Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures.

PubMed

Semple, S C; Klimuk, S K; Harasym, T O; Dos Santos, N; Ansell, S M; Wong, K F; Maurer, N; Stark, H; Cullis, P R; Hope, M J; Scherrer, P

2001-02-09

Typical methods used for encapsulating antisense oligodeoxynucleotides (ODN) and plasmid DNA in lipid vesicles result in very low encapsulation efficiencies or employ cationic lipids that exhibit unfavorable pharmacokinetic and toxicity characteristics when administered intravenously. In this study, we describe and characterize a novel formulation process that utilizes an ionizable aminolipid (1,2-dioleoyl-3-dimethylammonium propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities (0.15--0.25 g ODN/g lipid) of polyanionic ODN in lipid vesicles. This process requires the presence of up to 40% ethanol (v/v) and initial formulation at acidic pH values where the DODAP is positively charged. In addition, the presence of a poly(ethylene glycol)-lipid was required during the formulation process to prevent aggregation. The 'stabilized antisense-lipid particles' (SALP) formed are stable on adjustment of the external pH to neutral pH values and the formulation process allows encapsulation efficiencies of up to 70%. ODN encapsulation was confirmed by nuclease protection assays and (31)P NMR measurements. Cryo-electron microscopy indicated that the final particles consisted of a mixed population of unilamellar and small multilamellar vesicles (80--140 nm diameter), the relative proportion of which was dependent on the initial ODN to lipid ratio. Finally, SALP exhibited significantly enhanced circulation lifetimes in mice relative to free antisense ODN, cationic lipid/ODN complexes and SALP prepared with quaternary aminolipids. Given the small particle sizes and improved encapsulation efficiency, ODN to lipid ratios, and circulation times of this formulation compared to others, we believe SALP represent a viable candidate for systemic applications involving nucleic acid therapeutics.

Spontaneous charged lipid transfer between lipid vesicles.

PubMed

Richens, Joanna L; Tyler, Arwen I I; Barriga, Hanna M G; Bramble, Jonathan P; Law, Robert V; Brooks, Nicholas J; Seddon, John M; Ces, Oscar; O'Shea, Paul

2017-10-03

An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are fluorescently labelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE). Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting in a fluorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a first-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodified lipids, continuous monitoring of transfer and simplified experimental procedures.

Combinatorial pretreatment and fermentation optimization enabled a record yield on lignin bioconversion.

PubMed

Liu, Zhi-Hua; Xie, Shangxian; Lin, Furong; Jin, Mingjie; Yuan, Joshua S

2018-01-01

Lignin valorization has recently been considered to be an essential process for sustainable and cost-effective biorefineries. Lignin represents a potential new feedstock for value-added products. Oleaginous bacteria such as Rhodococcus opacus can produce intracellular lipids from biodegradation of aromatic substrates. These lipids can be used for biofuel production, which can potentially replace petroleum-derived chemicals. However, the low reactivity of lignin produced from pretreatment and the underdeveloped fermentation technology hindered lignin bioconversion to lipids. In this study, combinatorial pretreatment with an optimized fermentation strategy was evaluated to improve lignin valorization into lipids using R. opacus PD630. As opposed to single pretreatment, combinatorial pretreatment produced a 12.8-75.6% higher lipid concentration in fermentation using lignin as the carbon source. Gas chromatography-mass spectrometry analysis showed that combinatorial pretreatment released more aromatic monomers, which could be more readily utilized by lignin-degrading strains. Three detoxification strategies were used to remove potential inhibitors produced from pretreatment. After heating detoxification of the lignin stream, the lipid concentration further increased by 2.9-9.7%. Different fermentation strategies were evaluated in scale-up lipid fermentation using a 2.0-l fermenter. With laccase treatment of the lignin stream produced from combinatorial pretreatment, the highest cell dry weight and lipid concentration were 10.1 and 1.83 g/l, respectively, in fed-batch fermentation, with a total soluble substrate concentration of 40 g/l. The improvement of the lipid fermentation performance may have resulted from lignin depolymerization by the combinatorial pretreatment and laccase treatment, reduced inhibition effects by fed-batch fermentation, adequate oxygen supply, and an accurate pH control in the fermenter. Overall, these results demonstrate that combinatorial pretreatment, together with fermentation optimization, favorably improves lipid production using lignin as the carbon source. Combinatorial pretreatment integrated with fed-batch fermentation was an effective strategy to improve the bioconversion of lignin into lipids, thus facilitating lignin valorization in biorefineries.

Solid-state fermentation of Mortierella isabellina for lipid production from soybean hull.

PubMed

Zhang, Jianguo; Hu, Bo

2012-02-01

Soybean hull, generated from soybean processing, is a lignocellulosic material with limited industrial applications and little market value. This research is exploring a new application of soybean hull to be converted to fungal lipids for biodiesel production through solid-state fermentation. Mortierella isabellina was selected as the oil producer because of its high lipid content at low C/N ratio. Several cultivation factors were investigated, including moisture content, inoculums size, fungal spore age, and nutrient supplements, in an attempt to enhance the lipid production of the solid-state fermentation process. The results showed that lipid production with the increase of the moisture content and the spore age, while decreased as the size of inoculums increased. Nutrients addition (KH₂PO₄ 1.2 mg and MgSO₄ 0.6 mg/g soybean hull) improved the lipid production. The total final lipid reached 47.9 mg lipid from 1 g soybean hull after the conversion, 3.3-fold higher than initial lipid reserve in the soybean hull. The fatty acid profile analysis indicated that fatty acid content consisted of 30.0% of total lipid, and 80.4% of total fatty acid was C16 and C18. Therefore, lipid production from soybean hull is a possible option to enable soybean hull as a new resource for biodiesel production and to enhance the overall oil production from soybeans.

Alabama Coronary Artery Bypass Grafting Project

PubMed Central

Holman, William L.; Sansom, Monique; Kiefe, Catarina I.; Peterson, Eric D.; Hubbard, Steve G.; Delong, James F.; Allman, Richard M.

2004-01-01

Objective/Background: This report describes the first round of results for Phase II of the Alabama CABG Project, a regional quality improvement initiative. Methods: Charts submitted by all hospitals in Alabama performing CABG (ICD-9 codes 36.10–36.20) were reviewed by a Clinical Data Abstraction Center (CDAC) (preintervention 1999–2000; postintervention 2000–2001). Variables that described quality in Phase I were abstracted for Phase II and data describing the new variables of β-blocker use and lipid management were collected. Data samples collected onsite by participating hospitals were used for rapid cycle improvement in Phase II. Results: CDAC data (n = 1927 cases in 1999; n = 2001 cases in 2000) showed that improvements from Phase I in aspirin prescription, internal mammary artery use, and duration of intubation persisted in Phase II. During Phase II, use of β-blockers before, during, or after CABG increased from 65% to 76% of patients (P < 0.05). Appropriate lipid management, an aggregate variable, occurred in 91% of patients before and 91% after the educational intervention. However, there were improvements in 3 of 5 subcategories for lipid management (documenting a lipid disorder [52%–57%], initiating drug therapy [45%–53%], and dietary counseling [74%–91%]; P < 0.05). Conclusions: In Phase II, this statewide process-oriented quality improvement program added two new measures of quality. Achievements of quality improvement from Phase I persisted in Phase II, and improvements were seen in the new variables of lipid management and perioperative use of β-blockers. PMID:14685107

Lean production of taste improved lipidic sodium benzoate formulations.

PubMed

Eckert, C; Pein, M; Breitkreutz, J

2014-10-01

Sodium benzoate is a highly soluble orphan drug with unpleasant taste and high daily dose. The aim of this study was to develop a child appropriate, individually dosable, and taste masked dosage form utilizing lipids in melt granulation process and tableting. A saliva resistant coated lipid granule produced by extrusion served as reference product. Low melting hard fat was found to be appropriate as lipid binder in high-shear granulation. The resulting granules were compressed to minitablets without addition of other excipients. Compression to 2mm minitablets decreased the dissolved API amount within the first 2 min of dissolution from 33% to 23%. The Euclidean distances, calculated from electronic tongue measurements, were reduced, indicating an improved taste. The reference product showed a lag time in dissolution, which is desirable for taste masking. Although a lag time was not achieved for the lipidic minitablets, drug release in various food materials was reduced to 2%, assuming a suitable taste masking for oral sodium benzoate administration. Copyright © 2014 Elsevier B.V. All rights reserved.

Nutrient recycling of lipid-extracted waste in the production of an oleaginous thraustochytrid.

PubMed

Lowrey, Joshua; Brooks, Marianne S; Armenta, Roberto E

2016-05-01

Improving the economics of microalgae production for the recovery of microbial oil requires a comprehensive exploration of the measures needed to improve productivity as well as to reduce the overall processing costs. One avenue for cost reduction involves recycling the effluent waste water remaining after lipid extraction. This study investigates the feasibility of recycling those wastes for growing thraustochytrid biomass, a heterotrophic microalgae, where wastes were generated from the enzymatic extraction of the lipids from the cell biomass. It was demonstrated that secondary cultures of the tested thraustochytrid grown in the recycled wastes performed favorably in terms of cell and oil production (20.48 g cells L(-1) and 40.9 % (w/w) lipid) compared to the control (13.63 g cells L(-1) and 56.8 % (w/w) lipid). Further, the significant uptake of solubilized cell material (in the form of amino acids) demonstrated that the recycled waste has the potential for offsetting the need for fresh medium components. These results indicate that the implementation of a nutrient recycling strategy for industrial microalgae production could be possible, with significant added benefits such as conserving water resources, improving production efficiency, and decreasing material inputs.

Industrial wastes as a promising renewable source for production of microbial lipid and direct transesterification of the lipid into biodiesel.

PubMed

Cheirsilp, Benjamas; Louhasakul, Yasmi

2013-08-01

Two strategies of converting industrial wastes to microbial lipid and direct transesterification of obtained lipid into biodiesel were attempted. Several oleaginous yeasts were cultivated on industrial wastes. The yeasts grew well on the wastes with low C/N ratio (i.e. serum latex) but accumulated high lipid content only when the wastes had a high C/N ratio (i.e. palm oil mill effluent and crude glycerol). The yeast lipids have similar fatty acid composition to that of plant oil indicating their potential use as biodiesel feedstocks. The combination of these wastes and two-phase cultivation for cell growth and lipid accumulation improved lipid productivity of the selected yeast. The direct transesterification process that eliminates cell drying and lipid extraction steps, gave comparable yield of biodiesel (fatty acid methyl ester >70% within 1h) to that of conventional method. These two successful strategies may contribute greatly to industrializing oil production from microbes and industrial wastes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Consultancy on Large-Scale Submerged Aerobic Cultivation Process Design - Final Technical Report: February 1, 2016 -- June 30, 2016

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

Crater, Jason; Galleher, Connor; Lievense, Jeff

NREL is developing an advanced aerobic bubble column model using Aspen Custom Modeler (ACM). The objective of this work is to integrate the new fermentor model with existing techno-economic models in Aspen Plus and Excel to establish a new methodology for guiding process design. To assist this effort, NREL has contracted Genomatica to critique and make recommendations for improving NREL's bioreactor model and large scale aerobic bioreactor design for biologically producing lipids at commercial scale. Genomatica has highlighted a few areas for improving the functionality and effectiveness of the model. Genomatica recommends using a compartment model approach with an integratedmore » black-box kinetic model of the production microbe. We also suggest including calculations for stirred tank reactors to extend the models functionality and adaptability for future process designs. Genomatica also suggests making several modifications to NREL's large-scale lipid production process design. The recommended process modifications are based on Genomatica's internal techno-economic assessment experience and are focused primarily on minimizing capital and operating costs. These recommendations include selecting/engineering a thermotolerant yeast strain with lipid excretion; using bubble column fermentors; increasing the size of production fermentors; reducing the number of vessels; employing semi-continuous operation; and recycling cell mass.« less

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.

Manipulating environmental stresses and stress tolerance of microalgae for enhanced production of lipids and value-added products-A review.

PubMed

Chen, Bailing; Wan, Chun; Mehmood, Muhammad Aamer; Chang, Jo-Shu; Bai, Fengwu; Zhao, Xinqing

2017-11-01

Microalgae have promising potential to produce lipids and a variety of high-value chemicals. Suitable stress conditions such as nitrogen starvation and high salinity could stimulate synthesis and accumulation of lipids and high-value products by microalgae, therefore, various stress-modification strategies were developed to manipulate and optimize cultivation processes to enhance bioproduction efficiency. On the other hand, advancements in omics-based technologies have boosted the research to globally understand microalgal gene regulation under stress conditions, which enable further improvement of production efficiency via genetic engineering. Moreover, integration of multi-omics data, synthetic biology design, and genetic engineering manipulations exhibits a tremendous potential in the betterment of microalgal biorefinery. This review discusses the process manipulation strategies and omics studies on understanding the regulation of metabolite biosynthesis under various stressful conditions, and proposes genetic engineering of microalgae to improve bioproduction via manipulating stress tolerance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crystallization modifiers in lipid systems.

PubMed

Ribeiro, Ana Paula Badan; Masuchi, Monise Helen; Miyasaki, Eriksen Koji; Domingues, Maria Aliciane Fontenele; Stroppa, Valter Luís Zuliani; de Oliveira, Glazieli Marangoni; Kieckbusch, Theo Guenter

2015-07-01

Crystallization of fats is a determinant physical event affecting the structure and properties of fat-based products. The stability of these processed foods is regulated by changes in the physical state of fats and alterations in their crystallization behavior. Problems like polymorphic transitions, oil migration, fat bloom development, slow crystallization and formation of crystalline aggregates stand out. The change of the crystallization behavior of lipid systems has been a strategic issue for the processing of foods, aiming at taylor made products, reducing costs, improving quality, and increasing the applicability and stability of different industrial fats. In this connection, advances in understanding the complex mechanisms that govern fat crystallization led to the development of strategies in order to modulate the conventional processes of fat structuration, based on the use of crystallization modifiers. Different components have been evaluated, such as specific triacyglycerols, partial glycerides (monoacylglycerols and diacylglycerols), free fatty acids, phospholipids and emulsifiers. The knowledge and expertise on the influence of these specific additives or minor lipids on the crystallization behavior of fat systems represents a focus of current interest for the industrial processing of oils and fats. This article presents a comprehensive review on the use of crystallization modifiers in lipid systems, especially for palm oil, cocoa butter and general purpose fats, highlighting: i) the removal, addition or fractionation of minor lipids in fat bases; ii) the use of nucleating agents to modify the crystallization process; iii) control of crystallization in lipid bases by using emulsifiers. The addition of these components into lipid systems is discussed in relation to the phenomena of nucleation, crystal growth, morphology, thermal behavior and polymorphism, with the intention of providing the reader with a complete panorama of the associated mechanisms with crystallization of fats and oils.

Methods of downstream processing for the production of biodiesel from microalgae.

PubMed

Kim, Jungmin; Yoo, Gursong; Lee, Hansol; Lim, Juntaek; Kim, Kyochan; Kim, Chul Woong; Park, Min S; Yang, Ji-Won

2013-11-01

Despite receiving increasing attention during the last few decades, the production of microalgal biofuels is not yet sufficiently cost-effective to compete with that of petroleum-based conventional fuels. Among the steps required for the production of microalgal biofuels, the harvest of the microalgal biomass and the extraction of lipids from microalgae are two of the most expensive. In this review article, we surveyed a substantial amount of previous work in microalgal harvesting and lipid extraction to highlight recent progress in these areas. We also discuss new developments in the biodiesel conversion technology due to the importance of the connectivity of this step with the lipid extraction process. Furthermore, we propose possible future directions for technological or process improvements that will directly affect the final production costs of microalgal biomass-based biofuels. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Kyle, Jennifer E.; Zhang, Xing; Weitz, Karl K.

Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Liquid chromatography and mass spectrometry (LC-MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids’ biological roles is challenging duemore » to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are unresolvable using present LC-MS approaches. Here we show that combining structurally-based ion mobility spectrometry (IMS) with LC-MS measurements distinguishes lipid isomers and allows insight into biological and disease processes.« less

Techno-economic evaluation of simultaneous production of extra-cellular polymeric substance (EPS) and lipids by Cloacibacterium normanense NK6 using crude glycerol and sludge as substrate.

PubMed

Ram, S K; Kumar, L R; Tyagi, R D; Drogui, P

2018-05-01

This study used the technical, economic analysis tool, SuperPro designer in evaluating a novel technology for simultaneous production of extracellular polymeric substance (EPS) and biodiesel using crude glycerol and secondary sludge. As renewable energy sources are depleting, the process utilizes municipal sewage sludge for production of EPS and biodiesel along with crude glycerol, which is a waste byproduct of biodiesel industry providing an alternate way for disposal of municipal sludge and crude glycerol. Newly isolated Cloacibacterium normanense NK6 is used as micro-organism in the study as it is capable of producing high EPS concentration, using activated sludge and crude glycerol as the sole carbon source. The technology has many environmental and economic advantages like the simultaneous production of two major products: EPS and lipids. Sensitivity analysis of the process revealed that biomass lipid content is a most significant factor where unit cost production of biodiesel was highly sensitive to lipid content during bioreaction. B7 biodiesel unit production cost can be lowered from $1 to $0.6 if the lipid content of the biomass is improved by various process parameter modifications.

Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs.

PubMed

Dahan, Arik; Hoffman, Amnon

2008-07-02

As a consequence of modern drug discovery techniques, there has been a consistent increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered medications with sufficient bioavailability. One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based drug delivery system. Unfortunately, current development strategies in the area of lipid based delivery systems are mostly empirical. Hence, there is a need for a simplified in vitro method to guide the selection of a suitable lipidic vehicle composition and to rationalize the delivery system design. To address this need, a dynamic in vitro lipolysis model, which provides a very good simulation of the in vivo lipid digestion process, has been developed over the past few years. This model has been extensively used for in vitro assessment of different lipid based delivery systems, leading to enhanced understanding of the suitability of different lipids and surfactants as a delivery system for a given poorly water soluble drug candidate. A key goal in the development of the dynamic in vitro lipolysis model has been correlating the in vitro data of various drug-lipidic delivery system combinations to the resultant in vivo drug profile. In this paper, we discuss and review the need for this model, its underlying theory, practice and limitations, and the available data accumulated in the literature. Overall, the dynamic in vitro lipolysis model seems to provide highly useful initial guidelines in the development process of oral lipid based drug delivery systems for poorly water soluble drugs, and it predicts phenomena that occur in the pre-enterocyte stages of the intestinal absorption cascade.

Stratum corneum drying drives vertical compression and lipid organization and improves barrier function in vitro.

PubMed

Iwai, Ichiro; Kunizawa, Naomi; Yagi, Eiichiro; Hirao, Tetsuji; Hatta, Ichiro

2013-03-27

The stratum corneum dehydrates after exogenous hydration due to skincare or bathing. In this study, sheets of stratum corneum were isolated from reconstructed human epidermis and the barrier function and structure of these sheets were assessed during drying with the aim of improving our understanding of skincare. Water diffusion through the sheets of stratum corneum decreased with drying, accompanied by decreased thickness and increased visible light transmission through the sheets. Electron paramagnetic resonance revealed that the order parameter values of stratum corneum lipids increased with drying. X-ray diffraction analysis revealed increases in the diffraction intensity of lamellar structures, with an 11-12 nm periodicity and spacing of 0.42 nm for lattice structures with drying. These results suggest that the drying process improves the barrier function of the stratum corneum by organizing the intercellular lipids in a vertically compressed arrangement.

Delivery of multiple siRNAs using lipid-coated PLGA nanoparticles for treatment of prostate cancer.

PubMed

Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S; Enlow, Elizabeth M; Luft, J Christopher; Tian, Shaomin; Napier, Mary E; Pohlhaus, Patrick D; Rolland, Jason P; DeSimone, Joseph M

2012-01-11

Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called Particle Replication In Nonwetting Templates (PRINT). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32-46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer. © 2011 American Chemical Society

Identification of synergistic impacts during anaerobic co-digestion of organic wastes.

PubMed

Astals, S; Batstone, D J; Mata-Alvarez, J; Jensen, P D

2014-10-01

Anaerobic co-digestion has been widely investigated, but there is limited analysis of interaction between substrates. The objective of this work was to assess the role of carbohydrates, protein and lipids in co-digestion behaviour separately, and together. Two sets of batch tests were done, each set consisting of the mono-digestion of three substrates, and the co-digestion of seven mixtures. The first was done with pure substrates--cellulose, casein and olive oil--while in the second slaughterhouse waste--paunch, blood and fat--were used as carbohydrate, protein and lipid sources, respectively. Synergistic effects were mainly improvement of process kinetics without a significant change in biodegradability. Kinetics improvement was linked to the mitigation of inhibitory compounds, particularly fats dilution. The exception was co-digestion of paunch with lipids, which resulted in an improved final yield with model based analysis indicating the presence of paunch improved degradability of the fatty feed. Copyright © 2014 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.

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.

Effect of Dietary Processed Sulfur Supplementation on Water-holding Capacity, Color, and Lipid Profiles of Pork

PubMed Central

Yang, FengQi; Kim, Ji-Han; Yeon, Su Jung; Hong, Go-Eun; Park, Woojoon; Lee, Chi-Ho

2015-01-01

This study was performed to investigate the effect of dietary processed sulfur supplementation on water-holding capacity, color, and lipid profiles of pork according to the level of dietary processed sulfur (0%, CON; 0.3%, S). The pigs were slaughtered at an average final weight of 120 kg, and the longissimus dorsi muscles were collected from the carcasses. As results, pork processed with sulfur had significantly higher moisture and ash contents compared to those of CON but lower crude fat, pH, expressible drip, lower redness and yellowness, and greater lightness. Pork processed with sulfur showed significantly lower total lipid content, triglycerides, and atherosclerosis index but significantly higher high-density lipoprotein cholesterol. Feeding processed sulfur significantly lowered myristic acid, heptadecanoic acid, and stearic acid contents, whereas monounsaturated fatty acids and oleic acids were significantly higher compared to those in the CON. Higher amounts of polyunsaturated fatty acids and n-6 fatty acids were observed in the pork processed with sulfur than that of the CON. Therefore, supplementing pigs with dietary sulfur improved nutrient and meat quality. PMID:26877643

Biodiesel production by various oleaginous microorganisms from organic wastes.

PubMed

Cho, Hyun Uk; Park, Jong Moon

2018-05-01

Biodiesel is a biodegradable and renewable fuel. A large amount of research has considered microbial oil production using oleaginous microorganisms, but the commercialization of microbial lipids produced in this way remains uncertain due to the high cost of feedstock or low lipid yield. Microbial lipids can be typically produced by microalgae, yeasts, and bacteria; the lipid yields of these microorganisms can be improved by using sufficient concentrations of organic carbon sources. Therefore, combining low-cost organic compounds contained in organic wastes with cultivation of oleaginous microorganisms can be a promising approach to obtain commercial viability. However, to achieve effective bioconversion of low-cost substrates to microbial lipids, the characteristics of each microorganism and each substrate should be considered simultaneously. This article discusses recent approaches to developing cost-effective microbial lipid production processes that use various oleaginous microorganisms and organic wastes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acid-Catalyzed Algal Biomass Pretreatment for Integrated Lipid and Carbohydrate-Based Biofuels Production

DOE PAGES

Laurens, L. M. L.; Nagle, N.; Davis, R.; ...

2014-11-12

One of the major challenges associated with algal biofuels production in a biorefinery-type setting is improving biomass utilization in its entirety, increasing the process energetic yields and providing economically viable and scalable co-product concepts. We demonstrate the effectiveness of a novel, integrated technology based on moderate temperatures and low pH to convert the carbohydrates in wet algal biomass to soluble sugars for fermentation, while making lipids more accessible for downstream extraction and leaving a protein-enriched fraction behind. We studied the effect of harvest timing on the conversion yields, using two algal strains; Chlorella and Scenedesmus, generating biomass with distinctive compositionalmore » ratios of protein, carbohydrate, and lipids. We found that the late harvest Scenedesmus biomass had the maximum theoretical biofuel potential at 143 gasoline gallon equivalent (GGE) combined fuel yield per dry ton biomass, followed by late harvest Chlorella at 128 GGE per ton. Our experimental data show a clear difference between the two strains, as Scenedesmus was more successfully converted in this process with a demonstrated 97 GGE per ton. Our measurements indicated a release of >90% of the available glucose in the hydrolysate liquors and an extraction and recovery of up to 97% of the fatty acids from wet biomass. Techno-economic analysis for the combined product yields indicates that this process exhibits the potential to improve per-gallon fuel costs by up to 33% compared to a lipids-only process for one strain, Scenedesmus, grown to the mid-point harvest condition.« less

Fungal fermentation on anaerobic digestate for lipid-based biofuel production.

PubMed

Zhong, Yuan; Liu, Zhiguo; Isaguirre, Christine; Liu, Yan; Liao, Wei

2016-01-01

Anaerobic digestate is the effluent from anaerobic digestion of organic wastes. It contains a significant amount of nutrients and lignocellulosic materials, even though anaerobic digestion consumed a large portion of organic matters in the wastes. Utilizing the nutrients and lignocellulosic materials in the digestate is critical to significantly improve efficiency of anaerobic digestion technology and generate value-added chemical and fuel products from the organic wastes. Therefore, this study focused on developing an integrated process that uses biogas energy to power fungal fermentation and converts remaining carbon sources, nutrients, and water in the digestate into biofuel precursor-lipid. The process contains two unit operations of anaerobic digestion and digestate utilization. The digestate utilization includes alkali treatment of the mixture feed of solid and liquid digestates, enzymatic hydrolysis for mono-sugar release, overliming detoxification, and fungal fermentation for lipid accumulation. The experimental results conclude that 5 h and 30 °C were the preferred conditions for the overliming detoxification regarding lipid accumulation of the following fungal cultivation. The repeated-batch fungal fermentation enhanced lipid accumulation, which led to a final lipid concentration of 3.16 g/L on the digestate with 10% dry matter. The mass and energy balance analysis further indicates that the digestate had enough water for the process uses and the biogas energy was able to balance the needs of individual unit operations. A fresh-water-free and energy-positive process of lipid production from anaerobic digestate was achieved by integrating anaerobic digestion and fungal fermentation. The integration addresses the issues that both biofuel industry and waste management encounter-high water and energy demand of biofuel precursor production and few digestate utilization approaches of organic waste treatment.

Characterization of the Aroma-Active, Phenolic, and Lipid Profiles of the Pistachio (Pistacia vera L.) Nut as Affected by the Single and Double Roasting Process.

PubMed

Rodríguez-Bencomo, Juan José; Kelebek, Hasim; Sonmezdag, Ahmet Salih; Rodríguez-Alcalá, Luis Miguel; Fontecha, Javier; Selli, Serkan

2015-09-09

The pistachio (Pistacia vera L.) nut is one of the most widely consumed edible nuts in the world. However, it is the roasting process that makes the pistachio commercially viable and valuable as it serves as the key step to improving the nut's hallmark sensory characteristics including flavor, color, and texture. Consequently, the present study explores the effects of the single-roasting and double-roasting process on the pistachio's chemical composition, specifically aroma-active compounds, polyphenols, and lipids. Results showed the total polyphenol content of increased with the roasting treatment; however, not all phenolic compounds demonstrated this behavior. With regard to the aroma and aroma-active compounds, the results indicated that roasting process results in the development of characteristics and pleasant aroma of pistachio samples due to the Maillard reaction. With regard to lipids, the pistachio roasting treatment reduced the concentration of CN38 diacylglycerides while increasing the amount of elaidic acid.

