and investigating lipid-membrane processes.« less

On-Chip Electrophoresis in Supported Lipid Bilayer Membranes Achieved Using Low Potentials

PubMed Central

2013-01-01

A micro supported lipid bilayer (SLB) electrophoresis method was developed, which functions at low potentials and appreciable operating times. To this end, (hydroxymethyl)-ferrocene (FcCH2OH) was employed to provide an electrochemical reaction at the anode and cathode at low applied potential to avoid electrolysis of water. The addition of FcCH2OH did not alter the SLB characteristics or affect biomolecule function, and pH and temperature variations and bubble formation were eliminated. Applying potentials of 0.25–1.2 V during flow gave homogeneous electrical fields and a fast, reversible, and strong build-up of a charged dye-modified lipid in the direction of the oppositely charged electrode. Moreover, streptavidin mobility could be modulated. This method paves the way for further development of analytical devices. PMID:24345193

Aeration strategy for biofilm cultivation of the microalga Scenedesmus dimorphus.

PubMed

Ji, Chunli; Wang, Junfeng; Liu, Tianzhong

2015-10-01

Biofilm cultivation of microalgae may be useful for biofuel production. However, many aspects for this cultivation method have not been well assessed. Accordingly, aeration strategy for biofilm cultivation of Scenedesmus dimorphus has been explored. Biomass, lipid and triacylglycerol (TAG) productivity in increased S. dimorphus as the CO2 concentration increased within 0.038-0.5% and kept constant with further increases. The biomass, lipid and TAG productivity increased with the speed increasing and an obvious threshold point was observed at 6.6 ml(-2) min(-1). The lipid and TAG content was unaffected by the aeration rate. Both the CO2 concentration as well as aeration speed affected the growth of S. dimorphus in biofilm cultivation. The optimized aeration strategy for biofilm cultivation was continuous air flow enriched with 1% CO2 (v/v) at 6.6 ml(-2) min(-1).

Effect of gamma 60Co irradiation on the lipid content and fatty acid composition of Nannochloropsis sp. microalgae

NASA Astrophysics Data System (ADS)

Ermavitalini, Dini; Sari, Ika Puspita; Prasetyo, Endry Nugroho; Abdulgani, Nurlita; Saputro, Triono Bagus

2017-06-01

Nannochloropsissp. has been identified as a promising feed stock for biodiesel production in recent years. Nannochloropsis sp. have high lipid content between 31-68 % of dry biomass weight. Mutagenesis induced by Gamma 60Co irradiation can be utilized to alter Nannochloropsis sp. characteristic to get microalgae mutant strain that can produce a higher lipid content than the wild strain. The aim of this research was to know the effect of gamma 60Co irradiation to the biomass, lipid content and fatty acid compotition of Nannochloropsis sp. microalgae. In this research, irradiation was done in different doses there were 0, 2, 4, 6 and 10 Gray (Gy). Measuring microalgae biomass and lipid content were done in late exponential phase at the end of each treatment. Research design used is random complete with 95 % confident level for quantitative analysis based on biomass and lipid content. Fatty acid compotition was analyzed by gas chromatography-mass spectrometry (GC-MS). Results showed that gamma irradiated gave an effect on lipid content and fatty acid profile of Nannochloropsis sp. Tukey test showed total lipid content of control micoalgae (0 Gy) was significat different with 10 Gy irradiated microalgae, but no significant different with 2,4 and 6 Gy irradiated microalgae. The highest lipid content were found in 10 Gy irradiated microalgae equal to 62.65 %. Fatty acid profile of 10 Gy irradiated Nannochloropsis sp. had 9 fatty acids while control Nannochloropsis sp. had 6 fatty acids.

Enhanced lipid production by Rhodosporidium toruloides using different fed-batch feeding strategies with lignocellulosic hydrolysate as the sole carbon source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fei, Qiang; O'Brien, Marykate; Nelson, Robert

Industrial biotechnology that is able to provide environmentally friendly bio-based products has attracted more attention in replacing petroleum-based industries. Currently, most of the carbon sources used for fermentation-based bioprocesses are obtained from agricultural commodities that are used as foodstuff for human beings. Lignocellulose-derived sugars as the non-food, green, and sustainable alternative carbon sources have great potential to avoid this dilemma for producing the renewable, bio-based hydrocarbon fuel precursors, such as microbial lipid. Efficient bioconversion of lignocellulose-based sugars into lipids is one of the critical parameters for industrial application. Therefore, the fed-batch cultivation, which is a common method used in industrialmore » applications, was investigated to achieve a high cell density culture along with high lipid yield and productivity. In this study, several fed-batch strategies were explored to improve lipid production using lignocellulosic hydrolysates derived from corn stover. Compared to the batch culture giving a lipid yield of 0.19 g/g, the dissolved-oxygen-stat feeding mode increased the lipid yield to 0.23 g/g and the lipid productivity to 0.33 g/L/h. The pulse feeding mode further improved lipid productivity to 0.35 g/L/h and the yield to 0.24 g/g. However, the highest lipid yield (0.29 g/g) and productivity (0.4 g/L/h) were achieved using an automated online sugar control feeding mode, which gave a dry cell weight of 54 g/L and lipid content of 59 % (w/w). The major fatty acids of the lipid derived from lignocellulosic hydrolysates were predominately palmitic acid and oleic acid, which are similar to those of conventional oilseed plants. Our results suggest that the fed-batch feeding strategy can strongly influence the lipid production. Lastly, the online sugar control feeding mode was the most appealing strategy for high cell density, lipid yield, and lipid productivity using lignocellulosic hydrolysates as the sole carbon source.« less

Enhanced lipid production by Rhodosporidium toruloides using different fed-batch feeding strategies with lignocellulosic hydrolysate as the sole carbon source

DOE PAGES

Fei, Qiang; O'Brien, Marykate; Nelson, Robert; ...

2016-06-23

Industrial biotechnology that is able to provide environmentally friendly bio-based products has attracted more attention in replacing petroleum-based industries. Currently, most of the carbon sources used for fermentation-based bioprocesses are obtained from agricultural commodities that are used as foodstuff for human beings. Lignocellulose-derived sugars as the non-food, green, and sustainable alternative carbon sources have great potential to avoid this dilemma for producing the renewable, bio-based hydrocarbon fuel precursors, such as microbial lipid. Efficient bioconversion of lignocellulose-based sugars into lipids is one of the critical parameters for industrial application. Therefore, the fed-batch cultivation, which is a common method used in industrialmore » applications, was investigated to achieve a high cell density culture along with high lipid yield and productivity. In this study, several fed-batch strategies were explored to improve lipid production using lignocellulosic hydrolysates derived from corn stover. Compared to the batch culture giving a lipid yield of 0.19 g/g, the dissolved-oxygen-stat feeding mode increased the lipid yield to 0.23 g/g and the lipid productivity to 0.33 g/L/h. The pulse feeding mode further improved lipid productivity to 0.35 g/L/h and the yield to 0.24 g/g. However, the highest lipid yield (0.29 g/g) and productivity (0.4 g/L/h) were achieved using an automated online sugar control feeding mode, which gave a dry cell weight of 54 g/L and lipid content of 59 % (w/w). The major fatty acids of the lipid derived from lignocellulosic hydrolysates were predominately palmitic acid and oleic acid, which are similar to those of conventional oilseed plants. Our results suggest that the fed-batch feeding strategy can strongly influence the lipid production. Lastly, the online sugar control feeding mode was the most appealing strategy for high cell density, lipid yield, and lipid productivity using lignocellulosic hydrolysates as the sole carbon source.« less

Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults.

PubMed

Engler, Mary B; Engler, Marguerite M; Chen, Chung Y; Malloy, Mary J; Browne, Amanda; Chiu, Elisa Y; Kwak, Ho-Kyung; Milbury, Paul; Paul, Steven M; Blumberg, Jeffrey; Mietus-Snyder, Michele L

2004-06-01

Dark chocolate derived from the plant (Theobroma cacao) is a rich source of flavonoids. Cardioprotective effects including antioxidant properties, inhibition of platelet activity, and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids. To investigate the effects of flavonoid-rich dark chocolate on endothelial function, measures of oxidative stress, blood lipids, and blood pressure in healthy adult subjects. The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz). High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 +/- 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 +/- 0.5%) (p = 0.024). No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or body mass index (BMI) between the two groups. Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group (204.4 +/- 18.5 nmol/L, p < or = 0.001) but not in the low-flavonoid group (17.5 +/- 9 nmol/L, p = 0.99). Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults. No changes in oxidative stress measures, lipid profiles, blood pressure, body weight or BMI were seen.

State-dependent alterations of lipid profiles in patients with bipolar disorder.

PubMed

Huang, Yu-Jui; Tsai, Shang-Ying; Chung, Kuo-Hsuan; Chen, Pao-Huan; Huang, Shou-Hung; Kuo, Chian-Jue

2018-07-01

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p < 0.025). The lowest rate of dyslipidemia (hypertriglyceridemia or low high-density lipoprotein cholesterol) was observed in acute bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states.

Effects of perfluorinated chemicals on adipocyte development ...

EPA Pesticide Factsheets

Obesity is a growing concern in the US population. Current interest is high in the role played by environmental factors called obesogens that may contribute to obesity through developmental exposure. One class of potential obesogens is the family of perfluorinated chemicals used as surfactants in a variety of industrial applications. Given the importance of understanding the role these compounds play in lipid homeostasis we used pre-adipocyte 3T3-L1 mouse fibroblast cells (Zen-Bio, RTP NC) to study their effects on adipogenesis and lipid accumulation. These cells differentiate into adipocytes accumulating large lipid droplets. Cultures were treated with perfluorooctanoic acid (PFOA) (1-200uM), perfluorononanoic acid (PFNA) (5-lOOuM), perfluorooctane sulfonate (PFOS) (5O-300uM), and perfluorohexane sulfonate (PFHxS) (40- 250uM). Cell size number, and lipid content were assessed using morphomeiric analysis. All four compounds decreased cell size compared to control, and PFNA was most potent, in terms of lowest observed effect concentration (LOEC), whereas PFOA was least potent. Cell number increased for all perfluorinated chemicals tested, most potently for PFNA and least for PFOS. Interestingly, average lipid area per cell for all four chemicals decreased compared to control, but PFOS and PFHxS had increased total lipid area. Additionally, significant increases in total triglyceride were noted for all compounds compared to controls. PFOA and PFNA increased trigly

Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

PubMed

Famurewa, Ademola C; Ekeleme-Egedigwe, Chima A; Nwali, Sophia C; Agbo, Ngozi N; Obi, Joy N; Ezechukwu, Goodness C

2018-05-04

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na + ), potassium (K + ), chloride (Cl - ), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Total antioxidant status and lipid peroxidation with and without in vitro zinc supplementation in infertile men.

PubMed

Ajina, T; Sallem, A; Haouas, Z; Mehdi, M

2017-09-01

The aim of this study was to assess the total antioxidant capacity (TAC) and malondialdehyde (MDA) level in infertile men with asthenozoospermia and asthenoteratozoospermia compared to fertile donors, and to examine the effect of zinc on sperm lipid peroxidation and antioxidant status in infertile and fertile men. Semen samples provided by infertile men (n = 38) and fertile donors (controls; n = 12) were exposed to 6 mmol/L of zinc for 2 hr at 37°C. After semen analysis, lipid peroxidation was detected by MDA assay and seminal TAC was assessed by colorimetric method using TAS (total antioxidant status) Kit. TAC was significantly lower in infertile group compared to controls (p = .037). However, lipid peroxidation did not alter in infertile patients compared to controls (p > .05). After in vitro incubation of samples with zinc, a significant increase in TAC level was found only in infertile men (p < .001). Meanwhile, zinc had no effect on sperm lipid peroxidation in both fertile and infertile men (p > .05). Our data indicate that antioxidant treatment based on zinc in vitro supplementation may be helpful to enhance the rate of seminal antioxidant status in infertile men; however, it does not prevent sperm lipid peroxidation. © 2016 Blackwell Verlag GmbH.

A Bioengineered Human Skin Equivalent (HSE) for the Evaluation of Protectants

DTIC Science & Technology

2006-11-01

agonist clofibrate to the growth media. Medium supplemented with 25 μM palmitic acid , 15 μM linoleic acid , 25 μM oleic acid , 7 μM arachidonic acid , 0.25...granules (indicated by arrows). Fig. 6: A cross section of the HSE with lipids, ascorbic acid and clofibrate supplementation. The combination of... Clofibrate , Ascorbic Acid and Lipids Compared With the Lipid Profile of Native Human Skin. Clofibrate 300 μM Lipid class Control No ascorbic

Passive dosing of polycyclic aromatic hydrocarbon (PAH) mixtures to terrestrial springtails: linking mixture toxicity to chemical activities, equilibrium lipid concentrations, and toxic units.

PubMed

Schmidt, Stine N; Holmstrup, Martin; Smith, Kilian E C; Mayer, Philipp

2013-07-02

A 7-day mixture toxicity experiment with the terrestrial springtail Folsomia candida was conducted, and the effects were linked to three different mixture exposure parameters. Passive dosing from silicone was applied to tightly control exposure levels and compositions of 12 mixture treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑C(lipid eq.)), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LC(lipid eq 50)) of 133 mmol kg(-1) lipid in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Finally, the effective lethal toxic unit (LTU50) of 1.20 was rather close to the expected value of 1. Altogether, passive dosing provided tightly controlled mixture exposure in terms of both level and composition, while ∑a, ∑C(lipid eq.), and ∑TU allowed baseline toxicity to be linked to mixture exposure.

Evaluation of hepatic steatosis in dogs with congenital portosystemic shunts using Oil Red O staining.

PubMed

Hunt, G B; Luff, J A; Daniel, L; Van den Bergh, R

2013-11-01

The aims of this prospective study were to quantify steatosis in dogs with congenital portosystemic shunts (CPS) using a fat-specific stain, to compare the amount of steatosis in different lobes of the liver, and to evaluate intra- and interobserver variability in lipid point counting. Computer-assisted point counting of lipid droplets was undertaken following Oil Red O staining in 21 dogs with congenital portosystemic shunts and 9 control dogs. Dogs with congenital portosystemic shunts had significantly more small lipid droplets (<6 μ) than control dogs (P = .0013 and .0002, respectively). There was no significant difference in steatosis between liver lobes for either control dogs and CPS dogs. Significant differences were seen between observers for the number of large lipid droplets (>9 μ) and lipogranulomas per tissue point (P = .023 and .01, respectively). In conclusion, computer-assisted counting of lipid droplets following Oil Red O staining of liver biopsy samples allows objective measurement and detection of significant differences between dogs with CPS and normal dogs. This method will allow future evaluation of the relationship between different presentations of CPS (anatomy, age, breed) and lipidosis, as well as the impact of hepatic lipidosis on outcomes following surgical shunt attenuation.

Evaluating quality and its determinants in lipid control for secondary prevention of heart disease and stroke in primary care: a study in an inner London Borough.

PubMed

Dodhia, Hiten; Kun, Liu; Logan Ellis, Hugh; Crompton, James; Wierzbicki, Anthony S; Williams, Helen; Hodgkinson, Anna; Balazs, John

2015-12-09

To assess quality of management and determinants in lipid control for secondary prevention of cardiovascular disease (CVD) using multilevel regression models. Cross-sectional study. Inner London borough, with a primary care registered population of 378,000 (2013). 48/49 participating general practices with 7869 patients on heart disease/stroke registers were included. (1) Recording of current total cholesterol levels and lipid control according to national evidence-based standards. (2) Assessment of quality by age, sex, ethnicity, deprivation, presence of other risks or comorbidity in meeting both lipid measurement and control standards. Some process standards were not met. Patients with a current cholesterol measurement >5 mmol/L were less likely to have a current statin prescription (adjusted OR=3.10; 95% CI 2.70 to 3.56). They were more likely to have clustering of other CVD risk factors. Women were significantly more likely to have raised cholesterol after adjustment for other factors (adjusted OR=1.74; 95% CI 1.53 to 1.98). In this study, the key factor that explained poor lipid control in people with CVD was having no current prescription record of a statin. Women were more likely to have poorly controlled cholesterol (independent of comorbid risk factors and after adjusting for age, ethnicity, deprivation index and practice-level variation). Women with CVD should be offered statin prescription and may require higher statin dosage for improved control. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Single cell-type analysis of cellular lipid remodelling in response to salinity in the epidermal bladder cells of the model halophyte Mesembryanthemum crystallinum.

PubMed

Barkla, Bronwyn J; Garibay-Hernández, Adriana; Melzer, Michael; Rupasinghe, Thusitha W T; Roessner, Ute

2018-05-29

Salt stress causes dramatic changes in the organization and dynamic properties of membranes, however, little is known about the underlying mechanisms involved. Modified trichomes, known as epidermal bladder cells (EBC), on the leaves and stems of the halophyte Mesembryanthemum crystallinum can be successfully exploited as a single-cell-type system to investigate salt-induced changes to cellular lipid composition. In this study alterations in key molecular species from different lipid classes highlighted an increase in phospholipid species, particularly those from phosphatidylcholine (PC) and phosphatidic acid (PA), where the latter is central to the synthesis of membrane lipids. Triacylglycerol (TG) species decreased during salinity, while there was little change in plastidic galactolipids. EBC transcriptomic and proteomic data mining revealed changes in genes and proteins involved in lipid metabolism and the upregulation of transcripts for PIPKIB, PI5PII, PIPKIII, and PLDδ, suggested the induction of signalling processes mediated by phosphoinositides and PA. TEM and flow cytometry showed the dynamic nature of lipid droplets in these cells under salt stress. Altogether, this work indicates the metabolism of TG might play an important role in EBC response to salinity as either an energy reserve for sodium accumulation and/or driving membrane biosynthesis for EBC expansion. This article is protected by copyright. All rights reserved.

Lipid droplets accumulation and other biochemical changes induced in the fungal pathogen Ustilago maydis under nitrogen-starvation.

PubMed

Aguilar, Lucero Romero; Pardo, Juan Pablo; Lomelí, Mónica Montero; Bocardo, Oscar Ivan Luqueño; Juárez Oropeza, Marco A; Guerra Sánchez, Guadalupe

2017-10-01

In many organisms, the growth under nitrogen-deprivation or a poor nitrogen source impacts on the carbon flow distribution and causes accumulation of neutral lipids, which are stored as lipid droplets (LDs). Efforts are in progress to find the mechanism of LDs synthesis and degradation, and new organisms capable of accumulating large amounts of lipids for biotechnological applications. In this context, when Ustilago maydis was cultured in the absence of a nitrogen source, there was a large accumulation of lipid bodies containing mainly triacylglycerols. The most abundant fatty acids in lipid bodies at the stationary phase were palmitic, linoleic, and oleic acids, and they were synthesized de novo by the fatty-acid synthase. In regard to the production of NADPH for the synthesis of fatty acids, the cytosolic NADP + -dependent isocitrate dehydrogenase and the glucose-6-phosphate and 6-phosphogluconate dehydrogenases couple showed the highest specific activities, with a lower activity of the malic enzyme. The ATP-citrate lyase activity was not detected in any of the culture conditions, which points to a different mechanism for the transfer of acetyl-CoA into the cytosol. Protein and RNA contents decreased when U. maydis was grown without a nitrogen source. Due to the significant accumulation of triacylglycerols and the particular composition of fatty acids, U. maydis can be considered an alternative model for biotechnological applications.

Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids.

PubMed

Kulkarni, Prajakta; Haldar, Manas K; Katti, Preeya; Dawes, Courtney; You, Seungyong; Choi, Yongki; Mallik, Sanku

2016-08-17

Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide-lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia-responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions.

Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome.

PubMed

Basu, Arpita; Sanchez, Karah; Leyva, Misti J; Wu, Mingyuan; Betts, Nancy M; Aston, Christopher E; Lyons, Timothy J

2010-02-01

To compare the effects of supplementation of green tea beverage or green tea extracts with controls on body weight, glucose and lipid profile, biomarkers of oxidative stress, and safety parameters in obese subjects with metabolic syndrome. Randomized, controlled prospective trial. General Clinical Research Center (GCRC) at University of Oklahoma Health Sciences Center (OUHSC). Thirty-five subjects with obesity and metabolic syndrome were recruited in age- and gender-matched trios and were randomly assigned to the control (4 cups water/d), green tea (4 cups/d), or green tea extract (2 capsules and 4 cups water/d) group for 8 weeks. The tea and extract groups had similar dosing of epiogallocatechin-3-gallate (EGCG), the active compound in green tea. Anthropometrics, blood pressure, fasting glucose and lipids, nuclear magnetic resonance (NMR)-based lipid particle size, safety parameters, biomarkers of oxidative stress (oxidized low-density lipoprotein [LDL], myeloperoxidase [MPO], malondialdehyde and hydroxynonenals [MDA and HNE]), and free catechins were analyzed at screen and at 4 and 8 weeks of the study. Pairwise comparisons showed green tea beverage and green tea extracts caused a significant decrease in body weight and body mass index (BMI) versus controls at 8 weeks (-2.5 +/- 0.7 kg, p < 0.01, and -1.9 +/- 0.6, p < 0.05, respectively). Green tea beverage showed a decreasing trend in LDL-cholesterol and LDL/high-density lipoprotein (HDL) versus controls (p < 0.1). Green tea beverage also significantly decreased MDA and HNE (-0.39 +/- 0.06 microM, p < 0.0001) versus controls. Plasma free catechins were detectable in both beverage and extract groups versus controls at screen and at 8 weeks, indicating compliance and bioavailability of green tea catechins. Green tea beverage consumption (4 cups/d) or extract supplementation (2 capsules/d) for 8 weeks significantly decreased body weight and BMI. Green tea beverage further lowered lipid peroxidation versus age- and gender-matched controls, suggesting the role of green tea flavonoids in improving features of metabolic syndrome in obese patients.

Influence of thermally oxidized vegetable oils and animal fats on energy and nutrient digestibility in young pigs.

PubMed

Liu, P; Kerr, B J; Chen, C; Weber, T E; Johnston, L J; Shurson, G C

2014-07-01

A total of 108 barrows (6.67 ± 0.03 kg BW) were assigned to 12 dietary treatments in a 4 × 3 factorial design plus a corn-soybean meal control diet to evaluate the effect of lipid source and peroxidation level on DE, ME, and apparent total tract digestibility (ATTD) of DM, GE, ether extract (EE), N, and C in young pigs. Main effects were lipid source (corn oil [CN], canola oil [CA], poultry fat [PF], and tallow [TL]) and peroxidation level (original lipids [OL], slow oxidation [SO] of lipids heated for 72 h at 95°C, or rapid oxidation [RO] of lipids heated for 7 h at 185°C). Pigs were provided ad libitum access to diets for 28 d followed by an 8-d period of controlled feed intake equivalent to 4% BW daily. Diets were formulated based on the ME content of CA with the standardized ileal digestible Lys, Met, Thr, Trp, total Ca, and available P:ME balanced relative to NRC (1998) recommendations. Lipid peroxidation analysis indicated that compared with the OL, SO and RO had a markedly increased concentrations of lipid peroxidation products, and the increase of peroxidation products in CN and CA were greater than those in PF and TL. Addition of lipids to diets increased (P < 0.05) ATTD of EE and tended to improve (P = 0.06) ATTD of GE compared with pigs fed the control diet. Feeding CN or CA increased (P < 0.05) ATTD of DM, GE, EE, N, and C compared with feeding TL, while feeding PF improved (P < 0.05) ATTD of GE and EE and tended to increase (P = 0.06) ATTD of C compared with TL. Pigs fed CN had increased (P = 0.05) percentage N retention than pigs fed TL. No peroxidation level effect or interaction between lipid source and peroxidation level on DE and ME was observed. Lipid source tended (P = 0.08) to affect DE but not ME values of experimental lipids (P > 0.12). Digestible energy values for CA (8,846, 8,682, and 8,668 kcal/kg) and CN (8,867, 8,648, and 8,725 kcal/kg) were about 450 kcal/kg greater than that of TL (8,316, 8,168, and 8,296 kcal/kg), with PF being intermediate (8,519, 8,274, and 8,511 kcal/kg), for OL, SO, and RO lipids, respectively, respectively. In conclusion, lipid source affected ATTD of dietary DM, GE, EE, N, and C, and N retention and tended to influence the DE value of the lipid but did not significantly affect their ME value. Rapid and slow heating of lipids used in this study increased lipid peroxidation products but had no detectable effects on nutrient and energy digestibility as well as DE and ME values of the various lipids.

Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

PubMed

Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

2009-07-01

Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

Expression Profiling of Nonpolar Lipids in Meibum From Patients With Dry Eye: A Pilot Study

PubMed Central

Chen, Jianzhong; Keirsey, Jeremy K.; Green, Kari B.; Nichols, Kelly K.

2017-01-01

Purpose The purpose of this investigation was to characterize differentially expressed lipids in meibum samples from patients with dry eye disease (DED) in order to better understand the underlying pathologic mechanisms. Methods Meibum samples were collected from postmenopausal women with DED (PW-DED; n = 5) and a control group of postmenopausal women without DED (n = 4). Lipid profiles were analyzed by direct infusion full-scan electrospray ionization mass spectrometry (ESI-MS). An initial analysis of 145 representative peaks from four classes of lipids in PW-DED samples revealed that additional manual corrections for peak overlap and isotopes only slightly affected the statistical analysis. Therefore, analysis of uncorrected data, which can be applied to a greater number of peaks, was used to compare more than 500 lipid peaks common to PW-DED and control samples. Statistical analysis of peak intensities identified several lipid species that differed significantly between the two groups. Data from contact lens wearers with DED (CL-DED; n = 5) were also analyzed. Results Many species of the two types of diesters (DE) and very long chain wax esters (WE) were decreased by ∼20% in PW-DED, whereas levels of triacylglycerols were increased by an average of 39% ± 3% in meibum from PW-DED compared to that in the control group. Approximately the same reduction (20%) of similar DE and WE was observed for CL-DED. Conclusions Statistical analysis of peak intensities from direct infusion ESI-MS results identified differentially expressed lipids in meibum from dry eye patients. Further studies are warranted to support these findings. PMID:28426869

Comparison of Effects of Separate and Combined Sugammadex and Lipid Emulsion Administration on Hemodynamic Parameters and Survival in a Rat Model of Verapamil Toxicity.

PubMed

Tulgar, Serkan; Kose, Halil Cihan; Demir Piroglu, Isılay; Karakilic, Evvah; Ates, Nagihan Gozde; Demir, Ahmet; Gergerli, Ruken; Guven, Selin; Piroglu, Mustafa Devrim

2016-03-25

Toxicity of calcium channel blockers leads to high patient mortality and there is no effective antidote. The benefit of using 20% lipid emulsion and sugammadex has been reported. The present study measured the effect of sugammadex and 20% lipid emulsion on hemodynamics and survival in a rat model of verapamil toxicity. In this single-blinded randomized control study, rats were separated into 4 groups of 7 rats each: Sugammadex (S), Sugammadex plus 20% lipid emulsion (SL), 20% lipid emulsion (L), and control (C). Heart rates and mean arterial pressures were monitored and noted each minute until death. Average time to death was 21.0±9.57 minutes for group C, 35.57±10.61 minutes for group S, 37.14±16.6 minutes for group L and 49.86±27.56 minutes for group SL. Time to death was significantly longer in other groups than in the control group (p<0.05). Verapamil overdose is has a comparatively high mortality rate and there is no effective antidote. Treatment generally involves gastric decontamination and symptomatic treatment to counteract the drug's negative effects. In animal studies sugammadex and lipid emulsion had a positive effect on survival in patients with calcium channel blocker toxicity. Sugammadex and intralipid increased survival in a rat model of verapamil toxicity. The combination of both drugs may decrease cardiotoxicity. Sugammadex alone or combined with 20% lipid emulsion reduce the need for inotropic agents. The mechanism requires clarification with larger studies.