Changes of biomass, lipid content and fatty acids composition under a light-dark cyclic culture of Chlorella pyrenoidosa in response to different temperature.

PubMed

Han, Feifei; Wang, Weiliang; Li, Yuanguang; Shen, Guomin; Wan, Minxi; Wang, Jun

2013-03-01

For outdoor culture with light-dark cycle, the biomass and lipid losing at night resulted in lowering the biomass and lipid productivity. Previous studies focused on the contents of carbohydrate and protein in response to temperature for production of animal feed and nutritional supplements. In this study, the effects of temperature on the variations of biomass concentration, lipid content and fatty acids composition for production of biofuels were investigated under a light-dark cyclic culture. The results showed that 30 °C was the optimal daytime temperature for achieving high biomass and lipid; raising daytime temperature can lessen night biomass loss and stimulate lipid accumulation. Subsequently, outdoor culture strategy has been improved: keeping culture broth no less than 30 °C during the daytime. Consequently, the net biomass and lipid productivity were increased by 37.8% and 44.9% when compared to the former culture process in the same outdoor climatic conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Understanding the mechanisms of lipid extraction from microalga Chlamydomonas reinhardtii after electrical field solicitations and mechanical stress within a microfluidic device.

PubMed

Bensalem, Sakina; Lopes, Filipa; Bodénès, Pierre; Pareau, Dominique; Français, Olivier; Le Pioufle, Bruno

2018-06-01

One way envisioned to overcome part of the issues biodiesel production encounters today is to develop a simple, economically viable and eco-friendly process for the extraction of lipids from microalgae. This study investigates the lipid extraction efficiency from the microalga Chlamydomonas reinhardtii as well as the underlying mechanisms. We propose a new methodology combining a pulsed electric field (PEF) application and mechanical stresses as a pretreatment to improve lipid extraction with solvents. Cells enriched in lipids are therefore submitted to electric field pulses creating pores on the cell membrane and then subjected to a mechanical stress by applying cyclic pressures on the cell wall (using a microfluidic device). Results showed an increase in lipid extraction when cells were pretreated by the combination of both methods. Microscopic observations showed that both pretreatments affect the cell structure. Finally, the dependency of solvent lipid extraction efficiency with the cell wall structure is discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

The physiology of long-distance migration: extending the limits of endurance metabolism.

PubMed

Weber, Jean-Michel

2009-03-01

Long-distance migrants have evolved specific adaptations that make their athletic records possible. Unique mechanisms explaining their amazing capacity for endurance exercise have now been uncovered, particularly with respect to energy storage, mobilization, transport and utilization. Birds are champions of migration because flying offers a key compromise: it allows more rapid movement than swimming, but has a lower cost of transport than running. High efficiency for muscle contraction, pointed wings, low wingloading, travelling in V-formations, storing fuel as energy-dense lipids and atrophy of non-essential organs are some of their strategies to decrease the cost of transport. The ability to process lipids rapidly also emerges as a crucial component of the migrant phenotype. High lipid fluxes are made possible by lipoprotein shuttles and fatty acid binding proteins (FABPs) that accelerate lipid transport and by upgrading the metabolic machinery for lipolysis and lipid oxidation. Preparation for long flights can include natural doping on n-3 polyunsaturated fatty acids (n-3 PUFAs) from unique invertebrate diets. Muscle performance is improved by restructuring membrane phospholipids and by activating key genes of lipid metabolism through peroxisome proliferator-activated receptors (PPARs). The physiological secret to long migrations does not depend on a single ;magic' adaptation but on the integration of multiple adjustments in morphology, biomechanics, behavior, nutrition and metabolism. Research on the physiology of migrants improves the fundamental knowledge of exercise biology, but it also has important implications for wildlife conservation, treating obesity and improving the performance of human athletes.

The effect of a herbal paste and oil extract on the lipid content of canine hair fibres.

PubMed

Momota, Yutaka; Shimada, Kenichiro; Kadoya, Chihiro; Gin, Azusa; Kobayashi, Jun; Nakamura, Yuka; Matsubara, Takako; Sako, Toshinori

2017-08-01

Application of herbal paste and oil to a dog's coat and body before rinsing (often combining with shampooing) is a cosmetic therapy available in Japan. It is highly appreciated by users, who claim that the treatment makes the coat shinier, improves volume and eliminates tangles. However, there has been no scientific evaluation of such treatments. Improvement of hair condition is derived from oils such as sebum and conditioning oils because chemicals are not used. Therefore, we examined nonpolar lipids (the primary lipids in dog hair) and the botanical oils used in this therapy. Hair samples were obtained from six beagle dogs. Groups were based on different combinations of the following processes: rinsing, shampooing, herbal therapy and herbal therapy with oil extract. Analysis of lipids was performed by high performance thin layer chromatography. The processes of shampooing and herbal therapy were associated with an equivalent reduction in cholesterol ester and triglyceride (TG). However, hair treated by herbal therapy combined with oil extract had an almost three-fold higher TG content, even after shampooing. This study demonstrated that the herbal therapy was able to coat hair samples with TG that was not removed with rinsing. Further investigation is required to evaluate the possible benefits of the application of botanical products containing lipids, such as TG, on hair coat quality in dogs. © 2017 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and ACVD.

Identification of regulatory network hubs that control lipid metabolism in Chlamydomonas reinhardtii

DOE PAGES

Gargouri, Mahmoud; Park, Jeong -Jin; Holguin, F. Omar; ...

2015-05-28

Microalgae-based biofuels are promising sources of alternative energy, but improvements throughout the production process are required to establish them as economically feasible. One of the most influential improvements would be a significant increase in lipid yields, which could be achieved by altering the regulation of lipid biosynthesis and accumulation. Chlamydomonas reinhardtii accumulates oil (triacylglycerols, TAG) in response to nitrogen (N) deprivation. Although a few important regulatory genes have been identified that are involved in controlling this process, a global understanding of the larger regulatory network has not been developed. In order to uncover this network in this species, a combinedmore » omics (transcriptomic, proteomic and metabolomic) analysis was applied to cells grown in a time course experiment after a shift from N-replete to N-depleted conditions. Changes in transcript and protein levels of 414 predicted transcription factors (TFs) and transcriptional regulators (TRs) were monitored relative to other genes. The TF and TR genes were thus classified by two separate measures: up-regulated versus down-regulated and early response versus late response relative to two phases of polar lipid synthesis (before and after TAG biosynthesis initiation). Lipidomic and primary metabolite profiling generated compound accumulation levels that were integrated with the transcript dataset and TF profiling to produce a transcriptional regulatory network. In conclusion, evaluation of this proposed regulatory network led to the identification of several regulatory hubs that control many aspects of cellular metabolism, from N assimilation and metabolism, to central metabolism, photosynthesis and lipid metabolism.« less

A sustainable use of Ricotta Cheese Whey for microbial biodiesel production.

PubMed

Carota, Eleonora; Crognale, Silvia; D'Annibale, Alessandro; Gallo, Anna Maria; Stazi, Silvia Rita; Petruccioli, Maurizio

2017-04-15

The increasing demand of plant oils for biodiesel production has highlighted the need for alternative strategies based either on non-food crops or agro-industrial wastes that do not compete with food and feed production. In this context, the combined use of wastewater and oleaginous microorganisms could be a valuable production option. Ricotta cheese whey (RCW), one of the major byproducts of the dairy industry, is produced in very high and steadily increasing amounts and, due to its high organic load, its disposal is cost-prohibitive. In the present study, in order to assess the adequacy of RCW as a growth medium for lipid production, 18 strains of oleaginous yeasts were investigated in shaken flask for their growth and lipid-producing capabilities on this substrate. Among them, Cryptococcus curvatus NRRL Y-1511 and Cryptococcus laurentii UCD 68-201 adequately grew therein producing substantial amounts of lipids (6.8 and 5.1gL -1 , respectively). A high similarity between the percent fatty acid methyl esters (FAME) composition of lipids from the former and the latter strain was found with a predominance of oleic acid (52.8 vs. 48.7%) and of total saturated fatty acids (37.9 vs. 40.8%). The subsequent scale transfer of the C. laurentii UCD 68-201 lipid production process on RCW to a 3-L STR led to significantly improved biomass and total lipid productions (14.4 and 9.9gL -1 , respectively) with the biodiesel yield amounting to 32.6%. Although the C. laurentii FAME profile was modified upon process transfer, it resembled that of the Jatropha oil, a well established feedstock for biodiesel production. In conclusion, C. laurentii UCD 68-201, for which there is very limited amount of available information, turned out to be a very promising candidate for biodiesel production and wide margins of process improvement might be envisaged. Copyright © 2017 Elsevier B.V. All rights reserved.

Quality of care for patients with type 2 diabetes mellitus in the Netherlands and the United States: a comparison of two quality improvement programs.

PubMed

Valk, Gerlof D; Renders, Carry M; Kriegsman, Didi M W; Newton, Katherine M; Twisk, Jos W R; van Eijk, Jacques Th M; van der Wal, Gerrit; Wagner, Edward H

2004-08-01

To assess differences in diabetes care and patient outcomes by comparing two multifaceted quality improvement programs in two different countries, and to increase knowledge of effective elements of such programs. Primary care in the ExtraMural Clinic (EMC) of the Department of General Practice of the Vrije Universiteit in Amsterdam, the Netherlands, and the Group Health Cooperative (GHC), a group-model health maintenance organization (HMO) in western Washington State in the United States. Data were collected from 1992 to 1997. In this observational study two diabetes cohorts in which a quality improvement program was implemented were compared. Both programs included a medical record system, clinical practice guidelines, physician educational meetings, audit, and feedback. Only the Dutch program (EMC) included guidelines on the structure of diabetes care and a recall system. Only the GHC program included educational outreach visits, formation of multidisciplinary teams, and patient self-management support. Included were 379 EMC patients, and 2,119 GHC patients with type 2 diabetes mellitus. Main process outcomes were: annual number of diabetes visits, and number of HbA1c and blood lipid measurements. Main patient outcomes were HbA1c and blood lipid levels. Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices. In the EMC process outcomes and glycemic control improved more than at GHC, however, GHC had better baseline measures. There were no differences between programs on blood lipid control. During follow-up, intensification of pharmacotherapy was noted at both sites. Differences noted between programs were in line with differences in diabetes guidelines. Following implementation of guidelines and organizational improvement efforts, change occurred primarily in the process outcomes, rather than in the patient outcomes. Although much effort was put into improving process and patient outcomes, both complex programs still showed only moderate effects.

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.

Cyclosporine a loaded solid lipid nanoparticles: optimization of formulation, process variable and characterization.

PubMed

Varia, Jigisha K; Dodiya, Shamsunder S; Sawant, Krutika K

2008-01-01

Solid lipid nanoparticles (SLNs) loaded with Cyclosporine A using glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) as lipid matrices were prepared by melt-homogenization using high-pressure homogenizer. Various process parameters such as homogenization pressure, homogenization cycles and formulation parameters such as ratio of drug: lipid, emulsifier: lipid and emulsifier: co-emulsifier were optimized using particle size and entrapment efficiencies as the dependent variables. The mean particle size of optimized batches of the GMS SLN and GPS SLN were found to be 131 nm and 158 nm and their entrapment efficiencies were 83 +/- 3.08% and 97 +/- 2.59% respectively. To improve the handling processing and stability of the prepared SLNs, the SLN dispersions were spray dried and its effect on size and reconstitution parameters were evaluated. The spray drying of SLNs did not significantly alter the size of SLNs and they exhibited good redispersibility. Solid state studies such as Infra Red Spectroscopy and Differential Scanning Calorimetry indicated absence of any chemical interaction between Cyclosporine A and the lipids. Scanning Electron Microscopy of optimized formulations showed spherical shape with smooth and non porous surface. In vitro release studies revealed that GMS based SLNs released the drug faster (41.12% in 20 hours) than GPS SLNs (7.958% in 20 hours). Release of Cyclosporine A from GMS SLN followed Higuchi equation better than first order while release from GPS SLN followed first order better than Higuchi model.

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.

Utility of Adipocyte Fractions in Fat Grafting in an Athymic Rat Model.

PubMed

Akgul, Yucel; Constantine, Ryan; Bartels, Mason; Scherer, Philipp; Davis, Kathryn; Kenkel, Jeffrey M

2018-05-02

Multiple processing and handling methods of autologous fat yields to variations in graft retention and viability, which results in unpredictable clinical outcomes. This study aims to understand the skin effects of fat graft preparations that contain a varying ratio of free-lipid and stem-cell-bearing stromal vascular fractions (SVF). Lipoaspirates from consenting patients were processed into emulsified fat and then SVF and adipocyte fractions (free-lipid). SVF enriched with 0%, 5%, and 15% free-lipid were grafted along the dorsum of athymic rats. The xenografts were collected 45 days after grafting and then prepped for immunostaining. Xenografts resulted in viable tissue mass under the panniculus carnosus of rats as confirmed with human specific markers. A low percentage of human cells was also detected in the lower reticular dermis. Although grafts with SVF formed adipocytes of normal architecture, grafts formed with free-lipid alone resulted in large lipid vacuoles in varying sizes. Among graft preparations, SVF with 10% free-lipid resulted in much-developed adipocyte architecture with collagen and elastin. Compared with SVF alone grafts, SVF with free-lipid had higher CD44 expression, suggesting a localized immune response of adipocytes. Current studies suggest that SVF enriched with approximately 10% free-lipid provides the best conditions for fat graft differentiation into viable fat tissue formation as well as collagen and elastin production to provide mechanical support for overlaying skin in an athymic rat model. Additionally, application of this therapeutic modality in a simple clinical setting may offer a practical way to concentrate SVF with free-lipid in a small volume for the improvement of clinical defects.

Algal Pretreatment Improves Biofuels Yield and Value; Highlights in Science, NREL (National Renewable Energy Laboratory)

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

None

2015-05-15

One of the major challenges associated with algal biofuels production in a biorefinery-type setting is improving biomass utilization in its entirety, increasing the process energetic yields and providing economically viable and scalable co-product concepts. We demonstrate the effectiveness of a novel, integrated technology based on moderate temperatures and low pH to convert the carbohydrates in wet algal biomass to soluble sugars for fermentation, while making lipids more accessible for downstream extraction and leaving a protein-enriched fraction behind. This research has been highlighted in the Green Chemistry journal article mentioned above and a milestone report, and is based on the workmore » the researchers are doing for the AOP projects Algal Biomass Conversion and Algal Biofuels Techno-economic Analysis. That work has demonstrated an advanced process for algal biofuel production that captures the value of both the algal lipids and carbohydrates for conversion to biofuels.  With this process, as much as 150 GGE/ton of biomass can be produced, 2-3X more than can be produced by terrestrial feedstocks.  This can also reduce the cost of biofuel production by as much as 40%. This also represents the first ever design case for the algal lipid upgrading pathway.« less

Improvement of lipid yield from microalgae Spirulina platensis using ultrasound assisted osmotic shock extraction method

NASA Astrophysics Data System (ADS)

Adetya, NP; Hadiyanto, H.

2018-01-01

Microalgae Spirulina sp. has been identified as potential source of natural food supplement and food colorant. The high water content of microalgae (70-90%) causes an obstacle in biomass dehydration which requires large amounts of energy, eventually damaging the lipid in the microalgae. Therefore, the lipid must be extracted by using a suitable method which complies to wet biomass conditions. One of the methods is applying osmotic shock. This study was aimed to investigate the influence of osmotic agent (NaCl) concentration (10-30%) and extraction time (20-50 min) on yield of lipid and also to determine the optimal conditions in the extraction process through response surface methodology. The extraction was conducted at a temperature of 40°C under ultrasound frequency of 40 kHz. The result showed that the optimum yield lipid obtained was 6.39% in 16.98% NaCl concentration for 36 minutes 10 seconds.

Simultaneous cell disruption and lipid extraction of wet aurantiochytrium sp. KRS101 using a high shear mixer.

PubMed

Kwak, Minsoo; Kang, Seul Gi; Hong, Won-Kyung; Han, Jong-In; Chang, Yong Keun

2018-05-01

Microalgae are regarded as a promising source of biofuels, and the concept of a microalgae-based biorefinery has attracted increasing attention in recent years. From an economic perspective, however, the process remains far from competitive with fossil fuels. This is particularly true of lipid extraction, due in part to the energy-intensive drying step. As a result, wet extraction methods have been studied as an economic alternative. In the present study, a novel extraction approach which utilizes high shear stress mixing was adopted and demonstrated for simultaneous lipid extraction and cell disruption to enable the retrieval of lipids directly from concentrated wet biomass. When a high shear mixer (HSM) was used to extract lipid from a dense biomass (> 350 g/L) of the oleaginous algae Aurantiochytrium sp., it exhibited a yield of esterifiable lipids which exceeded 80% in 10 min at 15,000 rpm with various solvent types. The HSM was found to improve the lipid yields substantially with solvents less miscible with either lipids or water, such that the range of Hansen solubility parameters for the usable solvents became 3.3 times wider (14.9-26.5 MPa 1/2 ). The HSM, which appeared effectively to loosen the water barrier that prevents solvent molecules from penetrating through the cell envelope, was found to be more efficient with hexane, hexane/isopropanol, and ethanol, all of which showed nearly identical lipid yields compared to the dry extraction process. The HSM can, indeed, offer a powerful mechanical means of lipid extraction with non-polar and less toxic solvents from wet biomass.

[Abnormal metabolism of triglycerides fractions in chronic pancreatitis and results after the operation treatment].

PubMed

Diakowska, Dorota; Knast, Witold; Diakowski, Witold; Grabowski, Krzysztof; Szelachowski, Piotr; Pelczar, Piotr

2005-06-01

This study was undertaken to determine how fats digestion processes were damaged due to chronic pancreatitis, and identify, whether lipid metabolism improved after surgical treatment the patients with chronic pancreatitis. Total lipids, triglycerides, diglycerides and free fatty acids levels in serum and stool were analysed, using chemical tests, thin-layer chromatography and electrophoresis of serum lipoproteins. The patients before the operations showed higher total lipids and triglycerides concentrations, and lower concentrations of diglycerides and free fatty acids in stool. These patients had high triglycerides, chylomicrons, VLDL, LDL-CH concentrations, and low-diglycerides, free fatty acids, HDL-CH concentrations in serum. These data were statistically significant. After the operations and substitution therapy it was observed normalization of the total lipids and lipids fractions levels in stool and in serum. Concentrations of LDL-CH and HDL-CH fractions were irregular. We conclude, that these lipids parameters could be used in diagnosing and monitoring the results of chronic pancreatitis surgical treatment.

Comprehensive metabolomic, lipidomic and microscopic profiling of Yarrowia lipolytica during lipid accumulation identifies targets for increased lipogenesis

DOE PAGES

Pomraning, Kyle R.; Wei, Siwei; Karagiosis, Sue A.; ...

2015-04-23

Yarrowia lipolytica is an oleaginous ascomycete yeast that accumulates large amounts of lipids and has potential as a biofuel producing organism. Despite a growing scientific literature focused on lipid production by Y. lipolytica, there remain significant knowledge gaps regarding the key biological processes involved. We applied a combination of metabolomic and lipidomic profiling approaches as well as microscopic techniques to identify and characterize the key pathways involved in de novo lipid accumulation from glucose in batch cultured, wild-type Y. lipolytica. We found that lipids accumulated rapidly and peaked at 48 hours during the five day experiment, concurrent with a shiftmore » in amino acid metabolism. We also report that Y. lipolytica secretes disaccharides early in batch culture and reabsorbs them when extracellular glucose is depleted. Exhaustion of extracellular sugars coincided with thickening of the cell wall, suggesting that genes involved in cell wall biogenesis may be a useful target for improving the efficiency of lipid producing yeast strains.« less

Progress on lipid extraction from wet algal biomass for biodiesel production.

PubMed

Ghasemi Naghdi, Forough; González González, Lina M; Chan, William; Schenk, Peer M

2016-11-01

Lipid recovery and purification from microalgal cells continues to be a significant bottleneck in biodiesel production due to high costs involved and a high energy demand. Therefore, there is a considerable necessity to develop an extraction method which meets the essential requirements of being safe, cost-effective, robust, efficient, selective, environmentally friendly, feasible for large-scale production and free of product contamination. The use of wet concentrated algal biomass as a feedstock for oil extraction is especially desirable as it would avoid the requirement for further concentration and/or drying. This would save considerable costs and circumvent at least two lengthy processes during algae-based oil production. This article provides an overview on recent progress that has been made on the extraction of lipids from wet algal biomass. The biggest contributing factors appear to be the composition of algal cell walls, pre-treatments of biomass and the use of solvents (e.g. a solvent mixture or solvent-free lipid extraction). We compare recently developed wet extraction processes for oleaginous microalgae and make recommendations towards future research to improve lipid extraction from wet algal biomass. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Enhancement in lipid content of Chlorella sp. MJ 11/11 from the spent medium of thermophilic biohydrogen production process.

PubMed

Ghosh, Supratim; Roy, Shantonu; Das, Debabrata

2017-01-01

The present study investigates the effect of spent media of acetogenic dark fermentation for mixotrophic algal cultivation for biodiesel production. Mixotrophic growth conditions were optimized in culture flask (250mL) using Chlorella sp. MJ 11/11. Maximum lipid accumulation (58% w/w) was observed under light intensity, pH, nitrate and phosphate concentration of 100μmolm -2 s -1 , 7, 2.7mM and 1.8mM, respectively. Air lift (1.4L) and flat panel (1.4L) reactors were considered for algal cultivation. Air lift showed significant improvement in biomass and lipid production as compared to flat panel reactor. The results could help in development of sustainable technology involving acetogenic hydrogen production integrated with sequential mitigation of spent media by algal cultivation for improved energy recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improvement in lipids extraction processes for biodiesel production from wet microalgal pellets grown on diammonium phosphate and sodium bicarbonate combinations.

PubMed

Shah, Syed Hasnain; Raja, Iftikhar Ahmed; Mahmood, Qaisar; Pervez, Arshid

2016-08-01

Biomass productivity and growth kinetics for microalgae grown on sodium bicarbonate and diammonium phosphate were investigated. Different carbon and nitrogen ratios have shown different growth rates and biomass productivity and C:N ratio 50:10 as mgL(-1) has shown the best production than all. For effective lipids extraction from biomass thermolysis and sonolysis were carried out from wet biomass. Sonolysis at 2.3W intensity for 5min has released 8.58mg at neutral pH. More quantity of lipids was extracted when extraction was made at pH 4 and 10 which resulted 9mg and 9.28mg lipids respectively. Thermal treatment at 100°C for 10min has released 12.82mg lipid at neutral pH. In the same thermolysis at pH 4 and 10 more quantity of lipids was extracted which were 15.16mg and 14.81mg respectively. Finally transesterified lipids were analyzed through GC-MS for FAME composition analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Charge-reversal Lipids, Peptide-based Lipids, and Nucleoside-based Lipids for Gene Delivery

PubMed Central

LaManna, Caroline M.; Lusic, Hrvoje; Camplo, Michel; McIntosh, Thomas J.; Barthélémy, Philippe; Grinstaff, Mark W.

2013-01-01

Conspectus Twenty years after gene therapy was introduced in the clinic, advances in the technique continue to garner headlines as successes pique the interest of clinicians, researchers, and the public. Gene therapy’s appeal stems from its potential to revolutionize modern medical therapeutics by offering solutions to a myriad of diseases by tailoring the treatment to a specific individual’s genetic code. Both viral and non-viral vectors have been used in the clinic, but the low transfection efficiencies when utilizing non-viral vectors have lead to an increased focus on engineering new gene delivery vectors. To address the challenges facing non-viral or synthetic vectors, specifically lipid-based carriers, we have focused on three main themes throughout our research: 1) that releasing the nucleic acid from the carrier will increase gene transfection; 2) that utilizing biologically inspired designs, such as DNA binding proteins, to create lipids with peptide-based headgroups will improve delivery; and 3) that mimicking the natural binding patterns observed within DNA, by using lipids having a nucleoside headgroup, will give unique supramolecular assembles with high transfection efficiency. The results presented in this Account demonstrate that cellular uptake and transfection efficacy can be improved by engineering the chemical components of the lipid vectors to enhance nucleic acid binding and release kinetics. Specifically, our research has shown that the incorporation of a charge-reversal moiety to initiate change of the lipid from positive to negative net charge during the transfection process improves transfection. In addition, by varying the composition of the spacer (rigid, flexible, short, long, and aromatic) between the cationic headgroup and the hydrophobic chains, lipids can be tailored to interact with different nucleic acids (DNA, RNA, siRNA) and accordingly affect delivery, uptake outcomes, and transfection efficiency. Introduction of a peptide headgroup into the lipid provides a mechanism to affect the binding of the lipid to the nucleic acid, to influence the supramolecular lipoplex structure, and to enhance gene transfection activity. Lastly, we discuss the in-vitro successes we have had when using lipids possessing a nucleoside headgroup to create unique self-assembled structures and to deliver DNA to cells. In this Account, we state our hypotheses and design elements as well as describe the techniques that we have utilized in our research, in order to provide readers with the tools to characterize and engineer new vectors. PMID:22439686

Algal Lipids and Omega-3 Production via Autotrophic and Heterotrophic Pathways at Cellana?s Kona Demonstration Facility, Hawaii

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

Bai, Xuemei; Knurek, Emily; Goes, Nikki

2012-05-05

Cellana?s Kona Demonstration Facility (KDF) is a 2.5 hectare facility, with 17,000 sq. ft. under roof and 1 hectare of cultivation systems. KDF is designed to execute and support all stages of the production process at pilot scale, from cultivation through extraction. Since Feb. 2009, KDF has been producing up to 0.7MT dry weight of algal biomass per month, while at the same time optimizing processes of cultivation, harvesting, dewatering and extraction. The cultivation system at KDF uses ALDUO? technology, a hybrid system of photobioreactors (PBRs) and open ponds. All fluid transfers related to KDF cultivation and harvesting processes aremore » operated and monitored by a remote Process-Control System. Fluid transfer data, together with biochemical data, enable the mass balance calculations necessary to measure productivity. This poster summarizes methods to improve both biomass and lipids yield by 1) alleviating light limitation in open ponds, 2) de-oxygenation and 3) heterotrophic lipid production for post-harvesting cultures.« less

Interfacial & colloidal aspects of lipid digestion.

PubMed

Wilde, P J; Chu, B S

2011-06-09

Amongst the main issues challenging the food manufacturing sector, health and nutrition are becoming increasingly important. Global concerns such as obesity, the ageing population and food security will have to be addressed. Food security is not just about assuring food supply, but is also about optimising nutritional delivery from the food that is available [1]. Therefore one challenge is to optimise the health benefits from the lipids and lipid soluble nutrients. Colloid scientists have an affinity for lipids because they are water insoluble, however this presents a challenge to the digestive system, which has to convert them to structures that are less insoluble so they are available for uptake. Despite this, the human digestive system is remarkably effective at digesting and absorbing most lipids. This is primarily driven through maximising energy intake, as lipids possess the highest calorific value, which was a survival trait to survive times of famine, but is now an underlying cause of obesity in developed countries with high food availability. The critical region here is the lipid-water interface, where the key reactions take place to solubilise lipids and lipid soluble nutrients. Digestive lipases have to adsorb to the oil water interface in order to hydrolyse triacylglycerols into fatty acids and mono glycerides, which accumulate at the interface [2], and inhibit lipase activity. Pancreatic lipase, which is responsible for the majority of lipid hydrolysis, also requires the action of bile salts and colipase to function effectively. Bile salts both aid the adsorption of co-lipase and lipase, and help solubilise the lipolysis products which have accumulated at the interface, into mixed micelles composing bile salts and a range of other lipids, to facilitate transport to the gut mucosal surface prior to uptake and absorption. The process can be affected by the lipid type, as shorter chain, fatty acids are more easily absorbed, whereas the uptake of longer chain fatty acids, particularly the very long chain n-3 fatty acids from fish oils are dependent on source and so may depend on food microstructure for optimal uptake [3]. The uptake of some poorly water soluble nutrients are enhanced by the presence of lipids, but the mechanisms are not clear. In addition, controlling the digestion of lipids can be beneficial as slower release of lipids into the bloodstream can reduce risk of cardiovascular disease, and can promote gut feedback processes that reduce appetite. This presents an opportunity to colloid and interfacial science, as there are many unanswered questions regarding the specific physicochemical mechanisms underlying the process of lipid digestion and uptake. I will review our current knowledge of lipid digestion and present examples of how fundamental research in colloidal and interface science is beginning to address these issues. These include the adsorption behaviour of physiological surfactants such as bile salts; interfacial processes by which different polar lipids can influence lipolysis; and the effect of emulsion based delivery systems on cellular uptake of lipid soluble nutrients. A fundamental understanding of these processes is required if we are to develop intelligent design strategies for foods that will deliver optimal nutrition and improved health benefits in order to address the global challenges facing the food sector in the future. Copyright © 2011 Elsevier B.V. All rights reserved.

Modulating interactions between ligand-coated nanoparticles and phase-separated lipid bilayers by varying the ligand density and the surface charge.

PubMed

Chen, Xiaojie; Tieleman, D Peter; Liang, Qing

2018-02-01

The interactions between nanoparticles and lipid bilayers are critical in applications of nanoparticles in nanomedicine, cell imaging, toxicology, and elsewhere. Here, we investigate the interactions between nanoparticles coated with neutral and/or charged ligands and phase-separated lipid bilayers using coarse-grained molecular dynamics simulation. Both penetration and adsorption processes as well as the final distribution of the nanoparticles can be readily modulated by varying the ligand density and the surface charge of the nanoparticles. Completely hydrophobic (neutral) nanoparticles with larger size initially preferentially penetrate into the liquid-disordered region of the lipid bilayer and finally transfer into the liquid-ordered region; partially hydrophilic nanoparticles with low or moderate surface charge tend to either distribute in the liquid-disordered region or be adsorbed on the surface of the lipid bilayer, while strongly hydrophilic nanoparticles with high surface charge always reside on the surface of the lipid bilayer. Interactions of the nanoparticles with the lipid bilayers are affected by the surface charge of nanoparticles, hydrophobic mismatch, bending of the ligands, and the packing state of the lipids. Insight in these factors can be used to improve the efficiency of designing nanoparticles for specific applications.

Oleaginous yeasts: Promising platforms for the production of oleochemicals and biofuels.

PubMed

Adrio, José L

2017-09-01

Oleaginous yeasts have a unique physiology that makes them the best suited hosts for the production of lipids, oleochemicals, and diesel-like fuels. Their high lipogenesis, capability of growing on many different carbon sources (including lignocellulosic sugars), easy large-scale cultivation, and an increasing number of genetic tools are some of the advantages that have encouraged their use to develop sustainable processes. This mini-review summarizes the metabolic engineering strategies developed in oleaginous yeasts within the last 2 years to improve process metrics (titer, yield, and productivity) for the production of lipids, free fatty acids, fatty acid-based chemicals (e.g., fatty alcohols, fatty acid ethyl esters), and alkanes. During this short period of time, tremendous progress has been made in Yarrowia lipolytica, the model oleaginous yeast, which has been engineered to improve lipid production by different strategies including increasing lipogenic pathway flux and biosynthetic precursors, and blocking degradation pathways. Moreover, remarkable advances have also been reported in Rhodosporidium toruloides and Lipomyces starkey despite the limited genetic tools available for these two very promising hosts. Biotechnol. Bioeng. 2017;114: 1915-1920. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Stress and dietary factors modify boar sperm for processing.

PubMed

Radomil, L; Pettitt, M J; Merkies, K M; Hickey, K D; Buhr, M M

2011-09-01

This paper reviews stresses boar sperm undergo during processing and presents preliminary results of dietary modification that minimize this damage. Processing for artificial insemination (AI) stresses boar sperm by osmotic effects; altering cell size, shape and membranes; intracellular ice formation; and production of reactive oxygen species (ROS). Sperm response to ROS is concentration-dependent, with low levels activating the ERK pathway to stimulate tyrosine phosphorylation (Tyr-P) and capacitation, but high concentrations or inappropriately timed onset of ROS pathways can harm sperm. Fresh boar sperm exposed to ROS increased intracellular hydrogen peroxide (H(2) O(2) ) phospholipase and lipid peroxidation, maintained viability but lost motility and underwent acrosome reactions (AR). Direct incorporation of lipids ± the antioxidant Vitamin E improves the survival of liquid- and frozen-stored semen. Boars fed dietary flaxseed for 8 weeks to increase n-3 fatty acids displayed improved sperm morphology (p < 0.05), increased membrane fluidity (p < 0.05) and better retention of motility and viability during 5-7 day storage (p < 0.05). Processes reducing oxidative damage to stored sperm should be evaluated. © 2011 Blackwell Verlag GmbH.

CHARMM-GUI Membrane Builder toward realistic biological membrane simulations.

PubMed

Wu, Emilia L; Cheng, Xi; Jo, Sunhwan; Rui, Huan; Song, Kevin C; Dávila-Contreras, Eder M; Qi, Yifei; Lee, Jumin; Monje-Galvan, Viviana; Venable, Richard M; Klauda, Jeffery B; Im, Wonpil

2014-10-15

CHARMM-GUI Membrane Builder, http://www.charmm-gui.org/input/membrane, is a web-based user interface designed to interactively build all-atom protein/membrane or membrane-only systems for molecular dynamics simulations through an automated optimized process. In this work, we describe the new features and major improvements in Membrane Builder that allow users to robustly build realistic biological membrane systems, including (1) addition of new lipid types, such as phosphoinositides, cardiolipin (CL), sphingolipids, bacterial lipids, and ergosterol, yielding more than 180 lipid types, (2) enhanced building procedure for lipid packing around protein, (3) reliable algorithm to detect lipid tail penetration to ring structures and protein surface, (4) distance-based algorithm for faster initial ion displacement, (5) CHARMM inputs for P21 image transformation, and (6) NAMD equilibration and production inputs. The robustness of these new features is illustrated by building and simulating a membrane model of the polar and septal regions of E. coli membrane, which contains five lipid types: CL lipids with two types of acyl chains and phosphatidylethanolamine lipids with three types of acyl chains. It is our hope that CHARMM-GUI Membrane Builder becomes a useful tool for simulation studies to better understand the structure and dynamics of proteins and lipids in realistic biological membrane environments. Copyright © 2014 Wiley Periodicals, Inc.

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.

The antihyperlipidemic activities of enzymatic and acidic intracellular polysaccharides by Termitomyces albuminosus.

PubMed

Zhao, Huajie; Li, Shangshang; Zhang, Jianjun; Che, Gen; Zhou, Meng; Liu, Min; Zhang, Chen; Xu, Nuo; Lin, Lin; Liu, Yu; Jia, Le

2016-10-20

Two polysaccharides, EIPS and AIPS were obtained by the hydrolysis of IPS from Termitomyces albuminosus, and their pharmacological effects on blood lipid profiles metabolism and oxidative stress were investigated. The results demonstrated that EIPS was superior to IPS and AIPS on reducing hepatic lipid levels and preventing oxidative stress by improving serum enzyme activities (ALT, AST, and ALP), serum lipid levels (TC, TG, HDL-C, LDL-C and VLDL-C), hepatic lipid levels (TC and TG), and antioxidant status (SOD, GSH-Px, CAT, T-AOC, MDA, and LPO). These conclusions indicated that EIPS, AIPS and IPS might be suitable for functional foods and natural drugs on preventing the high-fat emulsion-induced hyperlipidemia. In addition, the monosaccharide compositions of IPS and its hydrolyzate were also processed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quality of Care for Patients with Type 2 Diabetes Mellitus in the Netherlands and the United States: A Comparison of Two Quality Improvement Programs

PubMed Central

Valk, Gerlof D; Renders, Carry M; Kriegsman, Didi MW; Newton, Katherine M; Twisk, Jos WR; van Eijk, Jacques ThM; van der Wal, Gerrit; Wagner, Edward H

2004-01-01

Objective To assess differences in diabetes care and patient outcomes by comparing two multifaceted quality improvement programs in two different countries, and to increase knowledge of effective elements of such programs. Study Setting Primary care in the ExtraMural Clinic (EMC) of the Department of General Practice of the Vrije Universiteit in Amsterdam, the Netherlands, and the Group Health Cooperative (GHC), a group-model health maintenance organization (HMO) in western Washington State in the United States. Data were collected from 1992 to 1997. Study Design In this observational study two diabetes cohorts in which a quality improvement program was implemented were compared. Both programs included a medical record system, clinical practice guidelines, physician educational meetings, audit, and feedback. Only the Dutch program (EMC) included guidelines on the structure of diabetes care and a recall system. Only the GHC program included educational outreach visits, formation of multidisciplinary teams, and patient self-management support. Data Collection Included were 379 EMC patients, and 2,119 GHC patients with type 2 diabetes mellitus. Main process outcomes were: annual number of diabetes visits, and number of HbA1c and blood lipid measurements. Main patient outcomes were HbA1c and blood lipid levels. Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices. Principal Findings In the EMC process outcomes and glycemic control improved more than at GHC, however, GHC had better baseline measures. There were no differences between programs on blood lipid control. During follow-up, intensification of pharmacotherapy was noted at both sites. Differences noted between programs were in line with differences in diabetes guidelines. Conclusions Following implementation of guidelines and organizational improvement efforts, change occurred primarily in the process outcomes, rather than in the patient outcomes. Although much effort was put into improving process and patient outcomes, both complex programs still showed only moderate effects. PMID:15230924

LipidFrag: Improving reliability of in silico fragmentation of lipids and application to the Caenorhabditis elegans lipidome

PubMed Central

Neumann, Steffen; Schmitt-Kopplin, Philippe

2017-01-01

Lipid identification is a major bottleneck in high-throughput lipidomics studies. However, tools for the analysis of lipid tandem MS spectra are rather limited. While the comparison against spectra in reference libraries is one of the preferred methods, these libraries are far from being complete. In order to improve identification rates, the in silico fragmentation tool MetFrag was combined with Lipid Maps and lipid-class specific classifiers which calculate probabilities for lipid class assignments. The resulting LipidFrag workflow was trained and evaluated on different commercially available lipid standard materials, measured with data dependent UPLC-Q-ToF-MS/MS acquisition. The automatic analysis was compared against manual MS/MS spectra interpretation. With the lipid class specific models, identification of the true positives was improved especially for cases where candidate lipids from different lipid classes had similar MetFrag scores by removing up to 56% of false positive results. This LipidFrag approach was then applied to MS/MS spectra of lipid extracts of the nematode Caenorhabditis elegans. Fragments explained by LipidFrag match known fragmentation pathways, e.g., neutral losses of lipid headgroups and fatty acid side chain fragments. Based on prediction models trained on standard lipid materials, high probabilities for correct annotations were achieved, which makes LipidFrag a good choice for automated lipid data analysis and reliability testing of lipid identifications. PMID:28278196

Self-Assembled Core-Shell-Type Lipid-Polymer Hybrid Nanoparticles: Intracellular Trafficking and Relevance for Oral Absorption.

PubMed

Li, Qiuxia; Xia, Dengning; Tao, Jinsong; Shen, Aijun; He, Yuan; Gan, Yong; Wang, Chi

2017-10-01

Lipid-polymer hybrid nanoparticles (NPs) are advantageous for drug delivery. However, their intracellular trafficking mechanism and relevance for oral drug absorption are poorly understood. In this study, self-assembled core-shell lipid-polymer hybrid NPs made of poly(lactic-co-glycolic acid) (PLGA) and various lipids were developed to study their differing intracellular trafficking in intestinal epithelial cells and their relevance for oral absorption of a model drug saquinavir (SQV). Our results demonstrated that the endocytosis and exocytosis of hybrid NPs could be changed by varying the kind of lipid. A glyceride mixture (hybrid NPs-1) decreased endocytosis but increased exocytosis in Caco-2 cells, whereas the phospholipid (E200) (hybrid NPs-2) decreased endocytosis but exocytosis was unaffected as compared with PLGA nanoparticles. The transport of hybrid NPs-1 in cells involved various pathways, including caveolae/lipid raft-dependent endocytosis, and clathrin-mediated endocytosis and macropinocytosis, which was different from the other groups of NPs that involved only caveolae/lipid raft-dependent endocytosis. Compared with that of the reference formulation (nanoemulsion), the oral absorption of SQV-loaded hybrid NPs in rats was poor, probably due to the limited drug release and transcytosis of NPs across the intestinal epithelium. In conclusion, the intracellular processing of hybrid NPs in intestinal epithelia can be altered by adding lipids to the NP. However, it appears unfavorable to use PLGA-based NPs to improve oral absorption of SQV compared with nanoemulsion. Our findings will be essential in the development of polymer-based NPs for the oral delivery of drugs with the purpose of improving their oral absorption. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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.

Recovery of Fuel-Precursor Lipids from Oleaginous Yeast

DOE PAGES

Kruger, Jacob S.; Cleveland, Nicholas S.; Yeap, Rou Yi; ...

2018-01-24

Bio-derived lipids offer a potentially promising intermediate to displace petroleum-derived diesel. One of the key challenges for the production of lipids via microbial cell mass is that these products are stored intracellularly and must be extracted and recovered efficiently and economically. Thus, improved methods of cell lysis and lipid extraction are needed. In this study, we examine lipid extraction from wet oleaginous yeast in combination with seven different cell lysis approaches encompassing both physical and chemical techniques (high-pressure homogenization, microwave and conventional thermal treatments, bead beating, acid, base, and enzymatic treatments) to facilitate lipid extraction from a model oleaginous yeastmore » strain, Lipomyces starkeyi. Of the seven techniques investigated, acid treatment led to the highest lipid recovery yields. Further exploration of acid treatment and integration with an economic model revealed that treatment at 170 degrees C for 60 min at 1 wt% H 2SO 4 and 8 wt% yeast solids represents a viable option for both lipid recovery yield and process economics, enabling experimental lipid recovery yields of 88.5-93.0% to be achieved at a corresponding estimated minimum fuel selling price (MFSP) of $5.13-$5.61/gallon of gasoline equivalent (GGE). The same acid treatment conditions applied to two other strains of oleaginous yeast (Cutaneotrichosporon curvatus and Rhodotorula toruloides) resulted in similar lipid recovery yields. In pretreatment experiments scaled up to 300 mL, slightly lower temperatures or shorter pretreatment times, along with higher yeast solids loading, resulted in higher lipid yields than the conditions identified from the small-scale runs. Two replicate runs carried out at 170 degrees C for 30 min using 1 wt% H2SO4 and 19 wt% yeast solids achieved an average lipid recovery of 96.1% at a corresponding estimated MFSP of $4.89/GGE. In all cases, the lipids are primarily triglycerides and free fatty acids comprised mainly of palmitic, stearic, and oleic acids, with smaller fractions of polar lipids. The fatty acid composition of the lipids extracted from the wet treated cell mass is the same as that in freeze-dried whole oleaginous yeast cell mass, suggesting the acid treatment renders all lipids extractable. This work demonstrates that acid treatment is a robust and effective cell lysis technique in a microbial lipid-based biofuel scenario and provides a baseline for further scale-up and process integration.« less

Recovery of Fuel-Precursor Lipids from Oleaginous Yeast

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

Kruger, Jacob S.; Cleveland, Nicholas S.; Yeap, Rou Yi

Bio-derived lipids offer a potentially promising intermediate to displace petroleum-derived diesel. One of the key challenges for the production of lipids via microbial cell mass is that these products are stored intracellularly and must be extracted and recovered efficiently and economically. Thus, improved methods of cell lysis and lipid extraction are needed. In this study, we examine lipid extraction from wet oleaginous yeast in combination with seven different cell lysis approaches encompassing both physical and chemical techniques (high-pressure homogenization, microwave and conventional thermal treatments, bead beating, acid, base, and enzymatic treatments) to facilitate lipid extraction from a model oleaginous yeastmore » strain, Lipomyces starkeyi. Of the seven techniques investigated, acid treatment led to the highest lipid recovery yields. Further exploration of acid treatment and integration with an economic model revealed that treatment at 170 degrees C for 60 min at 1 wt% H 2SO 4 and 8 wt% yeast solids represents a viable option for both lipid recovery yield and process economics, enabling experimental lipid recovery yields of 88.5-93.0% to be achieved at a corresponding estimated minimum fuel selling price (MFSP) of $5.13-$5.61/gallon of gasoline equivalent (GGE). The same acid treatment conditions applied to two other strains of oleaginous yeast (Cutaneotrichosporon curvatus and Rhodotorula toruloides) resulted in similar lipid recovery yields. In pretreatment experiments scaled up to 300 mL, slightly lower temperatures or shorter pretreatment times, along with higher yeast solids loading, resulted in higher lipid yields than the conditions identified from the small-scale runs. Two replicate runs carried out at 170 degrees C for 30 min using 1 wt% H2SO4 and 19 wt% yeast solids achieved an average lipid recovery of 96.1% at a corresponding estimated MFSP of $4.89/GGE. In all cases, the lipids are primarily triglycerides and free fatty acids comprised mainly of palmitic, stearic, and oleic acids, with smaller fractions of polar lipids. The fatty acid composition of the lipids extracted from the wet treated cell mass is the same as that in freeze-dried whole oleaginous yeast cell mass, suggesting the acid treatment renders all lipids extractable. This work demonstrates that acid treatment is a robust and effective cell lysis technique in a microbial lipid-based biofuel scenario and provides a baseline for further scale-up and process integration.« less

Supercritical fluid precipitation of ketoprofen in novel structured lipid carriers for enhanced mucosal delivery--a comparison with solid lipid particles.

PubMed

Gonçalves, V S S; Matias, A A; Rodríguez-Rojo, S; Nogueira, I D; Duarte, C M M

2015-11-10

Structured lipid carriers based on mixture of solid lipids with liquid lipids are the second generation of solid lipid particles, offering the advantage of improved drug loading capacity and higher storage stability. In this study, structured lipid carriers were successfully prepared for the first time by precipitation from gas saturated solutions. Glyceryl monooleate (GMO), a liquid glycerolipid, was selected in this work to be incorporated into three solid glycerolipids with hydrophilic-lipophilic balance (HLB) ranging from 1 to 13, namely Gelucire 43/01™, Geleol™ and Gelucire 50/13™. In general, microparticles with a irregular porous morphology and a wide particle size distribution were obtained. The HLB of the individual glycerolipids might be a relevant parameter to take into account during the processing of solid:liquid lipid blends. As expected, the addition of a liquid lipid into a solid lipid matrix led to increased stability of the lipid carriers, with no significant modifications in their melting enthalpy after 6 months of storage. Additionally, Gelucire 43/01™:GMO particles were produced with different mass ratios and loaded with ketoprofen. The drug loading capacity of the structured lipid carriers increased as the GMO content in the particles increased, achieving a maximum encapsulation efficiency of 97% for the 3:1 mass ratio. Moreover, structured lipid carriers presented an immediate release of ketoprofen from its matrix with higher permeation through a mucous-membrane model, while solid lipid particles present a controlled release of the drug with less permeation capacity. Copyright © 2015. Published by Elsevier B.V.

Salt stress induced lipid accumulation in heterotrophic culture cells of Chlorella protothecoides: Mechanisms based on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration.

PubMed

Wang, Tao; Ge, Haiyan; Liu, Tingting; Tian, Xiwei; Wang, Zejian; Guo, Meijin; Chu, Ju; Zhuang, Yingping

2016-06-20

Salt stress as an effective stress factor that could improve the lipid content and lipid yield of glucose in the heterotrophic culture cells of Chlorella protothecoides was demonstrated in this study. The highest lipid content of 41.2% and lipid yield of 185.8mg/g were obtained when C. protothecoides was stressed under 30g/L NaCl condition at its late logarithmic growth phase. Moreover, the effects of salt and osmotic stress on lipid accumulation were comparatively analyzed, and it was found that the effects of NaCl and KCl stress had no significant differences at the same osmolarity level of 1150mOsm/kg with lipid contents of 41.7 and 40.8% as well as lipid yields of 192.9 and 186.8mg/g, respectively, whereas these results were obviously higher than those obtained under the iso-osmotic glycerol and sorbitol stresses. Furthermore, basing on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration, the superior performance of salt stress driving lipid over-synthesis was probably ascribed to the more ROS production as a result of additional ion effect besides the osmotic effect, subsequently mediating the alteration from carbohydrate storage to lipid accumulation in signal transduction process of C. protothecoides. Copyright © 2016. Published by Elsevier B.V.

Combining micro-structures and micro-algae to increase lipid production for bio-fuel

NASA Astrophysics Data System (ADS)

Vyawahare, Saurabh; Zhu, Emilly; Mestler, Troy; Estévez-Torres, André.; Austin, Robert

2011-03-01

3rd generation bio-fuels like lipid producing micro-algae are a promising source of energy that could replace our dependence on petroleum. However, until there are improvements in algae oil yields, and a reduction in the energy needed for processing, algae bio-fuels are not economically competitive with petroleum. Here, we describe our work combining micro-fabricated devices with micro-algae Neochloris oleoabundans, a species first isolated on the sand dunes of Saudi Arabia. Inserting micro-algae of varying fitness into a landscape of micro-habitats allows us to evolve and select them based on a variety of conditions like specific gravity, starvation response and Nile Red fluorescence (which is a marker for lipid production). Hence, we can both estimate the production of lipids and generate conditions that allow the creation and isolation of algae which produce higher amounts of lipids, while discarding the rest. Finally, we can use micro-fabricated structures and flocculation to de-water these high lipid producing algae, reducing the need for expensive centrifugation and filtration.

Optimized Rapeseed Oils Rich in Endogenous Micronutrients Protect High Fat Diet Fed Rats from Hepatic Lipid Accumulation and Oxidative Stress

PubMed Central

Xu, Jiqu; Liu, Xiaoli; Gao, Hui; Chen, Chang; Deng, Qianchun; Huang, Qingde; Ma, Zhonghua; Huang, Fenghong

2015-01-01

Micronutrients in rapeseed exert a potential benefit to hepatoprotection, but most of them are lost during the conventional refining processing. Thus some processing technologies have been optimized to improve micronutrient retention in oil. The aim of this study is to assess whether optimized rapeseed oils (OROs) have positive effects on hepatic lipid accumulation and oxidative stress induced by a high-fat diet. Methods: Rats received experiment diets containing 20% fat and refined rapeseed oil or OROs obtained with various processing technologies as lipid source. After 10 weeks of treatment, liver was assayed for lipid accumulation and oxidative stress. Results: All OROs reduced hepatic triglyceride contents. Microwave pretreatment-cold pressing oil (MPCPO) which had the highest micronutrients contents also reduced hepatic cholesterol level. MPCPO significantly decreased hepatic sterol regulatory element-binding transcription factor 1 (SREBP1) but increased peroxisome proliferator activated receptor α (PPARα) expressions, and as a result, MPCPO significantly suppressed acetyl CoA carboxylase and induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. Hepatic catalase (CAT) and glutathione peroxidase (GPx) activities as well as reduced glutathione (GSH) contents remarkably increased and lipid peroxidation levels decreased in parallel with the increase of micronutrients. Conclusion: OROs had the ability to reduce excessive hepatic fat accumulation and oxidative stress, which indicated that OROs might contribute to ameliorating nonalcoholic fatty liver induced by high-fat diet. PMID:26473919

Microalgal lipids biochemistry and biotechnological perspectives.

PubMed

Bellou, Stamatia; Baeshen, Mohammed N; Elazzazy, Ahmed M; Aggeli, Dimitra; Sayegh, Fotoon; Aggelis, George

2014-12-01

In the last few years, there has been an intense interest in using microalgal lipids in food, chemical and pharmaceutical industries and cosmetology, while a noteworthy research has been performed focusing on all aspects of microalgal lipid production. This includes basic research on the pathways of solar energy conversion and on lipid biosynthesis and catabolism, and applied research dealing with the various biological and technical bottlenecks of the lipid production process. In here, we review the current knowledge in microalgal lipids with respect to their metabolism and various biotechnological applications, and we discuss potential future perspectives. The committing step in fatty acid biosynthesis is the carboxylation of acetyl-CoA to form malonyl-CoA that is then introduced in the fatty acid synthesis cycle leading to the formation of palmitic and stearic acids. Oleic acid may also be synthesized after stearic acid desaturation while further conversions of the fatty acids (i.e. desaturations, elongations) occur after their esterification with structural lipids of both plastids and the endoplasmic reticulum. The aliphatic chains are also used as building blocks for structuring storage acylglycerols via the Kennedy pathway. Current research, aiming to enhance lipogenesis in the microalgal cell, is focusing on over-expressing key-enzymes involved in the earlier steps of the pathway of fatty acid synthesis. A complementary plan would be the repression of lipid catabolism by down-regulating acylglycerol hydrolysis and/or β-oxidation. The tendency of oleaginous microalgae to synthesize, apart from lipids, significant amounts of other energy-rich compounds such as sugars, in processes competitive to lipogenesis, deserves attention since the lipid yield may be considerably increased by blocking competitive metabolic pathways. The majority of microalgal production occurs in outdoor cultivation and for this reason biotechnological applications face some difficulties. Therefore, algal production systems need to be improved and harvesting systems need to be more effective in order for their industrial applications to become more competitive and economically viable. Besides, a reduction of the production cost of microalgal lipids can be achieved by combining lipid production with other commercial applications. The combined production of bioactive products and lipids, when possible, can support the commercial viability of both processes. Hydrophobic compounds can be extracted simultaneously with lipids and then purified, while hydrophilic compounds such as proteins and sugars may be extracted from the defatted biomass. The microalgae also have applications in environmental biotechnology since they can be used for bioremediation of wastewater and to monitor environmental toxicants. Algal biomass produced during wastewater treatment may be further valorized in the biofuel manufacture. It is anticipated that the high microalgal lipid potential will force research towards finding effective ways to manipulate biochemical pathways involved in lipid biosynthesis and towards cost effective algal cultivation and harvesting systems, as well. Copyright © 2014 Elsevier Inc. All rights reserved.