Comparison of Effects of Separate and Combined Sugammadex and Lipid Emulsion Administration on Hemodynamic Parameters and Survival in a Rat Model of Verapamil Toxicity

PubMed Central

Tulgar, Serkan; Kose, Halil Cihan; Piroglu, Isılay Demir; Karakilic, Evvah; Ates, Nagihan Gozde; Demir, Ahmet; Gergerli, Ruken; Guven, Selin; Piroglu, Mustafa Devrim

2016-01-01

Background Toxicity of calcium channel blockers leads to high patient mortality and there is no effective antidote. The benefit of using 20% lipid emulsion and sugammadex has been reported. The present study measured the effect of sugammadex and 20% lipid emulsion on hemodynamics and survival in a rat model of verapamil toxicity. Material/Methods In this single-blinded randomized control study, rats were separated into 4 groups of 7 rats each: Sugammadex (S), Sugammadex plus 20% lipid emulsion (SL), 20% lipid emulsion (L), and control (C). Heart rates and mean arterial pressures were monitored and noted each minute until death. Results Average time to death was 21.0±9.57 minutes for group C, 35.57±10.61 minutes for group S, 37.14±16.6 minutes for group L and 49.86±27.56 minutes for group SL. Time to death was significantly longer in other groups than in the control group (p<0.05). Conclusions Verapamil overdose is has a comparatively high mortality rate and there is no effective antidote. Treatment generally involves gastric decontamination and symptomatic treatment to counteract the drug’s negative effects. In animal studies sugammadex and lipid emulsion had a positive effect on survival in patients with calcium channel blocker toxicity. Sugammadex and intralipid increased survival in a rat model of verapamil toxicity. The combination of both drugs may decrease cardiotoxicity. Sugammadex alone or combined with 20% lipid emulsion reduce the need for inotropic agents. The mechanism requires clarification with larger studies. PMID:27012816

Trojan particles: Large porous carriers of nanoparticles for drug delivery

PubMed Central

Tsapis, N.; Bennett, D.; Jackson, B.; Weitz, D. A.; Edwards, D. A.

2002-01-01

We have combined the drug release and delivery potential of nanoparticle (NP) systems with the ease of flow, processing, and aerosolization potential of large porous particle (LPP) systems by spray drying solutions of polymeric and nonpolymeric NPs into extremely thin-walled macroscale structures. These hybrid LPPs exhibit much better flow and aerosolization properties than the NPs; yet, unlike the LPPs, which dissolve in physiological conditions to produce molecular constituents, the hybrid LPPs dissolve to produce NPs, with the drug release and delivery advantages associated with NP delivery systems. Formation of the large porous NP (LPNP) aggregates occurs via a spray-drying process that ensures the drying time of the sprayed droplet is sufficiently shorter than the characteristic time for redistribution of NPs by diffusion within the drying droplet, implying a local Peclet number much greater than unity. Additional control over LPNPs physical characteristics is achieved by adding other components to the spray-dried solutions, including sugars, lipids, polymers, and proteins. The ability to produce LPNPs appears to be largely independent of molecular component type as well as the size or chemical nature of the NPs. PMID:12200546

Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection.

PubMed

Lovewell, Rustin R; Sassetti, Christopher M; VanderVen, Brian C

2016-02-01

The interplay between Mycobacterium tuberculosis lipid metabolism, the immune response and lipid homeostasis in the host creates a complex and dynamic pathogen-host interaction. Advances in imaging and metabolic analysis techniques indicate that M. tuberculosis preferentially associates with foamy cells and employs multiple physiological systems to utilize exogenously derived fatty-acids and cholesterol. Moreover, novel insights into specific host pathways that control lipid accumulation during infection, such as the PPARγ and LXR transcriptional regulators, have begun to reveal mechanisms by which host immunity alters the bacterial micro-environment. As bacterial lipid metabolism and host lipid regulatory pathways are both important, yet inherently complex, components of active tuberculosis, delineating the heterogeneity in lipid trafficking within disease states remains a major challenge for therapeutic design. Copyright © 2015. Published by Elsevier Ltd.

Lipid droplet formation on opposing sides of the endoplasmic reticulum

PubMed Central

Sturley, Stephen L.; Hussain, M. Mahmood

2012-01-01

In animal cells, the primary repositories of esterified fatty acids and alcohols (neutral lipids) are lipid droplets that form on the lumenal and/or cytoplasmic side of the endoplasmic reticulum (ER) membrane. A monolayer of amphipathic lipids, intermeshed with key proteins, serves to solubilize neutral lipids as they are synthesized and desorbed. In specialized cells, mobilization of the lipid cargo for delivery to other tissues occurs by secretion of lipoproteins into the plasma compartment. Serum lipoprotein assembly requires an obligate structural protein anchor (apolipoprotein B) and a dedicated chaperone, microsomal triglyceride transfer protein. By contrast, lipid droplets that form on the cytoplasmic face of the ER lack an obligate protein scaffold or any required chaperone/lipid transfer protein. Mobilization of neutral lipids from the cytosol requires regulated hydrolysis followed by transfer of the products to different organelles or export from cells. Several proteins play a key role in controlling droplet number, stability, and catabolism; however, it is our premise that their formation initiates spontaneously, solely as a consequence of neutral lipid synthesis. This default pathway directs droplets into the cytoplasm where they accumulate in many lipid disorders. PMID:22701043

Characterization of 3D Voronoi Tessellation Nearest Neighbor Lipid Shells Provides Atomistic Lipid Disruption Profile of Protein Containing Lipid Membranes

PubMed Central

Cheng, Sara Y.; Duong, Hai V.; Compton, Campbell; Vaughn, Mark W.; Nguyen, Hoa; Cheng, Kwan H.

2015-01-01

Quantifying protein-induced lipid disruptions at the atomistic level is a challenging problem in membrane biophysics. Here we propose a novel 3D Voronoi tessellation nearest-atom-neighbor shell method to classify and characterize lipid domains into discrete concentric lipid shells surrounding membrane proteins in structurally heterogeneous lipid membranes. This method needs only the coordinates of the system and is independent of force fields and simulation conditions. As a proof-of-principle, we use this multiple lipid shell method to analyze the lipid disruption profiles of three simulated membrane systems: phosphatidylcholine, phosphatidylcholine/cholesterol, and beta-amyloid/phosphatidylcholine/cholesterol. We observed different atomic volume disruption mechanisms due to cholesterol and beta-amyloid Additionally, several lipid fractional groups and lipid-interfacial water did not converge to their control values with increasing distance or shell order from the protein. This volume divergent behavior was confirmed by bilayer thickness and chain orientational order calculations. Our method can also be used to analyze high-resolution structural experimental data. PMID:25637891

Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in Yarrowia lipolytica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pomraning, Kyle R.; Bredeweg, Erin L.; Baker, Scott E.

ABSTRACT Fungi accumulate lipids in a manner dependent on the quantity and quality of the nitrogen source on which they are growing. In the oleaginous yeastYarrowia lipolytica, growth on a complex source of nitrogen enables rapid growth and limited accumulation of neutral lipids, while growth on a simple nitrogen source promotes lipid accumulation in large lipid droplets. Here we examined the roles of nitrogen catabolite repression and its regulation by GATA zinc finger transcription factors on lipid metabolism inY. lipolytica. Deletion of the GATA transcription factor genesgzf3andgzf2resulted in nitrogen source-specific growth defects and greater accumulation of lipids when the cells weremore » growing on a simple nitrogen source. Deletion ofgzf1, which is most similar to activators of genes repressed by nitrogen catabolite repression in filamentous ascomycetes, did not affect growth on the nitrogen sources tested. We examined gene expression of wild-type and GATA transcription factor mutants on simple and complex nitrogen sources and found that expression of enzymes involved in malate metabolism, beta-oxidation, and ammonia utilization are strongly upregulated on a simple nitrogen source. Deletion ofgzf3results in overexpression of genes with GATAA sites in their promoters, suggesting that it acts as a repressor, whilegzf2is required for expression of ammonia utilization genes but does not grossly affect the transcription level of genes predicted to be controlled by nitrogen catabolite repression. Both GATA transcription factor mutants exhibit decreased expression of genes controlled by carbon catabolite repression via the repressormig1, including genes for beta-oxidation, highlighting the complex interplay between regulation of carbon, nitrogen, and lipid metabolism. IMPORTANCENitrogen source is commonly used to control lipid production in industrial fungi. Here we identified regulators of nitrogen catabolite repression in the oleaginous yeastY. lipolyticato determine how the nitrogen source regulates lipid metabolism. We show that disruption of both activators and repressors of nitrogen catabolite repression leads to increased lipid accumulation via activation of carbon catabolite repression through an as yet uncharacterized method.« less

Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders.

PubMed

Pistorio, Elisabetta; Luca, Maria; Luca, Antonina; Messina, Vincenzo; Calandra, Carmela

2011-10-28

To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

The Role of Storage Lipids in the Relation between Fecundity, Locomotor Activity, and Lifespan of Drosophila melanogaster Longevity-Selected and Control Lines

PubMed Central

Nasiri Moghadam, Neda; Holmstrup, Martin; Manenti, Tommaso; Brandt Mouridsen, Marie; Pertoldi, Cino; Loeschcke, Volker

2015-01-01

The contribution of insect fat body to multiple processes, such as development, metamorphosis, activity, and reproduction results in trade-offs between life history traits. In the present study, age-induced modulation of storage lipid composition in Drosophila melanogaster longevity-selected (L) and non-selected control (C) lines was studied and the correlation between total body fat mass and lifespan assessed. The trade-offs between fecundity, locomotor activity, and lifespan were re-evaluated from a lipid-related metabolic perspective. Fewer storage lipids in the L lines compared to the C lines supports the impact of body fat mass on extended lifespan. The higher rate of fecundity and locomotor activity in the L lines may increase the lipid metabolism and enhance the lipolysis of storage lipids, reducing fat reserves. The correlation between neutral lipid fatty acids and fecundity, as well as locomotor activity, varied across age groups and between the L and C lines. The fatty acids that correlated with egg production were different from the fatty acids that correlated with locomotor activity. The present study suggests that fecundity and locomotor activity may positively affect the lifespan of D. melanogaster through the inhibition of fat accumulation. PMID:26115349

Evaluation of surface deformability of lipid nanocapsules by drop tensiometer technique, and its experimental assessment by dialysis and tangential flow filtration.

PubMed

Hirsjärvi, Samuli; Bastiat, Guillaume; Saulnier, Patrick; Benoît, Jean-Pierre

2012-09-15

Deformability of nanoparticles might affect their behaviour at biological interfaces. Lipid nanocapsules (LNCs) are semi-solid particles resembling a hybrid of polymer nanoparticles and liposomes. Deformability of LNCs of different sizes was modelled by drop tensiometer technique. Two purification methods, dialysis and tangential flow filtration (TFF), were applied to study experimental behaviour and deformability of LNCs in order to evaluate if these properties contributed to membrane passing. Rheological parameters obtained from the drop tensiometer analysis suggested decreasing surface deformability of LNCs with increase in diameter. Dialysis results showed that up to 10% of LNCs can be lost during the process (e.g. membrane accumulation) but no clear evidence of the membrane passing was observed. Instead, LNCs with initial size and size distribution could be found in the TFF filtrate although molecular weight cut-off (MWCO) of the membrane used was smaller than the LNC diameter. Copyright © 2012 Elsevier B.V. All rights reserved.

Presentation of lipid antigens to T cells.

PubMed

Mori, Lucia; De Libero, Gennaro

2008-04-15

T cells specific for lipid antigens participate in regulation of the immune response during infections, tumor immunosurveillance, allergy and autoimmune diseases. T cells recognize lipid antigens as complexes formed with CD1 antigen-presenting molecules, thus resembling recognition of MHC-peptide complexes. The biophysical properties of lipids impose unique mechanisms for their delivery, internalization into antigen-presenting cells, membrane trafficking, processing, and loading of CD1 molecules. Each of these steps is controlled at molecular and celular levels and determines lipid immunogenicity. Lipid antigens may derive from microbes and from the cellular metabolism, thus allowing the immune system to survey a large repertoire of immunogenic molecules. Recognition of lipid antigens facilitates the detection of infectious agents and the initiation of responses involved in immunoregulation and autoimmunity. This review focuses on the presentation mechanisms and specific recognition of self and bacterial lipid antigens and discusses the important open issues.

Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis

PubMed Central

Masterson, Joanne C; McNamee, Eóin N; Fillon, Sophie A; Hosford, Lindsay; Harris, Rachel; Fernando, Shahan D; Jedlicka, Paul; Iwamoto, Ryo; Jacobsen, Elizabeth; Protheroe, Cheryl; Eltzschig, Holger K; Colgan, Sean P; Arita, Makoto; Lee, James J; Furuta, Glenn T

2015-01-01

Objective Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. Design Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. Results Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. Conclusions Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators. PMID:25209655

Alterations of erythrocyte rheology and cellular susceptibility in end stage renal disease: Effects of peritoneal dialysis.

PubMed

Ertan, Nesrin Zeynep; Bozfakioglu, Semra; Ugurel, Elif; Sinan, Mukaddes; Yalcin, Ozlem

2017-01-01

In this study, we investigated the effects of peritoneal dialysis on hemorheological and hematological parameters and their relations with oxidant and antioxidant status of uremic patients. Hemorheological parameters (erythrocyte deformability, erythrocyte aggregation, osmotic deformability, blood and plasma viscosity) were measured in patients with renal insufficiency undergoing peritoneal dialysis (PD) and volunteers. Erythrocyte deformability, osmotic deformability and aggregation in both autologous plasma and 3% dextran 70 were measured by laser diffraction ektacytometry. Enzyme activities of glutathione peroxidase, superoxide dismutase and catalase were studied in erythrocytes; lipid peroxidation was studied by measuring the amount of malondialdehyde in both erythrocytes and plasma samples. Blood viscosity at native hematocrit was significantly lower in PD patients at all measured shear rates compared to controls, but it was high in PD patients at corrected (45%) hematocrit. Erythrocyte deformability did not show any difference between the two groups. Osmotic deformability was significantly lower in PD patients compared to controls. Aggregation index values were significantly high in PD patients in plasma Catalase and glutathione peroxidase activities in erythrocytes were decreased in PD patients whereas superoxide dismutase activity was increased compared to controls. Malondialdehyde was significantly increased in erythrocytes and plasma samples of PD patients which also shows correlations with aggregation parameters. It has been concluded that erythrocytes in PD patients are more prone to aggregation and this tendency could be influenced by lipid peroxidation activity in patient's plasma. These results imply that uremic conditions, loss of plasma proteins and an increased risk of oxidative stress because of decreasing levels of antioxidant enzymes affect erythrocyte rheology during peritoneal dialysis. This level of distortion may have crucial effects, impairing the blood flow dynamics and causing inadequate microcirculatory perfusion.

Abnormal lipid metabolism in skeletal muscle tissue of patients with muscular dystrophy: In vitro, high-resolution NMR spectroscopy based observation in early phase of the disease.

PubMed

Srivastava, Niraj Kumar; Yadav, Ramakant; Mukherjee, Somnath; Pal, Lily; Sinha, Neeraj

2017-05-01

Qualitative (assignment of lipid components) and quantitative (quantification of lipid components) analysis of lipid components were performed in skeletal muscle tissue of patients with muscular dystrophy in early phase of the disease as compared to control/normal subjects. Proton nuclear magnetic resonance (NMR) spectroscopy based experiment was performed on the lipid extract of skeletal muscle tissue of patients with muscular dystrophy in early phase of the disease and normal individuals for the analysis of lipid components [triglycerides, phospholipids, total cholesterol and unsaturated fatty acids (arachidonic, linolenic and linoleic acid)]. Specimens of muscle tissue were obtained from patients with Duchenne muscular dystrophy (DMD) [n=11; Age, Mean±SD; 9.2±1.4years; all were males], Becker muscular dystrophy (BMD) [n=12; Age, Mean±SD; 21.4±5.0years; all were males], facioscapulohumeral muscular dystrophy (FSHD) [n=11; Age, Mean±SD; 23.7±7.5years; all were males] and limb girdle muscular dystrophy-2B (LGMD-2B) [n=18; Age, Mean±SD; 24.2±4.1years; all were males]. Muscle specimens were also obtained from [n=30; Mean age±SD 23.1±6.0years; all were males] normal/control subjects. Assigned lipid components in skeletal muscle tissue were triglycerides (TG), phospholipids (PL), total cholesterol (CHOL) and unsaturated fatty acids (arachidonic, linolenic and linoleic acid)]. Quantity of lipid components was observed in skeletal muscle tissue of DMD, BMD, FSHD and LGMD-2B patients as compared to control/normal subjects. TG was significantly elevated in muscle tissue of DMD, BMD and LGMD-2B patients. Increase level of CHOL was found only in muscle of DMD patients. Level of PL was found insignificant for DMD, BMD and LGMD-2B patients. Quantity of TG, PL and CHOL was unaltered in the muscle of patients with FSHD as compared to control/normal subjects. Linoleic acids were significantly reduced in muscle tissue of DMD, BMD, FSHD and LGMD-2B as compared to normal/control individuals. Results clearly indicate alteration of lipid metabolism in patients with muscular dystrophy in early phase of the disease. Moreover, further evaluation is required to understand whether these changes are primary or secondary to muscular dystrophy. In future, these findings may prove an additional and improved approach for the diagnosis of different forms of muscular dystrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

Flow-through lipid nanotube arrays for structure-function studies of membrane proteins by solid-state NMR spectroscopy.

PubMed

Chekmenev, Eduard Y; Gor'kov, Peter L; Cross, Timothy A; Alaouie, Ali M; Smirnov, Alex I

2006-10-15

A novel method for studying membrane proteins in a native lipid bilayer environment by solid-state NMR spectroscopy is described and tested. Anodic aluminum oxide (AAO) substrates with flow-through 175 nm wide and 60-mum-long nanopores were employed to form macroscopically aligned peptide-containing lipid bilayers that are fluid and highly hydrated. We demonstrate that the surfaces of both leaflets of such bilayers are fully accessible to aqueous solutes. Thus, high hydration levels as well as pH and desirable ion and/or drug concentrations could be easily maintained and modified as desired in a series of experiments with the same sample. The method allows for membrane protein NMR experiments in a broad pH range that could be extended to as low as 1 and as high as 12 units for a period of up to a few hours and temperatures as high as 70 degrees C without losing the lipid alignment or bilayers from the nanopores. We demonstrate the utility of this method by a solid-state 19.6 T (17)O NMR study of reversible binding effects of mono- and divalent ions on the chemical shift properties of the Leu(10) carbonyl oxygen of transmembrane pore-forming peptide gramicidin A (gA). We further compare the (17)O shifts induced by binding metal ions to the binding of protons in the pH range from 1 to 12 and find a significant difference. This unexpected result points to a difference in mechanisms for ion and proton conduction by the gA pore. We believe that a large number of solid-state NMR-based studies, including structure-function, drug screening, proton exchange, pH, and other titration experiments, will benefit significantly from the method described here.

Short-term effects of an intensive lifestyle modification program on lipid peroxidation and antioxidant systems in patients with coronary artery disease.

PubMed

Jatuporn, Srisakul; Sangwatanaroj, Somkiat; Saengsiri, Aem-Orn; Rattanapruks, Sopida; Srimahachota, Suphot; Uthayachalerm, Wasan; Kuanoon, Wanpen; Panpakdee, Orasa; Tangkijvanich, Pisit; Tosukhowong, Piyaratana

2003-01-01

The purpose of this study was to compare the short-term effects of an intensive lifestyle modification (ILM) program on lipid peroxidation and antioxidant systems in patients with coronary artery disease (CAD). Twenty-two patients in the control group continued to receive their conventional treatment with lipid-lowering drugs, whereas 22 patients in the experimental group were assigned to intensive lifestyle modification (ILM) without taking any lipid-lowering agent. The ILM program comprised dietary advice on low-fat diets, high antioxidants and high fiber intakes, yoga exercise, stress management and smoking cessation. After 4 months of intervention, patients in the experimental group revealed a statistically significant increase in plasma total antioxidants, plasma vitamin E and erythrocyte glutathione (GSH) compared to patients in the control group. There was no significant change in plasma malondialdehyde (MDA), a circulating product of lipid peroxidation, in either group. We concluded that the ILM program increased circulating antioxidants and reduced oxidative stress in patients with CAD.

Phase separation in artificial vesicles driven by light and curvature

NASA Astrophysics Data System (ADS)

Rinaldin, Melissa; Pomp, Wim; Schmidt, Thomas; Giomi, Luca; Kraft, Daniela; Physics of Life Processes Team; Soft; Bio Mechanics Collaboration; Self-Assembly in Soft Matter Systems Collaboration

The role of phase-demixing in living cells, leading to the lipid-raft hypothesis, has been extensively studied. Lipid domains of higher lipid chain order are proposed to regulate protein spatial organization. Giant Unilamellar Vesicles provide an artificial model to study phase separation. So far temperature was used to initiate the process. Here we introduce a new methodology based on the induction of phase separation by light. To this aim, the composition of the lipid membrane is varied by photo-oxidation of lipids. The control of the process gained by using light allowed us to observe vesicle shape fluctuations during phase-demixing. The presence of fluctuations near the critical mixing point resembles features of a critical process. We quantitatively analyze these fluctuations using a 2d elastic model, from which we can estimate the material parameters such as bending rigidity and surface tension, demonstrating the non-equilibrium critical behaviour. Finally, I will describe recent attempts toward tuning the membrane composition by controlling the vesicle curvature.

Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6 deficiency in rats.

PubMed

Kitagawa, Erina; Yamamoto, Tatsuya; Fujishita, Mayuko; Ota, Yuki; Yamamoto, Kohei; Nakagawa, Tomoyuki; Hayakawa, Takashi

2017-02-01

We investigated the efficacy of supplementing the diet with choline or betaine in ameliorating lipid accumulation induced by vitamin B 6 (B 6 ) deficiency in rat liver. Male Wistar rats were fed a control, B 6 -deficient, choline-supplemented (2, 4, or 6 g choline bitartrate/kg diet) B 6 -deficient diet or betaine-supplemented (1, 2, or 4 g betaine anhydrous/kg diet) B 6 -deficient diet for 35 d; all diets contained 9 g L-methionine (Met)/kg diet. Choline or betaine supplementation attenuated liver lipid deposition and restored plasma lipid profiles to control levels. These treatments restored the disruptions in Met metabolism and the phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio induced by B 6 deficiency in liver microsomes. These results suggest that choline and betaine ameliorated liver lipid accumulation induced by B 6 deficiency via recovery of Met metabolism and very low-density lipoprotein secretion by restoring the supply of PC derived from PE.

Manipulating membrane lipid profiles to restore T-cell function in autoimmunity.

PubMed

Waddington, Kirsty E; Jury, Elizabeth C

2015-08-01

Plasma membrane lipid rafts are heterogeneous cholesterol and glycosphingolipid (GSL)-enriched microdomains, within which the tight packing of cholesterol with the saturated-acyl chains of GSLs creates a region of liquid-order relative to the surrounding disordered membrane. Thus lipid rafts govern the lateral mobility and interaction of membrane proteins and regulate a plethora of signal transduction events, including T-cell antigen receptor (TCR) signalling. The pathways regulating homoeostasis of membrane cholesterol and GSLs are tightly controlled and alteration of these metabolic processes coincides with immune cell dysfunction as is evident in atherosclerosis, cancer and autoimmunity. Indeed, membrane lipid composition is emerging as an important factor influencing the ability of cells to respond appropriately to microenvironmental stimuli. Consequently, there is increasing interest in targeting membrane lipids or their metabolic control as a novel therapeutic approach to modulate immune cell behaviour and our recent work demonstrates that this is a promising strategy in T-cells from patients with the autoimmune disease systemic lupus erythematosus (SLE). © 2015 Authors; published by Portland Press Limited.

Identification of the lipid biomarkers from plasma in idiopathic pulmonary fibrosis by Lipidomics.

PubMed

Yan, Feng; Wen, Zhensong; Wang, Rui; Luo, Wenling; Du, Yufeng; Wang, Wenjun; Chen, Xianyang

2017-12-06

Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease. In this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls. A total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC analysis. Our results provided vital information regarding lipid metabolism in IPF patients and more importantly, a few potentially promising biomarkers were firstly identified which may have a predictive role in monitoring and diagnosing IPF disease.

Canine epidermal lipid sampling by skin scrub revealed variations between different body sites and normal and atopic dogs

PubMed Central

2014-01-01

Background Previously, we evaluated a minimally invasive epidermal lipid sampling method called skin scrub, which achieved reproducible and comparable results to skin scraping. The present study aimed at investigating regional variations in canine epidermal lipid composition using the skin scrub technique and its suitability for collecting skin lipids in dogs suffering from certain skin diseases. Eight different body sites (5 highly and 3 lowly predisposed for atopic lesions) were sampled by skin scrub in 8 control dogs with normal skin. Additionally, lesional and non-lesional skin was sampled from 12 atopic dogs and 4 dogs with other skin diseases by skin scrub. Lipid fractions were separated by high performance thin layer chromatography and analysed densitometrically. Results No significant differences in total lipid content were found among the body sites tested in the control dogs. However, the pinna, lip and caudal back contained significantly lower concentrations of ceramides, whereas the palmar metacarpus and the axillary region contained significantly higher amounts of ceramides and cholesterol than most other body sites. The amount of total lipids and ceramides including all ceramide classes were significantly lower in both lesional and non-lesional skin of atopic dogs compared to normal skin, with the reduction being more pronounced in lesional skin. The sampling by skin scrub was relatively painless and caused only slight erythema at the sampled areas but no oedema. Histological examinations of skin biopsies at 2 skin scrubbed areas revealed a potential lipid extraction from the transition zone between stratum corneum and granulosum. Conclusions The present study revealed regional variations in the epidermal lipid and ceramide composition in dogs without skin abnormalities but no connection between lipid composition and predilection sites for canine atopic dermatitis lesions. The skin scrub technique proved to be a practicable sampling method for canine epidermal lipids, revealed satisfying results regarding alterations of skin lipid composition in canine atopic dermatitis and might be suitable for epidermal lipid investigations of further canine skin diseases. Although the ceramide composition should be unaffected by the deeper lipid sampling of skin scrub compared to other sampling methods, further studies are required to determine methodological differences. PMID:25012966

Shrinking microbubbles with microfluidics: mathematical modelling to control microbubble sizes.

PubMed

Salari, A; Gnyawali, V; Griffiths, I M; Karshafian, R; Kolios, M C; Tsai, S S H

2017-11-29

Microbubbles have applications in industry and life-sciences. In medicine, small encapsulated bubbles (<10 μm) are desirable because of their utility in drug/oxygen delivery, sonoporation, and ultrasound diagnostics. While there are various techniques for generating microbubbles, microfluidic methods are distinguished due to their precise control and ease-of-fabrication. Nevertheless, sub-10 μm diameter bubble generation using microfluidics remains challenging, and typically requires expensive equipment and cumbersome setups. Recently, our group reported a microfluidic platform that shrinks microbubbles to sub-10 μm diameters. The microfluidic platform utilizes a simple microbubble-generating flow-focusing geometry, integrated with a vacuum shrinkage system, to achieve microbubble sizes that are desirable in medicine, and pave the way to eventual clinical uptake of microfluidically generated microbubbles. A theoretical framework is now needed to relate the size of the microbubbles produced and the system's input parameters. In this manuscript, we characterize microbubbles made with various lipid concentrations flowing in solutions that have different interfacial tensions, and monitor the changes in bubble size along the microfluidic channel under various vacuum pressures. We use the physics governing the shrinkage mechanism to develop a mathematical model that predicts the resulting bubble sizes and elucidates the dominant parameters controlling bubble sizes. The model shows a good agreement with the experimental data, predicting the resulting microbubble sizes under different experimental input conditions. We anticipate that the model will find utility in enabling users of the microfluidic platform to engineer bubbles of specific sizes.

Controlling carbon-nanotube-phospholipid solubility by curvature-dependent self-assembly.

PubMed

Määttä, Jukka; Vierros, Sampsa; Sammalkorpi, Maria

2015-03-12

Control of aqueous dispersion is central in the processing and usage of nanoscale hydrophobic objects. However, selecting dispersive agents based on the size and form of the hydrophobic object and the role of coating morphology in dispersion efficiency remain important open questions. Here, the effect of the substrate and the dispersing molecule curvature, as well as, the influence of dispersant concentration on the adsorption morphology are examined by molecular simulations of graphene and carbon nanotube (CNT) substrates with phospholipids of varying curvature as the dispersing agents. Lipid spontaneous curvature is increased from close to zero (effectively cylindrical lipid) to highly positive (effectively conical lipid) by studying double tailed dipalmitoylphosphadidylcholine (DPPC) and single tailed lysophosphadidylcholine (LPC) which differ in the number of acyl chains but have identical headgroup. We find that lipids are good dispersion agents for both planar and curved nanoparticles and induce a dispersive barrier nonsize selectively. Differences in dispersion efficiency arise from lipid headgroup density and their extension from the hydrophobic substrate in the adsorption morphology. We map the packing morphology contributing factors and report that the aggregate morphologies depend on the competition of interactions rising from (1) hydrophobicity driven maximization of lipid-substrate contacts and lipid self-adhesion, (2) tail bending energy cost, (3) preferential alignment along the graphitic substrate principal axes, and (4) lipid headgroup preferential packing. Curved substrates adjust the morphology by changing the balance between the interaction strengths. Jointly, the findings show substrate curvature and dimensions are a way to tune lipid adsorption to desired, self-assembling patterns. Besides engineering dispersion efficiency, the findings could bear significance in designing materials with defined molecular scale, molecular coatings for orientation specific CNT assembly or lipid-based molecular masks and patterning on graphene.