Heterotrophic cultivation of Auxenochlorella protothecoides using forest biomass as a feedstock for sustainable biodiesel production.

PubMed

Patel, Alok; Matsakas, Leonidas; Rova, Ulrika; Christakopoulos, Paul

2018-01-01

The aim of this work was to establish a process for the heterotrophic growth of green microalgae using forest biomass hydrolysates. To provide a carbon source for the growth of the green microalgae, two forest biomasses (Norway spruce and silver birch) were pretreated with a hybrid organosolv-steam explosion method, resulting in inhibitor-free pretreated solids with a high cellulose content of 77.9% w/w (birch) and 72% w/w (spruce). Pretreated solids were hydrolyzed using commercial cellulolytic enzymes to produce hydrolysate for the culture of algae. The heterotrophic growth of A. protothecoides was assessed using synthetic medium with glucose as carbon source, where the effect of sugar concentration and the carbon-to-nitrogen ratio were optimized, resulting in accumulation of lipids at 5.42 ± 0.32 g/L (64.52 ± 0.53% lipid content) after 5 days of culture on glucose at 20 g/L. The use of birch and spruce hydrolysates was favorable for the growth and lipid accumulation of the algae, resulting in lipid production of 5.65 ± 0.21 g/L (66 ± 0.33% lipid content) and 5.28 ± 0.17 g/L (63.08 ± 0.71% lipid content) when grown on birch and spruce, respectively, after only 120 h of cultivation. To the best of our knowledge, this is the first report of using organosolv pretreated wood biomass hydrolysates for the growth and lipid production of microalgae in the literature. The pretreatment process used in this study provided high saccharification of biomass without the presence of inhibitors. Moreover, the lipid profile of this microalga showed similar contents to vegetable oils which improve the biodiesel properties.

Process optimization involving critical evaluation of oxygen transfer, oxygen uptake and nitrogen limitation for enhanced biomass and lipid production by oleaginous yeast for biofuel application.

PubMed

Chopra, Jayita; Sen, Ramkrishna

2018-04-20

Lipid accumulation in oleaginous yeast is generally induced by nitrogen starvation, while oxygen saturation can influence biomass growth. Systematic shake flask studies that help in identifying the right nitrogen source and relate its uptake kinetics to lipid biosynthesis under varying oxygen saturation conditions are very essential for addressing the bioprocessing-related issues, which are envisaged to occur in the fermenter scale production. In the present study, lipid bioaccumulation by P. guilliermondii at varying C:N ratios and oxygen transfer conditions (assessed in terms of k L a) was investigated in shake flasks using a pre-optimized N-source and a two-stage inoculum formulated in a hybrid medium. A maximum lipid concentration of 10.8 ± 0.5 g L -1 was obtained in shake flask study at the optimal condition with an initial C:N and k L a of 60:1 and 0.6 min -1 , respectively, at a biomass specific growth rate of 0.11 h -1 . Translating these optimal shake flask conditions to a 3.7 L stirred tank reactor resulted in biomass and lipid concentrations of 16.74 ± 0.8 and 8 ± 0.4 g L -1 . The fatty acid methyl ester (FAME) profile of lipids obtained by gas chromatography was found to be suitable for biodiesel application. We strongly believe that the rationalistic approach-based design of experiments adopted in the study would help in achieving high cell density with improved lipid accumulation and also minimize the efforts towards process optimization during bioreactor level operations, consequently reducing the research and development-associated costs.

Binary lipids-based nanostructured lipid carriers for improved oral bioavailability of silymarin.

PubMed

Shangguan, Mingzhu; Lu, Yi; Qi, Jianping; Han, Jin; Tian, Zhiqiang; Xie, Yunchang; Hu, Fuqiang; Yuan, Hailong; Wu, Wei

2014-02-01

The main purpose of this study was to prepare binary lipids-based nanostructured lipid carriers to improve the oral bioavailability of silymarin, a poorly water-soluble liver protectant. Silymarin-loaded nanostructured lipid carriers were prepared by the method of high-pressure homogenization with glycerol distearates (Precirol ATO-5) and oleic acid as the solid and liquid lipids, respectively, and lecithin (Lipoid E 100) and Tween-80 as the emulsifiers. The silymarin-nanostructured lipid carrier prepared under optimum conditions was spherical in shape with mean particle size of ∼78.87 nm, entrapment efficiency of 87.55%, loading capacity of 8.32%, and zeta potential of -65.3 mV, respectively. In vitro release of silymarin-nanostructured lipid carriers was very limited even after 12 h, while in vitro lipolysis showed fast digestion of nanostructured lipid carriers within 1 h. Relative oral bioavailability of silymarin-nanostructured lipid carriers in Beagle dogs was 2.54- and 3.10-fold that of marketed Legalon® and silymarin solid dispersion pellets, respectively. It was concluded that nanostructured lipid carriers were potential drug delivery systems to improve the bioavailability of silymarin. Other than improved dissolution, alternative mechanisms such as facilitated absorption as well as lymphatic transport may contribute to bioavailability enhancement.

Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application.

PubMed

Jain, Shashank; Patel, Niketkumar; Shah, Mansi K; Khatri, Pinak; Vora, Namrata

2017-02-01

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning

PubMed Central

Harada, Yuhei; Noda, Junpei; Yatabe, Rui; Ikezaki, Hidekazu; Toko, Kiyoshi

2016-01-01

A taste sensor that uses lipid/polymer membranes can evaluate aftertastes felt by humans using Change in membrane Potential caused by Adsorption (CPA) measurements. The sensor membrane for evaluating bitterness, which is caused by acidic bitter substances such as iso-alpha acid contained in beer, needs an immersion process in monosodium glutamate (MSG) solution, called “MSG preconditioning”. However, what happens to the lipid/polymer membrane during MSG preconditioning is not clear. Therefore, we carried out three experiments to investigate the changes in the lipid/polymer membrane caused by the MSG preconditioning, i.e., measurements of the taste sensor, measurements of the amount of the bitterness substance adsorbed onto the membrane and measurements of the contact angle of the membrane surface. The CPA values increased as the preconditioning process progressed, and became stable after 3 d of preconditioning. The response potentials to the reference solution showed the same tendency of the CPA value change during the preconditioning period. The contact angle of the lipid/polymer membrane surface decreased after 7 d of MSG preconditioning; in short, the surface of the lipid/polymer membrane became hydrophilic during MSG preconditioning. The amount of adsorbed iso-alpha acid was increased until 5 d preconditioning, and then it decreased. In this study, we revealed that the CPA values increased with the progress of MSG preconditioning in spite of the decrease of the amount of iso-alpha acid adsorbed onto the lipid/polymer membrane, and it was indicated that the CPA values increase because the sensor sensitivity was improved by the MSG preconditioning. PMID:26891299

Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry.

PubMed

Ejsing, Christer S; Sampaio, Julio L; Surendranath, Vineeth; Duchoslav, Eva; Ekroos, Kim; Klemm, Robin W; Simons, Kai; Shevchenko, Andrej

2009-02-17

Although the transcriptome, proteome, and interactome of several eukaryotic model organisms have been described in detail, lipidomes remain relatively uncharacterized. Using Saccharomyces cerevisiae as an example, we demonstrate that automated shotgun lipidomics analysis enabled lipidome-wide absolute quantification of individual molecular lipid species by streamlined processing of a single sample of only 2 million yeast cells. By comparative lipidomics, we achieved the absolute quantification of 250 molecular lipid species covering 21 major lipid classes. This analysis provided approximately 95% coverage of the yeast lipidome achieved with 125-fold improvement in sensitivity compared with previous approaches. Comparative lipidomics demonstrated that growth temperature and defects in lipid biosynthesis induce ripple effects throughout the molecular composition of the yeast lipidome. This work serves as a resource for molecular characterization of eukaryotic lipidomes, and establishes shotgun lipidomics as a powerful platform for complementing biochemical studies and other systems-level approaches.

Electrosprayed core-shell polymer-lipid nanoparticles for active component delivery

NASA Astrophysics Data System (ADS)

Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan

2013-11-01

A key challenge in the production of multicomponent nanoparticles for healthcare applications is obtaining reproducible monodisperse nanoparticles with the minimum number of preparation steps. This paper focus on the use of electrohydrodynamic (EHD) techniques to produce core-shell polymer-lipid structures with a narrow size distribution in a single step process. These nanoparticles are composed of a hydrophilic core for active component encapsulation and a lipid shell. It was found that core-shell nanoparticles with a tunable size range between 30 and 90 nm and a narrow size distribution could be reproducibly manufactured. The results indicate that the lipid component (stearic acid) stabilizes the nanoparticles against collapse and aggregation and improves entrapment of active components, in this case vanillin, ethylmaltol and maltol. The overall structure of the nanoparticles produced was examined by multiple methods, including transmission electron microscopy and differential scanning calorimetry, to confirm that they were of core-shell form.

Physiological-phased kinetic characteristics of microalgae Chlorella vulgaris growth and lipid synthesis considering synergistic effects of light, carbon and nutrients.

PubMed

Liao, Qiang; Chang, Hai-Xing; Fu, Qian; Huang, Yun; Xia, Ao; Zhu, Xun; Zhong, Nianbing

2018-02-01

To comprehensively understand kinetic characteristics of microalgae growth and lipid synthesis in different phases, a phase-feeding strategy was proposed to simultaneously regulate light, carbon and nutrients in adaption, growth and stationary phases of microalgae cultivation. Physiological-phased kinetic characteristics of microalgae Chlorella vulgaris growth and lipid synthesis under synergistic effects of light, carbon and nutrients were investigated, and supply-demand relationships of electrons and energy between light and dark reactions of photosynthesis process were discussed. Finally, the optimized cultivation strategy for microalgae in various phases were obtained, under which the lipid productivity was significantly improved from 130.11 mg/L/d to 163.42 mg/L/d. The study provided some important guidance for the large-scale production of biofuels from microalgae. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maintenance of improved lipid levels following attendance at a cardiovascular risk reduction clinic: a 10-year experience

PubMed Central

Pearson, Glen J; Olson, Kari L; Panich, Nicole E; Majumdar, Sumit R; Tsuyuki, Ross T; Gilchrist, Dawna M; Damani, Ali; Francis, Gordon A

2008-01-01

Background: Specialty cardiovascular risk reduction clinics (CRRC) increase the proportion of patients attaining recommended lipid targets; however, it is not known if the benefits are sustained after discharge. We evaluated the impact of a CRRC on lipid levels and assessed the long-term effect of a CRRC in maintaining improved lipid levels following discharge. Methods: The medical records of consecutive dyslipidemic patients discharged ×6 months from a tertiary hospital CRRC from January 1991 to January 2001 were retrospectively reviewed. The primary outcome was the change in patients’ lipid levels between the final CRRC visit and the most recent primary care follow-up. A worst-case analysis was conducted to evaluate the potential impact of the patients in whom the follow-up lipid profiles post-discharge from the CRRC were not obtained. Results: Within the CRRC (median follow-up = 1.28 years in 1064 patients), we observed statistically significant improvements in all lipid parameters. In the 411 patients for whom post-discharge lipid profiles were available (median follow-up = 2.41 years), there were no significant differences observed in low-density lipoprotein-cholesterol, total cholesterol (TC), or triglycerides since CRRC discharge; however, there were small improvements in high-density lipoprotein-cholesterol (HDL-C) and TC:HDL ratio (p < 0.05 for both). The unadjusted worst-case analysis (653 patients with no follow-up lipid profiles) demonstrated statistically significant worsening of all lipid parameters between CRRC discharge and the most recent follow-up. However, when the change in lipid parameters between the baseline and the most recent follow-up was assessed in this analysis, the changes in all lipid parameters were significantly improved (p < 0.05). Conclusions: This study demonstrates that a CRRC can improve lipid levels and suggests that these benefits are sustained once patients are returned to the care of their primary physician. PMID:19183763

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.

Doxorubicin Lipid Complex Injection

MedlinePlus

... has not improved or that has worsened after treatment with other medications. Doxorubicin lipid complex is also ... has not improved or that has worsened after treatment with other medications. Doxorubicin lipid complex is also ...

A single-step aerosol process for in-situ surface modification of nanoparticles: Preparation of stable aqueous nanoparticle suspensions.

PubMed

Sapra, Mahak; Pawar, Amol Ashok; Venkataraman, Chandra

2016-02-15

Surface modification of nanoparticles during aerosol or gas-phase synthesis, followed by direct transfer into liquid media can be used to produce stable water-dispersed nanoparticle suspensions. This work investigates a single-step, aerosol process for in-situ surface-modification of nanoparticles. Previous studies have used a two-step sublimation-condensation mechanism following droplet drying, for surface modification, while the present process uses a liquid precursor containing two solutes, a matrix lipid and a surface modifying agent. A precursor solution in chloroform, of stearic acid lipid, with 4 %w/w of surface-active, physiological molecules [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol)-sodium salt (DPPG) or 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) 2000]-ammonium salt (DPPE-PEG)] was processed in an aerosol reactor at a low gas temperatures. The surface modified nanoparticles were characterized for morphology, surface composition and suspension properties. Spherical, surface-modified lipid nanoparticles with median mobility diameters in the range of 105-150nm and unimodal size distributions were obtained. Fourier transform infra-red spectroscopy (FTIR) measurements confirmed the presence of surface-active molecules on external surfaces of modified lipid nanoparticles. Surface modified nanoparticles exhibited improved suspension stability, compared to that of pure lipid nanoparticles for a period of 30days. Lowest aggregation was observed in DPPE-PEG modified nanoparticles from combined electrostatic and steric effects. The study provides a single-step aerosol method for in-situ surface modification of nanoparticles, using minimal amounts of surface active agents, to make stable, aqueous nanoparticle suspensions. Copyright © 2015 Elsevier Inc. All rights reserved.

Physicochemical, pasting, and functional properties of amaranth seed flours: effects of lipids removal.

PubMed

Shevkani, Khetan; Singh, Narpinder; Kaur, Amritpal; Rana, Jai Chand

2014-07-01

The present work was carried out to evaluate physicochemical (composition, hunter color, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]), pasting, and functional properties (foaming, emulsification, water, and fat absorption capacity) of amaranth full-fat flours from 6 lines/cultivars (AFs), and to see the effects of lipid removal/defatting on these properties. Protein, ash, and lipid content of AFs ranged between 12.5% to 15.2%, 3.0% to 3.5%, and 7.1% to 8.0%, respectively. The flours showed a number of bands between 97 and 7 kDa, with main subunits of approximately 58, 37, 33, 31, 23, and 16 kDa in the SDS-PAGE profiles. The protein content and L* value increased, while b* values decreased following defatting for most of the lines/cultivars. The defatted flours (DAFs) had higher final viscosity and stability (lower breakdown viscosity) as compared to counterpart AFs. The protein profiling of the flours was not affected with the lipid removal/defatting. However, water absorption capacity and foam stability of the flours improved upon defatting. Principal component analysis revealed that pasting temperature was positively related to lipid content, while breakdown viscosity was negatively related to protein content. Foaming properties (capacity and stability) showed negative relationship with lipid content, and positive with protein content, ash content, water, and fat absorption capacity. Amaranth grains are known to have higher amount of proteins and lipids than cereals. Amaranth lipids are rich in unsaturated fatty acids, which are prone to oxidative rancidity. Removal of lipids or defatting of flours may be carried out to enhance product shelf life by preventing undesirable oxidative chain reactions. Therefore, this research was undertaken to see the effects of defatting on the functional properties of amaranth flours. The defatting was a value addition process as it improved the functional properties of the flours. © 2014 Institute of Food Technologists®

Co-digestion of municipal sewage sludge and solid waste: modelling of carbohydrate, lipid and protein content influence.

PubMed

Nielfa, A; Cano, R; Pérez, A; Fdez-Polanco, M

2015-03-01

Solid wastes from industrial, commercial and community activities are of growing concern as the total volume of waste produced continues to increase. The knowledge of the specific composition and characteristics of the waste is an important tool in the correct development of the anaerobic digestion process. The problems derived from the anaerobic digestion of sole substrates with high lipid, carbohydrate or protein content lead to the co-digestion of these substrates with another disposed waste, such as sewage sludge. The kinetic of the anaerobic digestion is especially difficult to explain adequately, although some mathematical models are able to represent the main aspects of a biological system, thus improving understanding of the parameters involved in the process. The aim of this work is to evaluate the experimental biochemical methane potential on the co-digestion of sewage sludge with different solid wastes (grease; spent grain and cow manure) through the implementation of four kinetic models. The co-digestion of grease waste and mixed sludge obtained the best improvements from the sole substrates, with additional positive synergistic effects. The Gompertz model fits the experimental biochemical methane potential to an accuracy of 99%, showing a correlation between the percentage of lipid in the substrates and co-digestions and the period of lag phase. © The Author(s) 2015.

Combined algal processing: A novel integrated biorefinery process to produce algal biofuels and bioproducts

DOE PAGES

Dong, Tao; Knoshaug, Eric P.; Davis, Ryan; ...

2016-01-18

Here, the development of an integrated biorefinery process capable of producing multiple products is crucial for commercialization of microalgal biofuel production. Dilute acid pretreatment has been demonstrated as an efficient approach to utilize algal biomass more fully, by hydrolyzing microalgal carbohydrates into fermentable sugars, while making the lipids more extractable, and a protein fraction available for other products. Previously, we have shown that sugar-rich liquor could be separated from solid residue by solid-liquid separation (SLS) to produce ethanol via fermentation. However, process modeling has revealed that approximately 37% of the soluble sugars were lost in the solid cake after themore » SLS. Herein, a Combined Algal Processing (CAP) approach with a simplified configuration has been developed to improve the total energy yield. In CAP, whole algal slurry after acid pretreatment is directly used for ethanol fermentation. The ethanol and microalgal lipids can be sequentially recovered from the fermentation broth by thermal treatment and solvent extraction. Almost all the monomeric fermentable sugars can be utilized for ethanol production without compromising the lipid recovery. The techno-economic analysis (TEA) indicates that the CAP can reduce microalgal biofuel cost by $0.95 per gallon gasoline equivalent (GGE), which is a 9% reduction compared to the previous biorefinery scenario.« less

Improvement of lipid production by the oleaginous yeast Rhodosporidium toruloides through UV mutagenesis.

PubMed

Yamada, Ryosuke; Kashihara, Tomomi; Ogino, Hiroyasu

2017-05-01

Oleaginous yeasts are considered a promising alternative lipid source for biodiesel fuel production. In this study, we attempted to improve the lipid productivity of the oleaginous yeast Rhodosporidium toruloides through UV irradiation mutagenesis and selection based on ethanol and H 2 O 2 tolerance or cerulenin, a fatty acid synthetase inhibitor. Glucose consumption, cell growth, and lipid production of mutants were evaluated. The transcription level of genes involved in lipid production was also evaluated in mutants. The ethanol and H 2 O 2 tolerant strain 8766 2-31M and the cerulenin resistant strain 8766 3-11C were generated by UV mutagenesis. The 8766 2-31M mutant showed a higher lipid production rate, and the 8766 3-11C mutant produced a larger amount of lipid and had a higher lipid production rate than the wild type strain. Transcriptional analysis revealed that, similar to the wild type strain, the ACL1 and GND1 genes were expressed at significantly low levels, whereas IDP1 and ME1 were highly expressed. In conclusion, lipid productivity in the oleaginous yeast R. toruloides was successfully improved via UV mutagenesis and selection. The study also identified target genes for improving lipid productivity through gene recombination.

Lipid-based nanocarriers as an alternative for oral delivery of poorly water- soluble drugs: peroral and mucosal routes.

PubMed

Silva, A C; Santos, D; Ferreira, D; Lopes, C M

2012-01-01

The hydrophobic character of most drug molecules and their potential for degradation under the hostile environment of the gastrointestinal tract (GIT) constitutes the main obstacle in the development of a successful oral drug delivery system, since these are related to limitations of bioavailability and absorption processes. However, according to the advantages of the oral route, alternative ways of drug administration in the oral cavity should be considered. In this context, it is essential to have a systematic knowledge of the GIT and the oral cavity components, for a better understanding of the processes taking place during the oral administration of drugs. This review gives an overview of those anatomical and physiological features and elucidates about the current approaches employed to enhance the bioavailability of oral poorly water-soluble drugs. Strategies including the uses of lipid-based nanocarriers, such as nanoemulsions, liposomes and lipid nanoparticles are discussed, considering their ability to improve solubility, dissolution kinetics, absorption and, consequently, biopharmaceutical properties. Some toxicological concerns are also highlighted.

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

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.

Lipid-associated Oral Delivery: Mechanisms and Analysis of Oral Absorption Enhancement

PubMed Central

Rezhdo, Oljora; Speciner, Lauren; Carrier, Rebecca L.

2016-01-01

The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented. PMID:27520734

Genetic improvement of feed conversion ratio via indirect selection against lipid deposition in farmed rainbow trout (Oncorhynchus mykiss Walbaum).

PubMed

Kause, Antti; Kiessling, Anders; Martin, Samuel A M; Houlihan, Dominic; Ruohonen, Kari

2016-11-01

In farmed fish, selective breeding for feed conversion ratio (FCR) may be possible via indirectly selecting for easily-measured indicator traits correlated with FCR. We tested the hypothesis that rainbow trout with low lipid% have genetically better FCR, and that lipid% may be genetically related to retention efficiency of macronutrients, making lipid% a useful indicator trait. A quantitative genetic analysis was used to quantify the benefit of replacing feed intake in a selection index with one of three lipid traits: body lipid%, muscle lipid% or viscera% weight of total body weight (reflecting visceral lipid). The index theory calculations showed that simultaneous selection for weight gain and against feed intake (direct selection to improve FCR) increased the expected genetic response in FCR by 1·50-fold compared with the sole selection for growth. Replacing feed intake in the selection index with body lipid%, muscle lipid% or viscera% increased genetic response in FCR by 1·29-, 1·49- and 1·02-fold, respectively, compared with the sole selection for growth. Consequently, indirect selection for weight gain and against muscle lipid% was almost as effective as direct selection for FCR. Fish with genetically low body and muscle lipid% were more efficient in turning ingested protein into protein weight gain. Both physiological and genetic mechanisms promote the hypothesis that low-lipid% fish are more efficient. These results highlight that in breeding programmes of rainbow trout, control of lipid deposition improves not only FCR but also protein-retention efficiency. This improves resource efficiency of aquaculture and reduces nutrient load to the environment.

Emulsion design to improve the delivery of functional lipophilic components.

PubMed

McClements, David Julian

2010-01-01

The food industry has used emulsion science and technology for many years to create a diverse range of food products, such as milk, cream, soft drinks, nutritional beverages, dressings, mayonnaise, sauces, dips, deserts, ice cream, margarine, and butter. The majority of these food products are conventional oil-in-water (O/W) or water-in-oil (W/O) type emulsions. Recently, there has been increasing interest within the food industry in either improving or extending the functional performance of foods using novel structured emulsions. This article reviews recent developments in the creation of structured emulsions that could be used by the food and other industries, including nanoemulsions, multiple emulsions, multilayer emulsions, solid lipid particles, and filled hydrogel particles. These structured emulsions can be produced from food-grade [generally recognized as safe (GRAS)] ingredients (e.g., lipids, proteins, polysaccharides, surfactants, and minerals), using simple processing operations (e.g., mixing, homogenizing, and thermal processing). The structure, production, performance, and potential applications of each type of structured emulsion system are discussed.

Messages from the Malaysian Diabetes Registries on Diabetes Care in Malaysian public healthcare facilities.

PubMed

Chew, Boon-How; Lee, Ping-Yein; Cheong, Ai-Theng; Ismail, Mastura; Shariff-Ghazali, Sazlina; Goh, Pik-Pin

2016-10-01

A persistent and increasing prevalence of diagnosed and undiagnosed diabetes mellitus has recently been reported in the National Health and Morbidity Survey 2015. This commentary recapitulates the relevant and valuable lessons in the Malaysian national diabetes registries to inform the healthcare stakeholders and policy makers on potential areas of clinical practice improvement and future researches. Under performance of the process measures and sub-optimal control of HbA1c, blood pressure and lipids profile were prevalent (<40% achieved treatment targets). Although these had improved slightly from 2009 to 2012, diabetes co-morbidities (hypertension and dyslipidaemia) and complications had also increased. Prevalence of insulin use had doubled, and lipid lowering agent use had increased about 50% in 2012 compared to 2009. We identified six clinical areas for urgent attention and improvement, and three potential areas for future research. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Role of surfactant protein A (SP-A)/lipid interactions for SP-A functions in the lung.

PubMed

Casals, C

2001-01-01

Surfactant protein A (SP-A), an oligomeric glycoprotein, is a member of a group of proteins named collectins that contain collagen-like and Ca(2+)-dependent carbohydrate recognition domains. SP-A interacts with a broad range of amphipathic lipids (glycerophospholipids, sphingophospholipids, glycosphingolipids, lipid A, and lipoglycans) that are present in surfactant or microbial membranes. This review summarizes SP-A/lipid interaction studies regarding the lipid system used (i.e., phospholipid vesicles, phospholipid monolayers, and lipids immobilized on silica or adsorbed on a solid support). The effect of calcium, ionic strength, and pH on the binding of SP-A to lipids and the subsequent lipid aggregation process is discussed. Current evidence suggests that hydrophobic-binding forces are involved in the peripherical association of SP-A to membranes. It is also proposed that fluid and liquid-ordered phase coexistence in surfactant membranes might favor partition of SP-A into those membranes. The binding of SP-A to surfactant membranes containing hydrophobic surfactant peptides makes possible the formation of a membrane reservoir in the alveolar fluid that is protected by SP-A against inactivation and improves the rate of surfactant film formation. In addition, the interaction of SP-A with membranes might enhance the affinity of SP-A for terminal carbohydrates of glycolipids or glycoproteins on the surface of invading microorganisms.

Effects of temperature and PEG grafting density on the translocation of PEGylated nanoparticles across asymmetric lipid membrane.

PubMed

Zhang, Zuoheng; Lin, Xubo; Gu, Ning

2017-12-01

Plasma membrane internalization of nanoparticles (NPs) is important for their biomedical applications such as drug-delivery carriers. On one hand, in order to improve their half-life in circulation, PEGylation has been widely used. However, it may hinder the NPs' membrane internalization ability. On the other hand, higher temperature could enhance the membrane permeability and may affect the NPs' ability to enter into or exit from cells. To make full use of their advantages, we systematically investigated the effects of temperature and PEG density on the translocation of PEGylated nanoparticles across the plasma asymmetric membrane of eukaryotic cells, using near-atom level coarse-grained molecular dynamics simulations. Our results showed that higher temperature could accelerate the translocation of NPs across membranes by making lipids more disorder and faster diffusion. On the contrary, steric hindrance effects of PEG would inhibit NPs' translocation process and promote lipids flip-flops. The PEG chains could rearrange themselves to minimize the contacts between PEG and lipid tails during the translocation, which was similar to 'snorkeling effect'. Moreover, lipid flip-flops were affected by PEGylated density as well as NPs' translocation direction. Higher PEG grafting density could promote lipid flip-flops, but inhibit lipid extraction from bilayers. The consequence of lipid flip-flop and extraction was that the membranes got more symmetric. Copyright © 2017. Published by Elsevier B.V.

Carbon Monoxide Improves Efficacy of Mesenchymal Stromal Cells During Sepsis by Production of Specialized Proresolving Lipid Mediators.

PubMed

Tsoyi, Konstantin; Hall, Sean R R; Dalli, Jesmond; Colas, Romain A; Ghanta, Sailaja; Ith, Bonna; Coronata, Anna; Fredenburgh, Laura E; Baron, Rebecca M; Choi, Augustine M K; Serhan, Charles N; Liu, Xiaoli; Perrella, Mark A

2016-12-01

Mesenchymal stromal cells are being investigated as a cell-based therapy for a number of disease processes, with promising results in animal models of systemic inflammation and sepsis. Studies are ongoing to determine ways to further improve the therapeutic potential of mesenchymal stromal cells. A gas molecule that improves outcome in experimental sepsis is carbon monoxide. We hypothesized that preconditioning of mesenchymal stromal cells with carbon monoxide ex vivo would promote further therapeutic benefit when cells are administered in vivo after the onset of polymicrobial sepsis in mice. Animal study and primary cell culture. Laboratory investigation. BALB/c mice. Polymicrobial sepsis was induced by cecal ligation and puncture. Mesenchymal stromal cells, mesenchymal stromal cells-conditioned with carbon monoxide, fibroblasts, or fibroblasts-conditioned with carbon monoxide were delivered by tail vein injections to septic mice. The mice were assessed for survival, bacterial clearance, and the inflammatory response during sepsis in each of the groups. Mesenchymal stromal cells were also assessed for their ability to promote bacterial phagocytosis by neutrophils, the production of specialized proresolving lipid mediators, and their importance for mesenchymal stromal cells function using gene silencing. Ex vivo preconditioning with carbon monoxide allowed mesenchymal stromal cells to be administered later after the onset of sepsis (6 hr), and yet maintain their therapeutic effect with increased survival. Carbon monoxide preconditioned mesenchymal stromal cells were also able to alleviate organ injury, improve bacterial clearance, and promote the resolution of inflammation. Mesenchymal stromal cells exposed to carbon monoxide, with docosahexaenoic acid substrate, produced specialized proresolving lipid mediators, particularly D-series resolvins, which promoted survival. Silencing of lipoxygenase pathways (5-lipoxygenase and 12/15-lipoxygenase), which are important enzymes for specialized proresolving lipid mediator biosynthesis, resulted in a loss of therapeutic benefit bestowed on mesenchymal stromal cells by carbon monoxide. Taken together, these data suggest that production of specialized proresolving lipid mediators contribute to improved mesenchymal stromal cell efficacy when exposed to carbon monoxide, resulting in an improved therapeutic response during sepsis.

Improved method to visualize lipid distribution within arterial vessel walls by 1.7 μm spectroscopic spectral-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Hirano, Mitsuharu; Tonosaki, Shozo; Ueno, Takahiro; Tanaka, Masato; Hasegawa, Takemi

2014-02-01

We report an improved method to visualize lipid distribution in axial and lateral direction within arterial vessel walls by spectroscopic spectral-domain Optical Coherence Tomography (OCT) at 1.7μm wavelength for identification of lipidrich plaque that is suspected to cause coronary events. In our previous method, an extended InGaAs-based line camera detects an OCT interferometric spectrum from 1607 to 1766 nm, which is then divided into twenty subbands, and A-scan OCT profile is calculated for each subband, resulting in a tomographic spectrum. This tomographic spectrum is decomposed into lipid spectrum having an attenuation peak at 1730 nm and non-lipid spectrum independent of wavelength, and the weight of each spectrum, that is, lipid and non-lipid score is calculated. In this paper, we present an improved algorithm, in which we have combined the lipid score and the non-lipid score to derive a corrected lipid score. We have found that the corrected lipid score is better than the raw lipid score in that the former is more robust against false positive occurring due to abrupt change in reflectivity at vessel surface. In addition, we have optimized spatial smoothing filter and reduced false positive and false negative due to detection noise and speckle. We have verified this improved algorithm by the use of measuring data of normal porcine coronary artery and lard as a model of lipid-rich plaque and confirmed that both the sensitivity and the specificity of lard are 92%.

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.

Lipid-associated oral delivery: Mechanisms and analysis of oral absorption enhancement.

PubMed

Rezhdo, Oljora; Speciner, Lauren; Carrier, Rebecca

2016-10-28

The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid in the understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism

PubMed Central

Molehin, Deborah

2016-01-01

Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

Cyclohexane Rings Reduce Membrane Permeability to Small Ions in Archaea-Inspired Tetraether Lipids.

PubMed

Koyanagi, Takaoki; Leriche, Geoffray; Onofrei, David; Holland, Gregory P; Mayer, Michael; Yang, Jerry

2016-01-26

Extremophile archaeal organisms overcome problems of membrane permeability by producing lipids with structural elements that putatively improve membrane integrity compared to lipids from other life forms. Herein, we describe a series of lipids that mimic some key structural features of archaeal lipids, such as: 1) single tethering of lipid tails to create fully transmembrane tetraether lipids and 2) the incorporation of small rings into these tethered segments. We found that membranes formed from pure tetraether lipids leaked small ions at a rate that was about two orders of magnitude slower than common bilayer-forming lipids. Incorporation of cyclopentane rings into the tetraether lipids did not affect membrane leakage, whereas a cyclohexane ring reduced leakage by an additional 40 %. These results show that mimicking certain structural features of natural archaeal lipids results in improved membrane integrity, which may help overcome limitations of many current lipid-based technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dissecting metabolic behavior of lipid over-producing strain of Mucor circinelloides through genome-scale metabolic network and multi-level data integration.

PubMed

Vongsangnak, Wanwipa; Kingkaw, Amornthep; Yang, Junhuan; Song, Yuanda; Laoteng, Kobkul

2018-09-05

Lipid accumulation is an important cellular process of oleaginous microorganisms. To dissect metabolic behavior of oleaginous Zygomycetes, the lipid over-producing strain, Mucor circinelloides WJ11, was subjected for omics-scale analysis. The genome annotation was improved and used for construction of genome-scale metabolic network of WJ11 strain. Then, the quality of the metabolic network was enhanced by incorporating gene and protein expression data. In addition to the known oleaginous genes, our results showed a number of newly identified unique genes of WJ11 strain, which involved in central carbon metabolism, lipid, amino acid and nitrogen metabolisms. The systematic compilations indicated the additional metabolic routes with the involvement in supplying precursors (acetyl-CoA, NADPH and fatty acyl substrate) for fatty acid and lipid biosynthesis. Interestingly, amino acid metabolism played a substantial role in responsive mechanism of the fungal cells to nutrient imbalance circumstance through lipogenesis as the finding of reporter metabolites (l-methionine, l-glutamate, l-aspartate, l-asparagine and l-glutamine) at lipid-accumulating stage. The cooperative function of certain lipid-degrading enzymes at the particular growth stage was elucidated by integrating the metabolic networks with gene expression data. The unique feature of carotenoid biosynthetic route in WJ11 strain was also identified by protein domain analysis. Taken together, there were cross-functional metabolisms in regulating lipid biosynthesis and retaining high level of cellular lipids in the representative of lipid over-producing strains. Copyright © 2018 Elsevier B.V. All rights reserved.

Recycling of lipid-extracted hydrolysate as nitrogen supplementation for production of thraustochytrid biomass.

PubMed

Lowrey, Joshua; Armenta, Roberto E; Brooks, Marianne S

2016-08-01

Efficient resource usage is important for cost-effective microalgae production, where the incorporation of waste streams and recycled water into the process has great potential. This study builds upon emerging research on nutrient recycling in thraustochytrid production, where waste streams are recovered after lipid extraction and recycled into future cultures. This research investigates the nitrogen flux of recycled hydrolysate derived from enzymatic lipid extraction of thraustochytrid biomass. Results indicated the proteinaceous content of the recycled hydrolysate can offset the need to supply fresh nitrogen in a secondary culture, without detrimental impact upon the produced biomass. The treatment employing the recycled hydrolysate with no nitrogen addition accumulated 14.86 g L(-1) of biomass in 141 h with 43.3 % (w/w) lipid content compared to the control which had 9.26 g L(-1) and 46.9 % (w/w), respectively. This improved nutrient efficiency and wastewater recovery represents considerable potential for enhanced resource efficiency of commercial thraustochytrid production.

Functional liposomes and supported lipid bilayers: towards the complexity of biological archetypes.

PubMed

Berti, Debora; Caminati, Gabriella; Baglioni, Piero

2011-05-21

This perspective paper provides some illustrative examples on the interplay between information gathered on planar supported lipid bilayers (SLB) and unilamellar lipid vesicles (ULV) to get an integrated description of phenomena occurring at the nanoscale that involve locally bilayered structures. Similarities and differences are underlined and critically compared in terms of biomimetic fidelity and instrumental accessibility to structural and dynamical parameters, focusing on some recent reports that either explicitly address this comparison or introducing some studies that separately investigate the same process in SLB and lipid vesicles. Despite the structural similarity on the nanoscale, the different topology implies radically different characterization techniques that have evolved in sectorial and separated approaches. The quest for increasing levels of compositional complexity for bilayered systems should not result in a loss of structural and dynamical control: this is the central challenge of future research in this area, where the integrated approach highlighted in this contribution would enable improved levels of understanding. © The Owner Societies 2011

Quality characteristics of chunked and formed hams from pale, average and dark muscles were improved using an ammonium hydroxide curing solution.

PubMed

Everts, A J; Wulf, D M; Everts, A K R; Nath, T M; Jennings, T D; Weaver, A D

2010-10-01

Cooking yield, cooked pH, purge loss, moisture, lipid oxidation, external and internal color, break strength and elongation distance were assessed for pale (PALE), average (AVG) and dark (DARK) inside hams injected with either a control cure solution (CON) or BPI-processing technology cure solution (BPT). Following enhancement, muscles were chunked, vacuum tumbled, smoked and cooked to 66 degrees C. Cooked ham pH was 6.49 for DARK, 6.40 for AVG, and 6.30 for PALE, respectively (P<0.0001). Cooked pH was higher (P<.0001) for BPT than CON. Cooked ham moisture content was higher (P<0.0001) for BPT hams than CON hams (74.83 vs. 74.11%) but BPT did not significantly influence cooking yield or lipid oxidation. Consumers (n=150) of diverse demographics rated hams for appearance and taste. Results indicated that BPI-processing technology improved visual appearance of hams made from pale, average, and dark muscles and improved the eating quality of hams made from pale muscles. Copyright (c) 2010 The American Meat Science Association. Published by Elsevier Ltd. All rights reserved.

Computer simulation studies on passive recruitment dynamics of lipids induced by the adsorption of charged nanoparticles.

PubMed

Li, Yang

2014-07-07

The recruitment dynamics of lipids in the biomembrane is believed to play an important role in a variety of cellular processes. In this work, we investigate the nanoparticle-induced recruitment dynamics of lipids in the heterogeneous phospholipid bilayers of distearoyl-phosphatidylcholine (DSPC) and dioleoyl-phosphatidylglycerol (DOPG) via coarse-grained molecular dynamics simulations. Three dynamic modes of individual charged DOPG lipid molecules have been taken into account in the recruitment process: lateral diffusion, protrusions, and flip-flops. Based on analysis of the mobility pattern of lipids, structural variations in the membrane as well as activation energy of the structure of lipid eyelids characterized by the potential of mean force, we have concluded that the electrostatic attraction of nanoparticles plays a crucial role in the recruitment process of lipids in phospholipid bilayers. These studies are consistent with experimental observations and to some extent give insight into the origin of some cellular processes such as signaling, formation of lipid rafts, and endocytosis.

Enhancement of Lipid Extraction from Marine Microalga, Scenedesmus Associated with High-Pressure Homogenization Process

PubMed Central

Cho, Seok-Cheol; Choi, Woon-Yong; Oh, Sung-Ho; Lee, Choon-Geun; Seo, Yong-Chang; Kim, Ji-Seon; Song, Chi-Ho; Kim, Ga-Vin; Lee, Shin-Young; Kang, Do-Hyung; Lee, Hyeon-Yong

2012-01-01

Marine microalga, Scenedesmus sp., which is known to be suitable for biodiesel production because of its high lipid content, was subjected to the conventional Folch method of lipid extraction combined with high-pressure homogenization pretreatment process at 1200 psi and 35°C. Algal lipid yield was about 24.9% through this process, whereas only 19.8% lipid can be obtained by following a conventional lipid extraction procedure using the solvent, chloroform : methanol (2 : 1, v/v). Present approach requires 30 min process time and a moderate working temperature of 35°C as compared to the conventional extraction method which usually requires >5 hrs and 65°C temperature. It was found that this combined extraction process followed second-order reaction kinetics, which means most of the cellular lipids were extracted during initial periods of extraction, mostly within 30 min. In contrast, during the conventional extraction process, the cellular lipids were slowly and continuously extracted for >5 hrs by following first-order kinetics. Confocal and scanning electron microscopy revealed altered texture of algal biomass pretreated with high-pressure homogenization. These results clearly demonstrate that the Folch method coupled with high-pressure homogenization pretreatment can easily destruct the rigid cell walls of microalgae and release the intact lipids, with minimized extraction time and temperature, both of which are essential for maintaining good quality of the lipids for biodiesel production. PMID:22969270

Collection and conversion of algal lipid

NASA Astrophysics Data System (ADS)

Lin, Ching-Chieh

Sustainable economic activities mandate a significant replacement of fossil energy by renewable forms. Algae-derived biofuels are increasingly seen as an alternative source of energy with potential to supplement the world's ever increasing demand. Our primary objective is, once the algae were cultivated, to eliminate or make more efficient energy-intensive processing steps of collection, drying, grinding, and solvent extraction prior to conversion. To overcome the processing barrier, we propose to streamline from cultivated algae to biodiesel via algal biomass collection by sand filtration, cell rupturing with ozone, and immediate transesterification. To collect the algal biomass, the specific Chlorococcum aquaticum suspension was acidified to pH 3.3 to promote agglomeration prior to sand filtration. The algae-loaded filter bed was drained of free water and added with methanol and ozonated for 2 min to rupture cell membrane to accelerate release of the cellular contents. The methanol solution now containing the dissolved lipid product was collected by draining, while the filter bed was regenerated by further ozonation when needed. The results showed 95% collection of the algal biomass from the suspension and a 16% yield of lipid from the algae, as well as restoration of filtration velocity of the sand bed via ozonation. The results further showed increased lipid yield upon cell rupturing and transesterified products composed entirely of fatty acid methyl ester (FAME) compounds, demonstrating that the rupture and transesterification processes could proceed consecutively in the same medium, requiring no separate steps of drying, extraction, and conversion. The FAME products from algae without exposure to ozone were mainly of 16 to 18 carbons containing up to 3 double bonds, while those from algae having been ozonated were smaller, highly saturated hydrocarbons. The new technique streamlines individual steps from cultivated algal lipid to transesterified products and represents an improvement over existing energy-intensive steps.

Programming Saposin-Mediated Compensatory Metabolic Sinks for Enhanced Ubiquinone Production.

PubMed

Xu, Wen; Yuan, Jifeng; Yang, Shuiyun; Ching, Chi-Bun; Liu, Jiankang

2016-12-16

Microbial synthesis of ubiquinone by fermentation processes has been emerging in recent years. However, as ubiquinone is a primary metabolite that is tightly regulated by the host central metabolism, tweaking the individual pathway components could only result in a marginal improvement on the ubiquinone production. Given that ubiquinone is stored in the lipid bilayer, we hypothesized that introducing additional metabolic sink for storing ubiquinone might improve the CoQ 10 production. As human lipid binding/transfer protein saposin B (hSapB) was reported to extract ubiquinone from the lipid bilayer and form the water-soluble complex, hSapB was chosen to build a compensatory metabolic sink for the ubiquinone storage. As a proof-of-concept, hSapB-mediated metabolic sink systems were devised and systematically investigated in the model organism of Escherichia coli. The hSapB-mediated periplasmic sink resulted in more than 200% improvement of CoQ 8 over the wild type strain. Further investigation revealed that hSapB-mediated sink systems could also improve the CoQ 10 production in a CoQ 10 -hyperproducing E. coli strain obtained by a modular pathway rewiring approach. As the design principles and the engineering strategies reported here are generalizable to other microbes, compensatory sink systems will be a method of significant interest to the synthetic biology community.

Tissue Fixation and Processing for the Histological Identification of Lipids.

PubMed

Carriel, Víctor; Campos, Fernando; Aneiros-Fernández, José; Kiernan, John A

2017-01-01

Lipids are a heterogeneous group of substances characterized by their solubility in organic solvents and insolubility in water. Lipids can be found as normal components of different tissues and organs, and they can be affected by several pathological conditions. The histochemical identification of lipids plays an important role in histopathological diagnosis and research, but successful staining depends on adequate fixation and processing of the tissue. Here we describe methods to fix and process tissue samples for the histochemical identification of lipids in frozen or paraffin-embedded tissues.

Temperature-Controlled High-Speed AFM: Real-Time Observation of Ripple Phase Transitions.

PubMed

Takahashi, Hirohide; Miyagi, Atsushi; Redondo-Morata, Lorena; Scheuring, Simon

2016-11-01

With nanometer lateral and Angstrom vertical resolution, atomic force microscopy (AFM) has contributed unique data improving the understanding of lipid bilayers. Lipid bilayers are found in several different temperature-dependent states, termed phases; the main phases are solid and fluid phases. The transition temperature between solid and fluid phases is lipid composition specific. Under certain conditions some lipid bilayers adopt a so-called ripple phase, a structure where solid and fluid phase domains alternate with constant periodicity. Because of its narrow regime of existence and heterogeneity ripple phase and its transition dynamics remain poorly understood. Here, a temperature control device to high-speed atomic force microscopy (HS-AFM) to observe dynamics of phase transition from ripple phase to fluid phase reversibly in real time is developed and integrated. Based on HS-AFM imaging, the phase transition processes from ripple phase to fluid phase and from ripple phase to metastable ripple phase to fluid phase could be reversibly, phenomenologically, and quantitatively studied. The results here show phase transition hysteresis in fast cooling and heating processes, while both melting and condensation occur at 24.15 °C in quasi-steady state situation. A second metastable ripple phase with larger periodicity is formed at the ripple phase to fluid phase transition when the buffer contains Ca 2+ . The presented temperature-controlled HS-AFM is a new unique experimental system to observe dynamics of temperature-sensitive processes at the nanoscopic level. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Current lipid extraction methods are significantly enhanced adding a water treatment step in Chlorella protothecoides.

PubMed

Ren, Xiaojie; Zhao, Xinhe; Turcotte, François; Deschênes, Jean-Sébastien; Tremblay, Réjean; Jolicoeur, Mario

2017-02-11

Microalgae have the potential to rapidly accumulate lipids of high interest for the food, cosmetics, pharmaceutical and energy (e.g. biodiesel) industries. However, current lipid extraction methods show efficiency limitation and until now, extraction protocols have not been fully optimized for specific lipid compounds. The present study thus presents a novel lipid extraction method, consisting in the addition of a water treatment of biomass between the two-stage solvent extraction steps of current extraction methods. The resulting modified method not only enhances lipid extraction efficiency, but also yields a higher triacylglycerols (TAG) ratio, which is highly desirable for biodiesel production. Modification of four existing methods using acetone, chloroform/methanol (Chl/Met), chloroform/methanol/H 2 O (Chl/Met/H 2 O) and dichloromethane/methanol (Dic/Met) showed respective lipid extraction yield enhancement of 72.3, 35.8, 60.3 and 60.9%. The modified acetone method resulted in the highest extraction yield, with 68.9 ± 0.2% DW total lipids. Extraction of TAG was particularly improved with the water treatment, especially for the Chl/Met/H 2 O and Dic/Met methods. The acetone method with the water treatment led to the highest extraction level of TAG with 73.7 ± 7.3 µg/mg DW, which is 130.8 ± 10.6% higher than the maximum value obtained for the four classical methods (31.9 ± 4.6 µg/mg DW). Interestingly, the water treatment preferentially improved the extraction of intracellular fractions, i.e. TAG, sterols, and free fatty acids, compared to the lipid fractions of the cell membranes, which are constituted of phospholipids (PL), acetone mobile polar lipids and hydrocarbons. Finally, from the 32 fatty acids analyzed for both neutral lipids (NL) and polar lipids (PL) fractions, it is clear that the water treatment greatly improves NL-to-PL ratio for the four standard methods assessed. Water treatment of biomass after the first solvent extraction step helps the subsequent release of intracellular lipids in the second extraction step, thus improving the global lipids extraction yield. In addition, the water treatment positively modifies the intracellular lipid class ratios of the final extract, in which TAG ratio is significantly increased without changes in the fatty acids composition. The novel method thus provides an efficient way to improve lipid extraction yield of existing methods, as well as selectively favoring TAG, a lipid of the upmost interest for biodiesel production.

Impact of thermal processing on the activity of gallotannins and condensed tannins from Hamamelis virginiana used as functional ingredients in seafood.

PubMed

González, María Jesús; Torres, Josep Lluís; Medina, Isabel

2010-04-14

Phenolic extracts from witch hazel, Hamamelis virginiana, are efficient antioxidants against fish lipid peroxidation. The impact of fish thermal processes on the hydrolyzable polyphenols from this source was studied. H. virginiana polyphenols included 80% of hydrolyzable tannins, characterized by a mixture of glucose gallates containing from 5 to 10 units of gallic acid, hamamelitannin, and 20% of proanthocyanidins. Structural modifications of the polyphenols during thermal processes were determined by HPLC-MS. Changes in their reducing and free radical scavenging capacities as a result of high temperatures were also determined. Thermal processes triggered a significant breakdown of hydrolyzable tannins with 6-10 galloyl units to give pentagalloyl glucose (PGG). The release of high concentrations of free gallic acid especially in long-term thermally processed samples leads to an increase of the antioxidant ability of heated H. virginiana extracts. Such an increase was evidenced by an increment in the reducing and radical scavenging capacities as well as an improvement in the antioxidant effectiveness for inhibiting lipid oxidation of processed fatty fish muscle.

Membrane Lipid Oscillation: An Emerging System of Molecular Dynamics in the Plant Membrane.

PubMed

Nakamura, Yuki

2018-03-01

Biological rhythm represents a major biological process of living organisms. However, rhythmic oscillation of membrane lipid content is poorly described in plants. The development of lipidomic technology has led to the illustration of precise molecular profiles of membrane lipids under various growth conditions. Compared with conventional lipid signaling, which produces unpredictable lipid changes in response to ever-changing environmental conditions, lipid oscillation generates a fairly predictable lipid profile, adding a new layer of biological function to the membrane system and possible cross-talk with the other chronobiological processes. This mini review covers recent studies elucidating membrane lipid oscillation in plants.

Analysis of Lipids and Lipid Rafts in Borrelia.

PubMed

Toledo, Alvaro; Huang, Zhen; Benach, Jorge L; London, Erwin

2018-01-01

Lipid rafts are membrane microdomains that are involved in cellular processes such as protein trafficking and signaling processes, and which play a fundamental role in membrane fluidity and budding. The lipid composition of the membrane and the biochemical characteristics of the lipids found within rafts define the ability of cells to form microdomains and compartmentalize the membrane. In this chapter, we describe the biophysical, biochemical, and molecular approaches used to define and characterize lipid rafts in the Lyme disease agent, Borrelia burgdorferi.

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.

Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics.

PubMed

Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

2013-08-01

In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available.

Lipids in the Stomach - Implications for the Evaluation of Food Effects on Oral Drug Absorption.

PubMed

Koziolek, Mirko; Carrière, Frédéric; Porter, Christopher J H

2018-02-08

Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to 'pre-process' lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.

Review of the harvesting and extraction program within the National Alliance for Advanced Biofuels and Bioproducts

DOE PAGES

Marrone, Babetta L.; Lacey, Ronald E.; Anderson, Daniel B.; ...

2017-08-07

Energy-efficient and scalable harvesting and lipid extraction processes must be developed in order for the algal biofuels and bioproducts industry to thrive. The major challenge for harvesting is the handling of large volumes of cultivation water to concentrate low amounts of biomass. For lipid extraction, the major energy and cost drivers are associated with disrupting the algae cell wall and drying the biomass before solvent extraction of the lipids. Here we review the research and development conducted by the Harvesting and Extraction Team during the 3-year National Alliance for Advanced Biofuels and Bioproducts (NAABB) algal consortium project. The harvesting andmore » extraction team investigated five harvesting and three wet extraction technologies at lab bench scale for effectiveness, and conducted a techoeconomic study to evaluate their costs and energy efficiency compared to available baseline technologies. Based on this study, three harvesting technologies were selected for further study at larger scale. We evaluated the selected harvesting technologies: electrocoagulation, membrane filtration, and ultrasonic harvesting, in a field study at minimum scale of 100 L/h. None of the extraction technologies were determined to be ready for scale-up; therefore, an emerging extraction technology (wet solvent extraction) was selected from industry to provide scale-up data and capabilities to produce lipid and lipid-extracted materials for the NAABB program. One specialized extraction/adsorption technology was developed that showed promise for recovering high value co-products from lipid extracts. Overall, the NAABB Harvesting and Extraction Team improved the readiness level of several innovative, energy efficient technologies to integrate with algae production processes and captured valuable lessons learned about scale-up challenges.« less

Review of the harvesting and extraction program within the National Alliance for Advanced Biofuels and Bioproducts

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

Marrone, Babetta L.; Lacey, Ronald E.; Anderson, Daniel B.

Energy-efficient and scalable harvesting and lipid extraction processes must be developed in order for the algal biofuels and bioproducts industry to thrive. The major challenge for harvesting is the handling of large volumes of cultivation water to concentrate low amounts of biomass. For lipid extraction, the major energy and cost drivers are associated with disrupting the algae cell wall and drying the biomass before solvent extraction of the lipids. Here we review the research and development conducted by the Harvesting and Extraction Team during the 3-year National Alliance for Advanced Biofuels and Bioproducts (NAABB) algal consortium project. The harvesting andmore » extraction team investigated five harvesting and three wet extraction technologies at lab bench scale for effectiveness, and conducted a techoeconomic study to evaluate their costs and energy efficiency compared to available baseline technologies. Based on this study, three harvesting technologies were selected for further study at larger scale. We evaluated the selected harvesting technologies: electrocoagulation, membrane filtration, and ultrasonic harvesting, in a field study at minimum scale of 100 L/h. None of the extraction technologies were determined to be ready for scale-up; therefore, an emerging extraction technology (wet solvent extraction) was selected from industry to provide scale-up data and capabilities to produce lipid and lipid-extracted materials for the NAABB program. One specialized extraction/adsorption technology was developed that showed promise for recovering high value co-products from lipid extracts. Overall, the NAABB Harvesting and Extraction Team improved the readiness level of several innovative, energy efficient technologies to integrate with algae production processes and captured valuable lessons learned about scale-up challenges.« less

Effect of sous vide processing on physicochemical, ultrastructural, microbial and sensory changes in vacuum packaged chicken sausages.