Effects of dietary lipid sources on performance and apparent total tract digestibility of lipids and energy when fed to nursery pigs.

PubMed

Mendoza, S M; van Heugten, E

2014-02-01

Acidulated fats and oils are by-products of the fat-refining industry. They contain high levels of FFA and are 10% to 20% less expensive than refined fats and oils. Two studies were designed to measure the effects of dietary lipid sources low or high in FFA on growth performance and apparent total tract digestibility (ATTD) of lipids and GE in nursery pigs. In Exp. 1, 189 pigs at 14 d postweaning (BW of 9.32 ± 0.11 kg) were used for 21 d with 9 replicate pens per treatment and 3 pigs per pen. Dietary treatments consisted of a control diet without added lipids and 6 diets with 6% inclusion of lipids. Four lipid sources were combined to create the dietary treatments with 2 levels of FFA (0.40% or 54.0%) and 3 degrees of fat saturation (iodine value [IV] = 77, 100, or 123) in a 2 × 3 factorial arrangement. Lipid sources were soybean oil (0.3% FFA and IV = 129.4), soybean-cottonseed acid oil blend (70.5% FFA and IV = 112.9), choice white grease (0.6% FFA and IV = 74.8), and choice white acid grease (56.0% FFA and IV = 79.0). Addition of lipid sources decreased ADFI (810 vs. 872 g/d; P = 0.018) and improved G:F (716 vs. 646 g/kg; P < 0.001). Diets high in FFA tended (P = 0.08) to improve final BW (21.35 vs. 21.01 kg) and ADG (576 vs. 560 g/d). Lipid-supplemented diets had greater ATTD of lipids than control diets (67.4% vs. 29.7%; P < 0.001). Apparent total tract digestibility of lipids was greater in diets with low FFA (69.9% vs. 64.9%; P < 0.001) and decreased linearly with increasing IV (73.2%, 69.1%, and 67.2%). For GE, ATTD was greater in diets with low FFA (83.1% vs. 80.9%; P = 0.001). In Exp. 2, 252 pigs at 7 d postweaning (BW of 7.0 ± 0.2 kg) were used for 28 d with 9 replicate pens per treatment and 4 pigs per pen. Diets included a control diet without added lipids and 6 treatments with 2.5%, 5.0%, or 7.5% of lipids from either poultry fat (1.9% FFA) or acidulated poultry fat (37.8% FFA) in a 2 × 3 factorial arrangement. Addition of lipids increased (P < 0.001) final BW (19.9 vs. 18.4 kg) and ADG (460 vs. 405 g/d) regardless of source. Fat increased (P < 0.001) ADFI when added at 2.5% and then decreased ADFI with each further increment (663, 740, 681, and 653 g for 0%, 2.5%, 5.0%, and 7.5% fat, respectively). Inclusion of lipids linearly (P < 0.001) improved G:F (615, 615, 688, and 692 g/kg for 0%, 2.5%, 5.0%, and 7.5% fat, respectively) and ATTD of lipids (17.8%, 50.2%, 71.0%, and 77.3% for 0, 2.5, 5.0, and 7.5% fat, respectively) and GE (76.1%, 76.4%, 83.3%, and 84.4% for 0%, 2.5%, 5.0%, and 7.5% fat, respectively). Acidulated lipids resulted in similar performance compared with refined lipids and could be economical alternatives to more expensive lipid sources.

INF-gamma rearranges membrane topography of MHC-I and ICAM-1 in colon carcinoma cells.

PubMed

Bacsó, Zsolt; Bene, László; Damjanovich, László; Damjanovich, Sándor

2002-01-18

Flow-cytometric fluorescence energy transfer (FCET) measurements between fluorescently labeled cell surface MHC-I and ICAM-1 molecules indicated similar receptor patterns in the plasma membrane of interferon-gamma (INF-gamma)-treated colon carcinoma cells as those observed earlier at the surface of lymphoid cells. INF-gamma activation significantly increased the density of MHC-I and ICAM-1 proteins in the membrane. This increase in receptor density was accompanied by decreased proximity level of the homo-associated MHC-I receptors. Hetero-association of MHC-I and ICAM-1 molecules was increased by INF-gamma treatment. INF-gamma changed neither hetero- nor homo-association of transferrin receptors. By staining the sphingomyelin/cholesterol-enriched lipid microdomains with fluorescently labeled cholera toxin B subunit, we found an increase in the amount of lipid-raft associated G(M1)-gangliosides due to INF-gamma treatment. Confocal microscopic results and FCET measurements show that MHC-I and ICAM-1 are components of G(M1)-ganglioside containing lipid-rafts and also support an increase in the size of these lipid-rafts upon INF-gamma treatment.

Preparation of Deep Sea Fish Oil-Based Nanostructured Lipid Carriers with Enhanced Cellular Uptake.

PubMed

Zhu, Qiu-Yun; Guissi, Fida; Yang, Ru-Ya; Wang, Qian; Wang, Ke; Chen, Dan; Han, Zhi-Hao; Ma, Yi; Zhang, Min; Gu, Yue-Qing

2015-12-01

Nanostructured lipid carriers (NLC) are a promising pharmaceutical delivery system with mean diameter less than 200 nm which are dispersed in an aqueous phase containing emulsifier(s), to increase the water solubility, stability and bioavailability of oil compounds. Herein we prepared a promising NLC with glyceryl monostearate (GMS) as the solid lipid template and deep sea fish oil as the liquid lipid template using melted-ultrasonic method. Fish oil-NLC had a mean size of 84.7 ± 2.6 nm and a zeta potential that ranged from -17.87 mV to -32.91 mV. The nanoparticles exhibited good stability for four weeks with a high encapsulation efficiency of 87.5 ± 5.2%. Afterwards, confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) were used to investigate the contribution of Fish oil-NLC in enhancing fluorescein isothiocyanate (FITC) cellular uptake in comparison with free FITC. The results of this study indicated the possibility of this carrier to overcome the shortcomings of deep sea fish oil and to provide a novel bifunctional carrier with nutritional potential and drug delivery ability.

Olive Leaf Extract from Sicilian Cultivar Reduced Lipid Accumulation by Inducing Thermogenic Pathway during Adipogenesis

PubMed Central

Palmeri, Rosa; Monteleone, Julieta I.; Spagna, Giovanni; Restuccia, Cristina; Raffaele, Marco; Vanella, Luca; Li Volti, Giovanni; Barbagallo, Ignazio

2016-01-01

Olive leaves contain a wide variety of phenolic compounds belonging to phenolic acids, phenolic alcohols, flavonoids, and secoiridoids, and include also many other pharmacological active compounds. They could play an important role in human diet and health because of their ability to lower blood pressure, increase coronary arteries blood flow and decrease the risk of cardiovascular diseases. The aim of this study was to investigate the effect of olive leaf extract (OLE) from Sicilian cultivar on adipogenic differentiation of human adipose derived mesenchymal stem cells and its impact on lipid metabolism. We showed that OLE treatment during adipogenic differentiation reduces inflammation, lipid accumulation and induces thermogenesis by activation of uncoupling protein uncoupling protein 1, sirtuin 1, peroxisome proliferator-activated receptor alpha, and coactivator 1 alpha. Furthermore, OLE significantly decreases the expression of molecules involved in adipogenesis and upregulates the expression of mediators involved in thermogenesis and lipid metabolism. Taken together, our results suggest that OLE may promote the brown remodeling of white adipose tissue inducing thermogenesis and improving metabolic homeostasis. PMID:27303302

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains

PubMed Central

Kassan, Adam; Herms, Albert; Fernández-Vidal, Andrea; Bosch, Marta; Schieber, Nicole L.; Reddy, Babu J.N.; Fajardo, Alba; Gelabert-Baldrich, Mariona; Tebar, Francesc; Enrich, Carlos; Gross, Steven P.

2013-01-01

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of “emerging” LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage. PMID:24368806

Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

PubMed Central

Burk, Raymond F.; Lawrence, Richard A.; Lane, James M.

1980-01-01

Paraquat and diquat facilitate formation of superoxide anion in biological systems, and lipid peroxidation has been postulated to be their mechanism of toxicity. Paraquat has been shown to be more toxic to selenium-deficient mice than to controls, presumably as the result of decreased activity of the selenoenzyme glutathione peroxidase. The present study was designed to measure lipid peroxidation and to assess toxicity in control and selenium-deficient rats given paraquat and diquat. Lipid peroxidation was measured by determining ethane production rates of intact animals; toxicity was assessed by survival and by histological and serum enzyme evidence of liver and kidney necrosis. Paraquat and diquat were both much more toxic to selenium-deficient rats than to control rats. Diquat (19.5 μmol/kg) caused rapid and massive liver and kidney necrosis and very high ethane production rates in selenium-deficient rats. The effect of paraquat (78 μmol/kg) was similar to that of diquat but was not as severe. Acutely lethal doses of paraquat (390 μmol/kg) and diquat (230 μmol/kg) in control rats caused very little ethane production and no evidence of liver necrosis. These findings suggest that paraquat and diquat exert their acute toxicity largely through lipid peroxidation in selenium-deficient rats. Selenium deficiency had no effect on superoxide dismutase activity in erythrocytes or in 105,000 g supernate of liver or kidney. Glutathione peroxidase, which represents the only well-characterized biochemical function of selenium in animals, was dissociated from the protective effect of selenium against diquat-induced lipid peroxidation and toxicity by a time-course study in which selenium-deficient rats were injected with 50 μg of selenium and later given diquat (19.5 μmol/kg). Within 10 h, the selenium injection provided significant protection against diquat-induced lipid peroxidation and mortality even though this treatment resulted in no rise in glutathione peroxidase activity of liver, kidney, lung, or plasma at 10 h. This suggests that a selenium-dependent factor in addition to glutathione peroxidase exists that protects against lipid peroxidation. Images PMID:7364936

Navy Bean and Rice Bran Intake Alters the Plasma Metabolome of Children at Risk for Cardiovascular Disease.

PubMed

Li, Katherine J; Borresen, Erica C; Jenkins-Puccetti, NaNet; Luckasen, Gary; Ryan, Elizabeth P

2017-01-01

Abnormal cholesterol in childhood predicts cardiovascular disease (CVD) risk in adulthood. Navy beans and rice bran have demonstrated efficacy in regulating blood lipids in adults and children; however, their effects on modulating the child plasma metabolome has not been investigated and warrants investigation. A pilot, randomized-controlled, clinical trial was conducted in 38 children (10 ± 0.8 years old) with abnormal cholesterol. Participants consumed a snack for 4 weeks containing either: no navy bean or rice bran (control); 17.5 g/day cooked navy bean powder; 15 g/day heat-stabilized rice bran; or 9 g/day navy beans and 8 g/day rice bran. Plasma metabolites were extracted using 80% methanol for global, non-targeted metabolic profiling via ultra-high performance liquid-chromatography tandem mass spectrometry. Differences in plasma metabolite levels after 4 weeks of dietary intervention compared to control and baseline were analyzed using analysis of variance and Welch's t -tests ( p  ≤ 0.05). Navy bean and/or rice bran consumption influenced 71 plasma compounds compared to control ( p  ≤ 0.05), with lipids representing 46% of the total plasma metabolome. Significant changes were determined for 18 plasma lipids in the navy bean group and 10 plasma lipids for the rice bran group compared to control, and 48 lipids in the navy bean group and 40 in the rice bran group compared to baseline. These results support the hypothesis that consumption of these foods impact blood lipid metabolism with implications for reducing CVD risk in children. Complementary and distinct lipid pathways were affected by the diet groups, including acylcarnitines and lysolipids (navy bean), sphingolipids (rice bran), and phospholipids (navy bean + rice bran). Navy bean consumption decreased free fatty acids associated with metabolic diseases (palmitate and arachidonate) and increased the relative abundance of endogenous anti-inflammatory lipids (endocannabinoids, N-linoleoylglycine, 12,13-diHOME). Several diet-derived amino acids, phytochemicals, and cofactors/vitamins with cardioprotective properties were increased compared to control and/or baseline, including 6-oxopiperidine-2-carboxylate (1.87-fold), N -methylpipecolate (1.89-fold), trigonelline (4.44- to 7.75-fold), S -methylcysteine (2.12-fold) (navy bean), salicylate (2.74-fold), and pyridoxal (3.35- to 3.96-fold) (rice bran). Findings from this pilot study support the need for investigating the effects of these foods for longer durations to reduce CVD risk. clinicaltrials.gov (identifier NCT01911390).

Navy Bean and Rice Bran Intake Alters the Plasma Metabolome of Children at Risk for Cardiovascular Disease

PubMed Central

Li, Katherine J.; Borresen, Erica C.; Jenkins-Puccetti, NaNet; Luckasen, Gary; Ryan, Elizabeth P.

2018-01-01

Abnormal cholesterol in childhood predicts cardiovascular disease (CVD) risk in adulthood. Navy beans and rice bran have demonstrated efficacy in regulating blood lipids in adults and children; however, their effects on modulating the child plasma metabolome has not been investigated and warrants investigation. A pilot, randomized-controlled, clinical trial was conducted in 38 children (10 ± 0.8 years old) with abnormal cholesterol. Participants consumed a snack for 4 weeks containing either: no navy bean or rice bran (control); 17.5 g/day cooked navy bean powder; 15 g/day heat-stabilized rice bran; or 9 g/day navy beans and 8 g/day rice bran. Plasma metabolites were extracted using 80% methanol for global, non-targeted metabolic profiling via ultra-high performance liquid-chromatography tandem mass spectrometry. Differences in plasma metabolite levels after 4 weeks of dietary intervention compared to control and baseline were analyzed using analysis of variance and Welch’s t-tests (p ≤ 0.05). Navy bean and/or rice bran consumption influenced 71 plasma compounds compared to control (p ≤ 0.05), with lipids representing 46% of the total plasma metabolome. Significant changes were determined for 18 plasma lipids in the navy bean group and 10 plasma lipids for the rice bran group compared to control, and 48 lipids in the navy bean group and 40 in the rice bran group compared to baseline. These results support the hypothesis that consumption of these foods impact blood lipid metabolism with implications for reducing CVD risk in children. Complementary and distinct lipid pathways were affected by the diet groups, including acylcarnitines and lysolipids (navy bean), sphingolipids (rice bran), and phospholipids (navy bean + rice bran). Navy bean consumption decreased free fatty acids associated with metabolic diseases (palmitate and arachidonate) and increased the relative abundance of endogenous anti-inflammatory lipids (endocannabinoids, N-linoleoylglycine, 12,13-diHOME). Several diet-derived amino acids, phytochemicals, and cofactors/vitamins with cardioprotective properties were increased compared to control and/or baseline, including 6-oxopiperidine-2-carboxylate (1.87-fold), N-methylpipecolate (1.89-fold), trigonelline (4.44- to 7.75-fold), S-methylcysteine (2.12-fold) (navy bean), salicylate (2.74-fold), and pyridoxal (3.35- to 3.96-fold) (rice bran). Findings from this pilot study support the need for investigating the effects of these foods for longer durations to reduce CVD risk. Trial registration: clinicaltrials.gov (identifier NCT01911390). PMID:29404331

Evidence for decreased lipofibroblast expression in hypoplastic rat lungs with congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro Daniel; Takahashi, Hiromizu; Gosemann, Jan-Hendrik; Puri, Prem

2014-10-01

Pulmonary hypoplasia (PH) is a serious condition in newborns with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) play an essential role in fetal lung maturation by stimulating alveolarization and lipid homeostasis. In rodents, LIFs are first evident during the canalicular phase of lung development with a significant increase over the last 4 days of gestation. Adipocyte differentiation-related protein (ADRP), a functional lipogenic molecular marker characterizing LIFs, is highly expressed in fetal lungs during this critical time period. We hypothesized that LIF expression in hypoplastic rat lungs is decreased in the nitrofen-induced CDH model, which is accompanied by reduced alveolar ADRP expression and lipid content. On embryonic day 9.5 (E9.5), time-mated rats received either nitrofen or vehicle. Fetuses were sacrificed on selected time points E18.5 and E21.5, and dissected lungs were divided into controls and CDH-associated PH. Pulmonary gene expression levels of ADRP were determined by quantitative real-time polymerase chain reaction. ADRP immunohistochemistry and oil red O staining were used to assess pulmonary protein expression and lipid content. Immunofluorescence double staining for alpha smooth muscle actin, which is known to be absent in LIFs, and lipid droplets was performed to evaluate the pulmonary expression of this specific subset of fibroblasts. Relative mRNA expression of ADRP was significantly reduced in lungs of CDH-associated PH on E18.5 and E21.5 compared to controls. ADRP immunoreactivity and lipid staining were markedly diminished in alveolar mesenchymal cells of CDH-associated PH on E18.5 and E21.5 compared to controls. Confocal laser scanning microscopy demonstrated markedly decreased LIF expression in alveolar interstitium of CDH-associated PH on E18.5 and E21.5 compared to controls. Decreased pulmonary LIF expression during late gestation suggests impaired LIF functioning in the nitrofen-induced CDH model, which may cause disruption in fetal alveolarization and lipid homeostasis, and thus contribute to the development of PH.

Effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome after radical gastrectomy.

PubMed

Sun, Li; Zhou, Pingping; Hua, Qingli; Jin, Changming; Guo, Chunling; Song, Bing

2018-06-01

This study aimed to investigate the effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome (MS) after radical gastrectomy. A total of 150 patients with gastric cancer, who were treated in Daqing Longnan Hospital from November, 2015 to May, 2017, were enrolled in this study. The patients were divided into the MS group (80 cases) and non-MS group (70 cases). Patients in the MS group were given corresponding drugs to control blood pressure, blood lipids and blood glucose, while patients in the non-MS group were not treated with those drugs. Patients in the MS group were divided into the normal and abnormal groups according to the levels of blood glucose, blood lipids and blood pressure. Moreover, occurrences of complications were compared between the normal and abnormal groups. Before surgery, blood glucose, blood lipids and blood pressure in the MS group were significantly higher than those in the non-MS group (p<0.05). One month after operation, blood glucose, blood lipids and blood pressure of the MS group decreased significantly compared to those before operation (p<0.05). Incidence of complications at 1 and 3 months after operation was significantly lower in the normal groups than that in the corresponding abnormal groups (p<0.05). Postoperative recovery was significantly better in the normal groups than that in the corresponding abnormal groups (p<0.05). Logistic regression analysis showed that the incidence of postoperative complications was related to fasting blood glucose, 2 h postprandial blood glucose, glycosylated hemoglobin, total triglycerides (TGs), LDL, mean blood pressure and BMI (p<0.05). The results show that, control of blood glucose, blood lipids and blood pressure in patients with gastric cancer complicated with MS after radical gastrectomy can reduce the incidence of postoperative complications and promote postoperative recovery.

Lipodystrophy, lipid profile changes, and low serum retinol and carotenoid levels in children and adolescents with acquired immunodeficiency syndrome.

PubMed

Battistini, Tânia Regina Beraldo; Sarni, Roseli Oselka Saccardo; de Souza, Fabíola Isabel Suano; Pitta, Tassiana Sacchi; Fernandes, Ana Paula; Hix, Sonia; Fonseca, Fernando Luiz Affonso; Tardini, Priscila Chemiotti; dos Santos, Valter Pinho; Lopez, Fábio Ancona

2010-06-01

To assess serum retinol and levels of carotenoids in children and adolescents with acquired immunodeficiency syndrome (AIDS) and to correlate low serum retinol and carotenoid levels with the presence of lipodystrophy, lipid profile changes, lipid peroxidation, and insulin resistance. A cross-sectional, controlled observational study was carried out with 30 children and adolescents with AIDS (mean age 9.1 y) receiving antiretroviral therapy (median length of treatment 28.4 mo), including 30 uninfected healthy controls matched for age and gender. Clinical and laboratory assessments were performed to determine nutritional status, presence of lipodystrophy, serum concentrations of retinol, beta-carotene, lycopene, lipid profile (high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols), lipid peroxidation (thiobarbituric acid-reactive substances), glycemia, and serum insulin (homeostasis model assessment for insulin resistance, cutoff point >3). Statistical analysis was done with chi-square test and Student's t test. Lipodystrophy was observed in 53.3% of patients with AIDS, and dyslipidemia was detected in 60% and 23% of subjects with human immunodeficiency virus and control subjects, respectively (P = 0.004). A higher prevalence of retinol deficiency (60% versus 26.7%, P = 0.009) and beta-carotene deficiency (23.3% versus 3.3%, P = 0.026) was found in the group with human immunodeficiency virus than in the control group. No correlation was found for low retinol and beta-carotene levels, changes in lipid and glucose metabolism, or lipodystrophy in children and adolescents with AIDS. Despite the high frequency of dyslipidemia, lipodystrophy, and retinol and beta-carotene deficiencies, it was not possible to demonstrate a correlation of these findings with lipid peroxidation and insulin resistance. More studies are needed to investigate the causes of retinol and beta-carotene deficiencies in this population and the clinical consequences of these findings. Copyright 2010 Elsevier Inc. All rights reserved.

The association between HIV (treatment), pregnancy serum lipid concentrations and pregnancy outcomes: a systematic review.

PubMed

Harmsen, Marissa J; Browne, Joyce L; Venter, Francois; Klipstein-Grobusch, Kerstin; Rijken, Marcus J

2017-07-11

Observed adverse effects of antiretroviral therapy (ART) on the lipid profile could be of significance in pregnancy. This systematic review aims to summarize studies that investigated the association between HIV, ART and serum lipids during pregnancy and adverse pregnancy outcomes. A systematic search was conducted in five electronic databases to obtain articles that measured serum lipid concentrations or the incidence of dyslipidaemia in HIV-infected pregnant women. Included articles were assessed for quality according to the Cochrane Risk of Bias Tool. The extracted data was analysed through descriptive analysis. Of the 1264 articles screened, 17 articles were included in this review; eleven reported the incidence of dyslipidaemia, and twelve on maternal serum lipid concentrations under the influence of HIV-infection and ART. No articles reported pregnancy outcomes in relation to serum lipids. Articles were of acceptable quality, but heterogenic in methods and study design. Lipid levels in HIV-infected women increased 1.5-3 fold over the trimesters of pregnancy, and remained within the physiological reference range. The percentage of women with dyslipidaemia was variable between the studies [0-88.9%] and highest in the groups on first generation protease inhibitors and for women on ART at conception. This systematic review observed physiologic concentrations of serum lipids for HIV-infected women receiving ART during pregnancy. Serum lipids were increased in users of first generation protease inhibitors and for those on treatment at conception. There was no information available about pregnancy outcomes. Future studies are needed which include HIV-uninfected control groups, control for potential confounders, and overcome limitations associated with included studies.

Integrated analysis, transcriptome-lipidome, reveals the effects of INO-level (INO2 and INO4) on lipid metabolism in yeast.

PubMed

Chumnanpuen, Pramote; Nookaew, Intawat; Nielsen, Jens

2013-10-16

In the yeast Saccharomyces cerevisiae, genes containing UASINO sequences are regulated by the Ino2/Ino4 and Opi1 transcription factors, and this regulation controls lipid biosynthesis. The expression level of INO2 and INO4 genes (INO-level) at different nutrient limited conditions might lead to various responses in yeast lipid metabolism. In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different components. In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different components. Our analysis showed the strength of using a combination of transcriptome and lipidome analysis to illustrate the effect of INO-levels on phospholipid metabolism and based on our analysis we established a global regulatory map.

[Factors affecting the control of blood pressure and lipid levels in patients with cardiovascular disease: the PREseAP Study].

PubMed

Orozco-Beltrán, Domingo; Brotons, Carlos; Moral, Irene; Soriano, Nuria; Del Valle, María A; Rodríguez, Ana I; Pepió, Josep M; Pastor, Ana

2008-03-01

The aim of this observational study was to identify factors influencing the control of blood pressure (i.e., <140/90 mmHg, or <130/80 mmHg in diabetic patients) and low-density lipoprotein (LDL) cholesterol level (<100 mg/dL) in 1223 patients with cardiovascular disease. Overall, 70.2% of patients were men, and their mean age was 66.4 years. Blood pressure was poorly controlled in 50.9% (95% confidence interval [CI], 46.9%-54.8%) and the LDL cholesterol level was poorly controlled in 60.1% (95% CI, 56.3%-63.9%). Determinants of poor blood pressure control were diabetes, hypertension, no previous diagnosis of heart failure, previous diagnosis of peripheral artery disease or stroke, obesity, and no lipid-lowering treatment. Determinants of poor LDL cholesterol control were no lipid-lowering treatment, no previous diagnosis of ischemic heart disease, no antihypertensive treatment, and dyslipidemia. The factors affecting blood pressure control were different from those affecting LDL cholesterol control, an observation that should be taken into account when implementing treatment recommendations for achieving therapeutic objectives in secondary prevention.

Radial elasticity of self-assembled lipid tubules.

PubMed

Zhao, Yue; Tamhane, Karan; Zhang, Xuejun; An, Linan; Fang, Jiyu

2008-07-01

Self-assembled lipid tubules with crystalline bilayer walls represent useful supramolecular architectures which hold promise as vehicles for the controlled release of preloaded drugs and templates for the synthesis of one-dimensional inorganic materials. We study the local elasticity of lipid tubules of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine by radial atomic force microscope indentation, coupled with finite element analysis. A reduced stiffness is found to extend a distance of approximately 600 nm from the ends of lipid tubules. The middle section of lipid tubules is homogeneous in terms of their radial elasticity with a Young's modulus of approximately 703 MPa. The inhomogeneous radial elasticity likely arises from the variation of lipid packing density near the tubule ends.

In vivo postprandial bioavailability of interesterified-lipids in sodium-caseinate or chitosan based O/W emulsions.

PubMed

Farfán, M; Villalón, M J; Ortíz, M E; Nieto, S; Bouchon, P

2015-03-15

Recent studies have shown that it should be possible to control lipid bioavailability through food structural approaches. Nevertheless, the gastrointestinal-tract physiological conditions must also be considered. To get a better understanding of this phenomenon, we evaluated the effect of emulsification, as well as the use of sodium caseinate or chitosan, on the postprandial bioavailability of interesterified-lipids in O/W emulsions after oral gastric feeding Sprague-Dawley rats. We verified that emulsification may increase lipid absorption, as determined after feeding sodium-caseinate emulsions. However, this result could not be generalised. Interesterified-lipids that were emulsified with chitosan were equally absorbed as those contained in non-emulsified interesterified-lipids/distilled-water blends. Copyright © 2014. Published by Elsevier Ltd.

Lipid emulsion enhances cardiac performance after ischemia-reperfusion in isolated hearts from summer-active arctic ground squirrels.

PubMed

Salzman, Michele M; Cheng, Qunli; Deklotz, Richard J; Dulai, Gurpreet K; Douglas, Hunter F; Dikalova, Anna E; Weihrauch, Dorothee; Barnes, Brian M; Riess, Matthias L

2017-07-01

Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45-min global ischemia and 60-min reperfusion. Coronary flow, isovolumetric left ventricular pressure, and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose-only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.

Randomly organized lipids and marginally stable proteins: a coupling of weak interactions to optimize membrane signaling.

PubMed

Rice, Anne M; Mahling, Ryan; Fealey, Michael E; Rannikko, Anika; Dunleavy, Katie; Hendrickson, Troy; Lohese, K Jean; Kruggel, Spencer; Heiling, Hillary; Harren, Daniel; Sutton, R Bryan; Pastor, John; Hinderliter, Anne

2014-09-01

Eukaryotic lipids in a bilayer are dominated by weak cooperative interactions. These interactions impart highly dynamic and pliable properties to the membrane. C2 domain-containing proteins in the membrane also interact weakly and cooperatively giving rise to a high degree of conformational plasticity. We propose that this feature of weak energetics and plasticity shared by lipids and C2 domain-containing proteins enhance a cell's ability to transduce information across the membrane. We explored this hypothesis using information theory to assess the information storage capacity of model and mast cell membranes, as well as differential scanning calorimetry, carboxyfluorescein release assays, and tryptophan fluorescence to assess protein and membrane stability. The distribution of lipids in mast cell membranes encoded 5.6-5.8bits of information. More information resided in the acyl chains than the head groups and in the inner leaflet of the plasma membrane than the outer leaflet. When the lipid composition and information content of model membranes were varied, the associated C2 domains underwent large changes in stability and denaturation profile. The C2 domain-containing proteins are therefore acutely sensitive to the composition and information content of their associated lipids. Together, these findings suggest that the maximum flow of signaling information through the membrane and into the cell is optimized by the cooperation of near-random distributions of membrane lipids and proteins. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014 Elsevier B.V. All rights reserved.

Nitrogen Starvation Induced Oxidative Stress in an Oil-Producing Green Alga Chlorella sorokiniana C3

PubMed Central

He, Chen-Liu; Wang, Qiang

2013-01-01

Microalgal lipid is one of the most promising feedstocks for biodiesel production. Chlorella appears to be a particularly good option, and nitrogen (N) starvation is an efficient environmental pressure used to increase lipid accumulation in Chlorella cells. The effects of N starvation of an oil-producing wild microalga, Chlorella sorokiniana C3, on lipid accumulation were investigated using thin layer chromatography (TLC), confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). The results showed that N starvation resulted in lipid accumulation in C. sorokiniana C3 cells, oil droplet (OD) formation and significant lipid accumulation in cells were detected after 2 d and 8 d of N starvation, respectively. During OD formation, reduced photosynthetic rate, respiration rate and photochemistry efficiency accompanied by increased damage to PSII were observed, demonstrated by chlorophyll (Chl) fluorescence, 77K fluorescence and oxygen evolution tests. In the mean time the rate of cyclic electron transportation increased correspondingly to produce more ATP for triacylglycerols (TAGs) synthesis. And 0.5 d was found to be the turning point for the early stress response and acclimation of cells to N starvation. Increased level of membrane peroxidation was also observed during OD formation, and superoxide dismutase (SOD), peroxide dismutase (POD) and catalase (CAT) enzyme activity assays suggested impaired reactive oxygen species (ROS) scavenging ability. Significant neutral lipid accumulation was also observed by artificial oxidative stress induced by H2O2 treatment. These results suggested coupled neutral lipid accumulation and oxidative stress during N starvation in C. sorokiniana C3. PMID:23874918

Differently localized lysophosphatidic acid acyltransferases crucial for triacylglycerol biosynthesis in the oleaginous alga Nannochloropsis.

PubMed

Nobusawa, Takashi; Hori, Koichi; Mori, Hiroshi; Kurokawa, Ken; Ohta, Hiroyuki

2017-05-01

The production of renewable bioenergy will be necessary to meet rising global fossil fuel demands. Members of the marine microalgae genus Nannochloropsis produce large quantities of oils (triacylglycerols; TAGs), and this genus is regarded as one of the most promising for biodiesel production. Recent genome sequencing and transcriptomic studies on Nannochloropsis have provided a foundation for understanding its oleaginous trait, but the mechanism underlying oil accumulation remains to be clarified. Here we report Nannochloropsis knock-out strains of four extraplastidic lysophosphatidic acid acyltransferases (LPAT1-LPAT4) that catalyze a major de novo biosynthetic step of TAGs and membrane lipids. We found that the four LPATs are differently involved in lipid metabolic flow in Nannochloropsis. Double knock-outs among the LPATs revealed the pivotal LPATs for TAG biosynthesis, and localization analysis indicated that the stramenopile-specific LPATs (LPAT3 and LPAT4) associated with TAG synthesis reside at the perimeter of lipid droplets. No homologous region has been found with other lipid droplet-associated proteins, however. Lipid droplets are an organelle found in nearly all organisms, and recently they were shown to play important roles in cellular metabolism and signaling. Our results provide direct evidence for the importance of the perimeter of lipid droplet in TAG synthesis in addition to its known role in maintaining TAG stability, and these findings suggest that the oleaginous trait of Nannochloropsis is enabled by the acquisition of LPATs at the perimeter of lipid droplets. © 2017 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Oxidative Risk for Atherothrombotic Cardiovascular Disease

PubMed Central

Leopold, Jane A.; Loscalzo, Joseph

2009-01-01

In the vasculature, reactive oxidant species including reactive oxygen, nitrogen, or halogenating species, and thiyl, tyrosyl, or protein radicals, may oxidatively modify lipids and proteins with deleterious consequences for vascular function. These biologically active free radical and non-radical species may be produced by increased activation of oxidant-generating sources and/or decreased cellular antioxidant capacity. Once formed, these species may engage in reactions to yield more potent oxidants that promote transition of the homeostatic vascular phenotype to a pathobiological state that is permissive for atherothrombogenesis. This dysfunctional vasculature is characterized by lipid peroxidation and aberrant lipid deposition, inflammation, immune cell activation, platelet activation, thrombus formation, and disturbed hemodynamic flow. Each of these pathobiological states is associated with an increase in the vascular burden of free radical species-derived oxidation products and, thereby, implicates increased oxidant stress in the pathogenesis of atherothrombotic vascular disease. PMID:19751821

Supported Lipid Bilayer Technology for the Study of Cellular Interfaces

PubMed Central

Crites, Travis J.; Maddox, Michael; Padhan, Kartika; Muller, James; Eigsti, Calvin; Varma, Rajat

2015-01-01

Glass-supported lipid bilayers presenting freely diffusing proteins have served as a powerful tool for studying cell-cell interfaces, in particular, T cell–antigen presenting cell (APC) interactions, using optical microscopy. Here we expand upon existing protocols and describe the preparation of liposomes by an extrusion method, and describe how this system can be used to study immune synapse formation by Jurkat cells. We also present a method for forming such lipid bilayers on silica beads for the study of signaling responses by population methods, such as western blotting, flow cytometry, and gene-expression analysis. Finally, we describe how to design and prepare transmembrane-anchored protein-laden liposomes, following expression in suspension CHO (CHOs) cells, a mammalian expression system alternative to insect and bacterial cell lines, which do not produce mammalian glycosylation patterns. Such transmembrane-anchored proteins may have many novel applications in cell biology and immunology. PMID:26331983

Autophagic Regulation of Lipid Homeostasis in Cardiometabolic Syndrome.

PubMed

Yang, Mingjie; Zhang, Yingmei; Ren, Jun

2018-01-01

As an important protein quality control process, autophagy is essential for the degradation and removal of long-lived or injured cellular components and organelles. Autophagy is known to participate in a number of pathophysiological processes including cardiometabolic syndrome. Recent findings have shown compelling evidence for the intricate interplay between autophagy and lipid metabolism. Autophagy serves as a major regulator of lipid homeostasis while lipid can also influence autophagosome formation and autophagic signaling. Lipophagy is a unique form of selective autophagy and functions as a fundamental mechanism for clearance of lipid excess in atherosclerotic plaques. Ample of evidence has denoted a novel therapeutic potential for autophagy in deranged lipid metabolism and management of cardiometabolic diseases such as atherosclerosis and diabetic cardiomyopathy. Here we will review the interplays between cardiac autophagy and lipid metabolism in an effort to seek new therapeutic options for cardiometabolic diseases.

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line.

PubMed

Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila M M; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy C R; Guterres, Silvia S; Collares, Tiago; Pohlmann, Adriana R; Seixas, Fabiana K

2014-01-01

Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line

PubMed Central

Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila MM; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy CR; Guterres, Silvia S; Collares, Tiago; Pohlmann, Adriana R; Seixas, Fabiana K

2014-01-01

Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors. PMID:24741306

Lipophorin Drives Lipid Incorporation and Metabolism in Insect Trypanosomatids.

PubMed

Ximenes, Aline dos Anjos; Silva-Cardoso, Lívia; De Cicco, Nuccia Nicole T; Pereira, Miria G; Lourenço, Daniela C; Fampa, Patricia; Folly, Evelize; Cunha-e-Silva, Narcisa L; Silva-Neto, Mario A C; Atella, Georgia C

2015-07-01

Insect trypanosomatids are inhabitants of the insect digestive tract. These parasites can be either monoxenous or dixenous. Plant trypanosomatids are known as insect trypanosomatids once they and are transmitted by phytophagous insects. Such parasites can be found in latex, phloem, fruits and seeds of many plant families. Infections caused by these pathogens are a major cause of serious economic losses. Studies by independent groups have demonstrated the metabolic flow of lipids from the vertebrate host to trypanosomatids. This mechanism is usually present when parasites possess an incomplete de novo lipid biosynthesis pathway. Here, we show that both insect trypanosomatids Phytomonas françai and Leptomonas wallacei incorporate (3)H-palmitic acid and inorganic phosphate. These molecules are used for lipid biosynthesis. Moreover, we have isolated the main hemolymphatic lipoprotein, Lipophorin (Lp) from Oncopeltus fasciatus, the natural insect vector of such parasites. Both parasites were able to incorporate Lp to be utilized both as a lipid and protein source for their metabolism. Also, we have observed the presence of Lp binding sites in the membrane of a parasite. In conclusion, we believe that the elucidation of trypanosomatid metabolic pathways will lead to a better understanding of parasite-host interactions and the identification of novel potential chemotherapy targets. Copyright © 2015 Elsevier GmbH. All rights reserved.

Investigation of the chemical mechanisms involved in the electropulsation of membranes at the molecular level.

PubMed

Breton, Marie; Mir, Lluis M

2018-02-01

The chemical consequences of electropulsation on giant unilamellar vesicles (GUVs), in particular the possible oxidation of unsaturated phospholipids, have been investigated by mass spectrometry, flow cytometry and absorbance methods. Pulse application induced oxidation of the GUV phospholipids and the oxidation level depended on the duration of the pulse. Light and O 2 increased the level of pulse-induced lipid peroxidation whereas the presence of antioxidants either in the membrane or in the solution completely suppressed peroxidation. Importantly, pulse application did not create additional reactive oxygen species (ROS) in GUV-free solution. Lipid peroxidation seems to result from a facilitation of the lipid peroxidation by the ROS already present in the solution before pulsing, not from a direct pulse-induced peroxidation. The pulse would facilitate the entrance of ROS in the core of the membrane, allowing the contact between ROS and lipid chains and provoking the oxidation. Our findings demonstrate that the application of electric pulses on cells could induce the oxidation of the membrane phospholipids since cell membranes contain unsaturated lipids. The chemical consequences of electropulsation will therefore have to be taken into account in future biomedical applications of electropulsation since oxidized phospholipids play a key role in many signaling pathways and diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

CFD modeling of an ultrasonic separator for the removal of lipid particles from pericardial suction blood.

PubMed

Trippa, Giuliana; Ventikos, Yiannis; Taggart, David P; Coussios, Constantin-C

2011-02-01

A computational fluid dynamics (CFD) model is presented to simulate the removal of lipid particles from blood using a novel ultrasonic quarter-wavelength separator. The Lagrangian-Eulerian CFD model accounts for conservation of mass and momentum, for the presence of lipid particles of a range of diameters, for the acoustic force as experienced by the particles in the blood, as well as for gravity and other particle-fluid interaction forces. In the separator, the liquid flows radially inward within a fluid chamber formed between a disc-shaped transducer and a disc-shaped reflector. Following separation of the lipid particles, blood exits the separator axially through a central opening on the disc-shaped reflector. Separator diameters studied varied between 12 and 18 cm, and gap sizes between the discs of 600 μm, 800 μm and 1 mm were considered. Results show a strong effect of residence time of the particles within the chamber on the separation performance. Different separator configurations were identified, which could give a lipid removal performance of 95% or higher when processing 62.5 cm (3)/min of blood. The developed model provides a design method for the selection of geometric and operating parameters for the ultrasonic separator.

Microbial lipid production by Rhodosporidium toruloides under sulfate-limited conditions.

PubMed

Wu, Siguo; Zhao, Xin; Shen, Hongwei; Wang, Qian; Zhao, Zongbao K

2011-01-01

Novel biochemical approaches remain to be developed to improve microbial lipid technology. This study demonstrated that sulfate limitation was effective to promote accumulating substantial amounts of intracellular lipid by the oleaginous yeast Rhodosporidium toruloides Y4. When it was cultivated using a medium with an initial carbon-to-sulfur (C/S) molar ratio of 46,750, cellular lipid content reached up to 58.3%. The time courses of cell growth, lipid accumulation and nutrient depletion were analyzed and discussed in terms of lipid biosynthesis. Moreover, lipid accumulation under sulfate-limited conditions was effective regardless of the presence of a high concentration of nitrogen sources. Thus, lipid contents almost held constant at near 57% in the media with an initial C/S molar ratio of 11,380 although the carbon-to-nitrogen molar ratio ranged from 28.3 to 5.7. Taken together, our results established the sulfate-limitation approach to control lipid biosynthesis, which should be valuable to explore nitrogen-rich raw materials as the feedstock for lipid production. Copyright © 2010 Elsevier Ltd. All rights reserved.

Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, enhances lipid peroxidation-mediated oxidative damage in U937 cells.

PubMed

Yang, Joon-Hyuck; Park, Jeen-Woo

2003-08-01

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Cytosolic NADP+-dependent isocitrate dehydrogenase (ICDH) in U937 cells produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of ICDH against lipid peroxidation-mediated oxidative damage in U937 cells was investigated in control cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the viability was lower and the protein oxidation, lipid peroxidation, and oxidative DNA damage, reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in oxalomalate-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin, as well as the significant decrease in the intracellular GSH level in oxalomalate-treated U937 cells upon exposure to AAPH. These results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against lipid peroxidation-mediated oxidative damage through the removal of reactive oxygen species.

Resveratrol restores the circadian rhythmic disorder of lipid metabolism induced by high-fat diet in mice.

PubMed

Sun, Linjie; Wang, Yan; Song, Yu; Cheng, Xiang-Rong; Xia, Shufang; Rahman, Md Ramim Tanver; Shi, Yonghui; Le, Guowei

2015-02-27

Circadian rhythmic disorders induced by high-fat diet are associated with metabolic diseases. Resveratrol could improve metabolic disorder, but few reports focused on its effects on circadian rhythm disorders in a variety of studies. The aim of the present study was to analyze the potential effects of resveratrol on high-fat diet-induced disorders about the rhythmic expression of clock genes and clock-controlled lipid metabolism. Male C57BL/6 mice were divided into three groups: a standard diet control group (CON), a high-fat diet (HFD) group and HFD supplemented with 0.1% (w/w) resveratrol (RES). The body weight, fasting blood glucose and insulin, plasma lipids and leptin, whole body metabolic status and the expression of clock genes and clock-controlled lipogenic genes were analyzed at four different time points throughout a 24-h cycle (8:00, 14:00, 20:00, 2:00). Resveratrol, being associated with rhythmic restoration of fasting blood glucose and plasma insulin, significantly decreased the body weight in HFD mice after 11 weeks of feeding, as well as ameliorated the rhythmities of plasma leptin, lipid profiles and whole body metabolic status (respiratory exchange ratio, locomotor activity, and heat production). Meanwhile, resveratrol modified the rhythmic expression of clock genes (Clock, Bmal1 and Per2) and clock-controlled lipid metabolism related genes (Sirt1, Pparα, Srebp-1c, Acc1 and Fas). The response pattern of mRNA expression for Acc1 was similar to the plasma triglyceride. All these results indicated that resveratrol reduced lipogenesis and ultimately normalized rhythmic expression of plasma lipids, possibly via its action on clock machinery. Copyright © 2015 Elsevier Inc. All rights reserved.

Coconut oil and beef tallow, but not tricaprylin, can replace menhaden oil in the diet of red drum (Sciaenops ocellatus) without adversely affecting growth or fatty acid composition.

PubMed

Craig, S R; Gatlin, D M

1995-12-01

The ability of juvenile red drum (Sciaenops ocellatus) to utilize medium-chain triglycerides (MCT) and other saturated dietary lipids was investigated in two 6-wk feeding experiments. Diets contained solvent-extracted menhaden fish meal to which menhaden fish oil (control), coconut oil, corn oil, beef tallow or various levels of MCT as tricaprylin (30, 46, 65 and 80% of total lipid) were added. Diets were fed to triplicate groups of juvenile red drum in aquaria containing brackish (6%) water. In the first feeding experiment, red drum fed the control diet had the greatest weight gains and feed efficiencies. Weight gain, but not feed was slightly, of fish fed corn oil and fish fed coconut oil was slightly (P < 0.05) lower. In the second feeding experiment, fish fed coconut oil and those fed beef tallow had significantly higher weight gains and feed efficiencies than did fish fed the control diet. Fish fed the diets containing tricaprylin at all inclusion levels in both feeding experiments had significantly lower weight gains and feed efficiencies and higher levels of beta-hydroxybutyric acid in plasma. Fish fed diets with high levels of MCT also had lower (n-3) and greater (n-6) fatty acid levels in the neutral lipid fraction of muscle tissue compared with fish fed the control diet. Coconut oil and beef tallow consistently resulted in greater liver lipid deposition but had variable effects on other tissue indices. Saturated dietary lipids had variable effects on fatty acid composition of muscle polar and neutral lipid fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of lipids in organs of the starfish Asterias amurensis associated with different treatments

NASA Astrophysics Data System (ADS)

Wang, Qi; Ikegame, Keita; Takahashi, Koretaro; Xue, Changhu; Zhang, Weinong; Wang, Hongxun; Hou, Wenfu; Wang, Yuming

2013-09-01

Lipids were extracted from organs of the starfish Asterias amurensis associated with different treatments (raw-control, boiling and heating), and then analyzed for lipid content, lipid oxidation index, lipid classes and fatty acid composition. Results showed that boiling softened the hard starfish shells, thus facilitating the collection of starfish organs. As compared with raw organs, the boiled organs had lower water content and higher lipid content, possibly due to the loss of water-holding capacity caused by protein denaturation. Both boiling and heating increased the peroxide value (PV), thiobarbituric acid (TBA) value and carbon value (CV) of lipids. Despite slight increases in the content of complex lipids, associated lipid composition had no substantial variations upon boiling and heating. For simple lipids, the content of 1, 2-diglyceride decreased in boiled and heated organs, with free fatty acids observed on thin layer chromatography (TLC). However, neither boiling nor heating significantly changed the fatty acid compositions of simple or complex lipids in starfish organs, suggesting that these two treatments had no significant effects on complex lipids in starfish organs. Together, our results indicated that boiling of starfish soon after capture facilitated the handling and extraction of useful complex lipids consisting of abundant glucosylceramide and eicosapentaenoic acid (EPA)-bounded phospholipids.

Analyzing life-history traits and lipid storage using CARS microscopy for assessing effects of copper on the fitness of Caenorhabditis elegans.

PubMed

Fueser, Hendrik; Majdi, Nabil; Haegerbaeumer, Arne; Pilger, Christian; Hachmeister, Henning; Greife, Paul; Huser, Thomas; Traunspurger, Walter

2018-07-30

Lipid storage provides energy for cell survival, growth, and reproduction and is closely related to the organismal response to stress imposed by toxic chemicals. However, the effects of toxicants on energy storage as it impacts certain life-history traits have rarely been investigated. Here, we used the nematode Caenorhabditis elegans as a test species for a chronic exposure to copper (Cu) at EC20 (0.50 mg Cu/l). Effects on the fatty acid distribution in C. elegans body were determined using coherent anti-Stokes Raman spectroscopy (CARS) to link population fitness responses with individual ecophysiological responses. Cu inhibited nematode reproductive capacity and offspring growth in addition to shortening the lifespan of exposed individuals. In adult nematodes, Cu exposure led to significant reduction of lipid storage compared to the Cu-free control: Under Cu, lipids filled only 0.5% of the nematode body volume vs. 7.5% in control nematodes, lipid droplets were on average 74% smaller and the number of tiny lipids (0-10 µm 2 ) was increased. These results suggest that (1) Cu has an important effect on the life-history traits of nematodes; (2) the quantification of lipid storage can provide important information on the response of organisms to toxic stress; and (3) CARS microscopy is a promising tool for non-invasive quantitative and qualitative analyses of lipids as a measure of nematode fitness. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization of oilseed lipids from "DHA-producing Camelina sativa": a new transformed land plant containing long-chain omega-3 oils.

PubMed

Mansour, Maged P; Shrestha, Pushkar; Belide, Srinivas; Petrie, James R; Nichols, Peter D; Singh, Surinder P

2014-02-21

New and sustainable sources of long-chain (LC, ≥C₂₀) omega-3 oils containing DHA (docosahexaenoic acid, 22:6ω3) are required to meet increasing demands. The lipid content of the oilseed of a novel transgenic, DHA-producing land plant, Camelina sativa, containing microalgal genes able to produce LC omega-3 oils, contained 36% lipid by weight with triacylglycerols (TAG) as the major lipid class in hexane extracts (96% of total lipid). Subsequent chloroform-methanol (CM) extraction recovered further lipid (~50% polar lipid, comprising glycolipids and phospholipids) and residual TAG. The main phospholipid species were phosphatidyl choline and phosphatidyl ethanolamine. The % DHA was: 6.8% (of total fatty acids) in the TAG-rich hexane extract and 4.2% in the polar lipid-rich CM extract. The relative level of ALA (α-linolenic acid, 18:3ω3) in DHA-camelina seed was higher than the control. Major sterols in both DHA- and control camelina seeds were: sitosterol, campesterol, cholesterol, brassicasterol and isofucosterol. C₁₆-C₂₂ fatty alcohols, including iso-branched and odd-chain alcohols were present, including high levels of iso-17:0, 17:0 and 19:0. Other alcohols present were: 16:0, iso-18:0, 18:0 and 18:1 and the proportions varied between the hexane and CM extracts. These iso-branched odd-chain fatty alcohols, to our knowledge, have not been previously reported. These components may be derived from wax esters, or free fatty alcohols.

The Arabidopsis MYB96 Transcription Factor Is a Positive Regulator of ABSCISIC ACID-INSENSITIVE4 in the Control of Seed Germination1

PubMed Central

Lee, Kyounghee; Lee, Hong Gil; Kim, Hyun Uk; Seo, Pil Joon

2015-01-01

Seed germination is a key developmental transition that initiates the plant life cycle. The timing of germination is determined by the coordinated action of two phytohormones, gibberellin and abscisic acid (ABA). In particular, ABA plays a key role in integrating environmental information and inhibiting the germination process. The utilization of embryonic lipid reserves contributes to seed germination by acting as an energy source, and ABA suppresses lipid degradation to modulate the germination process. Here, we report that the ABA-responsive R2R3-type MYB transcription factor MYB96, which is highly expressed in embryo, regulates seed germination by controlling the expression of ABSCISIC ACID-INSENSITIVE4 (ABI4) in Arabidopsis (Arabidopsis thaliana). In the presence of ABA, germination was accelerated in MYB96-deficient myb96-1 seeds, whereas the process was significantly delayed in MYB96-overexpressing activation-tagging myb96-ox seeds. Consistently, myb96-1 seeds degraded a larger extent of lipid reserves even in the presence of ABA, while reduced lipid mobilization was observed in myb96-ox seeds. MYB96 directly regulates ABI4, which acts as a repressor of lipid breakdown, to define its spatial and temporal expression. Genetic analysis further demonstrated that ABI4 is epistatic to MYB96 in the control of seed germination. Taken together, the MYB96-ABI4 module regulates lipid mobilization specifically in the embryo to ensure proper seed germination under suboptimal conditions. PMID:25869652

Impact of decision support in electronic medical records on lipid management in primary care.

PubMed

Gill, James M; Chen, Ying Xia; Glutting, Joseph J; Diamond, James J; Lieberman, Michael I

2009-10-01

Electronic decision-support tools may help to improve management of hyperlipidemia and other chronic diseases. This study examined the impact of lipid management tools integrated into an electronic medical record (EMR) in primary care practices. This randomized controlled trial was conducted in a national network of physicians who use an outpatient EMR. Adult primary care physicians were randomized by office to receive an electronic form that was embedded in the EMR. The form contained prompts regarding suboptimal care based on Adult Treatment Panel-III (ATP-III) guidelines, as well as reporting tools to identify patients outside of office visits whose lipid management was suboptimal. All active patients, ages 20-79 years, whose physicians participated in the study, were categorized as high, moderate, or low cardiovascular risk, and the proportion who were tested for hyperlipidemia, at lipid goal, and on lipid-lowering medications if not at goal were measured according to ATP-III guidelines. A total of 105 physicians from 25 offices and 64,150 patients were included in the study. Outcomes improved for most measures from before to 1 year after the intervention (November 1, 2005 to October 31, 2006). However, after controlling for confounding variables and for clustering in multilevel modeling, only up-to-date lipid testing for high-risk patients was statistically better in the intervention group as compared to the control group (adjusted odds ratio 15.0, P < 0.05). This study showed few differences in quality of lipid management after implementing an EMR-based disease management intervention in primary care settings. Future studies may need to examine more comprehensive interventions that include office staff in a team approach to care.

Single DNA molecules on freestanding and supported cationic lipid bilayers: diverse conformational dynamics controlled by the local bilayer properties

NASA Astrophysics Data System (ADS)

Herold, Christoph; Schwille, Petra; Petrov, Eugene P.

2016-02-01

We present experimental results on the interaction of DNA macromolecules with cationic lipid membranes with different properties, including freestanding membranes in the fluid and gel state, and supported lipid membranes in the fluid state and under conditions of fluid-gel phase coexistence. We observe diverse conformational dynamics of membrane-bound DNA molecules controlled by the local properties of the lipid bilayer. In case of fluid-state freestanding lipid membranes, the behaviour of DNA on the membrane is controlled by the membrane charge density: whereas DNA bound to weakly charged membranes predominantly behaves as a 2D random coil, an increase in the membrane charge density leads to membrane-driven irreversible DNA collapse and formation of subresolution-sized DNA globules. On the other hand, electrostatic binding of DNA macromolecules to gel-state freestanding membranes leads to completely arrested diffusion and conformational dynamics of membrane-adsorbed DNA. A drastically different picture is observed in case of DNA interaction with supported cationic lipid bilayers: When the supported bilayer is in the fluid state, membrane-bound DNA molecules undergo 2D translational Brownian motion and conformational fluctuations, irrespectively of the charge density of the supported bilayer. At the same time, when the supported cationic membrane shows fluid-gel phase coexistence, membrane-bound DNA molecules are strongly attracted to micrometre-sized gel-phase domains enriched with the cationic lipid, which results in 2D compaction of the membrane-bound macromolecules. This DNA compaction, however, is fully reversible, and disappears as soon as the membrane is heated above the fluid-gel coexistence. We also discuss possible biological implications of our experimental findings.

Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster

PubMed Central

Rai, Himanshu; Sinha, Nakul; Finn, James; Agrawal, Suraksha; Mastana, Sarabjit

2016-01-01

Abstract Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population. PMID:28261635

Identification of a potential biomarker for FABP4 inhibition: the power of lipidomics in preclinical drug testing.

PubMed

Suhre, Karsten; Römisch-Margl, Werner; de Angelis, Martin Hrabé; Adamski, Jerzy; Luippold, Gerd; Augustin, Robert

2011-06-01

The fatty acid binding protein 4 (FABP4) belongs to the family of lipid chaperones that control intracellular fluxes and compartmentalization of their respective ligands (e.g., fatty acids). FABP4, which is almost exclusively expressed in adipocytes and macrophages, contributes to the development of insulin resistance and atherosclerosis in mice. Lack of FABP4 protects against the development of insulin resistance associated with genetic or diet-induced obesity in mice. Furthermore, total or macrophage-specific FABP4 deficiency is protective against atherosclerosis in apolipoprotein E-deficient mice. The FABP4 small-molecule inhibitor BMS309403 has demonstrated efficacy in mouse models for type 2 diabetes mellitus and atherosclerosis, resembling phenotypes of mice with FABP4 deficiency. However, despite the therapeutically attractive long-term effects of FABP4 inhibition, an acute biomarker for drug action is lacking. The authors applied mass spectrometry lipidomics analysis to in vitro and in vivo (plasma and adipose tissue) samples upon inhibitor treatment. They report the identification of a potential biomarker for acute in vivo FABP4 inhibition that is applicable for further investigations and can be implemented in simple and fast-flow injection mass spectrometry assays. In addition, this approach can be considered a proof-of-principle study that can be applied to other lipid-pathway targeting mechanisms.