PubMed

Naveena, B M; Khansole, Panjab S; Shashi Kumar, M; Krishnaiah, N; Kulkarni, Vinayak V; Deepak, S J

2017-01-01

The processing of sous vide chicken sausages was optimized under vacuum packaging condition and cooking at 100 ℃ for 30 min (SV30), 60 min (SV60) and 120 min (SV120) and compared with aerobically cooked control at 100 ℃ for 30 min. Sous vide processing of chicken sausages (SV30) produced higher (p < 0.05) cooking yield, Hunterlab a* values and sensory attributes without affecting proximate composition and shear force values relative to control. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis and scanning electron microscopy results revealed no significant changes in protein quality and emulsion ultra-structure due to SV30 processing relative to control sausages. Sous vide processing of chicken sausages enriched with rosemary diterpene phenols retained the freshness and quality up to 120 days during storage at 4 ± 1 ℃ relative to control sausages that were spoiled on 20th day. Lipid oxidation and microbial growth remained below the spoilage levels for all the SV-processed sausages throughout the storage and addition of rosemary diterpene mixture at 0.02% v/w reduced the microbial growth and improved (p < 0.05) the sensory attributes. Our results demonstrate that sous vide processing minimizes lipid oxidation and microbial growth of chicken sausages with improved product quality and shelf-life at 4 ± 1 ℃. © The Author(s) 2016.

Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles.

PubMed

Curcio, Christine A; Presley, J Brett; Millican, C Leigh; Medeiros, Nancy E

2005-06-01

Neutral lipid, including esterified cholesterol, and apolipoproteins B and E are abundant in basal deposits and drusen of aged and age-related maculopathy (ARM) eyes. The principal component of basal linear deposit (BlinD), a specific ARM lesion, is membranous debris, which if actually derived from membranes cannot account for extracellular neutral lipid. We therefore used a lipid-preserving ultrastructural method to obtain improved images of membranous debris. Maculas from 44 human donors (71-96 yr) were preserved <7.5 hr after death. Blocks were post-fixed in 2% osmium or osmium-tannic acid-paraphenylenediamine (OTAP) to preserve neutral lipid for thin-section transmission electron microscopic (TEM) examination. Solid particles identified by OTAP were considered closest to the in vivo state of extracellular lipids. Micrographs were examined for intermediate forms, with greatest weight given to comparable images from different preparations of same or fellow eyes. Twenty eyes of older adults (12 with ARM including fellows treated with photodynamic and radiation therapies) had adequately preserved extracellular lipid. The exterior surface of membranous debris was thicker and more electron-dense than basal infoldings of retinal pigment epithelium (RPE) cells. By OTAP, individual membranous debris profiles were solid (diameters, 80-200 nm) and formed tracks across or aggregations within basal laminar deposits. Solid particles and/or pools of neutral lipid were visible in BlinD and drusen. When processed to preserve lipid, membranous debris resembles neither membranes of surrounding cells nor vesicles possessing aqueous interiors but rather solid particles. These results are consistent with recent evidence implicating lipoprotein particles of intra-ocular origin as a potential source of neutral lipids, including esterified cholesterol, in the specific lesions of ARM.

Implementing electronic clinical reminders for lipid management in patients with ischemic heart disease in the veterans health administration: QUERI Series

PubMed Central

Sales, Anne; Helfrich, Christian; Ho, P Michael; Hedeen, Ashley; Plomondon, Mary E; Li, Yu-Fang; Connors, Alison; Rumsfeld, John S

2008-01-01

Background Ischemic heart disease (IHD) affects at least 150,000 veterans annually in the United States. Lowering serum cholesterol has been shown to reduce coronary events, cardiac death, and total mortality among high risk patients. Electronic clinical reminders available at the point of care delivery have been developed to improve lipid measurement and management in the Veterans Health Administration (VHA). Our objective was to report on a hospital-level intervention to implement and encourage use of the electronic clinical reminders. Methods The implementation used a quasi-experimental design with a comparison group of hospitals. In the intervention hospitals (N = 3), we used a multi-faceted intervention to encourage use of the electronic clinical reminders. We evaluated the degree of reminder use and how patient-level outcomes varied at the intervention and comparison sites (N = 3), with and without adjusting for self-reported reminder use. Results The national electronic clinical reminders were implemented in all of the intervention sites during the intervention period. A total of 5,438 patients with prior diagnosis of ischemic heart disease received care in the six hospitals (3 intervention and 3 comparison) throughout the 12-month intervention. The process evaluation showed variation in use of reminders at each site. Without controlling for provider self-report of use of the reminders, there appeared to be a significant improvement in lipid measurement in the intervention sites (OR 1.96, 95% CI 1.34, 2.88). Controlling for use of reminders, the amount of improvement in lipid measurement in the intervention sites was even greater (OR 2.35, CI 1.96, 2.81). Adjusting for reminder use demonstrated that only one of the intervention hospitals had a significant effect of the intervention. There was no significant change in management of hyperlipidemia associated with the intervention. Conclusion There may be some benefit to focused effort to implement electronic clinical reminders, although reminders designed to improve relatively simple tasks, such as ordering tests, may be more beneficial than reminders designed to improve more complex tasks, such as initiating or titrating medications, because of the less complex nature of the task. There is value in monitoring the process, as well as outcome, of an implementation effort. PMID:18510748

Vitamin E Analogue Improves Rabbit Sperm Quality during the Process of Cryopreservation through Its Antioxidative Action

PubMed Central

Zhu, Zhendong; Fan, Xiaoteng; Lv, Yinghua; Zhang, Nan; Fan, Chuning; Zhang, Pengfei; Zeng, Wenxian

2015-01-01

The process of cryopreservation results in high concentration of reactive oxygen species which is detrimental to spermatozoa. The aim of this study was to investigate whether addition of vitamin E analogue to freezing extender can facilitate the cryosurvival of spermatozoa in rabbits, and how vitamin E protects spermatozoa against damages during the process of preservation. Freshly ejaculated semen was diluted with Tris-citrate-glucose extender supplemented with different concentrations of Trolox (a vitamin E analogue). The level of radical oxygen species (ROS) in spermatozoa that was exposed to Trolox was significantly lower than that of the control during each step of the process of preservation. The percentage of frozen-thawed spermatozoa with lipid peroxidation in the Trolox treatments was significantly lower than that of the control. The motility, intact acrosome, membrane integrity and mitochondrial potentials of the frozen-thawed spermatozoa in the treatment of 200 μM Trolox were significantly higher than those of the control. These observations suggest that addition of vitamin E to a freezing extender leads to higher integrity of acrosome, plasma membrane and mitochondrial membrane potential as well as higher motility. Vitamin E protects spermatozoa through its capacity to quench ROS accumulation and lipid peroxidation during the process of preservation. Addition of Trolox is recommended to facilitate the improvement of semen preservation for the rabbit breeding industry. PMID:26700473

Ultra-small lipid-polymer hybrid nanoparticles for tumor-penetrating drug delivery

NASA Astrophysics Data System (ADS)

Dehaini, Diana; Fang, Ronnie H.; Luk, Brian T.; Pang, Zhiqing; Hu, Che-Ming J.; Kroll, Ashley V.; Yu, Chun Lai; Gao, Weiwei; Zhang, Liangfang

2016-07-01

Lipid-polymer hybrid nanoparticles, consisting of a polymeric core coated by a layer of lipids, are a class of highly scalable, biodegradable nanocarriers that have shown great promise in drug delivery applications. Here, we demonstrate the facile synthesis of ultra-small, sub-25 nm lipid-polymer hybrid nanoparticles using an adapted nanoprecipitation approach and explore their utility for targeted delivery of a model chemotherapeutic. The fabrication process is first optimized to produce a monodisperse population of particles that are stable under physiological conditions. It is shown that these ultra-small hybrid nanoparticles can be functionalized with a targeting ligand on the surface and loaded with drug inside the polymeric matrix. Further, the in vivo fate of the nanoparticles after intravenous injection is characterized by examining the blood circulation and biodistribution. In a final proof-of-concept study, targeted ultra-small hybrid nanoparticles loaded with the cancer drug docetaxel are used to treat a mouse tumor model and demonstrate improved efficacy compared to a clinically available formulation of the drug. The ability to synthesize a significantly smaller version of the established lipid-polymer hybrid platform can ultimately enhance its applicability across a wider range of applications.

Techno-economic analysis of biodiesel and ethanol co-production from lipid-producing sugarcane: Biodiesel and Ethanol Co-Production from Lipid-Producing Sugarcane

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

Huang, Haibo; Long, Stephen; Singh, Vijay

Biodiesel production from vegetable oils has progressively increased over the past two decades. However, due to the low amounts of oil produced per hectare from temperate oilseed crops (e.g. soybean), the opportunities for further increasing biodiesel production are limited. Genetically modified lipid-producing sugarcane (lipid-cane) possesses great potential for producing biodiesel as an alternative feedstock because of sugarcane’s much higher productivity compared with soybean. In this study, techno-economic models were developed for biodiesel and ethanol coproduction from lipid-cane, assuming 2, 5, 10, or 20% lipid concentration in the harvested stem (dry mass basis). The models were compared with a conventional soybeanmore » biodiesel process model to assess lipid-cane’s competiveness. In the lipid-cane process model, the extracted lipids were used to produce biodiesel by transesterifi cation, and the remaining sugar was used to produce ethanol by fermentation. The results showed that the biodiesel production cost from lipid-cane decreased from $0.89/L to $0.59 /L as the lipid content increased from 2 to 20%; this cost was lower than that obtained for soybeans ($1.08/L). The ethanol production costs from lipid-cane were between $0.40/L and $0.46/L. The internal rate of return (IRR) for the soybean biodiesel process was 15.0%, and the IRR for the lipid-cane process went from 13.7 to 24.0% as the lipid content increased from 2 to 20%. Because of its high productivity, lipid-cane with 20% lipid content can produce 6700 L of biodiesel from each hectare of land, whereas soybean can only produce approximately 500 L of biodiesel from each hectare of land. This would indicate that continued efforts to achieve lipid-producing sugarcane could make large-scale replacement of fossil-fuel-derived diesel without unrealistic demands on land area.« less

Techno-economic analysis of biodiesel and ethanol co-production from lipid-producing sugarcane: Biodiesel and Ethanol Co-Production from Lipid-Producing Sugarcane

DOE PAGES

Huang, Haibo; Long, Stephen; Singh, Vijay

2016-03-07

Biodiesel production from vegetable oils has progressively increased over the past two decades. However, due to the low amounts of oil produced per hectare from temperate oilseed crops (e.g. soybean), the opportunities for further increasing biodiesel production are limited. Genetically modified lipid-producing sugarcane (lipid-cane) possesses great potential for producing biodiesel as an alternative feedstock because of sugarcane’s much higher productivity compared with soybean. In this study, techno-economic models were developed for biodiesel and ethanol coproduction from lipid-cane, assuming 2, 5, 10, or 20% lipid concentration in the harvested stem (dry mass basis). The models were compared with a conventional soybeanmore » biodiesel process model to assess lipid-cane’s competiveness. In the lipid-cane process model, the extracted lipids were used to produce biodiesel by transesterifi cation, and the remaining sugar was used to produce ethanol by fermentation. The results showed that the biodiesel production cost from lipid-cane decreased from $0.89/L to $0.59 /L as the lipid content increased from 2 to 20%; this cost was lower than that obtained for soybeans ($1.08/L). The ethanol production costs from lipid-cane were between $0.40/L and $0.46/L. The internal rate of return (IRR) for the soybean biodiesel process was 15.0%, and the IRR for the lipid-cane process went from 13.7 to 24.0% as the lipid content increased from 2 to 20%. Because of its high productivity, lipid-cane with 20% lipid content can produce 6700 L of biodiesel from each hectare of land, whereas soybean can only produce approximately 500 L of biodiesel from each hectare of land. This would indicate that continued efforts to achieve lipid-producing sugarcane could make large-scale replacement of fossil-fuel-derived diesel without unrealistic demands on land area.« less

[The use of bemitil in patients with progressive muscular dystrophies].

PubMed

Lobzin, V S; Saĭkova, L A; Chukhlovina, M L; Pustozerov, V G

1992-04-01

Bemithyl treatment was carried out in 22 patients with neuromuscular diseases (progressive myodystrophy). The actoprotector bemithyl inhibited in these patients the processes of lipid peroxidation, activation of neoglucogenesis favours improvement of interorganic exchange of metabolites. Bemithyl is recommended in patients with progressive myodystrophy along with drugs normalizing the protein, energy and electrolyte metabolism.

Lipid extraction of wet BLT0404 microalgae for biofuel application

NASA Astrophysics Data System (ADS)

Mansur, Dieni; Fitriady, Muhammad Arifuddin; Susilaningsih, Dwi; Simanungkalit, Sabar Pangihutan; Agustian, Egi

2017-01-01

Recently, research and development of microalgae for biodiesel production were conducted by researchers in the world. This research becomes popular because of an exponential growth of the microalgae under nutrient limitation. Lipid of microalgae grows faster than oil producing land crops. Therefore, microalgae lipid content could improve the economics of biodiesel production. The aim of this study was to investigate yield of lipid extract and chemicals compounds containing in non-acylglycerol neutral lipid from BLT 0404 microalga. The study was conducted because lipid extraction was an important step for biodiesel as well as biofuel production. The extraction was carried out using polar and non-polar mixture solvents. The polar solvent was methanol and non-polar one was chloroform. Process extraction was conducted under various stirring time between the microalgae and methanol and volume ratio between the methanol and chloroform. Methanol as a polar solvent was able to extract polar lipid (phospholipid and glycolipid) because it removed polar membrane lipid and lipid-associated to polar molecule. Moreover, the non-polar solvent was used for extraction non-acylglycerol neutral lipid (hydrocarbons, sterols, ketones, free fatty acids, carotenes, and chlorophylls) for biofuel production. Under ratio of microalgae: methanol: chloroform of 0.8: 4: 2 that stirring time of the microalgae with methanol was 30 min yielded 58% of total lipid extract. The yield value consisted of 14.5% of non-acylglycerol neutral lipid and 43.5% of polar lipid. The non-acylglycerol neutral lipid will be converted into biofuel. Therefore, analysis of its chemical compounds was required. The non-acylglycerol neutral lipid was analyzed by GCMS and found that the extract contained long chains of hydrocarbon compounds. The hydrocarbons consisted of C18-C30 that high peaks with larger percentage area were C20-C26. The results suggested that stirring between microalgae and methanol for 30 min was needed before additional of chloroform. Moreover, the ratio of methanol must be higher than chloroform due to the higher portion of polar lipid content in the microalgae.

[Studying the hepatoprotector effect of bemithyl on a model of chronic toxic liver damage].

PubMed

Oskovityĭ, S V; Bezborodkina, N N; Zarubina, I V; Mironova, O P; Kudrivtsev, B N; Shulenin, S N

2006-01-01

A prophylactic and therapeutic introduction of the synthetic adaptogen bemithyl (2-ethylthiobensimidasole hydrobromide) produces a hepatoprotector effect in rats with experimental cirrhosis. The drug exhibits an anticytolytic activity, restores liver participation in the pigment exchange, and normalizes the function of the microsomal oxidation system responsible for the metabolism of xenobiotics. The treatment with bemithyl also leads to a certain improvement of a histologic picture of the damaged liver and to a decrease in the degree of fibrosis. The drug is also capable of increasing the activity of the antioxidant system and inhibiting the process of lipid peroxidation of proteins and lipids in the liver.

Automation of a Nile red staining assay enables high throughput quantification of microalgal lipid production.

PubMed

Morschett, Holger; Wiechert, Wolfgang; Oldiges, Marco

2016-02-09

Within the context of microalgal lipid production for biofuels and bulk chemical applications, specialized higher throughput devices for small scale parallelized cultivation are expected to boost the time efficiency of phototrophic bioprocess development. However, the increasing number of possible experiments is directly coupled to the demand for lipid quantification protocols that enable reliably measuring large sets of samples within short time and that can deal with the reduced sample volume typically generated at screening scale. To meet these demands, a dye based assay was established using a liquid handling robot to provide reproducible high throughput quantification of lipids with minimized hands-on-time. Lipid production was monitored using the fluorescent dye Nile red with dimethyl sulfoxide as solvent facilitating dye permeation. The staining kinetics of cells at different concentrations and physiological states were investigated to successfully down-scale the assay to 96 well microtiter plates. Gravimetric calibration against a well-established extractive protocol enabled absolute quantification of intracellular lipids improving precision from ±8 to ±2 % on average. Implementation into an automated liquid handling platform allows for measuring up to 48 samples within 6.5 h, reducing hands-on-time to a third compared to manual operation. Moreover, it was shown that automation enhances accuracy and precision compared to manual preparation. It was revealed that established protocols relying on optical density or cell number for biomass adjustion prior to staining may suffer from errors due to significant changes of the cells' optical and physiological properties during cultivation. Alternatively, the biovolume was used as a measure for biomass concentration so that errors from morphological changes can be excluded. The newly established assay proved to be applicable for absolute quantification of algal lipids avoiding limitations of currently established protocols, namely biomass adjustment and limited throughput. Automation was shown to improve data reliability, as well as experimental throughput simultaneously minimizing the needed hands-on-time to a third. Thereby, the presented protocol meets the demands for the analysis of samples generated by the upcoming generation of devices for higher throughput phototrophic cultivation and thereby contributes to boosting the time efficiency for setting up algae lipid production processes.

Urea and urine are a viable and cost-effective nitrogen source for Yarrowia lipolytica biomass and lipid accumulation.

PubMed

Brabender, Matthew; Hussain, Murtaza Shabbir; Rodriguez, Gabriel; Blenner, Mark A

2018-03-01

Yarrowia lipolytica is an industrial yeast that has been used in the sustainable production of fatty acid-derived and lipid compounds due to its high growth capacity, genetic tractability, and oleaginous properties. This investigation examines the possibility of utilizing urea or urine as an alternative to ammonium sulfate as a nitrogen source to culture Y. lipolytica. The use of a stoichiometrically equivalent concentration of urea in lieu of ammonium sulfate significantly increased cell growth when glucose was used as the carbon source. Furthermore, Y. lipolytica growth was equally improved when grown with synthetic urine and real human urine. Equivalent or better lipid production was achieved when cells are grown on urea or urine. The successful use of urea and urine as nitrogen sources for Y. lipolytica growth highlights the potential of using cheaper media components as well as exploiting and recycling non-treated human waste streams for biotechnology processes.

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.

Carrier characteristics influence the kinetics of passive drug loading into lipid nanoemulsions.

PubMed

Göke, Katrin; Bunjes, Heike

2018-05-01

Passive loading as a novel screening approach is a material-saving tool for the efficient selection of a suitable colloidal lipid carrier system for poorly water soluble drug candidates. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles after removal of excess drug. For reliable routine use and to obtain meaningful loading results, information on the kinetics of the process is required. Passive loading proceeds via a dissolution-diffusion-based mechanism, where drug surface area and drug water solubility are key parameters for fast passive loading. While the influence of the drug characteristics is mostly understood, the influence of the carrier characteristics remains unknown. The aim of this study was to examine how the lipid nanocarriers' characteristics, i.e. the type of lipid, the lipid content and the particle size, influence the kinetics of passive loading. Fenofibrate was used as model drug and the loading progress was analyzed by UV spectroscopy. The saturation solubility in the nanocarrier particles, i.e. the lipid type, did not influence the passive loading rate constant. Low lipid content in the nanocarrier and a small nanocarrier particle size both increased passive loading speed. Both variations increase the diffusivity of the nanocarrier particles, which is the primary cause for fast loading at these conditions: The quicker the carrier particles diffuse, the higher is the speed of passive loading. The influence of the diffusivity of the lipid nanocarriers and the effect of drug dissolution rate were included in an overall mechanistic model developed for similar processes (A. Balakrishnan, B.D. Rege, G.L. Amidon, J.E. Polli, Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity, J. Pharm. Sci. 93 (2004) 2064-2075). The resulting mechanistic model gave a good estimate of the speed of passive loading in nanoemulsions. Whilst the drug's characteristics - apart from drug surface area - are basically fixed, the lipid nanocarriers can be customized to improve passive loading speed, e.g. by using small nanocarrier particles. The knowledge of the loading mechanism now allows the use of passive loading for the straightforward, material-saving selection of suitable lipid drug nanocarriers. Copyright © 2017 Elsevier B.V. All rights reserved.

HDL particles incorporate into lipid bilayers - a combined AFM and single molecule fluorescence microscopy study.

PubMed

Plochberger, Birgit; Röhrl, Clemens; Preiner, Johannes; Rankl, Christian; Brameshuber, Mario; Madl, Josef; Bittman, Robert; Ros, Robert; Sezgin, Erdinc; Eggeling, Christian; Hinterdorfer, Peter; Stangl, Herbert; Schütz, Gerhard J

2017-11-21

The process, how lipids are removed from the circulation and transferred from high density lipoprotein (HDL) - a main carrier of cholesterol in the blood stream - to cells, is highly complex. HDL particles are captured from the blood stream by the scavenger receptor, class B, type I (SR-BI), the so-called HDL receptor. The details in subsequent lipid-transfer process, however, have not yet been completely understood. The transfer has been proposed to occur directly at the cell surface across an unstirred water layer, via a hydrophobic channel in the receptor, or after HDL endocytosis. The role of the target lipid membrane for the transfer process, however, has largely been overlooked. Here, we studied at the single molecule level how HDL particles interact with synthetic lipid membranes. Using (high-speed) atomic force microscopy and fluorescence correlation spectroscopy (FCS) we found out that, upon contact with the membrane, HDL becomes integrated into the lipid bilayer. Combined force and single molecule fluorescence microscopy allowed us to directly monitor the transfer process of fluorescently labelled amphiphilic lipid probe from HDL particles to the lipid bilayer upon contact.

Lipids-based nanostructured lipid carriers (NLCs) for improved oral bioavailability of sirolimus.

PubMed

Yu, Qin; Hu, Xiongwei; Ma, Yuhua; Xie, Yunchang; Lu, Yi; Qi, Jianping; Xiang, Li; Li, Fengqian; Wu, Wei

2016-05-01

The main purpose of this study was to improve the oral bioavailability of sirolimus (SRL), a poorly water-soluble immunosuppressant, by encapsulating into lipids-based nanostructured lipid carriers (NLCs). SRL-loaded NLCs (SRL-NLCs) were prepared by a high-pressure homogenization method with glycerol distearates (PRECIROL ATO-5) as the solid lipid, oleic acid as the liquid lipids, and Tween 80 as the emulsifier. The SRL-NLCs prepared under optimum conditions was spherical in shape with a mean particle size of about 108.3 nm and an entrapment efficiency of 99.81%. In vitro release of SRL-NLCs was very slow, about 2.15% at 12 h, while in vitro lipolysis test showed fast digestion of the NLCs within 1 h. Relative oral bioavailability of SRL-NLCs in Beagle dogs was 1.81-folds that of the commercial nanocrystalline sirolimus tablets Rapamune®. In conclusion, the NLCs show potential to improve the oral bioavailability of SRL.

Rhodopsin-lipid interactions studied by NMR.

PubMed

Soubias, Olivier; Gawrisch, Klaus

2013-01-01

The biophysical properties of the lipid matrix are known to influence function of integral membrane proteins. We report on a sample preparation method for reconstitution of membrane proteins which uses porous anodic aluminum oxide (AAO) filters with 200-nm-wide pores of high density. The substrate permits formation of tubular, single membranes that line the inner surface of pores. One square centimeter of filter with a thickness of 60μm yields on the order of 500cm(2) of solid-supported single bilayer surface, sufficient for NMR studies. The tubular bilayers are free of detergent, fully hydrated, and accessible for ligands from one side of the membrane. The use of AAO filters greatly improves reproducibility of the reconstitution process such that the influence of protein on lipid order parameters can be studied with high resolution. As an example, results for the G protein-coupled receptor of class A, bovine rhodopsin, are shown. By (2)H NMR order parameter measurements, it is detected that rhodopsin insertion elastically deforms membranes near the protein. Furthermore, by (1)H saturation-transfer NMR under conditions of magic angle spinning, we demonstrate detection of preferences in interactions of rhodopsin with particular lipid species. It is assumed that function of integral membrane proteins depends on both protein-induced elastic deformations of the lipid matrix and preferences for interaction of the protein with particular lipid species in the first layer of lipids surrounding the protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Combined mutagenesis of Rhodosporidium toruloides for improved production of carotenoids and lipids.

PubMed

Zhang, Chaolei; Shen, Hongwei; Zhang, Xibin; Yu, Xue; Wang, Han; Xiao, Shan; Wang, Jihui; Zhao, Zongbao K

2016-10-01

To improve production of lipids and carotenoids by the oleaginous yeast Rhodosporidium toruloides by screening mutant strains. Upon physical mutagenesis of the haploid strain R. toruloides np11 with an atmospheric and room temperature plasma method followed by chemical mutagenesis with nitrosoguanidine, a mutant strain, R. toruloides XR-2, formed dark-red colonies on a screening plate. When cultivated in nitrogen-limited media, XR-2 cells grew slower but accumulated 0.23 g lipids/g cell dry wt and 0.75 mg carotenoids/g CDW. To improve its production capacity, different amino acids and vitamins were supplemented. p-Aminobenzoic acid and tryptophan had beneficial effects on cell growth. When cultivated in nitrogen-limited media in the presence of selected vitamins, XR-2 accumulated 0.41 g lipids/g CDW and 0.69 mg carotenoids/g CDW. A mutant R. toruloides strain with improved production profiles for lipids and carotenoids was obtained, indicating its potential to use combined mutagenesis for a more productive phenotype.

An evolutionary metabolic engineering approach for enhancing lipogenesis in Yarrowia lipolytica.

PubMed

Liu, Leqian; Pan, Anny; Spofford, Caitlin; Zhou, Nijia; Alper, Hal S

2015-05-01

Lipogenic organisms provide an ideal platform for biodiesel and oleochemical production. Through our previous rational metabolic engineering efforts, lipogenesis titers in Yarrowia lipolytica were significantly enhanced. However, the resulting strain still suffered from decreased biomass generation rates. Here, we employ a rapid evolutionary metabolic engineering approach linked with a floating cell enrichment process to improve lipogenesis rates, titers, and yields. Through this iterative process, we were able to ultimately improve yields from our prior strain by 55% to achieve production titers of 39.1g/L with upwards of 76% of the theoretical maximum yield of conversation. Isolated cells were saturated with up to 87% lipid content. An average specific productivity of 0.56g/L/h was achieved with a maximum instantaneous specific productivity of 0.89g/L/h during the lipid production phase in fermentation. Genomic sequencing of the evolved strains revealed a link between a decrease/loss of function mutation of succinate semialdehyde dehydrogenase, uga2, suggesting the importance of gamma-aminobutyric acid assimilation in lipogenesis. This linkage was validated through gene deletion experiments. This work presents an improved host strain that can serve as a platform for efficient oleochemical production. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Enhancement of Biomass and Lipid Productivities of Water Surface-Floating Microalgae by Chemical Mutagenesis

PubMed Central

Nojima, Daisuke; Ishizuka, Yuki; Muto, Masaki; Ujiro, Asuka; Kodama, Fumito; Yoshino, Tomoko; Maeda, Yoshiaki; Matsunaga, Tadashi; Tanaka, Tsuyoshi

2017-01-01

Water surface-floating microalgae have great potential for biofuel applications due to the ease of the harvesting process, which is one of the most problematic steps in conventional microalgal biofuel production. We have collected promising water surface-floating microalgae and characterized their capacity for biomass and lipid production. In this study, we performed chemical mutagenesis of two water surface-floating microalgae to elevate productivity. Floating microalgal strains AVFF007 and FFG039 (tentatively identified as Botryosphaerella sp. and Chlorococcum sp., respectively) were exposed to ethyl methane sulfonate (EMS) or 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), and pale green mutants (PMs) were obtained. The most promising FFG039 PM formed robust biofilms on the surface of the culture medium, similar to those formed by wild type strains, and it exhibited 1.7-fold and 1.9-fold higher biomass and lipid productivities than those of the wild type. This study indicates that the chemical mutation strategy improves the lipid productivity of water surface-floating microalgae without inhibiting biofilm formation and floating ability. PMID:28555001

Enhancement of Biomass and Lipid Productivities of Water Surface-Floating Microalgae by Chemical Mutagenesis.