Effect of replacing grass silage with red clover silage on ruminal lipid metabolism in lactating cows fed diets containing a 60:40 forage-to-concentrate ratio.

PubMed

Halmemies-Beauchet-Filleau, A; Vanhatalo, A; Toivonen, V; Heikkilä, T; Lee, M R F; Shingfield, K J

2013-09-01

Diets based on red clover silage (RCS) typically increase the concentration of polyunsaturated fatty acids (PUFA) in ruminant milk and meat compared with grass silages (GS), an effect that has been attributed to higher activity of polyphenol oxidase in red clover, promoting ruminal escape of dietary lipid. Four multiparous Finnish Ayrshire cows in mid lactation fitted with rumen cannulas were used in a 4×4 Latin Square design with 21-d experimental periods to evaluate the effects of incremental replacement of GS with RCS on ruminal lipid metabolism, using the omasal sampling technique in combination with Cr-EDTA, Yb acetate, and indigestible neutral detergent fiber as markers. Treatments comprised total mixed rations offered ad libitum containing 600 g of forage/kg of diet dry matter, with RCS replacing GS in a ratio of 0:100, 33:67, 67:33, and 100:0 on a dry matter basis. Silages contained a high proportion of lipid as nonesterified fatty acids (NEFA), with no difference between forage species (75 and 73% for GS and RCS, respectively). Substitution of GS with RCS had no influence on the intakes of NEFA, polar lipid, triacylglycerol, diacylglycerol, monoacylglycerol, or total fatty acids (FA), but altered the ingestion of specific FA. Replacing GS with RCS decreased linearly 18:3n-3 and increased linearly 18:2n-6 intakes. Changes in the proportion of RCS in the diet had no effect on the amounts or on the relative proportions of different lipid fractions at the omasum. On average, NEFA, polar lipid, triacylglycerol, diacylglycerol, and monoacylglycerol accounted for 80, 12, 4.4, 2.4, and 0.8% of total FA in omasal digesta, respectively. Replacement of GS with RCS increased linearly the amount of esterified and nonesterified 18:3n-3 at the omasum. Flows of cis-9 18:1 and 18:2n-6 were also increased linearly in response to RCS in the diet, whereas 3,7,11,15-tetramethyl-16:0 at the omasum was decreased. Replacing GS with RCS in the diet decreased linearly the lipolysis of dietary esterified lipids in the rumen from 85 to 70%. Effects on lipolysis due to forage species were also associated with linear decreases in apparent ruminal 18:3n-3 biohydrogenation from 93 to 85% and a trend toward lowered biohydrogenation of cis-9 18:1 and 18:2n-6 in the rumen. However, forage species had no effect on the flow of bound phenols formed as a consequence of polyphenol oxidase activity at the omasum. In conclusion, despite minimal differences in the extent of lipolysis in silo, lipid and constituent FA in RCS were less susceptible to ruminal lipolysis and biohydrogenation compared with GS. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Mammary lipid metabolism and milk fatty acid secretion in alpine goats fed vegetable lipids.

PubMed

Bernard, L; Rouel, J; Leroux, C; Ferlay, A; Faulconnier, Y; Legrand, P; Chilliard, Y

2005-04-01

Fourteen Alpine goats at midlactation were fed a diet of hay and concentrate (55:45), without (control) or with formaldehyde-treated linseed (FLS) or oleic sunflower oil (OSO) at 11.2 or 3.5% of dry matter intake, respectively, in a 3 x 3 Latin Square design with three 3-wk periods. Milk yield was lower in goats fed FLS than control or OSO (2.13 vs. 2.32 kg/d). Milk fat content was higher with FLS or OSO than control (40.8 vs. 33.8 g/kg). Formaldehyde-treated linseed and OSO caused a significant decrease (23 and 18%, respectively) of C10 to C17 fatty acids secretion compared with control. The secretion of cis-9 C18:1 and cis-9, trans-11 C18:2 were increased 1.44- and 1.54-fold for FLS and 1.78- and 1.36-fold for OSO, compared with control. The C18:3 (n-3) secretion was increased 2.61-fold with FLS compared with control. Milk cis-9 C14:1/C14:0, cis-9 C16:1/C16:0, and cis-9 C18:1/C18:0 ratios decreased with the supplemented diets compared with control. Mammary stearoyl-CoA desaturase mRNA and activity were decreased by the lipid supplements, whereas no significant change was observed for acetyl-CoA carboxylase and fatty acid synthase. The activities of glucose-6-phosphate dehydrogenase, malic enzyme, and glycerol-3-phosphate dehydrogenase were not affected by the lipid supplements. Mammary lipoprotein lipase mRNA increased with OSO, whereas lipoprotein lipase activity tended to decrease with FLS compared with control. Milk lipoprotein lipase activity sharply decreased with lipid supplement (by 59 and 71%, for FLS and OSO, respectively). The changes in milk fatty acid profile due to FLS and OSO supplements were partly related to changes in the levels of mammary enzyme activities or mRNA.

The effect of periodontal therapy on C-reactive protein, endothelial function, lipids and proinflammatory biomarkers in patients with stable coronary artery disease: study protocol for a randomized controlled trial.

PubMed

Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Rabelo-Silva, Eneida Rejane; Polanczyk, Carisi Anne; Rösing, Cassiano Kuchenbecker; Haas, Alex Nogueira

2013-09-06

Scarce information exists regarding the preventive effect of periodontal treatment in the recurrence of cardiovascular events. Prevention may be achieved by targeting risk factors for recurrent coronary artery disease (CAD) in patients with previous history of cardiovascular events. The aim of this trial is to compare the effect of two periodontal treatment approaches on levels of C-reactive protein, lipids, flow-mediated dilation and serum concentrations of proinflammatory and endothelial markers in stable CAD patients with periodontitis over a period of 12 months. This is a randomized, parallel design, examiner blinded, controlled clinical trial. Individuals from both genders, 35 years of age and older, with concomitant diagnosis of CAD and periodontitis will be included. CAD will be defined as the occurrence of at least one of the following events 6 months prior to entering the trial: documented history of myocardial infarction; surgical or percutaneous myocardial revascularization and lesion >50% in at least one coronary artery assessed by angiography; presence of angina and positive noninvasive testing of ischemia. Diagnosis of periodontitis will be defined using the CDC-AAP case definition (≥2 interproximal sites with clinical attachment loss ≥6 mm and ≥1 interproximal site with probing depth ≥5 mm). Individuals will have to present at least ten teeth present to be included. One hundred individuals will be allocated to test (intensive periodontal treatment comprised by scaling and root planing) or control (community periodontal treatment consisting of one session of supragingival plaque removal only) treatment groups. Full-mouth six sites per tooth periodontal examinations and subgingival biofilm samples will be conducted at baseline, 3, 6 and 12 months after treatment. The primary outcome of this study will be C-reactive protein changes over time. Secondary outcomes include levels of total cholesterol, LDL-C, HDL-C, triglycerides, IL-1β, IL-6, TNFα, fibrinogen, ICAM-1, VCAM-1 and E-selectin. These outcomes will be assessed at all time points over 12 months. Flow-mediated dilation will be assessed at baseline, 1, 3 and 6 months after periodontal therapy. This trial will provide new evidence regarding the effect of periodontal treatment on risk markers for recurrence of cardiovascular events in stable coronary artery disease patients. ClinicalTrials.gov Identifier, NCT01609725.

Evaluation of hepatic steatosis in dogs with congenital portosystemic shunts using Oil-Red-O staining

PubMed Central

Hunt, GB; Luff, J; Daniel, L; Van den Bergh, R.

2015-01-01

The aims of this prospective study were to quantify steatosis in dogs with congenital portosystemic shunts using a fat-specific stain, to compare the amount of steatosis in different lobes of the liver, and to evaluate intra- and inter-Observer variability in lipid point counting. Computer-assisted point counting of lipid droplets was undertaken following Oil-Red-O staining in 21 dogs with congenital portosystemic shunts and 9 control dogs. Dogs with congenital portosystemic shunts had significantly more small lipid droplets (< 6 μ) than control dogs (p = 0.0013 and 0.0002, respectively). There was no significant difference in steatosis between liver lobes for either control dogs and CPS dogs. Significant differences were seen between observers for the number of large lipid droplets (> 9 μ) and lipogranulomas per tissue point (p = 0.023 and 0.01, respectively). In conclusion, computer-assisted counting of lipid droplets following Oil Red O staining of liver biopsy samples allows objective measurement and detection of significant differences between dogs with CPS and normal dogs. This method will allow future evaluation of the relationship between different presentations of CPS (anatomy, age, breed) and lipidosis, as well as the impact of hepatic lipidosis on outcomes following surgical shunt attenuation. PMID:23528942

Effect of mycoprotein on blood lipids.

PubMed

Turnbull, W H; Leeds, A R; Edwards, G D

1990-10-01

This metabolic study was designed to investigate the effects of mycoprotein on blood lipids. Mycoprotein is a food produced by continuous fermentation of Fusarium graminearum (Schwabe) on a carbohydrate substrate. Two groups of subjects with slightly raised cholesterol concentrations took part in the 3-wk study. The experimental group was fed mycoprotein in place of meat and the control diet contained meat. There was no change in plasma cholesterol in the control group but there was a 13% reduction in the mycoprotein group. Low-density lipoprotein (LDL) increased in the control group by 12% and decreased by 9% in the mycoprotein group. High-density lipoprotein (HDL) decreased by 11% in the control group but increased by 12% in the mycoprotein group. In each case the group ANOVA differences between variables were statistically significant. It is clear from these results that lipid variables are advantageously altered by mycoprotein consumption.

Selective enrichment of Eicosapentaenoic acid (20:5n-3) in N. oceanica CASA CC201 by natural auxin supplementation.

PubMed

Udayan, Aswathy; Arumugam, Muthu

2017-10-01

The present study aims to evaluate the effect of different concentration of natural auxin, Indole-3 acetic acid (IAA) on growth, lipid yield, PUFA and EPA accumulation in Nannochloropsis oceanica CASA CC201. It was observed that the, treatment with 10ppm concentration of IAA resulted in high cell number 579.5×10 6 cells/ml than the control (215.5×10 6 cells/ml). Treatment with IAA at a concentration of 40ppm gives the highest cellular lipid accumulation of 60.9% DCW than the control 31.05% DCW). Lipid yield is also found to be increased by the addition of 40ppm IAA (319.5mg/L) compared with the control (121.5mg/L). EPA percentage is increased to 10.76% by the addition of 40ppm IAA compared to the control (1.87%). Copyright © 2017 Elsevier Ltd. All rights reserved.

Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation

PubMed Central

García-Mateo, Nadia; Ganfornina, Maria D.; Montero, Olimpio; Gijón, Miguel A.; Murphy, Robert C.; Sanchez, Diego

2014-01-01

Management of lipids, particularly signaling lipids that control neuroinflammation, is crucial for the regeneration capability of a damaged nervous system. Knowledge of pro- and anti-inflammatory signals after nervous system injury is extensive, most of them being proteins acting through well-known receptors and intracellular cascades. However, the role of lipid binding extracellular proteins able to modify the fate of lipids released after injury is not well understood. Apolipoprotein D (ApoD) is an extracellular lipid binding protein of the Lipocalin family induced upon nervous system injury. Our previous study shows that axon regeneration is delayed without ApoD, and suggests its participation in early events during Wallerian degeneration. Here we demonstrate that ApoD is expressed by myelinating and non-myelinating Schwann cells and is induced early upon nerve injury. We show that ApoD, known to bind arachidonic acid (AA), also interacts with lysophosphatidylcholine (LPC) in vitro. We use an in vivo model of nerve crush injury, a nerve explant injury model, and cultured macrophages exposed to purified myelin, to uncover that: (i) ApoD regulates denervated Schwann cell-macrophage signaling, dampening MCP1- and Tnf-dependent macrophage recruitment and activation upon injury; (ii) ApoD controls the over-expression of the phagocytosis activator Galectin-3 by infiltrated macrophages; (iii) ApoD controls the basal and injury-triggered levels of LPC and AA; (iv) ApoD modifies the dynamics of myelin-macrophage interaction, favoring the initiation of phagocytosis and promoting myelin degradation. Regulation of macrophage behavior by Schwann-derived ApoD is therefore a key mechanism conditioning nerve injury resolution. These results place ApoD as a lipid binding protein controlling the signals exchanged between glia, neurons and blood-borne cells during nerve recovery after injury, and open the possibility for a therapeutic use of ApoD as a regeneration-promoting agent. PMID:25426024

[Lipid control in patients with coronary artery disease in a healthcare area in Cáceres (Spain): LIPICERES study].

PubMed

Gómez-Barrado, José J; Ortiz, Carolina; Gómez-Turégano, Marta; Gómez-Turégano, Paula; Garcipérez-de-Vargas, Francisco J; Sánchez-Calderón, Pablo

Current guidelines recommend a low-density lipoprotein cholesterol (LDLc) target of <70mg/dl for patients with coronary artery disease. Despite the well-established benefits of strict lipid control, the most recent studies show that control rate of lipid targets are alarmingly low. An analysis was performed on the lipid targets attained according to current guidelines for the prevention of cardiovascular disease in coronary patients in a Caceres healthcare area. An observational and cross-sectional study was carried out in a healthcare area in Caceres (Spain). The study included a total of 741 patients admitted for coronary disease between 2009 and 2015 with available lipid profile in the last 3 years Total cholesterol, high-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), triglycerides (TG) and non-HDLc were analysed. The majority (74.4%) of patients were male, with a mean age of 68.5±13.1 years; 76.3±11.8 for women and 65.8±12.6 for men (P<.001). A total of 52.3% patients achieved the LDLc target of <70mg/dl, with no gender differences. Only 44.8% of the patients <55 years achieved their lipid targets, compared to 59.3% of the patients >75 years. About 68.2% of men had an HDLc>40mg/dl, and 54.8% of women had an HDLc>50mg/dl. Overall, 79.4% of patients had a TG<150mg/dl, with no gender differences, and 59.8% had a non-HDLc<100mg/dl. Approximately one half of patients with coronary disease do not achieve their target lipid levels as defined in the European guidelines, and this rate is less than reported in previous studies. There are no gender differences in achieving lipid goals, and age is a predictor of adherence. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

NASA Astrophysics Data System (ADS)

Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

2010-03-01

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and lipids (solid and liquid) inside the lipid nanoparticle systems are proposed.

Body Composition and Ectopic Lipid Changes With Biochemical Control of Acromegaly.

PubMed

Bredella, Miriam A; Schorr, Melanie; Dichtel, Laura E; Gerweck, Anu V; Young, Brian J; Woodmansee, Whitney W; Swearingen, Brooke; Miller, Karen K

2017-11-01

Acromegaly is characterized by growth hormone (GH) and insulinlike growth factor-1 (IGF-1) hypersecretion, and GH and IGF-1 play important roles in regulating body composition and glucose homeostasis. The purpose of our study was to investigate body composition including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared with age-, body mass index (BMI)-, and sex-matched controls and to determine changes in these parameters after biochemical control of acromegaly. Cross-sectional study of 20 patients with active acromegaly and 20 healthy matched controls. Prospective study of 16 patients before and after biochemical control of acromegaly. Body composition including ectopic lipids by magnetic resonance imaging/proton magnetic resonance spectroscopy; measures of glucose homeostasis by an oral glucose tolerance test; gonadal steroids. Patients with active acromegaly had lower mean intrahepatic lipid (IHL) and higher mean fasting insulin and insulin area under the curve (AUC) values than controls. Men with acromegaly had lower mean total testosterone, sex hormone-binding globulin, and estradiol values than male controls. After therapy, homeostasis model assessment of insulin resistance, fasting insulin level, and insulin AUC decreased despite an increase in IHL and abdominal and thigh adipose tissues and a decrease in muscle mass. Patients with acromegaly were characterized by insulin resistance and hyperinsulinemia but lower IHL compared with age-, BMI-, and sex-matched healthy controls. Biochemical control of acromegaly improved insulin resistance but led to a less favorable anthropometric phenotype with increased IHL and abdominal adiposity and decreased muscle mass. Copyright © 2017 Endocrine Society

Metabolic changes associated with tumor metastasis, part 2: Mitochondria, lipid and amino acid metabolism.

PubMed

Porporato, Paolo E; Payen, Valéry L; Baselet, Bjorn; Sonveaux, Pierre

2016-04-01

Metabolic alterations are a hallmark of cancer controlling tumor progression and metastasis. Among the various metabolic phenotypes encountered in tumors, this review focuses on the contributions of mitochondria, lipid and amino acid metabolism to the metastatic process. Tumor cells require functional mitochondria to grow, proliferate and metastasize, but shifts in mitochondrial activities confer pro-metastatic traits encompassing increased production of mitochondrial reactive oxygen species (mtROS), enhanced resistance to apoptosis and the increased or de novo production of metabolic intermediates of the TCA cycle behaving as oncometabolites, including succinate, fumarate, and D-2-hydroxyglutarate that control energy production, biosynthesis and the redox state. Lipid metabolism and the metabolism of amino acids, such as glutamine, glutamate and proline are also currently emerging as focal control points of cancer metastasis.

Lipogels: surface-adherent composite hydrogels assembled from poly(vinyl alcohol) and liposomes

NASA Astrophysics Data System (ADS)

Jensen, Bettina E. B.; Hosta-Rigau, Leticia; Spycher, Philipp R.; Reimhult, Erik; Städler, Brigitte; Zelikin, Alexander N.

2013-07-01

Drug-eluting engineered surface coatings are of paramount importance for many biomedical applications from implantable devices to tissue engineering. Herein, we present the assembly of lipogels, composite physical hydrogels assembled from poly(vinyl alcohol) and liposomes using thiol-disulfide exchange between end group modified PVA and thiocholesterol containing liposomes, and the response of adhering cells to these coatings. We demonstrate the controlled loading of liposomes into the polymer matrix and the preserved mechanical properties of the lipogels. Furthermore, the lipogels are successfully rendered cell adhesive by incorporation of poly(l-lysine) into the PVA polymer matrix or by poly(dopamine) coating of the lipogels. The successful lipid uptake from the lipogels by macrophages, hepatocytes, and myoblasts was monitored by flow cytometry. Finally, the delivery of active cargo, paclitaxel, to adherent myoblasts is shown, thus illustrating the potential of the lipogels as a drug eluting interface for biomedical applications.Drug-eluting engineered surface coatings are of paramount importance for many biomedical applications from implantable devices to tissue engineering. Herein, we present the assembly of lipogels, composite physical hydrogels assembled from poly(vinyl alcohol) and liposomes using thiol-disulfide exchange between end group modified PVA and thiocholesterol containing liposomes, and the response of adhering cells to these coatings. We demonstrate the controlled loading of liposomes into the polymer matrix and the preserved mechanical properties of the lipogels. Furthermore, the lipogels are successfully rendered cell adhesive by incorporation of poly(l-lysine) into the PVA polymer matrix or by poly(dopamine) coating of the lipogels. The successful lipid uptake from the lipogels by macrophages, hepatocytes, and myoblasts was monitored by flow cytometry. Finally, the delivery of active cargo, paclitaxel, to adherent myoblasts is shown, thus illustrating the potential of the lipogels as a drug eluting interface for biomedical applications. Electronic supplementary information (ESI) available: Paclitaxel calibration curve and images of DIC of PLL blended PVA physical hydrogels, lipogel FRAP, and different cell lines attached to lipogels are available. See DOI: 10.1039/c3nr01662e

pH-Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid-Based Delivery Systems.

PubMed

Oumzil, Khalid; Benizri, Sébastien; Tonelli, Giovanni; Staedel, Cathy; Appavoo, Ananda; Chaffanet, Max; Navailles, Laurence; Barthélémy, Philippe

2015-11-01

Lipid-based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3'-orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH-sensitive liposomes. ONL-based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH-cleavable nucleolipids to control the stability of lipid-based delivery systems represents a promising approach for the intracellular delivery of drug cargos. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy.

PubMed

Christ, Emanuel R; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

2016-01-21

Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

Cold flow properties of fatty acid methyl esters: Additives versus diluents

USDA-ARS?s Scientific Manuscript database

Biodiesel is typically composed of fatty acid methyl esters (FAME) converted from agricultural lipids. Common feedstocks include soybean oil, canola oil, rapeseed oil, sunflower oil, and palm oil. Recent debate on the conversion of edible oils into non-food products has created opportunities to deve...

Active lipids of Ganoderma lucidum spores-induced apoptosis in human leukemia THP-1 cells via MAPK and PI3K pathways.

PubMed

Wang, Jia-He; Zhou, Yi-Jun; Zhang, Meng; Kan, Liang; He, Ping

2012-01-31

Ganoderma lucidum (Lingzhi) is traditionally drug, which has been traditionally effective used in the treatment of chronic hepatopathy, hypertension, hyperglycemia and cancer. THP-1 and HL-60 apoptosis induced by active lipids of Ganoderma lucidum spores was quantified by flow cytometry using FITC-conjugated annexin V and PI; MAPK and Akt were measured by Western blot, and caspase-3, -8 and -9 activities were also detected by spectrophotometric assay. Our results showed that active lipids of Ganoderma lucidum spores decreased phosphorylation-ERK1/2 (P-ERK1/2), P-Akt and increased P-JNK1/2, but did not affect expressions of P-p38 MAPK in THP-1 cells. Moreover, treatment of THP-1 cells with active lipids of Ganoderma lucidum spores resulted in activation of caspase-3, -8 and -9. Furthermore, LY294002 (Akt inhibitor) or PD98059 (ERK1/2 inhibitor) significantly enhanced active lipids of Ganoderma lucidum spores-induced apoptosis in THP-1 cells, whereas caspase inhibitors or SP600125 (JNK inhibitor), decreased apoptosis in THP-1 cells. Taken together, our study for the first time suggests that active lipids of Ganoderma lucidum spores is able to enhance apoptosis in THP-1 cells, at least in part, through inhibition of ERK1/2, Akt and activation of JNK1/2 signaling pathways. Moreover, it also triggers caspase-3, -8 and -9 activation mediated apoptotic induction. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Lipid composition of slash pine tissue cultures grown with lunar and earth soils

NASA Technical Reports Server (NTRS)

Laseter, J. L.; Weete, J. D.; Baur, P. S.; Walkinshaw, C. H.

1973-01-01

Lipid analyses were conducted on slash pine tissues grown in culture in the presence of lunar (Apollo 15) and earth soils. Significant reductions in the total lipids, fatty acids, and sterol components were found in the tissues grown in contact with each of the soils employed when compared to the control. Tissues grown with lunar soil showed the greatest reductions. These results are discussed with respect to previous ultrastructural studies on similarly treated slash pine tissues and lipid analyses on tobacco tissue cultures.

Multi-omics analysis reveals regulators of the response to nitrogen limitation in Yarrowia lipolytica

DOE PAGES

Pomraning, Kyle R.; Kim, Young -Mo; Nicora, Carrie D.; ...

2016-02-25

Yarrowia lipolytica is an oleaginous ascomycete yeast that stores lipids in response to limitation of nitrogen. Furthermore, while the enzymatic pathways responsible for neutral lipid accumulation in Y. lipolytica are well characterized, regulation of these pathways has received little attention. We therefore sought to characterize the response to nitrogen limitation at system-wide levels, including the proteome, phosphoproteome and metabolome, to better understand how this organism regulates and controls lipid metabolism and to identify targets that may be manipulated to improve lipid yield.

Aspects of nonviral gene therapy: correlation of molecular parameters with lipoplex structure and transfection efficacy in pyridinium-based cationic lipids.

PubMed

Parvizi, Paria; Jubeli, Emile; Raju, Liji; Khalique, Nada Abdul; Almeer, Ahmed; Allam, Hebatalla; Manaa, Maryem Al; Larsen, Helge; Nicholson, David; Pungente, Michael D; Fyles, Thomas M

2014-01-30

This study seeks correlations between the molecular structures of cationic and neutral lipids, the lipid phase behavior of the mixed-lipid lipoplexes they form with plasmid DNA, and the transfection efficacy of the lipoplexes. Synthetic cationic pyridinium lipids were co-formulated (1:1) with the cationic lipid 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and these lipids were co-formulated (3:2) with the neutral lipids 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) or cholesterol. All lipoplex formulations exhibited plasmid DNA binding and a level of protection from DNase I degradation. Composition-dependent transfection (beta-galactosidase and GFP) and cytotoxicity was observed in Chinese hamster ovarian-K1 cells. The most active formulations containing the pyridinium lipids were less cytotoxic but of comparable activity to a Lipofectamine 2000™ control. Molecular structure parameters and partition coefficients were calculated for all lipids using fragment additive methods. The derived shape parameter values correctly correlated with observed hexagonal lipid phase behavior of lipoplexes as derived from small-angle X-ray scattering experiments. A transfection index applicable to hexagonal phase lipoplexes derived from calculated parameters of the lipid mixture (partition coefficient, shape parameter, lipoplex packing) produced a direct correlation with transfection efficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Localization of puroindoline-a and lipids in bread dough using confocal scanning laser microscopy.

PubMed

Dubreil, Laurence; Biswas, Samares C; Marion, Didier

2002-10-09

Puroindolines are lipid-binding proteins from wheat flour that play a significant role in bread crumb texture. The localization of wheat flour lipids and puroindoline-a (PIN-a) in bread dough was studied by confocal scanning laser microscopy (CSLM). Wheat lipids were located around gas cells (GC) and embedded within the protein-starch matrix (SPM) of the dough. PIN-a was mainly located in the matrix of dough, where it was associated with lipids. In contrast, in defatted dough, PIN-a was found around GC. Addition of puroindolines in bread dough induced a defatting of the gas bubble surface and a decrease of the lipid vesicles and/or droplet size embedded within the SPM. Therefore, puroindolines control the lipid partitioning within the different phases of dough, a phenomenon that should have important consequence on the gas bubble expansion and GC formation in the further stages (fermentation, baking) of the bread-making process.

In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters.

PubMed

Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming

2014-01-01

Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.

Lipid content and fatty acid composition of green algae Scenedesmus obliquus grown in a constant cell density apparatus

NASA Technical Reports Server (NTRS)

Choi, K. J.; Nakhost, Z.; Barzana, E.; Karel, M.

1987-01-01

The lipids of alga Scenedesmus obliquus grown under controlled conditions were separated and fractionated by column and thin-layer chromatography, and fatty acid composition of each lipid component was studied by gas-liquid chromatography (GLC). Total lipids were 11.17%, and neutral lipid, glycolipid and phospholipid fractions were 7.24%, 2.45% and 1.48% on a dry weight basis, respectively. The major neutral lipids were diglycerides, triglycerides, free sterols, hydrocarbons and sterol esters. The glycolipids were: monogalactosyl diglyceride, digalactosyl diglyceride, esterified sterol glycoside, and sterol glycoside. The phospholipids included: phosphatidyl choline, phosphatidyl glycerol and phosphatidyl ethanolamine. Fourteen fatty acids were identified in the four lipid fractions by GLC. The main fatty acids were C18:2, C16:0, C18:3(alpha), C18:1, C16:3, C16:1, and C16:4. Total unsaturated fatty acid and essential fatty acid compositions of the total algal lipids were 80% and 38%, respectively.

Inducing morphological changes in lipid bilayer membranes with microfabricated substrates

NASA Astrophysics Data System (ADS)

Liu, Fangjie; Collins, Liam F.; Ashkar, Rana; Heberle, Frederick A.; Srijanto, Bernadeta R.; Collier, C. Patrick

2016-11-01

Lateral organization of lipids and proteins into distinct domains and anchoring to a cytoskeleton are two important strategies employed by biological membranes to carry out many cellular functions. However, these interactions are difficult to emulate with model systems. Here we use the physical architecture of substrates consisting of arrays of micropillars to systematically control the behavior of supported lipid bilayers - an important step in engineering model lipid membrane systems with well-defined functionalities. Competition between attractive interactions of supported lipid bilayers with the underlying substrate versus the energy cost associated with membrane bending at pillar edges can be systematically investigated as functions of pillar height and pitch, chemical functionalization of the microstructured substrate, and the type of unilamellar vesicles used for assembling the supported bilayer. Confocal fluorescent imaging and AFM measurements highlight correlations that exist between topological and mechanical properties of lipid bilayers and lateral lipid mobility in these confined environments. This study provides a baseline for future investigations into lipid domain reorganization on structured solid surfaces and scaffolds for cell growth.

Emerging Roles for the Lysosome in Lipid Metabolism.

PubMed

Thelen, Ashley M; Zoncu, Roberto

2017-11-01

Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase. In turn, mTORC1 potently drives anabolic processes, including de novo lipid synthesis, while inhibiting lipid catabolism. Here, we describe the dual role of the lysosome in lipid transport and biogenesis, and we discuss how integration of these two processes may play important roles both in normal physiology and in disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional assessment of plant and microalgal lipid pathway genes in yeast to enhance microbial industrial oil production.

PubMed

Peng, Huadong; Moghaddam, Lalehvash; Brinin, Anthony; Williams, Brett; Mundree, Sagadevan; Haritos, Victoria S

2018-03-01

As promising alternatives to fossil-derived oils, microbial lipids are important as industrial feedstocks for biofuels and oleochemicals. Our broad aim is to increase lipid content in oleaginous yeast through expression of lipid accumulation genes and use Saccharomyces cerevisiae to functionally assess genes obtained from oil-producing plants and microalgae. Lipid accumulation genes DGAT (diacylglycerol acyltransferase), PDAT (phospholipid: diacylglycerol acyltransferase), and ROD1 (phosphatidylcholine: diacylglycerol choline-phosphotransferase) were separately expressed in yeast and lipid production measured by fluorescence, solvent extraction, thin layer chromatography, and gas chromatography (GC) of fatty acid methyl esters. Expression of DGAT1 from Arabidopsis thaliana effectively increased total fatty acids by 1.81-fold above control, and ROD1 led to increased unsaturated fatty acid content of yeast lipid. The functional assessment approach enabled the fast selection of candidate genes for metabolic engineering of yeast for production of lipid feedstocks. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Mechanisms of Lipid Accumulation in the Bone Morphogenetic Protein Receptor Type 2 Mutant Right Ventricle

PubMed Central

Brittain, Evan L.; Fessel, Joshua P.; Penner, Niki; Atkinson, James; Funke, Mitch; Grueter, Carrie; Jerome, W. Gray; Freeman, Michael; Newman, John H.; West, James; Hemnes, Anna R.

2016-01-01

Rationale: In heritable pulmonary arterial hypertension with germline mutation in the bone morphogenetic protein receptor type 2 (BMPR2) gene, right ventricle (RV) dysfunction is associated with RV lipotoxicity; however, the underlying mechanism for lipid accumulation is not known. Objectives: We hypothesized that lipid accumulation in cardiomyocytes with BMPR2 mutation occurs owing to alterations in lipid transport and impaired fatty acid oxidation (FAO), which is exacerbated by a high-lipid (Western) diet (WD). Methods: We used a transgenic mouse model of pulmonary arterial hypertension with mutant BMPR2 and generated a cardiomyocyte cell line with BMPR2 mutation. Electron microscopy and metabolomic analysis were performed on mouse RVs. Measurements and Main Results: By metabolomics analysis, we found an increase in long-chain fatty acids in BMPR2 mutant mouse RVs compared with controls, which correlated with cardiac index. BMPR2-mutant cardiomyocytes had increased lipid compared with controls. Direct measurement of FAO in the WD-fed BMPR2-mutant RV showed impaired palmitate-linked oxygen consumption, and metabolomics analysis showed reduced indices of FAO. Using both mutant BMPR2 mouse RVs and cardiomyocytes, we found an increase in the uptake of 14C-palmitate and fatty acid transporter CD36 that was further exacerbated by WD. Conclusions: Taken together, our data suggest that impaired FAO and increased expression of the lipid transporter CD36 are key mechanisms underlying lipid deposition in the BMPR2-mutant RV, which are exacerbated in the presence of dietary lipids. These findings suggest important features leading to RV lipotoxicity in pulmonary arterial hypertension and may point to novel areas of therapeutic intervention. PMID:27077479

Sorting of amphiphile membrane components in curvature and composition gradients

NASA Astrophysics Data System (ADS)

Tian, Aiwei

Phase and shape heterogeneities in biomembranes are of functional importance. However, it is difficult to elucidate the roles membrane heterogeneities play in maintaining cellular function due to the complexity of biomembranes. Therefore, investigations of phase behavior and composition/curvature coupling in lipid and polymer model membranes offer some advantages. In this thesis, phase properties in lipid and polymer giant vesicles were studied. Line tension at the fluid/fluid phase boundary of giant lipid unilamellar vesicles was determined directly by micropipette aspiration, and found to be composition-dependent. Dynamics of calcium-induced domains within polyanionic vesicles subject to chemical stimuli were investigated, which revealed the strength of molecular interaction and suggested applications in triggered delivery. In addition, curvature sorting of lipids and proteins was examined. Lipid membrane tethers were pulled from giant unilamellar vesicles using two micropipettes and a bead. Tether radius can be controlled and measured in this system. By examining fluorescence intensity of labeled molecules as a function of curvature, we found that DiI dyes (lipid analogues with spontaneous curvatures) had no curvature preference down to radii of 10 nm. Theoretical calculation predicted that the distribution of small lipids was dominated by entropy instead of bending energy. However protein Cholera toxin subunit B was efficiently sorted away from the high positive curvature due to its negative spontaneous curvature. Bending stiffness was determined to decrease as curvature increased in homogeneous membranes with ternary lipid mixtures near a critical consulate point, revealing the strong preferential intermolecular interactions of such mixtures. In addition, diffusion controlled domain growth was observed in tethers pulled from phase-separated vesicles, which provides a new dynamic sorting principle for lipids and proteins in curvature gradients.

[Effects of silkworm pupa oil on serum lipids level and platelet function in rats].

PubMed

Yang, Xuefeng; Huang, Lianzhen; Hu, Jianping; Li, Tao

2002-08-01

To observe the effects of silkworm pupa oil on serum lipids level and platelet function in rats, according to serum TG, TC level, 40 male Wistar rats are divided into four groups (normal control group, high fat control group, silkworm pupa oil group and silkworm pupa oil + VE group). The rats are fed different diets and six weeks later, serum lipids level and platelet function are measured. The results show that (1) Compared with high fat control group, serum TC, TG, LDL-C level, AI value, Platelet aggregability, plasma TXB2 level and T/P ratio decrease significantly while HDL-C level and 6-k-PGF1 level increase in silkworm pupa oil group; (2) Serum TC, LDL-C level, T/P ratio and platelet aggregability are significantly lower in silkworm pupa oil + VE group than in silkworm pupa oil group. It is suggested that silkworm pupa oil rich in alpha-linolenic acid can reduce serum lipids level and inhibit platelet aggregation, which is more effective with the supplementation with VE.

Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation in Oleaginous Microorganisms: The State of the Art and Future Perspectives

PubMed Central

Shi, Kun; Gao, Zhen; Shi, Tian-Qiong; Song, Ping; Ren, Lu-Jing; Huang, He; Ji, Xiao-Jun

2017-01-01

Microbial oils, which are mainly extracted from yeasts, molds, and algae, have been of considerable interest as food additives and biofuel resources due to their high lipid content. While these oleaginous microorganisms generally produce only small amounts of lipids under optimal growth conditions, their lipid accumulation machinery can be induced by environmental stresses, such as nutrient limitation and an inhospitable physical environmental. As common second messengers of many stress factors, reactive oxygen species (ROS) may act as a regulator of cellular responses to extracellular environmental signaling. Furthermore, increasing evidence indicates that ROS may act as a mediator of lipid accumulation, which is associated with dramatic changes in the transcriptome, proteome, and metabolome. However, the specific mechanisms of ROS involvement in the crosstalk between extracellular stress signaling and intracellular lipid synthesis require further investigation. Here, we summarize current knowledge on stress-induced lipid biosynthesis and the putative role of ROS in the control of lipid accumulation in oleaginous microorganisms. Understanding such links may provide guidance for the development of stress-based strategies to enhance microbial lipid production. PMID:28507542

Hypocholesterolemic effects of low calorie structured lipids on rats and rabbits fed on normal and atherogenic diet.

PubMed

Kanjilal, Sanjit; Kaki, Shiva Shanker; Rao, Bhamidipati V S K; Sugasini, Dhavamani; Rao, Yalagala Poornachandra; Prasad, Rachapudi B N; Lokesh, Belur R

2013-01-01

The hypocholesterolemic effects of two low calorie structured lipids (SL1 and SL2) containing essential fatty acids, prepared by lipase catalysed interesterification of ethyl behenate respectively with sunflower and soybean oils were studied in rats and rabbits. The feeding experiment conducted on rats as well as rabbits, fed on normal and atherogenic diet containing 10% of SL1 and SL2 (experimental) and sunflower oil (control) indicated no adverse effects on growth and food intake. However, the structured lipids beneficially lowered serum and liver lipids, particularly cholesterol, LDL cholesterol, triglycerides and also maintains the essential fatty acid status in serum and liver. The lipid deposition observed in the arteries of rabbits fed on atherogenic diets was significantly reduced when structured lipids were included in the diet. These observations coincided with reduced levels of serum cholesterol particularly LDL cholesterol observed in experimental groups. Therefore the structured lipids, designed to have low calorific value also beneficially lower serum lipids and lipid deposition in animals fed on atherogenic diets. Copyright © 2012 Elsevier Ltd. All rights reserved.

Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).

PubMed

Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

2013-11-01

Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans.

How effective are current dietary guidelines for cardiovascular disease prevention in healthy middle-aged and older men and women? A randomized controlled trial.

PubMed

Reidlinger, Dianne P; Darzi, Julia; Hall, Wendy L; Seed, Paul T; Chowienczyk, Philip J; Sanders, Thomas A B

2015-05-01

Controversy surrounds the effectiveness of dietary guidelines for cardiovascular disease (CVD) prevention in healthy middle-aged and older men and women. The objective was to compare effects on vascular and lipid CVD risk factors of following the United Kingdom dietary guidelines with a traditional British diet (control). With the use of a parallel-designed randomized controlled trial in 165 healthy nonsmoking men and women (aged 40-70 y), we measured ambulatory blood pressure (BP) on 5 occasions, vascular function, and CVD risk factors at baseline and during 12 wk after random assignment to treatment. The primary outcomes were differences between treatments in daytime ambulatory systolic BP, flow-mediated dilation, and total cholesterol/HDL cholesterol. Secondary outcomes were differences between treatment in carotid-to-femoral pulse wave velocity, high-sensitivity C-reactive protein, and a measure of insulin sensitivity (Revised Quantitative Insulin Sensitivity Check Index). Data were available on 162 participants, and adherence to the dietary advice was confirmed from dietary records and biomarkers of compliance. In the dietary guidelines group (n = 80) compared with control (n = 82), daytime systolic BP was 4.2 mm Hg (95% CI: 1.7, 6.6 mm Hg; P < 0.001) lower, the treatment effect on flow-mediated dilation [-0.62% (95% CI: -1.48%, 0.24%)] was not significant, the total cholesterol:HDL cholesterol ratio was 0.13 (95% CI: 0, 0.26; P = 0.044) lower, pulse wave velocity was 0.29 m/s (95% CI: 0.07, 0.52 m/s; P = 0.011) lower, high-sensitivity C-reactive protein was 36% (95% CI: 7%, 48%; P = 0.017) lower, the treatment effect on the Revised Quantitative Insulin Sensitivity Check Index [2% (95% CI: -2%, 5%)] was not significant, and body weight was 1.9 kg (95% CI: 1.3, 2.5 kg; P < 0.001) lower. Causal mediated effects analysis based on urinary sodium excretion indicated that sodium reduction explained 2.4 mm Hg (95% CI: 1.0, 3.9 mm Hg) of the fall in blood pressure. Selecting a diet consistent with current dietary guidelines lowers BP and lipids, which would be expected to reduce the risk of CVD by one-third in healthy middle-aged and older men and women. This study is registered at www.isrctn.com as 92382106. © 2015 American Society for Nutrition.

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

PubMed Central

Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

2011-01-01

Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein–lipid and protein–protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson’s disease (PD) and incidental Parkinson’s disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders. PMID:21717034

Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages.

PubMed

Tüzün, Sefa; Yücel, Ahmet Fikret; Pergel, Ahmet; Kemik, Ahu Sarbay; Kemik, Ozgür

2012-09-01

High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects. HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001). Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05). These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer.

Advanced glycation end products and antioxidant status in nondiabetic and streptozotocin induced diabetic rats: effects of copper treatment.

PubMed

Civelek, S; Gelişgen, R; Andican, G; Seven, A; Küçük, S H; Ozdoğan, M; Burçak, G

2010-02-01

The effects of Cu(II) supplementation on glycemic parameters, advanced glycation end products (AGEs), antioxidant status (glutathione; GSH and total antioxidant capacity; TAOC) and lipid peroxidative damage (thiobarbituric acid-reactive substances, TBARS) were investigated in streptozotocin (STZ) induced diabetic rats. The study was carried out on Wistar albino rats grouped as control (n = 10), CuCl(2) treated (n = 9), STZ (n = 10) and STZ,CuCl(2) treated (n = 9). STZ was administered intraperitoneally at a single dose of 65 mg/kg and CuCl(2), 4 mg copper/kg, subcutaneously, every 2 days for 60 days. At the end of this period, glucose(mg/dl), Cu(microg/dl), TBARS(micromol/l), TAOC(mmol/l) were measured in plasma, GSH(mg/gHb) in erythrocytes and glycated hemoglobin (GHb)(%) in blood. Plasma AGE-peptides(%) were measured by HPLC flow system with spectrofluorimetric and spectrophotometric detectors connected on-line. Data were analyzed by the non-parametric Kruskal-Wallis and Mann-Whitney U test. In the STZ group glucose, GHb and AGE-peptide levels were all significantly higher than the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). CuCl(2) treated group had significantly lower glucose but significantly higher GHb, TAOC and TBARS levels than the control group (P < 0.05, P < 0.001, P < 0.05 and P < 0.001, respectively). STZ,CuCl(2) treated group had significantly higher GHb, TAOC and TBARS levels compared with the control group (P < 0.001, P < 0.05 and P < 0.05, respectively); but only TAOC level was significantly higher than the STZ group (P < 0.01). This experimental study provides evidence that copper intake increases total antioxidant capacity in both nondiabetic and diabetic states. However despite the potentiated antioxidant defence, lipid peroxidation and glycation enhancing effects of CuCl(2) are evident under nondiabetic conditions.

Alteration of Lipid Parameters in Patients With Subclinical Hypothyroidism

PubMed Central

Laway, Bashir Ahmad; War, Fayaz Ahmad; Shah, Sonaullah; Misgar, Raiz Ahmad; Kumar Kotwal, Suman

2014-01-01

Background: Overt hypothyroidism is associated with abnormalities of lipid metabolism, but conflicting results regarding the degree of lipid changes in subclinical hypothyroidism (SCH) exist. Objectives: The aim of this study was to assess differences in lipid profile parameters between subjects with and without SCH in a north Indian population. Patients and Methods: Serum lipid parameters of 70 patients with subclinical hypothyroidism and 100 age and sex matched euthyroid controls were evaluated in a cross-sectional study. Results: Mean serum total cholesterol (TC), triglycerides (TG) and very low-density cholesterol (VLDL) were significantly higher in patients with SCH than controls (P < 0.05). Mean TC, TG and low-density cholesterol (LDL) concentrations were higher in patients with serum thyroid stimulating hormone (TSH) greater than 10 mU/L than those with serum TSH equal to or less than 10 mU/L, but this difference was not statistically significant. No association was found between serum high-density cholesterol (HDL-C) concentration and serum TSH level. Conclusions: High TC, TG and VLDL were observed in our patients with SCH. PMID:25237326

Transmembrane peptides as sensors of the membrane physical state

NASA Astrophysics Data System (ADS)

Piotto, Stefano; Di Biasi, Luigi; Sessa, Lucia; Concilio, Simona

2018-05-01

Cell membranes are commonly considered fundamental structures having multiple roles such as confinement, storage of lipids, sustain and control of membrane proteins. In spite of their importance, many aspects remain unclear. The number of lipid types is orders of magnitude larger than the number of amino acids, and this compositional complexity is not clearly embedded in any membrane model. A diffused hypothesis is that the large lipid palette permits to recruit and organize specific proteins controlling the formation of specialized lipid domains and the lateral pressure profile of the bilayer. Unfortunately, a satisfactory knowledge of lipid abundance remains utopian because of the technical difficulties in isolating definite membrane regions. More importantly, a theoretical framework where to fit the lipidomic data is still missing. In this work, we wish to utilize the amino acid sequence and frequency of the membrane proteins as bioinformatics sensors of cell bilayers. The use of an alignment-free method to find a correlation between the sequences of transmembrane portion of membrane proteins with the membrane physical state suggested a new approach for the discovery of antimicrobial peptides.

Effect of dietary alternative lipid sources on haematological parameters and serum constituents of Heterobranchus longifilis fingerlings.

PubMed

Babalola, T O O; Adebayo, M A; Apata, D F; Omotosho, J S

2009-03-01

The worldwide increase in aquaculture production and the decrease of wild fish stocks has made the replacement of fish oil (FO) in aquafeed industry a priority. Therefore, the use of terrestrial animal fats and vegetable oils, which has lower cost and larger supplies, may be good as substitute for FO. This study investigate the effects of total replacement of FO by two terrestrial animal fats (pork lard and poultry fat) and three vegetable oils (palm kernel oil, sheabutter oil and sunflower oil) on haematological and serum biochemical profile of Heterobranchus longifilis over 70 days. FO-diet was used as the control. The haematological parameters were significantly affected by dietary lipid sources. Serum total protein was not influenced by the dietary lipids. However, serum cholesterol was significantly higher in fish fed diet containing sunflower oil. Glucose and activities of liver enzymes in blood serum were significantly reduced in fish fed alternative lipids when compared with the control. These results indicate that FO can be replaced completely with alternative lipids without any serious negative health impacts.

Direct measurement of lateral transport in membranes by using time-resolved spatial photometry.

PubMed Central

Kapitza, H G; McGregor, G; Jacobson, K A

1985-01-01

Spatially resolving light detectors allow, with proper calibration, quantitative analysis of the variations in two-dimensional intensity distributions over time. An ultrasensitive microfluorometer was assembled by using as a detector a microchannel plate-intensified video camera. The camera was interfaced with a software-based digital video analysis system to digitize, average, and process images and to directly control the timing of the experiments to minimize exposure of the specimen to light. The detector system has been characterized to allow its use as a photometer. A major application has been to perform fluorescence recovery after photobleaching measurements by using the camera in place of a photomultiplier tube (video-FRAP) with the goal of detecting possible anisotropic diffusion or convective flow. Analysis of the data on macromolecular diffusion in homogenous aqueous glycol solutions yielded diffusion constants in agreement with previous measurements. Results on lipid probe diffusion in dimyristoylphosphatidylcholine multibilayers indicated that at temperatures above the gel-to-liquid crystalline phase transition diffusion is isotropic, and analysis of video-FRAP data yielded diffusion coefficients consistent with those measured previously by using spot photobleaching. However, lipid probes in these multibilayers held just below the main phase transition temperature exhibited markedly anisotropic diffusive fluxes when the bleaching beam was positioned proximate to domain boundaries in the P beta' phase. Lipid probes and lectin receptor complexes diffused isotropically in fibroblast surface membranes with little evidence for diffusion channeled parallel to stress fibers. A second application was to trace the time evolution of cell surface reactions such as patching. The feasibility of following, on the optical scale, the growth of individual receptor clusters induced by the ligand wheat germ agglutinin was demonstrated. PMID:3858869

Direct measurement of lateral transport in membranes by using time-resolved spatial photometry.

PubMed

Kapitza, H G; McGregor, G; Jacobson, K A

1985-06-01

Spatially resolving light detectors allow, with proper calibration, quantitative analysis of the variations in two-dimensional intensity distributions over time. An ultrasensitive microfluorometer was assembled by using as a detector a microchannel plate-intensified video camera. The camera was interfaced with a software-based digital video analysis system to digitize, average, and process images and to directly control the timing of the experiments to minimize exposure of the specimen to light. The detector system has been characterized to allow its use as a photometer. A major application has been to perform fluorescence recovery after photobleaching measurements by using the camera in place of a photomultiplier tube (video-FRAP) with the goal of detecting possible anisotropic diffusion or convective flow. Analysis of the data on macromolecular diffusion in homogenous aqueous glycol solutions yielded diffusion constants in agreement with previous measurements. Results on lipid probe diffusion in dimyristoylphosphatidylcholine multibilayers indicated that at temperatures above the gel-to-liquid crystalline phase transition diffusion is isotropic, and analysis of video-FRAP data yielded diffusion coefficients consistent with those measured previously by using spot photobleaching. However, lipid probes in these multibilayers held just below the main phase transition temperature exhibited markedly anisotropic diffusive fluxes when the bleaching beam was positioned proximate to domain boundaries in the P beta' phase. Lipid probes and lectin receptor complexes diffused isotropically in fibroblast surface membranes with little evidence for diffusion channeled parallel to stress fibers. A second application was to trace the time evolution of cell surface reactions such as patching. The feasibility of following, on the optical scale, the growth of individual receptor clusters induced by the ligand wheat germ agglutinin was demonstrated.

Platform for Lipid Based Nanocarriers' Formulation Components and their Potential Effects: A Literature Review.

PubMed

Farid, Ragwa Mohamed; Youssef, Nancy Abdel Hamid Abou; Kassem, Abeer Ahmed

2017-11-27

Lipid based nanocarriers have gained recently enormous interest for pharmaceutical application. They have the potential to provide controlled drug release and to target the drug to a specific area. In addition, lipid based nanocarriers can improve the bioavailability of drugs suffering from high hepatic first-pass metabolism, by enhancing their transport via the lymphatic system. The main components of lipid based nanocarriers are lipids and surfactants. Both have great influence on the prepared lipid based systems characteristics. The criteria for their selection are much related to physicochemical properties of the drug and the required administration route. This work gives an overview on the effect of both the type and amount of lipids and surfactants used in the manufacture of lipid based nanocarriers on their behavior and characteristics. Recent studies revealed that the properties of the final product including; particle size, homogeneity, drug loading capacity, zeta potential, drug release profile, stability, permeability, pharmacokinetic properties, crystallinity and cytotoxicity, may be significantly influenced not only by the type but also the amount of the lipids and/or surfactants included in the formulation of the lipid based nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Diffusion and spectroscopy of water and lipids in fully hydrated dimyristoylphosphatidylcholine bilayer membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, J.; Martí, J., E-mail: jordi.marti@upc.edu; Calero, C.

2014-03-14

Microscopic structure and dynamics of water and lipids in a fully hydrated dimyristoylphosphatidylcholine phospholipid lipid bilayer membrane in the liquid-crystalline phase have been analyzed with all-atom molecular dynamics simulations based on the recently parameterized CHARMM36 force field. The diffusive dynamics of the membrane lipids and of its hydration water, their reorientational motions as well as their corresponding spectral densities, related to the absorption of radiation, have been considered for the first time using the present force field. In addition, structural properties such as density and pressure profiles, a deuterium-order parameter, surface tension, and the extent of water penetration in themore » membrane have been analyzed. Molecular self-diffusion, reorientational motions, and spectral densities of atomic species reveal a variety of time scales playing a role in membrane dynamics. The mechanisms of lipid motion strongly depend on the time scale considered, from fast ballistic translation at the scale of picoseconds (effective diffusion coefficients of the order of 10{sup −5} cm{sup 2}/s) to diffusive flow of a few lipids forming nanodomains at the scale of hundreds of nanoseconds (diffusion coefficients of the order of 10{sup −8} cm{sup 2}/s). In the intermediate regime of sub-diffusion, collisions with nearest neighbors prevent the lipids to achieve full diffusion. Lipid reorientations along selected directions agree well with reported nuclear magnetic resonance data and indicate two different time scales, one about 1 ns and a second one in the range of 2–8 ns. We associated the two time scales of reorientational motions with angular distributions of selected vectors. Calculated spectral densities corresponding to lipid and water reveal an overall good qualitative agreement with Fourier transform infrared spectroscopy experiments. Our simulations indicate a blue-shift of the low frequency spectral bands of hydration water as a result of its interaction with lipids. We have thoroughly analyzed the physical meaning of all spectral features from lipid atomic sites and correlated them with experimental data. Our findings include a “wagging of the tails” frequency around 30 cm{sup −1}, which essentially corresponds to motions of the tail-group along the instantaneous plane formed by the two lipid tails, i.e., in-plane oscillations are clearly of bigger importance than those along the normal-to-the plane direction.« less

Characterization of Oilseed Lipids from “DHA-Producing Camelina sativa”: A New Transformed Land Plant Containing Long-Chain Omega-3 Oils

PubMed Central

Mansour, Maged P.; Shrestha, Pushkar; Belide, Srinivas; Petrie, James R.; Nichols, Peter D.; Singh, Surinder P.

2014-01-01

New and sustainable sources of long-chain (LC, ≥C20) omega-3 oils containing DHA (docosahexaenoic acid, 22:6ω3) are required to meet increasing demands. The lipid content of the oilseed of a novel transgenic, DHA-producing land plant, Camelina sativa, containing microalgal genes able to produce LC omega-3 oils, contained 36% lipid by weight with triacylglycerols (TAG) as the major lipid class in hexane extracts (96% of total lipid). Subsequent chloroform-methanol (CM) extraction recovered further lipid (~50% polar lipid, comprising glycolipids and phospholipids) and residual TAG. The main phospholipid species were phosphatidyl choline and phosphatidyl ethanolamine. The % DHA was: 6.8% (of total fatty acids) in the TAG-rich hexane extract and 4.2% in the polar lipid-rich CM extract. The relative level of ALA (α-linolenic acid, 18:3ω3) in DHA-camelina seed was higher than the control. Major sterols in both DHA- and control camelina seeds were: sitosterol, campesterol, cholesterol, brassicasterol and isofucosterol. C16–C22 fatty alcohols, including iso-branched and odd-chain alcohols were present, including high levels of iso-17:0, 17:0 and 19:0. Other alcohols present were: 16:0, iso-18:0, 18:0 and 18:1 and the proportions varied between the hexane and CM extracts. These iso-branched odd-chain fatty alcohols, to our knowledge, have not been previously reported. These components may be derived from wax esters, or free fatty alcohols. PMID:24566436

Nanostructured lipid dispersions for topical administration of crocin, a potent antioxidant from saffron (Crocus sativus L.).

PubMed

Esposito, Elisabetta; Drechsler, Markus; Mariani, Paolo; Panico, Anna Maria; Cardile, Venera; Crascì, Lucia; Carducci, Federica; Graziano, Adriana Carol Eleonora; Cortesi, Rita; Puglia, Carmelo

2017-02-01

Crocin, a potent antioxidant obtained from saffron, shows anticancer activity in in vivo models. Unfortunately unfavorable physicochemical features compromise its use in topical therapy. The present study describes the preparation and characterization of nanostructured lipid dispersions as drug delivery systems for topical administration of crocin and the evaluation of antioxidant and antiproliferative effects of crocin once encapsulated into nanostructured lipid dispersions. Nanostructured lipid dispersions based on monoolein in mixture with sodium cholate and sodium caseinate have been characterized by cryo-TEM and PCS. Crocin permeation was evaluated in vitro by Franz cells, while the oxygen radical absorbance capacity assay was used to evaluate the antioxidant activity. Furthermore, the antiproliferative activity was tested in vitro by the MTT test using a human melanoma cell line. The emulsification of monoolein with sodium cholate and sodium caseinate led to dispersions of cubosomes, hexasomes, sponge systems and vesicles, depending on the employed emulsifiers. Permeation and shelf life studies demonstrated that nanostructured lipid dispersions enabled to control both rate of crocin diffusion through the skin and crocin degradation. The oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of crocin while the MTT test showed an increase of crocin cytotoxic effect after incorporation in nanostructured lipid dispersions. This work has highlighted that nanostructured lipid dispersions can protect the labile molecule crocin from degradation, control its skin diffusion and prolong antioxidant activity, therefore suggesting the suitability of nanostructured lipid dispersions for crocin topical administration. Copyright © 2016 Elsevier B.V. All rights reserved.

Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

PubMed

Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

2005-10-01

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

Effect of different doses of nandrolone decanoate on lipid peroxidation, DNA fragmentation, sperm abnormality and histopathology of testes of male Wister rats.