PubMed

Nojima, Daisuke; Ishizuka, Yuki; Muto, Masaki; Ujiro, Asuka; Kodama, Fumito; Yoshino, Tomoko; Maeda, Yoshiaki; Matsunaga, Tadashi; Tanaka, Tsuyoshi

2017-05-27

Water surface-floating microalgae have great potential for biofuel applications due to the ease of the harvesting process, which is one of the most problematic steps in conventional microalgal biofuel production. We have collected promising water surface-floating microalgae and characterized their capacity for biomass and lipid production. In this study, we performed chemical mutagenesis of two water surface-floating microalgae to elevate productivity. Floating microalgal strains AVFF007 and FFG039 (tentatively identified as Botryosphaerella sp. and Chlorococcum sp., respectively) were exposed to ethyl methane sulfonate (EMS) or 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), and pale green mutants (PMs) were obtained. The most promising FFG039 PM formed robust biofilms on the surface of the culture medium, similar to those formed by wild type strains, and it exhibited 1.7-fold and 1.9-fold higher biomass and lipid productivities than those of the wild type. This study indicates that the chemical mutation strategy improves the lipid productivity of water surface-floating microalgae without inhibiting biofilm formation and floating ability.

A novel squarylium dye for monitoring oxidative processes in lipid membranes.

PubMed

Trusova, Valeriya M; Gorbenko, Galyna P; Deligeorgiev, Todor; Gadjev, Nikolai; Vasilev, Aleksey

2009-11-01

A novel squaraine probe SQ-1 has been found to be appropriate for monitoring the peroxidation processes in membrane systems. Formation of free radicals was triggered by methemoglobin (metHb) or cytochrome c (cyt c) binding to the model lipid membranes composed of zwitterionic lipid phosphatidylcholine (PC) and anionic lipid cardiolipin (CL). Protein association with the lipid vesicles was followed by drastic quenching of SQ-1 fluorescence. The observed spectral changes were suppressed in the presence of free radical scavengers, butylated hydroxytoluene (BHT) and thiourea (TM) suggesting that SQ-1 decolorization can be attributed to its reactions with lipid radicals.

Disease management programs in type 2 diabetes: quality of care.

PubMed

Berthold, Heiner K; Bestehorn, Kurt P; Jannowitz, Christina; Krone, Wilhelm; Gouni-Berthold, Ioanna

2011-06-01

To determine whether disease management programs (DMPs) for type 2 diabetes mellitus (T2DM) can improve some processes of care and intermediate outcomes. Two cross-sectional registries of patients with T2DM were used for data extraction before (previous cohort) and after (recent cohort) introduction of DMPs in Germany (N = 78,110). In the recent cohort, 15,293 patients were treated within the DMPs and 9791 were not. Processes of care, medications, and intermediate outcomes (achievement of treatment targets for low-density lipoprotein [LDL] cholesterol, blood pressure, and glycosylated hemoglobin [A1C]) were analyzed using multi- variable, multilevel logistic regression, adjusting for patient case-mix and physician-level clustering to derive odds ratios and 95% confidence intervals (CIs). Availability of structured diabetes education and of lipid, blood pressure, and A1C measurements increased over time. In DMP patients, availability was significantly higher for blood pressure and A1C but not for lipid measurements. Prescription of angiotensin-converting enzyme inhibitors, oral antidiabetic drugs, and insulin increased over time and was more common in DMP patients. Statin prescription increased over time but was not influenced by DMP status. Intermediate outcomes improved over time, but DMPs had no influence on intermediate outcomes except for reaching LDL cholesterol targets (odds ratio 1.12 [95% CI 1.06, 1.19] in favor of DMPs). While there may be some unmeasured confounding, our data suggest that improvement in processes of care by DMPs, as implemented in Germany, only partially translates into improvement of intermediate outcomes.

The Influence of Religious Affiliation on Participant Responsiveness to the Complete Health Improvement Program (CHIP) Lifestyle Intervention.

PubMed

Kent, L M; Morton, D P; Ward, E J; Rankin, P M; Ferret, R B; Gobble, J; Diehl, H A

2016-10-01

Seventh-day Adventist (SDA) and non-SDA (21.3 and 78.7 %, respectively) individuals (n = 7172) participating in the Complete Health Improvement Program, a 30-day diet and lifestyle intervention, in North America (241 programs, 2006-2012) were assessed for changes in selected chronic disease risk factors: body mass index (BMI), blood pressure (BP), pulse, lipid profile and fasting plasma glucose (FPG). Reductions were greater among the non-SDA for BMI, pulse and blood lipids. Furthermore, the majority of non-SDA in the highest risk classifications for BP, lipids and FPG, but only some lipids among SDA, were able to show improvement by 20 % or more.

Hypothyroidism affects lipid and glycogen content and peroxisome proliferator-activated receptor ? expression in the ovary of the rabbit.

PubMed

Rodríguez-Castelán, Julia; Méndez-Tepepa, Maribel; Rodríguez-Antolín, Jorge; Castelán, Francisco; Cuevas-Romero, Estela

2018-05-03

Dyslipidaemia and hyperglycaemia are associated with ovarian failure and both have been related to hypothyroidism. Hypothyroidism promotes anovulation and ovarian cysts in women and reduces the size of follicles and the expression of aromatase in the ovary of rabbits. Considering that ovarian steroidogenesis and ovulation depend on lipid metabolism and signalling, the aim of the present study was to analyse the effect of hypothyroidism on the lipid content and expression of peroxisome proliferator-activated receptor (PPAR) δ in the ovary. Ovaries from female rabbits belonging to the control (n=7) and hypothyroid (n=7) groups were processed to measure total cholesterol (TC), triacylglycerol (TAG) and glycogen content, as well as to determine the presence of granules containing oxidized lipids (oxysterols and lipofuscin) and the relative expression of perilipin A (PLIN-A) and PPARδ. Hypothyroidism increased TC and glycogen content, but reduced TAG content in the ovary. This was accompanied by a reduction in the expression of PLIN-A in total and cytosolic extracts, changes in the presence of granules containing oxidative lipids and low PPARδ expression. The results of the present study suggest that hypothyroidism modifies the content and signalling of lipids in the ovary, possibly affecting follicle maturation. These results could improve our understanding of the association between hypothyroidism and infertility in females.

Sustainability and economic evaluation of microalgae grown in brewery wastewater.

PubMed

Mata, Teresa M; Mendes, Adélio M; Caetano, Nídia S; Martins, António A

2014-09-01

This article evaluates the sustainability and economic potential of microalgae grown in brewery wastewater for biodiesel and biomass production. Three sustainability and two economic indicators were considered in the evaluation within a life cycle perspective. For the production system the most efficient process units were selected. Results show that harvesting and oil separation are the main process bottlenecks. Microalgae with higher lipid content and productivity are desirable for biodiesel production, although comparable to other biofuel's feedstock concerning sustainability. However, improvements are still needed to reach the performance level of fossil diesel. Profitability reaches a limit for larger cultivation areas, being higher when extracted biomass is sold together with microalgae oil, in which case the influence of lipid content and areal productivity is smaller. The values of oil and/or biomass prices calculated to ensure that the process is economically sound are still very high compared with other fuel options, especially biodiesel. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Using of reamberin for correction of free radicals disturbances in patients with acute severe methadone poisonings].

PubMed

Shilov, V V; Vasil'ev, S A; Batotsyrenov, B V; Loladze, A T; Kuznetsov, O A

2012-03-01

The article deals with the materials, which have been received in the process of the examination and treatment of 44 patients with acute severe methadone poisonings. It has been revealed, that gravity of these patient's condition depends on intensity of hypoxia due to breath deficiency because of the methadone. The development of hypoxia, in its turn, cause violations of antiradical protection system and intensification of processes of peroxide lipid oxidation. It has been registered that the including of reamberin into the complex program of the intensive therapy of acute severe methadone poisonings lead to a more rapid restoration of antiradical protection system and to a decrease of activity of processes of peroxide lipid oxidation. The correction of hypoxia and free-radical violations led to improvement of the acute poisonings clinic, what had been characterized by a decrease of coma-period duration, duration of treatment with artificial lung ventilation, a decrease of secondary lung complications and a decrease of lethality.

Vitamins C and E improve regrowth and reduce lipid peroxidation of blackberry shoot tips following cryopreservation.

PubMed

Uchendu, Esther E; Leonard, Scott W; Traber, Maret G; Reed, Barbara M

2010-01-01

Oxidative processes involved in cryopreservation protocols may be responsible for the reduced viability of tissues after liquid nitrogen exposure. Antioxidants that counteract these reactions should improve recovery. This study focused on oxidative lipid injury and the effects of exogenous vitamin E (tocopherol, Vit E) and vitamin C (ascorbic acid, Vit C) treatments on regrowth at four critical steps of the plant vitrification solution number 2 (PVS2) vitrification cryopreservation technique; pretreatment, loading, rinsing, and regrowth. Initial experiments showed that Vit E at 11-15 mM significantly increased regrowth (P < 0.001) when added at any of the four steps. There was significantly more malondialdehyde (MDA), a lipid peroxidation product, at each of the steps than in fresh untreated shoot tips. Vit E uptake was assayed at each step and showed significantly more alpha- and gamma-tocopherols in treated shoots than those without Vit E. Vit E added at each step significantly reduced MDA formation and improved shoot regrowth. Vit C (0.14-0.58 mM) also significantly improved regrowth of shoot tips at each step compared to the controls. Regrowth medium with high iron concentrations and Vit C decreased recovery. However, in iron-free medium, Vit C significantly improved recovery. Treatments with Vit E (11 mM) and Vit C (0.14 mM) combined were not significantly better than Vit C alone. We recommend adding Vit C (0.28 mM) to the pretreatment medium, the loading solution or the rinse solution in the PVS2 vitrification protocol. This is the first report of the application of vitamins for improving cryopreservation of plant tissues by minimizing oxidative damage.

The Effect of Exercise Training on Serum Lipids in the Elderly.

PubMed

Ades, Philip A.; Poehlman, Eric T.

1996-10-01

Numerous intervention trials in young subjects suggest that aerobic exercise training exerts favorable effects on specific lipid subfractions, in particular serum triglycerides and high density lipoprotein (HDL) cholesterol. Cross sectional studies in older individuals suggest that active individuals have more favorable lipid profiles than inactive individuals. However, it remains controversial as to whether leisure time activity or fitness levels per se are independent predictors of lipid measures in the elderly versus their intermediate effects on body composition and body fat distribution. That is, a greater deposition of abdominal fat in the least fit individuals is associated with adverse lipid profiles. Short-term (8-weeks) aerobic exercise in elders is not associated with any significant changes in lipid profiles, however, longer term programs, particularly if associated with improvements in body fat distribution and/or weight loss, have been demonstrated to yield significant improvements in lipid subfractions, in particular triglycerides and HDL cholesterol.

Prediction of Adult Dyslipidemia Using Genetic and Childhood Clinical Risk Factors: The Cardiovascular Risk in Young Finns Study.

PubMed

Nuotio, Joel; Pitkänen, Niina; Magnussen, Costan G; Buscot, Marie-Jeanne; Venäläinen, Mikko S; Elo, Laura L; Jokinen, Eero; Laitinen, Tomi; Taittonen, Leena; Hutri-Kähönen, Nina; Lyytikäinen, Leo-Pekka; Lehtimäki, Terho; Viikari, Jorma S; Juonala, Markus; Raitakari, Olli T

2017-06-01

Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures. Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3-18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811; P =0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758; P <0.01). The overall net reclassification improvement and integrated discrimination improvement were significant for all outcomes. The inclusion of weighted genetic risk scores to lipid-screening programs in childhood could modestly improve the identification of those at highest risk of dyslipidemia in adulthood. © 2017 American Heart Association, Inc.

Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids

NASA Astrophysics Data System (ADS)

Simovic, Spomenka; Barnes, Timothy J.; Tan, Angel; Prestidge, Clive A.

2012-02-01

Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

The Physiology of Protein S-acylation

PubMed Central

Chamberlain, Luke H.; Shipston, Michael J.

2015-01-01

Protein S-acylation, the only fully reversible posttranslational lipid modification of proteins, is emerging as a ubiquitous mechanism to control the properties and function of a diverse array of proteins and consequently physiological processes. S-acylation results from the enzymatic addition of long-chain lipids, most typically palmitate, onto intracellular cysteine residues of soluble and transmembrane proteins via a labile thioester linkage. Addition of lipid results in increases in protein hydrophobicity that can impact on protein structure, assembly, maturation, trafficking, and function. The recent explosion in global S-acylation (palmitoyl) proteomic profiling as a result of improved biochemical tools to assay S-acylation, in conjunction with the recent identification of enzymes that control protein S-acylation and de-acylation, has opened a new vista into the physiological function of S-acylation. This review introduces key features of S-acylation and tools to interrogate this process, and highlights the eclectic array of proteins regulated including membrane receptors, ion channels and transporters, enzymes and kinases, signaling adapters and chaperones, cell adhesion, and structural proteins. We highlight recent findings correlating disruption of S-acylation to pathophysiology and disease and discuss some of the major challenges and opportunities in this rapidly expanding field. PMID:25834228

Non-conventional approaches to food processing in CELSS. I - Algal proteins: Characterization and process optimization

NASA Technical Reports Server (NTRS)

Nakhost, Z.; Karel, M.; Krukonis, V. J.

1987-01-01

Protein isolate obtained from green algae (Scenedesmus obliquus) cultivated under controlled conditions was characterized. Molecular weight determination of fractionated algal proteins using SDS-polyacrylamide gel electrophoresis revealed a wide spectrum of molecular weights ranging from 15,000 to 220,000. Isoelectric points of dissociated proteins were in the range of 3.95 to 6.20. Amino acid composition of protein isolate compared favorably with FAO standards. High content of essential amino acids leucine, valine, phenylalanine and lysine makes algal protein isolate a high quality component of CELSS diets. To optimize the removal of algal lipids and pigments supercritical carbon dioxide extraction (with and without ethanol as a co-solvent) was used. Addition of ethanol to supercritical CO2 resulted in more efficient removal of algal lipids and produced protein isolate with a good yield and protein recovery. The protein isolate extracted by the above mixture had an improved water solubility.

Non-conventional approaches to food processing in CELSS, 1. Algal proteins: Characterization and process optimization

NASA Technical Reports Server (NTRS)

Nakhost, Z.; Karel, M.; Krukonis, V. J.

1987-01-01

Protein isolate obtained from green algae cultivated under controlled conditions was characterized. Molecular weight determination of fractionated algal proteins using SDS-polyacrylamide gel electrophoresis revealed a wide spectrum of molecular weights ranging from 15,000 to 220,000. Isoelectric points of dissociated proteins were in the range of 3.95 to 6.20. Amino acid composition of protein isolate compared favorably with FAO standards. High content of essential amino acids leucine, valine, phenylalanine and lysine make algal protein isolate a high quality component of closed ecological life support system diets. To optimize the removal of algal lipids and pigments supercritical carbon dioxide extraction (with and without ethanol as a co-solvent) was used. Addition of ethanol to supercritical carbon dioxide resulted in more efficient removal of algal lipids and produced protein isolate with a good yield and protein recovery. The protein isolate extracted by the above mixture had an improved water solubility.

Solvent-free melting techniques for the preparation of lipid-based solid oral formulations.

PubMed

Becker, Karin; Salar-Behzadi, Sharareh; Zimmer, Andreas

2015-05-01

Lipid excipients are applied for numerous purposes such as taste masking, controlled release, improvement of swallowability and moisture protection. Several melting techniques have evolved in the last decades. Common examples are melt coating, melt granulation and melt extrusion. The required equipment ranges from ordinary glass beakers for lab scale up to large machines such as fluid bed coaters, spray dryers or extruders. This allows for upscaling to pilot or production scale. Solvent free melt processing provides a cost-effective, time-saving and eco-friendly method for the food and pharmaceutical industries. This review intends to give a critical overview of the published literature on experiences, formulations and challenges and to show possibilities for future developments in this promising field. Moreover, it should serve as a guide for selecting the best excipients and manufacturing techniques for the development of a product with specific properties using solvent free melt processing.

Mesophilic co-digestion of dairy manure and lipid rich solid slaughterhouse wastes: process efficiency, limitations and floating granules formation.

PubMed

Pitk, Peep; Palatsi, Jordi; Kaparaju, Prasad; Fernández, Belén; Vilu, Raivo

2014-08-01

Lipid and protein rich solid slaughterhouse wastes are attractive co-substrates to increase volumetric biogas production in co-digestion with dairy manure. Addition of decanter sludge (DS), containing 42.2% of lipids and 35.8% of proteins (total solids basis), up to 5% of feed mixture resulted in a stable process without any indication of long chain fatty acids (LCFA) or free ammonia (NH3) inhibition and in 3.5-fold increase of volumetric biogas production. Contrary, only lipids addition as technical fat (TF) at over 2% of feed mixture resulted in formation of floating granules (FG) and process efficiency decrease. Formed FG had low biodegradability and its organic part was composed of lipids and calcium salts of LCFAs. Anaerobic digestion process intentionally directed to FG formation, could be a viable option for mitigation and control of lipids overload and derived LCFA inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lipids, lysosomes, and autophagy

PubMed Central

2016-01-01

Lipids are essential components of a cell providing energy substrates for cellular processes, signaling intermediates, and building blocks for biological membranes. Lipids are constantly recycled and redistributed within a cell. Lysosomes play an important role in this recycling process that involves the recruitment of lipids to lysosomes via autophagy or endocytosis for their degradation by lysosomal hydrolases. The catabolites produced are redistributed to various cellular compartments to support basic cellular function. Several studies demonstrated a bidirectional relationship between lipids and lysosomes that regulate autophagy. While lysosomal degradation pathways regulate cellular lipid metabolism, lipids also regulate lysosome function and autophagy. In this review, we focus on this bidirectional relationship in the context of dietary lipids and provide an overview of recent evidence of how lipid-overload lipotoxicity, as observed in obesity and metabolic syndrome, impairs lysosomal function and autophagy that may eventually lead to cellular dysfunction or cell death. PMID:27330054

Enhanced biological fixation of methane for microbial lipid production by recombinant Methylomicrobium buryatense

DOE PAGES

Fei, Qiang; Puri, Aaron W.; Smith, Holly; ...

2018-05-04

Due to the success of shale gas development in the US, the production cost of natural gas has been reduced significantly, which in turn has made methane (CH 4), the major component of natural gas, a potential alternative substrate for bioconversion processes compared with other high-price raw material sources or edible feedstocks. Therefore, exploring effective ways to use CH 4 for the production of biofuels is attractive. Biological fixation of CH 4 by methanotrophic bacteria capable of using CH 4 as their sole carbon and energy source has obtained great attention for biofuel production from this resource. Here, a fast-growingmore » and lipid-rich methanotroph, Methylomicrobium buryatense 5GB1 and its glycogen-knock-out mutant (AP18) were investigated for the production of lipids derived from intracellular membranes, which are key precursors for the production of green diesel. The effects of culture conditions on cell growth and lipid production were investigated in high cell density cultivation with continuous feeding of CH 4 and O2. The highest dry cell weight observed was 21.4 g/L and the maximum lipid productivity observed was 45.4 mg/L/h obtained in batch cultures, which corresponds to a 2-fold enhancement in cell density and 3-fold improvement in lipid production, compared with previous reported data from cultures of 5GB1. A 90% enhancement of lipid content was achieved by limiting the biosynthesis of glycogen in strain AP18. Increased CH 4/O 2 uptake and CO 2 evaluation rates were observed in AP18 cultures suggesting that more carbon substrate and energy are needed for AP18 growth while producing lipids. The lipid produced by M. buryatense was estimated to have a cetane number of 75, which is 50% higher than biofuel standards requested by US and EU. Cell growth and lipid production were significantly influenced by culture conditions for both 5GB1 and AP18. Enhanced lipid production in terms of titer, productivity, and content was achieved under high cell density culture conditions by blocking glycogen accumulation as a carbon sink in the strain AP18. Differences observed in CH 4/O 2 gas uptake and CO 2 evolution rates as well as cell growth and glycogen accumulation between 5GB1 and AP18 suggest changes in the metabolic network between these strains. This bioconversion process provides a promising opportunity to transform CH 4 into biofuel molecules and encourages further investigation to elucidate the remarkable CH 4 biofixation mechanism used by these bacteria.« less

Enhanced biological fixation of methane for microbial lipid production by recombinant Methylomicrobium buryatense

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

Fei, Qiang; Puri, Aaron W.; Smith, Holly

Due to the success of shale gas development in the US, the production cost of natural gas has been reduced significantly, which in turn has made methane (CH 4), the major component of natural gas, a potential alternative substrate for bioconversion processes compared with other high-price raw material sources or edible feedstocks. Therefore, exploring effective ways to use CH 4 for the production of biofuels is attractive. Biological fixation of CH 4 by methanotrophic bacteria capable of using CH 4 as their sole carbon and energy source has obtained great attention for biofuel production from this resource. Here, a fast-growingmore » and lipid-rich methanotroph, Methylomicrobium buryatense 5GB1 and its glycogen-knock-out mutant (AP18) were investigated for the production of lipids derived from intracellular membranes, which are key precursors for the production of green diesel. The effects of culture conditions on cell growth and lipid production were investigated in high cell density cultivation with continuous feeding of CH 4 and O2. The highest dry cell weight observed was 21.4 g/L and the maximum lipid productivity observed was 45.4 mg/L/h obtained in batch cultures, which corresponds to a 2-fold enhancement in cell density and 3-fold improvement in lipid production, compared with previous reported data from cultures of 5GB1. A 90% enhancement of lipid content was achieved by limiting the biosynthesis of glycogen in strain AP18. Increased CH 4/O 2 uptake and CO 2 evaluation rates were observed in AP18 cultures suggesting that more carbon substrate and energy are needed for AP18 growth while producing lipids. The lipid produced by M. buryatense was estimated to have a cetane number of 75, which is 50% higher than biofuel standards requested by US and EU. Cell growth and lipid production were significantly influenced by culture conditions for both 5GB1 and AP18. Enhanced lipid production in terms of titer, productivity, and content was achieved under high cell density culture conditions by blocking glycogen accumulation as a carbon sink in the strain AP18. Differences observed in CH 4/O 2 gas uptake and CO 2 evolution rates as well as cell growth and glycogen accumulation between 5GB1 and AP18 suggest changes in the metabolic network between these strains. This bioconversion process provides a promising opportunity to transform CH 4 into biofuel molecules and encourages further investigation to elucidate the remarkable CH 4 biofixation mechanism used by these bacteria.« less

Enhanced biological fixation of methane for microbial lipid production by recombinant Methylomicrobium buryatense.

PubMed

Fei, Qiang; Puri, Aaron W; Smith, Holly; Dowe, Nancy; Pienkos, Philip T

2018-01-01

Due to the success of shale gas development in the US, the production cost of natural gas has been reduced significantly, which in turn has made methane (CH 4 ), the major component of natural gas, a potential alternative substrate for bioconversion processes compared with other high-price raw material sources or edible feedstocks. Therefore, exploring effective ways to use CH 4 for the production of biofuels is attractive. Biological fixation of CH 4 by methanotrophic bacteria capable of using CH 4 as their sole carbon and energy source has obtained great attention for biofuel production from this resource. In this study, a fast-growing and lipid-rich methanotroph , Methylomicrobium buryatense 5GB1 and its glycogen-knock-out mutant (AP18) were investigated for the production of lipids derived from intracellular membranes, which are key precursors for the production of green diesel. The effects of culture conditions on cell growth and lipid production were investigated in high cell density cultivation with continuous feeding of CH 4 and O 2 . The highest dry cell weight observed was 21.4 g/L and the maximum lipid productivity observed was 45.4 mg/L/h obtained in batch cultures, which corresponds to a 2-fold enhancement in cell density and 3-fold improvement in lipid production, compared with previous reported data from cultures of 5GB1. A 90% enhancement of lipid content was achieved by limiting the biosynthesis of glycogen in strain AP18. Increased CH 4 /O 2 uptake and CO 2 evaluation rates were observed in AP18 cultures suggesting that more carbon substrate and energy are needed for AP18 growth while producing lipids. The lipid produced by M. buryatense was estimated to have a cetane number of 75, which is 50% higher than biofuel standards requested by US and EU. Cell growth and lipid production were significantly influenced by culture conditions for both 5GB1 and AP18. Enhanced lipid production in terms of titer, productivity, and content was achieved under high cell density culture conditions by blocking glycogen accumulation as a carbon sink in the strain AP18. Differences observed in CH 4 /O 2 gas uptake and CO 2 evolution rates as well as cell growth and glycogen accumulation between 5GB1 and AP18 suggest changes in the metabolic network between these strains. This bioconversion process provides a promising opportunity to transform CH 4 into biofuel molecules and encourages further investigation to elucidate the remarkable CH 4 biofixation mechanism used by these bacteria.

Emerging targets in lipid-based therapy☆

PubMed Central

Tucker, Stephanie C.; Honn, Kenneth V.