PubMed

Mohamed, Hanaa Mahmoud; Mohamed, Manal Abdul-Hamid

2015-01-01

The present study aims of to investigate the effects of low and high doses of nandrolone decanoate (ND) on histopathology and apoptosis of the spermatogenic cells as well as lipid peroxidation, antioxidant enzyme activities, sperm abnormality and DNA fragmentation. Eighteen animals were divided into three groups each group contain six animals. The rats were divided into three groups as following: Group 1 was administered saline (control). Group 2, received nandrolone decanoate (3 mg/kg/weekly) (low dose) with intramuscular injection. Group 3, received intramuscular injection dose of nandrolone decanoate (10 mg/kg/weekly) (high dose). After 8 weeks, caspase-3 assay was used to determine the apoptotic cells. The sperm parameters, lipid peroxidation, antioxidant enzyme activities and testosterone concentration were also investigated in the experimental groups of both low and high dose compared to the control groups. Treated group with high dose showed degenerated germinal epithelial cells sloughed in the lumina of seminiferous tubules, where almost seminiferous tubules were devoid of spermatids and spermatozoa compared to control and group treated with low dose. Also, a significant increase of lipid peroxidation levels and heat shock proteins was observed in two groups administrated with two different doses of ND while, antioxidant enzyme activities, and testosterone concentration was significantly decreased in two treated group when compared with control. Administration of ND at high and low doses leads to deteriorated sperm parameters, DNA fragmentation and testicular apoptosis. In conclusion, the administration ND at high doses more effective on lipid peroxidation, antioxidant enzyme activities, sperm abnormality, histopathology, apoptotic and DNA changes compared to low dose group and to control group. Published by Elsevier GmbH.

Effects of taurodihydrofusidate, a bile salt analogue, on bile formation and biliary lipid secretion in the rhesus monkey.

PubMed Central

Beaudoin, M; Carey, M C; Small, D M

1975-01-01

Bile salts play a major role in bile formation and biliary lipid secretion. Sodium taurodihydrofusidate (TDHF), a derivative of the antibiotic fusidic acid, closely resembles bile salts in terms of structure, micellar characteristics, and capacity ot solubilize otherwise insolbule lipids. We have therefore studied the biliary secretion of this bile salt analogue and its influence on bile formation and biliary lipid secretion in primates. Alert, unanesthetized female rhesus monkeys prepared with a total biliary fistula were allowed to reach a steady bile salt secretion rate before each study. In three animals (group I),[14C]TDHF was infused intravenously. Most of the compound was secreted rapidly in bile chemically unchanged. The biliary secretion of this drug produced a twofold increase in bile flow; however, the bile salt output was markedly reduced during the infusion. In spite of this reduction, the phospholipid output remained essentially unchanged whereas the cholesterol output increased almost twofold. In five other animals (group II), the effect of TDHF on the bile salt secretion was further investigated by an intravenous infusion of [14C]taurocholate followed by a combined infusion of [14C]taurocholate and TDHF. When TDHF was added to the infusate, a reduction in the [14C]taurocholate output and a progressive rise in the plasma [14C]taurocholate concentration were observed in each animal. An analysis of the data in both groups indicates that (a) the most likely explanation to account for the decreased bile salt output is that the bile salt analogue, TDHF, interfered with bile salt secretion into the biliary canaliculi; (b) TDHF induces a greater secretion of biliary water than was observed with bile salts, an effect consistent with a stimulation of the bile salt-independent canalicular flow; (c) at similar 3alpha-hydroxysteroid secretion rates TDHF caused a significant increase in cholesterol secretion compared to that induced by bile salt. This finding suggests that TDHF affects cholesterol metabolism or secretion in a way distinct from bile salts. Thus, the solubilization of biliary lipids in mixed micelles, although essential, is only one of the factors which determine their secretion into bile. PMID:811689

Dyslipidaemia in woman with polycystic ovarian syndrome: a case control study in tertiary care hospital of Karachi.

PubMed

Hussain, Amna; Alam, Junaid Mahmood

2014-09-01

To compare lipid profile in lean and obese women with polycystic ovary syndrome with normal weight and obese controls. The case-control study was conducted at the Department of Chemical Pathology, Liaquat National Hospital, Karachi, from March 2006 to April 2007. It comprised 50 cases of polycystic ovary syndrome along with 50 healthy controls matching for age, gender and weight. SPSS 14 was used for statistical analysis. The mean fasting levels of triglyceride and Low density lipoprotein cholesterol were considerably higher in women with polycystic ovary syndrome than those in the control group (p < 0.05), while high-density lipoprotein cholesterolwas significantly low in patients than the controls (p <0.001). Obese patients had high triglyceride value (p < 0.05). There was significant interaction between polycystic ovary syndrome, obesity and triglyceride levels (p < 0.05). Polycystic ovary syndrome is associated with a more pronounced atherogenic lipid profile. Lipid parameters were adversely affected in a subgroup that was obese. As such, women with polycystic ovary syndrome are at high risk of developing cardiovascular disease due to the presence of dyslipidaemia.

Trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine induces lipid peroxidation-associated apoptosis via the intrinsic and extrinsic apoptosis pathways in a first-trimester placental cell line.

PubMed

Elkin, Elana R; Harris, Sean M; Loch-Caruso, Rita

2018-01-01

Trichloroethylene (TCE), a prevalent environmental contaminant, is a potent renal and hepatic toxicant through metabolites such as S-(1, 2-dichlorovinyl)-l-cysteine (DCVC). However, effects of TCE on other target organs such as the placenta have been minimally explored. Because elevated apoptosis and lipid peroxidation in placenta have been observed in pregnancy morbidities involving poor placentation, we evaluated the effects of DCVC exposure on apoptosis and lipid peroxidation in a human extravillous trophoblast cell line, HTR-8/SVneo. We exposed the cells in vitro to 10-100μM DCVC for various time points up to 24h. Following exposure, we measured apoptosis using flow cytometry, caspase activity using luminescence assays, gene expression using qRT-PCR, and lipid peroxidation using a malondialdehyde quantification assay. DCVC significantly increased apoptosis in time- and concentration-dependent manners (p<0.05). DCVC also significantly stimulated caspase 3, 7, 8 and 9 activities after 12h (p<0.05), suggesting that DCVC stimulates the activation of both the intrinsic and extrinsic apoptotic signaling pathways simultaneously. Pre-treatment with the tBID inhibitor Bl-6C9 partially reduced DCVC-stimulated caspase 3 and 7 activity, signifying crosstalk between the two pathways. Additionally, DCVC treatment increased lipid peroxidation in a concentration-dependent manner. Co-treatment with the antioxidant peroxyl radical scavenger (±)-α-tocopherol attenuated caspase 3 and 7 activity, suggesting that lipid peroxidation mediates DCVC-induced apoptosis in extravillous trophoblasts. Our findings suggest that DCVC-induced apoptosis and lipid peroxidation in extravillous trophoblasts could contribute to poor placentation if similar effects occur in vivo in response to TCE exposure, indicating that further studies into this mechanism are warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Multinuclear NMR studies of single lipid bilayers supported in cylindrical aluminum oxide nanopores.

PubMed

Gaede, Holly C; Luckett, Keith M; Polozov, Ivan V; Gawrisch, Klaus

2004-08-31

Lipid bilayers were deposited inside the 0.2 microm pores of anodic aluminum oxide (AAO) filters by extrusion of multilamellar liposomes and their properties studied by 2H, 31P, and 1H solid-state NMR. Only the first bilayer adhered strongly to the inner surface of the pores. Additional layers were washed out easily by a flow of water as demonstrated by 1H magic angle spinning NMR experiments with addition of Pr3+ ions to shift accessible lipid headgroup resonances. A 13 mm diameter Anopore filter of 60 microm thickness oriented approximately 2.5 x 10(-7) mol of lipid as a single bilayer, corresponding to a total membrane area of about 500 cm2. The 2H NMR spectra of chain deuterated POPC are consistent with adsorption of wavy, tubular bilayers to the inner pore surface. By NMR diffusion experiments, we determined the average length of those lipid tubules to be approximately 0.4 microm. There is evidence for a thick water layer between lipid tubules and the pore surface. The ends of tubules are well sealed against the pore such that Pr3+ ions cannot penetrate into the water underneath the bilayers. We successfully trapped poly(ethylene glycol) (PEG) with a molecular weight of 8000 in this water layer. From the quantity of trapped PEG, we calculated an average water layer thickness of 3 nm. Lipid order parameters and motional properties are unperturbed by the solid support, in agreement with existence of a water layer. Such unperturbed, solid supported membranes are ideal for incorporation of membrane-spanning proteins with large intra- and extracellular domains. The experiments suggest the promise of such porous filters as membrane support in biosensors.

Surface phase behavior and microstructure of lipid/PEG-emulsifier monolayer-coated microbubbles.

PubMed

Borden, Mark A; Pu, Gang; Runner, Gabriel J; Longo, Marjorie L

2004-06-01

Langmuir trough methods and fluorescence microscopy were combined to investigate the phase behavior and microstructure of monolayer shells coating micron-scale bubbles (microbubbles) typically used in biomedical applications. The monolayer shell consisted of a homologous series of saturated acyl chain phospholipids and an emulsifier containing a single hydrophobic stearate chain and polyethylene glycol (PEG) head group. PEG-emulsifier was fully miscible with expanded phase lipids and phase separated from condensed phase lipids. Phase coexistence was observed in the form of dark condensed phase lipid domains surrounded by a sea of bright, emulsifier-rich expanded phase. A rich assortment of condensed phase area fractions and domain morphologies, including networks and other novel structures, were observed in each batch of microbubbles. Network domains were reproduced in Langmuir monolayers under conditions of heating-cooling followed by compression-expansion, as well as in microbubble shells that underwent surface flow with slight compression. Domain size decreased with increased cooling rate through the phase transition temperature, and domain branching increased with lipid acyl chain length at high cooling rates. Squeeze-out of the emulsifier at a surface pressure near 35 mN/m was indicated by a plateau in Langmuir isotherms and directly visualized with fluorescence microscopy, although collapse of the solid lipid domains occurred at much higher surface pressures. Compression of the monolayer past the PEG-emulsifier squeeze-out surface pressure resulted in a dark shell composed entirely of lipid. Under certain conditions, the PEG-emulsifier was reincorporated upon subsequent expansion. Factors that affect shell formation and evolution, as well as implications for the rational design of microbubbles in medical applications, are discussed.

Enteric-coated capsules filled with mono-disperse micro-particles containing PLGA-lipid-PEG nanoparticles for oral delivery of insulin.

PubMed

Yu, Fei; Li, Yang; Liu, Chang Sheng; Chen, Qin; Wang, Gui Huan; Guo, Wei; Wu, Xue E; Li, Dong Hui; Wu, Winston Duo; Chen, Xiao Dong

2015-04-30

The success of the oral delivery of insulin (INS) as a therapeutic protein drug would significantly improve the quality of life of diabetic patients who would otherwise receive multiple daily INS injections. The oral delivery of INS, however, is still limited in its delivery efficiency, which could be due to the chemical, enzymatic, and adsorption barriers. In this work, in an attempt to improve the delivery efficiency, the INS-loaded polymer-lipid hybrid nanoparticles (INS-PLGA-lipid-PEG NPs) were designed and constructed through a double-emulsion solvent evaporation technique, followed by formulation of the spherical micro-particles using a spray freeze dryer (SFD). This kind of dryers has a uniquely designed microfluidic aerosol nozzle (MFAN), ensuring the formation of uniform particles. The resulted particles of ∼212 μm could easily be reverted to discrete INS-PLGA-lipid-PEG NPs in an aqueous solution. The INS-PLGA-lipid-PEG NPs created in this work showed a highly negative surface charge, excellent entrapment efficiency (92.3%) and a sustained drug release (∼24 h). Confocal laser scanning microscopy and flow cytometer were used to show that the cellular uptake efficiency for the INS-PLGA-lipid-PEG NPs was more effective than the INS in Caco-2 cells. More importantly, the in vivo pharmacodynamics demonstrated that the orally delivered system induced a prolonged decrease in blood glucose levels among diabetic rats. The relative bioavailability of INS compared with subcutaneous injection in diabetic rats was found to be approximately 12%. These results suggested that the encapsulated INS-PLGA-lipid-PEG NPs are promising and should be investigated further in the near future as an effective INS oral delivery system. Copyright © 2015. Published by Elsevier B.V.

Thermodynamic evidence of non-muscle myosin II-lipid-membrane interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schewkunow, Vitali; Sharma, Karan P.; Diez, Gerold

2008-02-08

A unique feature of protein networks in living cells is that they can generate their own force. Proteins such as non-muscle myosin II are an integral part of the cytoskeleton and have the capacity to convert the energy of ATP hydrolysis into directional movement. Non-muscle myosin II can move actin filaments against each other, and depending on the orientation of the filaments and the way in which they are linked together, it can produce contraction, bending, extension, and stiffening. Our measurements with differential scanning calorimetry showed that non-muscle myosin II inserts into negatively charged phospholipid membranes. Using lipid vesicles mademore » of DMPG/DMPC at a molar ratio of 1:1 at 10 mg/ml in the presence of different non-muscle myosin II concentrations showed a variation of the main phase transition of the lipid vesicle at around 23 deg. C. With increasing concentrations of non-muscle myosin II the thermotropic properties of the lipid vesicle changed, which is indicative of protein-lipid interaction/insertion. We hypothesize that myosin tail binds to acidic phospholipids through an electrostatic interaction using the basic side groups of positive residues; the flexible, amphipathic helix then may partially penetrate into the bilayer to form an anchor. Using the stopped-flow method, we determined the binding affinity of non-muscle myosin II when anchored to lipid vesicles with actin, which was similar to a pure actin-non-muscle myosin II system. Insertion of myosin tail into the hydrophobic region of lipid membranes, a model known as the lever arm mechanism, might explain how its interaction with actin generates cellular movement.« less

Lung Surfactant Microbubbles Increase Lipophilic Drug Payload for Ultrasound-Targeted Delivery

PubMed Central

Sirsi, Shashank R.; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y.; Mountford, Paul A.; Borden, Mark A.

2013-01-01

The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta®, Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload. PMID:23781287

Lung surfactant microbubbles increase lipophilic drug payload for ultrasound-targeted delivery.

PubMed

Sirsi, Shashank R; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y; Mountford, Paul A; Borden, Mark A

2013-01-01

The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta(®), Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload.

Transcriptome analysis of the effects of chitosan on the hyperlipidemia and oxidative stress in high-fat diet fed mice.

PubMed

Wang, Bin; Zhang, Sicong; Wang, Xiaoya; Yang, Shuo; Jiang, Qixing; Xu, Yanshun; Xia, Wenshui

2017-09-01

Transcriptome analysis was performed to investigate the alterations in gene expression after chitosan (CS) treatment on the liver of mice fed with high-fat diet (HFD). The results showed that the body weight, the liver weight and the epididymal fat mass of HFD mice, which were 62.98%, 46.51% and 239.37%, respectively, higher than those of control mice, could be significantly decreased by chitosan supplementation. Also, high-fat diet increased both plasma lipid and liver lipid as compared with the control mice. Chitosan supplementation decreased the plasma lipid and liver lipid, increased the lipoprotein lipase (LPL) and hepatic lipase (HL) activity, increased T-AOC and decreased MDA in the liver and the epididymis adipose as compared with the HFD mice. Transcriptome analysis indicated that increased Mups, Lcn2, Gstm3 and CYP2E1 expressions clearly indicated HFD induced lipid metabolism disorder and oxidative damage. Especially, chitosan treatment decreased the Mup17 and Lcn2 expressions by 64.32% and 82.43% respectively as compared with those of HFD mice. These results indicated that chitosan possess the ability to improve the impairment of lipid metabolism as strongly associated with increased Mups expressions and gene expressions related to oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Pretreatment of different food rest materials for bioconversion into fungal lipid-rich biomass.

PubMed

Tzimorotas, D; Afseth, N K; Lindberg, D; Kjørlaug, O; Axelsson, L; Shapaval, V

2018-04-13

Food rest materials have the potential to be used as media components in various types of fermentations. Oleaginous filamentous fungi can utilize those components and generate a high-value lipid-rich biomass, which could be further used for animal and human use. One of the main limitations in this process is the pretreatment of food rest materials, needed to provide homogenization, sterilization and solubilization. In this study, two pretreatment processes-steam explosion and enzymatic hydrolysis-were evaluated for potato and animal protein-rich food rest materials. The pretreated food rest materials were used for the production of fungal lipid-rich biomass in submerged fermentation by the oleaginous fungus Mucor circinelloides. Cultivation media based on malt extract broth and glucose were used as controls of growth and lipid production, respectively. It was observed that media based on food rest materials can support growth and lipid production in M. circinelloides to a similar extent as the control media. More specifically, the use of potato hydrolysate combined with chicken auto-hydrolysate resulted in a higher fungal total biomass weight than using malt extract broth. When the same C/N ratio was used for glucose and rest materials-based media, similar lipid content was obtained or even higher using the latter media.

Lipid raft components cholesterol and sphingomyelin increase H+/OH− permeability of phosphatidylcholine membranes

PubMed Central

Gensure, Rebekah H.; Zeidel, Mark L.; Hill, Warren G.

2006-01-01

H+/OH− permeation through lipid bilayers occurs at anomalously high rates and the determinants of proton flux through membranes are poorly understood. Since all life depends on proton gradients, it is important to develop a greater understanding of proton leak phenomena. We have used stopped-flow fluorimetry to probe the influence of two lipid raft components, chol (cholesterol) and SM (sphingomyelin), on H+/OH− and water permeability. Increasing the concentrations of both lipids in POPC (palmitoyl-2-oleoyl phosphatidylcholine) liposomes decreased water permeability in a concentration-dependent manner, an effect that correlated with increased lipid order. Surprisingly, proton flux was increased by increasing the concentration of chol and SM. The chol effect was complex with molar concentrations of 17.9, 33 and 45.7% giving 2.8-fold (P<0.01), 2.2-fold (P<0.001) and 5.1-fold (P<0.001) increases in H+/OH− permeability from a baseline of 2.4×10−2 cm/s. SM at 10 mole% effected a 2.8-fold increase (P<0.01), whereas 20 and 30 mole% enhanced permeability by 3.6-fold (P<0.05) and 4.1-fold respectively (P<0.05). Supplementing membranes containing chol with SM did not enhance H+/OH− permeability. Of interest was the finding that chol addition to soya-bean lipids decreased H+/OH− permeability, consistent with an earlier report [Ira and Krishnamoorthy (2001) J. Phys. Chem. B 105, 1484–1488]. We speculate that the presence of proton carriers in crude lipid extracts might contribute to this result. We conclude that (i) chol and SM specifically and independently increase rates of proton permeation in POPC bilayers, (ii) domains enriched in these lipids or domain interfaces may represent regions with high H+/OH− conductivity, (iii) H+/OH− fluxes are not governed by lipid order and (iv) chol can inhibit or promote H+/OH− permeability depending on the total lipid environment. Theories of proton permeation are discussed in the light of these results. PMID:16706750

QCM-D and ToF-SIMS Investigation to Deconvolute the Relationship between Lipid Adsorption and Orientation on Lipase Activity.

PubMed

Joyce, Paul; Kempson, Ivan; Prestidge, Clive A

2015-09-22

Quartz crystal microbalance with dissipation (QCM-D) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were used to provide insights into the relationship between lipid adsorption kinetics and molecular behavior in porous silica particles of varying hydrophobicities on lipase activity. Lipase (an interfacial enzyme that cleaves ester bonds to break down lipids to fatty acids and monoglycerides) activity was controlled by loading triglycerides at different surface coverages in hydrophilic and hydrophobic porous silica particles. The rate of lipid adsorption increased 2-fold for the hydrophobic surface compared to the hydrophilic surface. However, for submonolayer lipid coverage, the hydrophilic surface enhanced lipase activity 4-fold, whereas the hydrophobic surface inhibited lipase activity 16-fold, compared to lipid droplets in water. A difference in lipid orientation for low surface coverage, evidenced by ToF-SIMS, indicated that lipid adsorbs to hydrophilic silica in a conformation promoting hydrolysis. Multilayer coverage on hydrophobic and hydrophilic surfaces was indistinguishable with ToF-SIMS analysis. Increased lipid adsorption for both substrates facilitated digestion kinetics comparable to a conventional emulsion. Improved understanding of the interfacial adsorption and orientation of lipid and its digestibility in porous silica has implications in improving the uptake of pharmaceuticals and nutrients from lipid-based delivery systems.

Heterogeneous behavior of lipids according to HbA1c levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey

PubMed Central

2012-01-01

Background Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1c above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1c values; 2) detect a threshold of HbA1c beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1c individuals with type 1 diabetes. Methods Effects of HbA1c quintiles (1st: ≤7.4%; 2nd: 7.5-8.5%; 3rd: 8.6-9.6%; 4th: 9.7-11.3%; and 5th: >11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls. Results Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1c quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1c, OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1c quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1c in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control. Conclusions Correlation of serum lipids with HbA1c is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1c with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1c, refuting a unified explanation for cardiovascular risk in type 1 diabetes. PMID:23270560

In vivo real-time fluorescence visualization and brain-targeting mechanisms of lipid nanocarriers with different fatty ester:oil ratios.

PubMed

Wen, Chih-Jen; Yen, Tzu-Chen; Al-Suwayeh, Saleh A; Chang, Hui-Wen; Fang, Jia-You

2011-11-01

The objective of the present work was to investigate the influence of the inner cores of lipid nanocarriers on the efficiency of brain targeting. Cetyl palmitate and squalene were respectively chosen as the solid lipid and liquid oil in the inner phase of the nanocarriers. Nanoparticulate systems with different cetyl palmitate/squalene ratios were compared by evaluating the size, zeta potential, molecular environment, and mobility of lipids in the systems. The particulate diameter ranged from 190 to 210 nm, with systems containing 100% cetyl palmitate in the matrix (solid lipid nanoparticles [SLN]) showing the smallest size, followed by systems with both cetyl palmitate and squalene (nanostructured lipid carriers [NLC]) and with 100% squalene (lipid emulsions [LE]). A cationic surfactant, Forestall, was used to produce a positive surface charge of 40-55 mW. The in vitro release was evaluated using various dyes located in different phases of the nanocarriers. The release of sulforhodamine B occurred in a sustained manner from the shell of the nanocarriers. The in vivo brain distribution of lipid nanosystems after an intravenous injection into rats was monitored by a real-time fluorescence imaging system. LE showed higher brain accumulation than SLN and NLC. NLC only exhibited a slightly higher brain accumulation compared with the aqueous control. Incorporation of sulforhodamine B into LE could prolong its retention in the brain from 20 to 50 min. The results were further confirmed by imaging the entire brain and brain slices. The specific association of lipid nanocarriers with rat brain endothelial cells (bEnd3) was demonstrated using fluorescence microscopy. The cellular uptake of LE and SLN was higher compared with NLC and the aqueous control. LE were observed to be internalized by cells through caveola-mediated and macropinocytotic energy-dependent endocytosis. The experimental profiles indicated that LE with moderate additives are a promising brain-targeting nanocarrier. The composition of the lipid matrix played a significant role in delivering compounds to the brain.

Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei

ABSTRACT The yeastYarrowia lipolyticais a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis inY. lipolyticaand identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination ofDGA1overexpression with nitrogen limitationmore » resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor. IMPORTANCEThe ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeastYarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.« less

Optical droplet vaporization of nanoparticle-loaded stimuli-responsive microbubbles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Si, Ting; Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210; Li, Guangbin

2016-03-14

A capillary co-flow focusing process is developed to generate stimuli-responsive microbubbles (SRMs) that comprise perfluorocarbon (PFC) suspension of silver nanoparticles (SNPs) in a lipid shell. Upon continuous laser irradiation at around their surface plasmon resonance band, the SNPs effectively absorb electromagnetic energy, induce heat accumulation in SRMs, trigger PFC vaporization, and eventually lead to thermal expansion and fragmentation of the SRMs. This optical droplet vaporization (ODV) process is further simulated by a theoretical model that combines heat generation of SNPs, phase change of PFC, and thermal expansion of SRMs. The model is validated by benchtop experiments, where the ODV processmore » is monitored by microscopic imaging. The effects of primary process parameters on behaviors of ODV are predicted by the theoretical model, indicating the technical feasibility for process control and optimization in future drug delivery applications.« less

Unsaturated C3,5,7,9-Monocarboxylic Acids by Aqueous, One-Pot Carbon Fixation: Possible Relevance for the Origin of Life

PubMed Central

Scheidler, Christopher; Sobotta, Jessica; Eisenreich, Wolfgang; Wächtershäuser, Günter; Huber, Claudia

2016-01-01

All scientific approaches to the origin of life share a common problem: a chemical path to lipids as main constituents of extant cellular enclosures. Here we show by isotope-controlled experiments that unsaturated C3,5,7,9-monocarboxylic acids form by one-pot reaction of acetylene (C2H2) and carbon monoxide (CO) in contact with nickel sulfide (NiS) in hot aqueous medium. The primary products are toto-olefinic monocarboxylic acids with CO-derived COOH groups undergoing subsequent stepwise hydrogenation with CO as reductant. In the resulting unsaturated monocarboxylic acids the double bonds are mainly centrally located with mainly trans-configuration. The reaction conditions are compatible with an origin of life in volcanic-hydrothermal sub-seafloor flow ducts. PMID:27283227

Idiopathic sudden sensorineural hearing loss and ménière syndrome: The role of cerebral venous drainage.

PubMed

Ciccone, M M; Scicchitano, P; Gesualdo, M; Cortese, F; Zito, A; Manca, F; Boninfante, B; Recchia, P; Leogrande, D; Viola, D; Damiani, M; Gambacorta, V; Piccolo, A; De Ceglie, V; Quaranta, N

2018-02-01

To evaluate the influence of cerebral venous drainage on the pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) and Ménière syndrome (MD). Observational, prospective, cohort study. ENT and Cardiology Departments (University of Bari, Policlinico Hospital, Bari, Italy). We enrolled 59 consecutive patients (32 males, mean age 53.05 + 15.37 years): 40 ISSHL and 19 MD. All patients underwent physical examination, biochemical evaluation (glycemic and lipid profile, viral serology, C reactive protein, etc), audiometric (tonal, vocal, vestibular evoked myogenic potentials and auditory brainstem response test) and impedentiometric examination. The pure tone average (PTA) was calculated for the following frequencies: 250, 500, 1000, 2000, 3000, 4000, 8000. An echo-color Doppler evaluation of the venous cerebral veins, internal jugular (IJV) and vertebral veins (VV) at supine and 90° position was performed. No morphological alterations were found both in patients and controls. There were no signs of stenosis, blocked flow, membranes, etc. We found lower minimum, mean and maximum velocities in distal IJVs (P = .019; P = .013; P = .022; respectively) and left VVs (P = .027; P = .008; P = .001; respectively) in supine (0°) position in both MD and ISSHL patients as compared to controls. The same was for orthostatic position (90°). We found negative correlations between the velocities in extracranial veins and PTA values: therefore, the worst the audiometric performance of the subjects, the lower the velocities in the venous cerebral drainage. Idiopathic sudden sensorineural hearing loss and Ménière syndrome patients showed altered venous flow in IJVs and VVs as compared to controls, independently from posture. This different behavior of venous tone control can influence the ear performance and may have a role in the pathogenesis of both diseases. © 2017 John Wiley & Sons Ltd.

Endothelial dysfunction in normoglycaemic first-degree relatives of type 2 diabetes mellitus complicated with hyperuricaemia.

PubMed

Zhang, Junxia; Xiang, Lin; Zhang, Bilin; Cheng, Yangyang

2017-03-01

To reveal the effect of hyperuricaemia on endothelial function in normoglycaemic first-degree relatives of type 2 diabetes mellitus. In all, 40 first-degree relatives of type 2 diabetes mellitus with hyperuricaemia, 40 first-degree relatives of type 2 diabetes mellitus with normouricaemia and 35 healthy subjects without diabetic family history were recruited in this study. Anthropometric parameters as well as blood pressure, blood lipids, fasting blood glucose, fasting insulin, C-reactive protein, tumour necrosis factor-α and interleukin-6 were measured. Insulin resistance was assessed with homoeostasis model assessment index-insulin resistance index. To assess endothelial function, high-resolution ultrasonography was used for measuring flow- and nitroglycerine-mediated brachial artery vasodilation. When compared with control, flow-mediated dilation was lower in first-degree relatives with or without hyperuricaemia (both p < 0.001). When compared with first-degree relative subjects with normouricaemia, there were lower flow-mediated dilation ( p < 0.001) and higher levels of uric acid ( p < 0.001), fasting blood glucose ( p < 0.001), C-reactive protein ( p = 0.001), tumour necrosis factor-α ( p < 0.001) and interleukin-6 ( p < 0.001) in first-degree relative subjects with hyperuricaemia. Flow-mediated dilation was found to be negatively related to uric acid ( r = -0.597, p < 0.001). Stepwise multiple regressions demonstrated that uric acid was a significant determinant of flow-mediated dilation independent of other variables in first-degree relatives of type 2 diabetes mellitus (β = -0.677, p < 0.001; confidence interval: -0.010 to -0.006). Further endothelial dysfunction is found in normoglycaemic first-degree relatives of type 2 diabetes mellitus complicated with hyperuricaemia.

Water-Based Aerobic Training Successfully Improves Lipid Profile of Dyslipidemic Women: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Costa, Rochelle Rocha; Pilla, Carmen; Buttelli, Adriana Cristine Koch; Barreto, Michelle Flores; Vieiro, Priscila Azevedo; Alberton, Cristine Lima; Bracht, Cláudia Gomes; Kruel, Luiz Fernando Martins

2018-01-01

Purpose: This study aimed to investigate the effects of water-based aerobic training on the lipid profile and lipoprotein lipase (LPL) levels in premenopausal women with dyslipidemia. Method: Forty women were randomly assigned to: aquatic training (WA; n = 20) or a control group (CG; n = 20). The WA group underwent 12 weeks of water-based interval…

The relationship between the enzyme activity, lipid peroxidation and red blood cells deformability in hemizygous and heterozygous glucose-6-phosphate dehydrogenase deficient individuals.

PubMed

Gurbuz, N; Yalcin, O; Aksu, T A; Baskurt, O K

2004-01-01

Glucose-6-phosphate dehydrogenase (G6PD) activity, red blood cell (RBC) lipid peroxidation and deformability were investigated in hemizygous and heterozygous G6PD deficient subjects and compared with normal individuals. None of the subjects were in acute hemolytic crises. G6PD activity was assessed based on the spectrophotometric determination of generated NADPH. Lipid peroxidation was measured as thiobarbutiric acid reactive substances (TBARS). RBC deformability was analyzed by ektacytometry. RBC lipid peroxidation was found to be significantly higher in hemizygous subjects compared to control and heterozygous subjects, while RBC deformability was found to be significantly impaired. However, although lipid peroxidation was higher than control, RBC deformability was not significantly different from control in heterozygous individuals, characterized by significantly lower RBC G6PD activity. There were no significant correlations between these three parameters when the three groups were analyzed separately, but a significant negative correlation was found to exist between G6PD activity and TBARS when the pooled data from the three groups were used for the analysis. This was also true for the relationship between RBC deformability and G6PD activity. It has been concluded that G6PD activity is not a good predictor of oxidative damage resulting in mechanical impairment in heterozygous individuals.

Effects of a sphingolipid-enriched dairy formulation on postprandial lipid concentrations.

PubMed

Ohlsson, L; Burling, H; Duan, R-D; Nilsson, A

2010-11-01

The digestion of sphingolipids (SL) is slow and is catalyzed by mucosal enzymes. Dietary SL was shown to inhibit cholesterol absorption and to lower plasma cholesterol, triglycerides (TG) and hepatic fat accumulation in animal models. A dairy formulation based on fractionation of buttermilk, which is enriched in milk polar lipids of which SL account for a large part is now available. In this study, we examined whether this formulation, when ingested with a standard breakfast, exerted a different influence on postprandial lipids than an equivalent control formulation lacking the polar milk lipids. A total of 18 healthy male volunteers aged 22-65 years ingested a high-fat (40 g) standard breakfast together with a milk-like formulation containing 975 mg of milk SL (A) or the control formulation (B). Postprandial levels of TG, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, apolipoprotein AI (ApoAI), ApoB, glucose and insulin were measured 1 to 7 h after the meal. No difference was seen between experimental and control groups in postprandial levels of TG, insulin, ApoA1 or ApoB. After 1 hour there was a trend of lower cholesterol concentrations in large TG-rich lipoproteins after formulation A. The SL-rich buttermilk drink may affect cholesterol concentrations in TG-rich lipoproteins, but has no effect on postprandial TG after a breakfast with butter fat as the major lipid.

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

PubMed Central

2013-01-01

Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease. PMID:23899561

Using RNA as a tool to modify lipid nanoparticles

NASA Astrophysics Data System (ADS)

Wilner, Samantha E.

Lipid nanoparticles (LNPs) provide an attractive option for therapeutic applications because they can self-assemble and carry a diverse set of cargoes ranging from hydrophobic drugs to small interfering RNA (siRNA). Liposomes and micelles represent two classes of LNPs that have been developed for medicinal purposes; however, active targeting of LNPs to specific tissues and LNP stability in vivo remain significant challenges. We have exploited the structural characteristics and targeting ability of nucleic acids to address these obstacles. Specifically, we have introduced short nucleic acid targeting species, called aptamers, to the surface of stable nucleic acid lipid particles (SNALPs), a subset of liposomes used in siRNA delivery. In this manner, we have actively targeted SNALPs to cancer cells that overexpress the transferrin receptor (TfR). HeLa cells expressing enhanced green fluorescent protein (EGFP) were treated with SNALPs bearing an antiTfR aptamer (C2) that was identified in our lab. C2-conjugated SNALPs showed increased levels of uptake by cells by flow cytometry. More importantly, the enhanced uptake by C2-conjugated SNALPs translated to an increased level of gene knockdown when SNALPs were loaded with anti-EGFP siRNA or anti-Lamin NC siRNA. Expression of EGFP and Lamin NC decreased, respectively. These preliminary studies illustrate that aptamer-conjugated SNALPs can be designed to knock down both endogenous and exogenous genes in cancer cells with high specificity. We have also used nucleic acids to stabilize lipid micelles by introducing short quadruplex forming oligonucleotide sequences at the lipid headgroup. Micelle formation was confirmed via dynamic light scattering, transmission electron microscopy, and small angle X-ray scattering. Micelle stability was assessed using NMR and by a FRET-based assay in the presence of serum proteins. Quadruplex-stabilized micelles demonstrated enhanced stability suggesting that alterations to oligonucleotide headgroup interactions could be used to tune micelle stability. Therefore, we engineered stabilized micelles with an oligonucleotide extension and have shown that the addition of an antisense oligonucleotide leads to micelle destabilization and cargo release. The ability to control particle stability with antisense oligonucleotides represents a new paradigm in the design of programmed nanoscale devices, which we envision will find utility in the development of novel diagnostics and therapeutics.

Properties of Plasma Membrane from Pea Root Seedlings under Altered Gravity

NASA Astrophysics Data System (ADS)

Klymchuk, D.; Baranenko, V.; Vorobyova, T. V.; Kurylenko, I.; Chyzhykova, O.; Dubovoy, V.

In this study, the properties of pea (Pisum sativum L.) plasma membrane were examined to determine how the membrane structure and functions are regulated in response to clinorotation (2 rev/min) conditions. Membrane preparations enriched by plasma membrane vesicles were obtained by aqueous two-phase partitioning from 6-day seedling roots. The specific characteristics of H^+-ATPase, lípid composition and peroxidation intensity as well as fluidity of lipid bilayer were analysed. ATP hydrolytic activity was inhibited by ortovanadate and was insensitive to aside and nitrate in sealed plasma membrane vesicles isolated from both clinorotated and control seedlings. Plasma membrane vesicles from clinorotated seedlings in comparison to controls were characterised by increase in the total lipid/protein ratio, ATP hydrolytic activity and intensifying of lipid peroxidation. Sitosterol and campesterol were the predominant free sterol species. Clinorotated seedlings contained a slightly higher level of unsaturated fatty acid than controls. Plasma membrane vesicles were labelled with pyrene and fluorescence originating from monomeric (I_M) molecules and excimeric (I_E) aggregates were measured. The calculated I_E/I_M values were higher in clinorotated seedlings compared with controls reflecting the reduction in membrane microviscosity. The involvement of the changes in plasma membrane lipid content and composition, fluidity and H^+-ATPase activity in response of pea seedlings to altered gravity is discussed.

Membrane Proteomic Insights into the Physiology and Taxonomy of an Oleaginous Green Microalga1

PubMed Central

Vera-Estrella, Rosario

2017-01-01

Ettlia oleoabundans is a nonsequenced oleaginous green microalga. Despite the significant biotechnological interest in producing value-added compounds from the acyl lipids of this microalga, a basic understanding of the physiology and biochemistry of oleaginous microalgae is lacking, especially under nitrogen deprivation conditions known to trigger lipid accumulation. Using an RNA sequencing-based proteomics approach together with manual annotation, we are able to provide, to our knowledge, the first membrane proteome of an oleaginous microalga. This approach allowed the identification of novel proteins in E. oleoabundans, including two photoprotection-related proteins, Photosystem II Subunit S and Maintenance of Photosystem II under High Light1, which were considered exclusive to higher photosynthetic organisms, as well as Retinitis Pigmentosa Type 2-Clathrin Light Chain, a membrane protein with a novel domain architecture. Free-flow zonal electrophoresis of microalgal membranes coupled to liquid chromatography-tandem mass spectrometry proved to be a useful technique for determining the intracellular location of proteins of interest. Carbon-flow compartmentalization in E. oleoabundans was modeled using this information. Molecular phylogenetic analyses of protein markers and 18S ribosomal DNA support the reclassification of E. oleoabundans within the trebouxiophycean microalgae, rather than with the Chlorophyceae class, in which it is currently classified, indicating that it may not be closely related to the model green alga Chlamydomonas reinhardtii. A detailed survey of biological processes taking place in the membranes of nitrogen-deprived E. oleoabundans, including lipid metabolism, provides insights into the basic biology of this nonmodel organism. PMID:27837088

Human Adipose-Derived Mesenchymal Stem/Stromal Cells Handling Protocols. Lipid Droplets and Proteins Double-Staining

PubMed Central

Gojanovich, Aldana D.; Gimenez, María C.; Masone, Diego; Rodriguez, Tania M.; Dewey, Ricardo A.; Delgui, Laura R.; Bustos, Diego M.; Uhart, Marina

2018-01-01

Human Adipose-derived mesenchymal stem/stromal cells (hASCs) are of great interest because of their potential for therapeutic approaches. The method described here covers every single step necessary for hASCs isolation from subcutaneous abdominal adipose tissue, multicolor phenotyping by flow cytometry, and quantitative determination of adipogenic differentiation status by means of lipid droplets (LDs) accumulation, and Western blot analysis. Moreover, to simultaneously analyze both LDs accumulation and cellular proteins localization by fluorescence microscopy, we combined Oil Red O (ORO) staining with immunofluorescence detection. For LDs quantification we wrote a program for automatic ORO-stained digital image processing implemented in Octave, a freely available software package. Our method is based on the use of the traditional low cost neutral lipids dye ORO, which can be imaged both by bright-field and fluorescence microscopy. The utilization of ORO instead of other more expensive lipid-specific dyes, together with the fact that the whole method has been designed employing cost-effective culture reagents (standard culture medium and serum), makes it affordable for tight-budget research laboratories. These may be replaced, if necessary or desired, by defined xeno-free reagents for clinical research and applications. PMID:29670879

Human Adipose-Derived Mesenchymal Stem/Stromal Cells Handling Protocols. Lipid Droplets and Proteins Double-Staining.

PubMed

Gojanovich, Aldana D; Gimenez, María C; Masone, Diego; Rodriguez, Tania M; Dewey, Ricardo A; Delgui, Laura R; Bustos, Diego M; Uhart, Marina

2018-01-01

Human Adipose-derived mesenchymal stem/stromal cells (hASCs) are of great interest because of their potential for therapeutic approaches. The method described here covers every single step necessary for hASCs isolation from subcutaneous abdominal adipose tissue, multicolor phenotyping by flow cytometry, and quantitative determination of adipogenic differentiation status by means of lipid droplets (LDs) accumulation, and Western blot analysis. Moreover, to simultaneously analyze both LDs accumulation and cellular proteins localization by fluorescence microscopy, we combined Oil Red O (ORO) staining with immunofluorescence detection. For LDs quantification we wrote a program for automatic ORO-stained digital image processing implemented in Octave, a freely available software package. Our method is based on the use of the traditional low cost neutral lipids dye ORO, which can be imaged both by bright-field and fluorescence microscopy. The utilization of ORO instead of other more expensive lipid-specific dyes, together with the fact that the whole method has been designed employing cost-effective culture reagents (standard culture medium and serum), makes it affordable for tight-budget research laboratories. These may be replaced, if necessary or desired, by defined xeno-free reagents for clinical research and applications.

Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

PubMed

Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

2012-06-01

A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

PubMed

Doğan, Berçem Ayçiçek; Karakılıç, Ersen; Tuna, Mazhar Müslüm; Arduç, Ayşe; Berker, Dilek; Güler, Serdar

2015-03-01

Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. The carotid intima-media thickness (P < 0·001) was higher and the brachial flow-mediated diameter (P = 0·002) was lower in patients with idiopathic hypogonadotropic hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = <0·001). The carotid intima-media thickness and per cent flow-mediated diameter were significantly improved in the patient group 6 months after the androgen replacement therapy (P = 0·002 and 0·026, respectively). This study indicated that low total testosterone levels can be considered a significant marker of atherosclerosis in patients with idiopathic hypogonadotropic hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months. © 2014 John Wiley & Sons Ltd.

Subterahertz Longitudinal Phonon Modes Propagating in a Lipid Bilayer Immersed in an Aqueous Medium

NASA Astrophysics Data System (ADS)

Zakhvataev, V. E.

2018-04-01

The properties of subterahertz longitudinal acoustic phonon modes in the hydrophobic region of a lipid bilayer immersed in a compressible viscous aqueous medium are investigated theoretically. An approximate expression is obtained for the Mandelstam-Brillouin components of the dynamic structure factor of a bilayer. The analysis is based on a generalized hydrodynamic model of the "two-dimensional lipid bilayer + three-dimensional fluid medium" system, as well as on known sharp estimates for the frequencies and lifetimes of long-wavelength longitudinal acoustic phonons in a free hydrated lipid bilayer and in water, obtained from inelastic X-ray scattering experiments and molecular dynamics simulations. It is shown that, for characteristic values of the parameters of the membrane system, subterahertz longitudinal phonon-like excitations in the hydrophobic part of the bilayer are underdamped. In this case, the contribution of the viscous flow of the aqueous medium to the damping of a longitudinal membrane mode is small compared with the contribution of the lipid bilayer. Quantitative estimates of the damping ratio agree well with the experimental results for the vibration mode of the enzyme lysozyme in aqueous solution [1]. It is also shown that a coupling between longitudinal phonon modes of the bilayer and relaxation processes in its fluid environment gives rise to an additional peak in the scattering spectrum, which corresponds to a non-propagating mode.

Highly selective water channel activity measured by voltage clamp: analysis of planar lipid bilayers reconstituted with purified AqpZ.

PubMed

Pohl, P; Saparov, S M; Borgnia, M J; Agre, P

2001-08-14

Aquaporins are membrane channels selectively permeated by water or water plus glycerol. Conflicting reports have described ion conductance associated with some water channels, raising the question of whether ion conductance is a general property of the aquaporin family. To clarify this question, a defined system was developed to simultaneously measure water permeability and ion conductance. The Escherichia coli water channel aquaporin-Z (AqpZ) was studied, because it is a highly stable tetramer. Planar lipid bilayers were formed from unilamellar vesicles containing purified AqpZ. The hydraulic conductivity of bilayers made from the total extract of E. coli lipids increased 3-fold if reconstituted with AqpZ, but electric conductance was unchanged. No channel activity was detected under voltage-clamp conditions, indicating that less than one in 10(9) transport events is electrogenic. Microelectrode measurements were simultaneously undertaken adjacent to the membrane. Changes in sodium concentration profiles accompanying transmembrane water flow permitted calculation of the activation energies: 14 kcal/mol for protein-free lipid bilayers and 4 kcal/mol for lipid bilayers containing AqpZ. Neither the water permeability nor the electric conductivity exhibited voltage dependence. This sensitive system demonstrated that AqpZ is permeated by water but not charged ions and should permit direct analyses of putative electrogenic properties of other aquaporins.

Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages.

PubMed

Wang, Ji; Kang, Yu-Xia; Pan, Wen; Lei, Wan; Feng, Bin; Wang, Xiao-Juan

2016-06-20

Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%-8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

Lipid flopping in the liver.

PubMed

Linton, Kenneth J

2015-10-01

Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids (BAs; which act as detergent molecules), the membrane phospholipid phosphatidylcholine (PC), cholesterol and a variety of endogenous metabolites and waste products. Over the last 20 years, the combined effort of clinicians, geneticists, physiologists and biochemists has shown that each of these bile components is transported across the canalicular membrane of the hepatocyte by its own specific ATP-binding cassette (ABC) transporter. The bile salt export pump (BSEP) ABCB11 transports the BAs and drives bile flow from the liver, but it is now clear that two lipid transporters, ABCB4 (which flops PC into the bile) and the P-type ATPase ATP8B1/CDC50 (which flips a different phospholipid in the opposite direction) play equally critical roles that protect the biliary tree from the detergent activity of the bile acids. Understanding the interdependency of these lipid floppases and flippases has allowed the development of an assay to measure ABCB4 function. ABCB4 harbours numerous mis-sense mutations which probably reflects the spectrum of liver disease rooted in ABCB4 aetiology. Characterization of the effect of these mutations at the protein level opens the possibility for the development of personalized prognosis and treatment. © 2015 Authors; published by Portland Press Limited.

A randomized study of coconut oil versus sunflower oil on cardiovascular risk factors in patients with stable coronary heart disease.

PubMed

Vijayakumar, Maniyal; Vasudevan, D M; Sundaram, K R; Krishnan, Sajitha; Vaidyanathan, Kannan; Nandakumar, Sandya; Chandrasekhar, Rajiv; Mathew, Navin

2016-01-01

Coronary artery disease (CAD) and its pathological atherosclerotic process are closely related to lipids. Lipids levels are in turn influenced by dietary oils and fats. Saturated fatty acids increase the risk for atherosclerosis by increasing the cholesterol level. This study was conducted to investigate the impact of cooking oil media (coconut oil and sunflower oil) on lipid profile, antioxidant mechanism, and endothelial function in patients with established CAD. In a single center randomized study in India, patients with stable CAD on standard medical care were assigned to receive coconut oil (Group I) or sunflower oil (Group II) as cooking media for 2 years. Anthropometric measurements, serum, lipids, Lipoprotein a, apo B/A-1 ratio, antioxidants, flow-mediated vasodilation, and cardiovascular events were assessed at 3 months, 6 months, 1 year, and 2 years. Hundred patients in each arm completed 2 years with 98% follow-up. There was no statistically significant difference in the anthropometric, biochemical, vascular function, and in cardiovascular events after 2 years. Coconut oil even though rich in saturated fatty acids in comparison to sunflower oil when used as cooking oil media over a period of 2 years did not change the lipid-related cardiovascular risk factors and events in those receiving standard medical care. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

NASA Astrophysics Data System (ADS)

Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

2011-06-01

Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

Lipids, curvature, and nano-medicine*

PubMed Central

Mouritsen, Ole G

2011-01-01

The physical properties of the lamellar lipid-bilayer component of biological membranes are controlled by a host of thermodynamic forces leading to overall tensionless bilayers with a conspicuous lateral pressure profile and build-in curvature-stress instabilities that may be released locally or globally in terms of morphological changes. In particular, the average molecular shape and the propensity of the different lipid and protein species for forming non-lamellar and curved structures are a source of structural transitions and control of biological function. The effects of different lipids, sterols, and proteins on membrane structure are discussed and it is shown how one can take advantage of the curvature-stress modulations brought about by specific molecular agents, such as fatty acids, lysolipids, and other amphiphilic solutes, to construct intelligent drug-delivery systems that function by enzymatic triggering via curvature. Practical applications: The simple concept of lipid molecular shape and how it impacts on the structure of lipid aggregates, in particular the curvature and curvature stress in lipid bilayers and liposomes, can be exploited to construct liposome-based drug-delivery systems, e.g., for use as nano-medicine in cancer therapy. Non-lamellar-forming lysolipids and fatty acids, some of which may be designed to be prodrugs, can be created by phospholipase action in diseased tissues thereby providing for targeted drug release and proliferation of molecular entities with conical shape that break down the permeability barrier of the target cells and may hence enhance efficacy. PMID:22164124

EFFECTS OF AQUEOUS AND DIETARY EXPOSURE OF DIELDRIN ON SURVIVAL, GROWTH AND BIOCONCENTRATION IN MALLARD DUCKLINGS

EPA Science Inventory

Tests were conducted to determine the effects of dieldrin in continuous-flow water and in food on survival, growth, and bioconcentration in mallard ducklings. ieldrin had no effect on survival or growth at concentrations at or below water saturation (0.2 mg/L), but tissue (lipid,...

Benefits of commercial weight-loss programs on blood pressure and lipids: a systematic review.

PubMed

Mehta, Ambereen K; Doshi, Ruchi S; Chaudhry, Zoobia W; Jacobs, David K; Vakil, Rachit M; Lee, Clare J; Bleich, Sara N; Clark, Jeanne M; Gudzune, Kimberly A

2016-09-01

Our objective was to compare the effect of commercial weight-loss programs on blood pressure and lipids to control/education or counseling among individuals with overweight/obesity. We conducted a systematic review by searching MEDLINE and Cochrane Database of Systematic Reviews from inception to November 2014 and references identified by the programs. We included randomized, controlled trials ≥12weeks in duration. Two reviewers extracted information on study design, interventions, and mean change in systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, and total cholesterol and assessed risk of bias. We included 27 trials. Participants' blood pressure and lipids were normal at baseline in most trials. At 12months, Weight Watchers showed little change in blood pressure or lipid outcomes as compared to control/education (2 trials). At 12months, Atkins' participants had higher HDL-c and lower triglycerides than counseling (4 trials). Other programs had inconsistent effects or lacked long-term studies. Risk of bias was high for most trials of all programs. In conclusion, limited data exist regarding most commercial weight-loss programs' long-term effects on blood pressure and lipids. Clinicians should be aware that Weight Watchers has limited data that demonstrate CVD risk factor benefits relative to control/education. Atkins may be a reasonable option for patients with dyslipidemia. Additional well-designed, long-term trials are needed to confirm these conclusions and evaluate other commercial programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Maternal Circulating Lipid Profile during Early Pregnancy: Racial/Ethnic Differences and Association with Spontaneous Preterm Delivery.

PubMed

Chen, Xinhua; Scholl, Theresa O; Stein, Thomas P; Steer, Robert A; Williams, Keith P

2017-01-01

Prior reports on the association between altered maternal serum lipid levels with preterm delivery are inconsistent. Ethnic differences in serum lipids during pregnancy and their relation to preterm delivery have not been studied. We examined the relationships of six maternal lipids during early pregnancy with the risk of spontaneous preterm delivery (SPTD). The design represents a case-control study nested within a large prospective, multiethnic cohort of young, generally healthy pregnant women. SPTD cases ( n = 183) and controls who delivered at term ( n = 376) were included. SPTD is defined as delivery at <37 completed weeks of gestation without indicated conditions. We found that African-American women had significantly increased levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1), and lower triglyceride (TG) and apolipoprotein B (apoB) levels compared to Hispanic and non-Hispanic Caucasians combined. Elevated HDL-C and apoA1 concentrations were significantly associated with an increased odds of SPTD after controlling for potential confounding factors. The adjusted odds ratio (AOR) was 1.91 (95% confidence interval (CI) 1.15, 3.20) for the highest quartile of HDL-C relative to the lowest quartile, and for apoA1 the AOR was 1.94 (95% CI 1.16, 3.24). When controlling for ethnicity, the results remained comparable. These data suggest that pregnant African-American women had a more favorable lipid profile suggestive of a reduction in cardiovascular risk. Despite this, increased HDL-C and apoA1 were both found to be associated with SPTD.

Increased Nutrient Sensitivity and Plasma Concentrations of Enteral Hormones during Duodenal Nutrient Infusion in Functional Dyspepsia

PubMed Central

Bharucha, Adil E.; Camilleri, Michael; Burton, Duane D.; Thieke, Shannon L.; Feuerhak, Kelly J.; Basu, Ananda; Zinsmeister, Alan R.

2015-01-01

Objectives Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in functional dyspepsia vs health. Design Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 minutes each, with a 120-minute washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagonlike peptide 1 (GLP1), and peptide YY were measured during infusions. Results Moderate or more severe symptoms during lipid (4 controls vs 14 patients) and dextrose (1 control vs 12 patients) infusions were more prevalent in patients than controls (P≤.01), associated with higher dyspepsia symptom score (P=.01), worse QOL (P=.01), and greater plasma hormone concentrations (eg, GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively. Conclusions Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia. PMID:25403365

Investigation of ABCA1 C69T polymorphism in patients with type 2 diabetes mellitus.

PubMed

Ergen, H Arzu; Zeybek, Umit; Gök, Ozlem; Karaali, Z Ermis

2012-01-01

Non insulin dependent diabetes mellitus is the most common type of diabetes. Genetic factors, lipid profiles, hypertension are potential risk factors for diabetes mellitus. Adenosine binding cassette transporter proteins 1 (ABCA1) plays a role in cholesterol metabolism, especially high density lipoprotein (HDL-cholesterol). There are multiple mechanisms by which HDL-cholesterol can be atheroprotective, it is clear that the relative activity of ABCA1 plays a major role. We aimed to investigate association of ABCA1 C69T gene polymorphism with lipid levels in Turkish type 2 diabetic patients. After isolation of DNA by ethanol precipitation we determined ABCA1 gene polymorphism by using polimerase chain reaction--restriction fragment lenght polymorphism (PCR-RFLP) method in 107 type 2 diabetic patients and 50 healthy controls. We have observed that the frequency of TT genotype is significantly higher in healthy controls compared to patients (14% vs. 3%; P = 0.008). Also frequency of T allele was higher in controls than in patients (34% vs. 21%; P = 0.020; OR (95% CI) = 0.52 (0.30-0.88)). There was no association of lipid levels and ABCA1 C69T polymorphism subgroups. We have found significantly higher frequency of both T allele and genotype in control group when compared to patients that made us think that T allele may be a protective factor against diabetes mellitus. But, we could not find a relationship between genotypes and lipid concentrations in our two groups. Larger studies will help us to understand the relationship between ABCA1 C69T genotype and lipid parameters in diabetes mellitus.

Epidermal hydration and skin surface lipids in patients with long-term complications of sulfur mustard poisoning.

PubMed

Layegh, Pouran; Maleki, Masoud; Mousavi, Seyed Reza; Yousefzadeh, Hadis; Momenzadeh, Akram; Golmohammadzadeh, Shiva; Balali-Mood, Mahdi

2015-07-01

Despite almost the three decades passed since the chemical attacks of Iraqi's army against the Iranian troops, some veterans are still suffering from long-term complications of sulfur mustard (SM) poisoning, including certain skin complaints specially dryness, burning, and pruritus. We thus aimed to evaluate the skin's water and lipid content in patients with a disability of >25% due to complications of SM poisoning and compare them with a matched control group. Sixty-nine male participants were included in this study; 43 SM-exposed patients, and 26 normal controls from their close relatives. The water and lipid content was measured in four different locations: Extensor and flexor sides of forearms and lateral and medial sides of legs by the Corneometer CM 820/Sebumeter SM 810. Collected data was analyzed and P ≤ 0.05 was considered as statistically significant. The mean age of the patients and controls was 49.53 ± 11.34 (ranges: 40-71) and 29.08 ± 8.836 (ranges: 15-49 years), respectively. In the veterans group, the main cutaneous complaint was itching and skin dryness. Cherry angioma, dry skin, and pruritus were significantly more common in the SM-exposed cases than in the controls. (P = 0.01, 0.05, and 0.04, respectively). The moisture and lipid content of all areas were lower in the SM-exposed group, but it was only significant in skin sebum of lateral sides of legs (P = 0.02). Exposure to SM could decrease the function of stratum corneum and lipid production as a barrier, even after several years of its exposure.

Stability of lipid encapsulated ferulic acid particles

USDA-ARS?s Scientific Manuscript database

Encapsulation of bioactive compounds by a solid lipid matrix provides stability and a mechanism for controlled release in formulated products. Phenolic compounds exhibit antioxidant and antimicrobial activities and have applications as functional food and feed additives. Ferulic acid, a common pheno...