2013-01-01

The use of prostaglandins and NSAIDS in the clinic has proven that lipid mediators and their associated pathways make attractive therapeutic targets. When contemplating therapies involving lipid pathways, several basic agents come to mind. There are the enzymes and accessory proteins that lead to the metabolism of lipid substrates, provided through diet or through actions of lipases, the subsequent lipid products, and finally the lipid sensors or receptors. There is abundant evidence that molecules along this lipid continuum can serve as prognostic and diagnostic indicators and are in fact viable therapeutic targets. Furthermore, lipids themselves can be used as therapeutics. Despite this, the vernacular dialog pertaining to “biomarkers” does not routinely include mention of lipids, though this is rapidly changing. Collectively these agents are becoming more appreciated for their respective roles in diverse disease processes from cancer to preterm labor and are receiving their due appreciation after decades of ground work in the lipid field. By relating examples of disease processes that result from dysfunction along the lipid continuum, as well as examples of lipid therapies and emerging technologies, this review is meant to inspire further reading and discovery. PMID:23261527

The processing and presentation of lipids and glycolipids to the immune system

PubMed Central

Vartabedian, Vincent F.; Savage, Paul B.; Teyton, Luc

2016-01-01

Summary The recognition of CD1-lipid complexes by T cells was discovered twenty years ago and has since been an emerging and expanding field of investigation. Unlike protein antigens, which are presented on MHC class I and II molecules, lipids can only be presented by CD1 molecules, a unique family of MHC-like proteins whose singularity is a hydrophobic antigen binding groove. The processing and loading of lipid antigens inside this groove of CD1 molecules require localization to late endosomal and lysosomal subcellular compartments and their acidic pHs. This particular environment provides the necessary glycolytic enzymes and lipases that process lipid and glycolipid antigens, as well as a set of lipid transfer proteins that load the final version of the antigen inside the groove of CD1. The overall sequence of events needed for efficient presentation of lipid antigens is now understood and presented in this review. However, a large number of important details have been elusive. This elusiveness is linked to the inherent technical difficulties of studying lipids and the lipid-protein interface in vitro and in vivo. Here, we will expose some of those limitations and describe new approaches to address them during the characterization of lipids and glycolipids antigen presentation. PMID:27319346

Micronutrients-fortified rapeseed oil improves hepatic lipid accumulation and oxidative stress in rats fed a high-fat diet

PubMed Central

2013-01-01

Intake of high-fat diet is associated with increased fatty livers. Hepatic lipid accumulation and oxidative stress are key pathophysiological mechanisms in this disease. Micronutrients polyphenols, tocopherols and phytosterols in rapeseed exert potential benefit to hepatoprotection, but most of these micronutrients are removed by the traditional refining process. The purpose of the present study was to determine whether rapeseed oil fortified with these micronutrients can decrease hepatic lipid accumulation and oxidative stress induced by high-fat diet. Sprague–Dawley rats received rodent diet contained 20% fat whose source was refined rapeseed oil (RRO) or fortified RRO with low, middle and high quantities of these micronutrients for 10 weeks. Intake of RRO caused a remarkable hepatic steatosis. Micronutrients supplementation was effective in reducing steatosis as well as total triglyceride and total cholesterol contents in liver. These micronutrients also significantly increased hepatic antioxidant defense capacities, as evaluated by the significant elevation in the activities of SOD and GPx as well as the level of GSH, and the significant decline in lipid peroxidation. These findings suggest that rapeseed oil fortified with micronutrients polyphenols, tocopherols and phytosterols may contribute to prevent fatty livers such as nonalcoholic fatty liver disease by ameliorating hepatic lipid accumulation and oxidative stress. PMID:23510587

Microalgal Cultivation in Secondary Effluent: Recent Developments and Future Work

PubMed Central

Lv, Junping; Feng, Jia; Liu, Qi; Xie, Shulian

2017-01-01

Eutrophication of water catchments and the greenhouse effect are major challenges in developing the global economy in the near future. Secondary effluents, containing high amounts of nitrogen and phosphorus, need further treatment before being discharged into receiving water bodies. At the same time, new environmentally friendly energy sources need to be developed. Integrating microalgal cultivation for the production of biodiesel feedstock with the treatment of secondary effluent is one way of addressing both issues. This article provides a comprehensive review of the latest progress in microalgal cultivation in secondary effluent to remove pollutants and accumulate lipids. Researchers have discovered that microalgae remove nitrogen and phosphorus effectively from secondary effluent, accumulating biomass and lipids in the process. Immobilization of appropriate microalgae, and establishing a consortium of microalgae and/or bacteria, were both found to be feasible ways to enhance pollutant removal and lipid production. Demonstrations of pilot-scale microalgal cultures in secondary effluent have also taken place. However there is still much work to be done in improving pollutants removal, biomass production, and lipid accumulation in secondary effluent. This includes screening microalgae, constructing the consortium, making use of flue gas and nitrogen, developing technologies related to microalgal harvesting, and using lipid-extracted algal residues (LEA). PMID:28045437

A rapid and accurate quantification method for real-time dynamic analysis of cellular lipids during microalgal fermentation processes in Chlorella protothecoides with low field nuclear magnetic resonance.

PubMed

Wang, Tao; Liu, Tingting; Wang, Zejian; Tian, Xiwei; Yang, Yi; Guo, Meijin; Chu, Ju; Zhuang, Yingping

2016-05-01

The rapid and real-time lipid determination can provide valuable information on process regulation and optimization in the algal lipid mass production. In this study, a rapid, accurate and precise quantification method of in vivo cellular lipids of Chlorella protothecoides using low field nuclear magnetic resonance (LF-NMR) was newly developed. LF-NMR was extremely sensitive to the algal lipids with the limits of the detection (LOD) of 0.0026g and 0.32g/L in dry lipid samples and algal broth, respectively, as well as limits of quantification (LOQ) of 0.0093g and 1.18g/L. Moreover, the LF-NMR signal was specifically proportional to the cellular lipids of C. protothecoides, thus the superior regression curves existing in a wide detection range from 0.02 to 0.42g for dry lipids and from 1.12 to 8.97gL(-1) of lipid concentration for in vivo lipid quantification were obtained with all R(2) higher than 0.99, irrespective of the lipid content and fatty acids profile variations. The accuracy of this novel method was further verified to be reliable by comparing lipid quantification results to those obtained by GC-MS. And the relative standard deviation (RSD) of LF-NMR results were smaller than 2%, suggesting the precision of this method. Finally, this method was successfully used in the on-line lipid monitoring during the algal lipid fermentation processes, making it possible for better understanding of the lipid accumulation mechanism and dynamic bioprocess control. Copyright © 2016 Elsevier B.V. All rights reserved.

Initial differences in lipid processing leading to pig-and beef-derived mature adipocyte differentiation

USDA-ARS?s Scientific Manuscript database

Clonal cultures of pig-derived mature adipocytes are capable of dedifferentiating and forming proliferative-competent progeny cells in vitro. Initial lipid processing, is different to that observed in cultures of beef-derived adipocytes. Mature pig adipocytes extrude lipid before proliferation, wher...

Noncatalytic transformation of the crude lipid of ChlorellaI vulgaris into fatty acid methyl ester (FAME) with charcoal via a thermo-chemical process.

PubMed

Kwon, Eilhann E; Jeon, Young Jae; Yi, Haakrho

2013-02-01

The noncatalytic transformation of the crude lipid of Chlorella vulgaris (C. vulgaris) into fatty acid methyl ester (FAME) via a thermo-chemical process was mainly investigated in this work. The crude lipid of C. vulgaris was recovered by means of solvent extraction from C. vulgaris cultivated in a raceway pond. The conventional catalyzed transesterification of crude lipid of C. vulgaris is notably inhibited by the impurities contained in the crude lipid of C. vulgaris. These impurities are inevitably derived from the solvent extraction process for C. vulgaris. However, this work presents the noncatalytic transesterification of microalgal lipid into FAME, which could be an alternative option. For example, the noncatalytic transformation of microalgal lipid into FAME provides evidence that the esterification of free fatty acids (FFAs) and the transesterification of triglycerides can be combined into a single step less susceptible to the impurities and with a high conversion efficiency (∼97%). Copyright © 2012 Elsevier Ltd. All rights reserved.

Lipids of mitochondria.

PubMed

Horvath, Susanne E; Daum, Günther

2013-10-01

A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol. Other mitochondrial membrane lipids such as phosphatidylcholine, phosphatidylserine, phosphatidylinositol, sterols and sphingolipids have to be imported. The mitochondrial lipid composition, the biosynthesis and the import of mitochondrial lipids as well as the regulation of these processes will be main issues of this review article. Furthermore, interactions of lipids and mitochondrial proteins which are highly important for various mitochondrial processes will be discussed. Malfunction or loss of enzymes involved in mitochondrial phospholipid biosynthesis lead to dysfunction of cell respiration, affect the assembly and stability of the mitochondrial protein import machinery and cause abnormal mitochondrial morphology or even lethality. Molecular aspects of these processes as well as diseases related to defects in the formation of mitochondrial membranes will be described. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Biddy, Mary J.; Davis, Ryan; Humbird, David

Biorefinery process development relies on techno-economic analysis (TEA) to identify primary cost drivers, prioritize research directions, and mitigate technical risk for scale-up through development of detailed process designs. Here, we conduct TEA of a model 2000 dry metric ton-per-day lignocellulosic biorefinery that employs a two-step pretreatment and enzymatic hydrolysis to produce biomass-derived sugars, followed by biological lipid production, lipid recovery, and catalytic hydrotreating to produce renewable diesel blendstock (RDB). On the basis of projected near-term technical feasibility of these steps, we predict that RDB could be produced at a minimum fuel selling price (MFSP) of USD $9.55/gasoline-gallon-equivalent (GGE), predicated onmore » the need for improvements in the lipid productivity and yield beyond current benchmark performance. This cost is significant given the limitations in scale and high costs for aerobic cultivation of oleaginous microbes and subsequent lipid extraction/recovery. In light of this predicted cost, we developed an alternative pathway which demonstrates that RDB costs could be substantially reduced in the near term if upgradeable fractions of biomass, in this case hemicellulose-derived sugars, are diverted to coproducts of sufficient value and market size; here, we use succinic acid as an example coproduct. The coproduction model predicts an MFSP of USD $5.28/GGE when leaving conversion and yield parameters unchanged for the fuel production pathway, leading to a change in biorefinery RDB capacity from 24 to 15 MM GGE/year and 0.13 MM tons of succinic acid per year. Additional analysis demonstrates that beyond the near-term projections assumed in the models here, further reductions in the MFSP toward $2-3/GGE (which would be competitive with fossil-based hydrocarbon fuels) are possible with additional transformational improvements in the fuel and coproduct trains, especially in terms of carbon efficiency to both fuels and coproducts, recovery and purification of fuels and coproducts, and coproduct selection and price. Overall, this analysis documents potential economics for both a hydrocarbon fuel and bioproduct process pathway and highlights prioritized research directions beyond the current benchmark to enable hydrocarbon fuel production via an oleaginous microbial platform with simultaneous coproduct manufacturing from lignocellulosic biomass.« less

Potential application of algicidal bacteria for improved lipid recovery with specific algae.

PubMed

Lenneman, Eric M; Wang, Ping; Barney, Brett M

2014-05-01

The utility of specific strains of natural algicidal bacteria isolated from shallow wetland sediments was evaluated against several strains of algae with potential immediate or future commercial value. Two strains of bacteria, Pseudomonas pseudoalcaligenes AD6 and Aeromonas hydrophila AD9, were identified and demonstrated to have algicidal activity against the microalgae Neochloris oleoabundans and Dunaliella tertiolecta. These bacteria were further evaluated for the potential to improve lipid extraction using a mild solvent extraction approach. Aeromonas hydrophila AD9 showed a nearly 12-fold increase in lipid extraction with D. tertiolecta, while both bacteria showed a sixfold improvement in lipid extraction with N. oleoabundans. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

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.

Simultaneous improvement in production of microalgal biodiesel and high-value alpha-linolenic acid by a single regulator acetylcholine.

PubMed

Parsaeimehr, Ali; Sun, Zhilan; Dou, Xiao; Chen, Yi-Feng

2015-01-01

Photoautotrophic microalgae are a promising avenue for sustained biodiesel production, but are compromised by low yields of biomass and lipids at present. We are developing a chemical approach to improve microalgal accumulation of feedstock lipids as well as high-value alpha-linolenic acid which in turn might provide a driving force for biodiesel production. We demonstrate the effectiveness of the small bioactive molecule "acetylcholine" on accumulation of biomass, total lipids, and alpha-linolenic acid in Chlorella sorokiniana. The effectiveness exists in different species of Chlorella. Moreover, the precursor and analogs of acetylcholine display increased effectiveness at higher applied doses, with maximal increases by 126, 80, and 60% over controls for biomass, total lipids, and alpha-linolenic acid, respectively. Production of calculated biodiesel was also improved by the precursor and analogs of acetylcholine. The biodiesel quality affected by changes in microalgal fatty acid composition was addressed. The chemical approach described here could improve the lipid yield and biodiesel production of photoautotrophic microalgae if combined with current genetic approaches.

CARS microscopy for the monitoring of lipid storage in C. elegans

NASA Astrophysics Data System (ADS)

Enejder, Annika; Brackmann, Christian; Axäng, Claes; Åkeson, Madeleine; Pilon, Marc

2008-02-01

After several years of proof-of-principle measurements and focus on technological development, it is timely to make full use of the capabilities of CARS microscopy within the biosciences. We have here identified an urgent biological problem, to which CARS microscopy provides unique insights and consequently may become a widely accepted experimental procedure. In order to improve present understanding of mechanisms underlying dysfunctional metabolism regulation reported for many of our most wide-spread diseases (obesity, diabetes, cardio-vascular diseases etc.), we have monitored genetic and environmental impacts on cellular lipid storage in the model organism C. elegans in vivo in a full-scale biological study. Important advantages of CARS microscopy could be demonstrated compared to present technology, i.e. fluorescence microscopy of labelled lipid stores. The fluorescence signal varies not only with the presence of lipids, but also with the systemic distribution of the fluorophore and the chemical properties of the surrounding medium. By instead probing high-density regions of CH bonds naturally occurring in the sample, the CARS process was shown to provide a consistent representation of the lipid stores. The increased accumulation of lipid stores in mutants with deficiencies in the insulin and transforming growth factor signalling pathways could hereby be visualized and quantified. Furthermore, spectral CARS microscopy measurements in the C-H bond region of 2780-2930 cm -1 provided the interesting observation that this accumulation comes with a shift in the ordering of the lipids from gel- to liquid phase. The present study illustrates that CARS microscopy has a strong potential to become an important instrument for systemic studies of lipid storage mechanisms in living organisms, providing new insights into the phenomena underlying metabolic disorders.

Characterization, stabilization and activity of uricase loaded in lipid vesicles.

PubMed

Tan, Q Y; Wang, N; Yang, H; Zhang, L K; Liu, S; Chen, L; Liu, J; Zhang, L; Hu, N N; Zhao, C J; Zhang, J Q

2010-01-15

Uricase-containing lipid vesicles (UOXLVs) were prepared by reverse-phase evaporation method with high efficiency and the characteristics of UOXLVs were described. The average size and zeta potential of UOXLVs obtained by the optimized formulation were 205.47 nm and -37.33 mV, respectively. Uricase was encapsulated in the alkaline aqueous phase of the lipid vesicle and the stability of its tetrameric structure was thus improved and its activity preserved. The storage stability of uricase in lipid vesicles was significantly increased compared to that of free uricase at 4 degrees C in borate buffer of pH 8.5. At 55 degrees C, free uricase was deactivated much more quickly especially at lower concentration predominantly due to enhanced dissociation of uricase into subunits. An intrinsic tryptophan of uricase recovered from the lipid vesicle thermally treated at 55 degrees C revealed that a partially denatured uricase molecule was stabilized through its hydrophobic interaction with lipid vesicle membrane. This interaction was depressed mainly by dissociation of uricase into subunits. At the physiological pH, significant increase of enzyme activity was found for the uricase entrapped in the lipid vesicles (1.8 times that of free uricase) at their respective optimum pH. The shift of optimum pH and increased uricolytic activity suggested the conformation change of the uricase during the entrapment process. The stability to proteolytic digestion was increased obviously by entrapping the uricase in the lipid vesicles. UOXLVs also showed relatively slower loss in activity compared with free uricase when treated with some chemical reagents. Lastly, in vitro study explicitly indicated that the uricase entrapped by UOXLVs possessed higher uricolytic activity than that of native uricase solution.

Rosiglitazone and Fenofibrate Additive Effects on Lipids

DTIC Science & Technology

2011-10-01

Metabolic effects of trogiltazone on fructose-induced insulin resistance in the rat,” Diabetes, vol. 43, pp. 1435–1439, 1995. [3] T. P. Ciaraldi...re- mains unclear. It is possible that these agents indirectly alter plasma lipid and lipoprotein levels indirectly by improving insulin sensitivity...induced by TZDs remains unclear. It is possible that these agents indi- rectly alter plasma lipid and lipoprotein levels indirectly by improving insulin

Effects of lipid concentration on anaerobic co-digestion of municipal biomass wastes

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

Sun, Yifei, E-mail: sunif@buaa.edu.cn; Wang, Dian; Yan, Jiao

2014-06-01

Highlights: • Lipid in municipal biomass would not inhibited the anaerobic digestion process. • A lipid concentration of 65% of total VS was the inhibition concentration. • The amount of Brevibacterium decreased with the increasing of the lipid contents. • Long chain fatty acids stacked on the methanogenic bacteria and blocked the mass transfer process. - Abstract: The influence of the lipid concentration on the anaerobic co-digestion of municipal biomass waste and waste-activated sludge was assessed by biochemical methane potential (BMP) tests and by bench-scale tests in a mesophilic semi-continuous stirred tank reactor. The effect of increasing the volatile solidmore » (VS) concentration of lipid from 0% to 75% was investigated. BMP tests showed that lipids in municipal biomass waste could enhance the methane production. The results of bench-scale tests showed that a lipids concentration of 65% of total VS was the inhibition concentration. Methane yields increased with increasing lipid concentration when lipid concentrations were below 60%, but when lipid concentration was set as 65% or higher, methane yields decreased sharply. When lipid concentrations were below 60%, the pH values were in the optimum range for the growth of methanogenic bacteria and the ratios of volatile fatty acid (VFA)/alkalinity were in the range of 0.2–0.6. When lipid concentrations exceeded 65%, the pH values were below 5.2, the reactor was acidized and the values of VFA/alkalinity rose to 2.0. The amount of Brevibacterium decreased with increasing lipid content. Long chain fatty acids stacked on the methanogenic bacteria and blocked the mass transfer process, thereby inhibiting anaerobic digestion.« less

Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity.

PubMed

Anderson, Rachel C; MacGibbon, Alastair K H; Haggarty, Neill; Armstrong, Kelly M; Roy, Nicole C

2018-01-01

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation.

Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity

PubMed Central

MacGibbon, Alastair K. H.; Haggarty, Neill; Armstrong, Kelly M.; Roy, Nicole C.

2018-01-01

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation. PMID:29304106

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.

Lipidomic profiling of patient-specific iPSC-derived hepatocyte-like cells

PubMed Central

Viiri, Leena E.; Vihervaara, Terhi; Koistinen, Kaisa M.; Hilvo, Mika; Ekroos, Kim; Käkelä, Reijo; Aalto-Setälä, Katriina

2017-01-01

ABSTRACT Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs) offer an alternative model to primary human hepatocytes to study lipid aberrations. However, the detailed lipid profile of HLCs is yet unknown. In the current study, functional HLCs were differentiated from iPSCs generated from dermal fibroblasts of three individuals by a three-step protocol through the definitive endoderm (DE) stage. In parallel, detailed lipidomic analyses as well as gene expression profiling of a set of lipid-metabolism-related genes were performed during the entire differentiation process from iPSCs to HLCs. Additionally, fatty acid (FA) composition of the cell culture media at different stages was determined. Our results show that major alterations in the molecular species of lipids occurring during DE and early hepatic differentiation stages mainly mirror the quality and quantity of the FAs supplied in culture medium at each stage. Polyunsaturated phospholipids and sphingolipids with a very long FA were produced in the cells at a later stage of differentiation. This work uncovers the previously unknown lipid composition of iPSC-HLCs and its alterations during the differentiation in conjunction with the expression of key lipid-associated genes. Together with biochemical, functional and gene expression measurements, the lipidomic analyses allowed us to improve our understanding of the concerted influence of the exogenous metabolite supply and cellular biosynthesis essential for iPSC-HLC differentiation and function. Importantly, the study describes in detail a cell model that can be applied in exploring, for example, the lipid metabolism involved in the development of fatty liver disease or atherosclerosis. PMID:28733363

[Neurosecretory activity and the dynamics of the lipid content in the CNS neurons in the bivalve mollusk, Gray's mussel (Crenomytilus grayanus Dunker)].

PubMed

Reunova, O V; Kalinina, G G; Motavkin, P A

1996-01-01

Neurosecretory process was studied in the aspect of lipid exchange in the CNS ganglia in the bivalve mollusk using light optics, electron microscopy, cytological and biochemical methods. Neurosecretory material forming was shown to be followed by changes in volume in neuron, nucleus and nucleolus, increase of nucleolar-plasmic relations, granular endoplasmic reticulum proliferation of mitochondria and complex dictyosomes. Changes in lipid content are inversely proportional to the neurosecreted amount in the neuron. The more active secretory process is, the smaller grows the number of lipid-containing cells, common lipids phospholipids. It is concluded that lipids structurally and energetically maintain the neurosecretory material synthesis.

Plant Products for Pharmacology: Application of Enzymes in Their Transformations

PubMed Central

Zarevúcka, Marie; Wimmer, Zdeněk

2008-01-01

Different plant products have been subjected to detailed investigations due to their increasing importance for improving human health. Plants are sources of many groups of natural products, of which large number of new compounds has already displayed their high impact in human medicine. This review deals with the natural products which may be found dissolved in lipid phase (phytosterols, vitamins etc.). Often subsequent convenient transformation of natural products may further improve the pharmacological properties of new potential medicaments based on natural products. To respect basic principles of sustainable and green procedures, enzymes are often employed as efficient natural catalysts in such plant product transformations. Transformations of lipids and other natural products under the conditions of enzyme catalysis show increasing importance in environmentally safe and sustainable production of pharmacologically important compounds. In this review, attention is focused on lipases, efficient and convenient biocatalysts for the enantio- and regioselective formation / hydrolysis of ester bond in a wide variety of both natural and unnatural substrates, including plant products, eg. plant oils and other natural lipid phase compounds. The application of enzymes for preparation of acylglycerols and transformation of other natural products provides big advantage in comparison with employing of conventional chemical methods: Increased selectivity, higher product purity and quality, energy conservation, elimination of heavy metal catalysts, and sustainability of the employed processes, which are catalyzed by enzymes. Two general procedures are used in the transformation of lipid-like natural products: (a) Hydrolysis/alcoholysis of triacylglycerols and (b) esterification of glycerol. The reactions can be performed under conventional conditions or in supercritical fluids/ionic liquids. Enzyme-catalyzed reactions in supercritical fluids combine the advantages of biocatalysts (substrate specificity under mild reaction conditions) and supercritical fluids (high mass-transfer rate, easy separation of reaction products from the solvent, environmental benefits based on excluding organic solvents from the production process). PMID:19330086

New biofuel alternatives: integrating waste management and single cell oil production.

PubMed

Martínez, Elia Judith; Raghavan, Vijaya; González-Andrés, Fernando; Gómez, Xiomar

2015-04-24

Concerns about greenhouse gas emissions have increased research efforts into alternatives in bio-based processes. With regard to transport fuel, bioethanol and biodiesel are still the main biofuels used. It is expected that future production of these biofuels will be based on processes using either non-food competing biomasses, or characterised by low CO₂ emissions. Many microorganisms, such as microalgae, yeast, bacteria and fungi, have the ability to accumulate oils under special culture conditions. Microbial oils might become one of the potential feed-stocks for biodiesel production in the near future. The use of these oils is currently under extensive research in order to reduce production costs associated with the fermentation process, which is a crucial factor to increase economic feasibility. An important way to reduce processing costs is the use of wastes as carbon sources. The aim of the present review is to describe the main aspects related to the use of different oleaginous microorganisms for lipid production and their performance when using bio-wastes. The possibilities for combining hydrogen (H₂) and lipid production are also explored in an attempt for improving the economic feasibility of the process.

New Biofuel Alternatives: Integrating Waste Management and Single Cell Oil Production

PubMed Central

Martínez, Elia Judith; Raghavan, Vijaya; González-Andrés, Fernando; Gómez, Xiomar

2015-01-01

Concerns about greenhouse gas emissions have increased research efforts into alternatives in bio-based processes. With regard to transport fuel, bioethanol and biodiesel are still the main biofuels used. It is expected that future production of these biofuels will be based on processes using either non-food competing biomasses, or characterised by low CO2 emissions. Many microorganisms, such as microalgae, yeast, bacteria and fungi, have the ability to accumulate oils under special culture conditions. Microbial oils might become one of the potential feed-stocks for biodiesel production in the near future. The use of these oils is currently under extensive research in order to reduce production costs associated with the fermentation process, which is a crucial factor to increase economic feasibility. An important way to reduce processing costs is the use of wastes as carbon sources. The aim of the present review is to describe the main aspects related to the use of different oleaginous microorganisms for lipid production and their performance when using bio-wastes. The possibilities for combining hydrogen (H2) and lipid production are also explored in an attempt for improving the economic feasibility of the process. PMID:25918941

Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion - Solvent evaporation method.

PubMed

Amasya, Gulin; Badilli, Ulya; Aksu, Buket; Tarimci, Nilufer

2016-03-10

With Quality by Design (QbD), a systematic approach involving design and development of all production processes to achieve the final product with a predetermined quality, you work within a design space that determines the critical formulation and process parameters. Verification of the quality of the final product is no longer necessary. In the current study, the QbD approach was used in the preparation of lipid nanoparticle formulations to improve skin penetration of 5-Fluorouracil, a widely-used compound for treating non-melanoma skin cancer. 5-Fluorouracil-loaded lipid nanoparticles were prepared by the W/O/W double emulsion - solvent evaporation method. Artificial neural network software was used to evaluate the data obtained from the lipid nanoparticle formulations, to establish the design space, and to optimize the formulations. Two different artificial neural network models were developed. The limit values of the design space of the inputs and outputs obtained by both models were found to be within the knowledge space. The optimal formulations recommended by the models were prepared and the critical quality attributes belonging to those formulations were assigned. The experimental results remained within the design space limit values. Consequently, optimal formulations with the critical quality attributes determined to achieve the Quality Target Product Profile were successfully obtained within the design space by following the QbD steps. Copyright © 2016 Elsevier B.V. All rights reserved.

Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics.

PubMed

Kumar, Venishetty Vinay; Chandrasekar, Durairaj; Ramakrishna, Sistla; Kishan, Veerabrahma; Rao, Yamsani Madhusudan; Diwan, Prakash Vamanrao

2007-04-20

Nitrendipine is an antihypertensive drug with poor oral bioavailability ranging from 10 to 20% due to the first pass metabolism. For improving the oral bioavailability of nitrendipine, nitrendipine loaded solid lipid nanoparticles have been developed using triglyceride (tripalmitin), monoglyceride (glyceryl monostearate) and wax (cetyl palmitate). Poloxamer 188 was used as surfactant. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. SLN were characterized for particle size, zeta potential, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in phosphate buffer of pH 6.8 using Franz diffusion cell. Pharmacokinetics of nitrendipine loaded solid lipid nanoparticles after intraduodenal administration to conscious male Wistar rats was studied. Bioavailability of nitrendipine was increased three- to four-fold after intraduodenal administration compared to that of nitrendipine suspension. The obtained results are indicative of solid lipid nanoparticles as carriers for improving the bioavailability of lipophilic drugs such as nitrendipine by minimizing first pass metabolism.

The effect of physician feedback and an action checklist on diabetes care measures.

PubMed

Schectman, Joel M; Schorling, John B; Nadkarni, Mohan M; Lyman, Jason A; Siadaty, Mir S; Voss, John D

2004-01-01

The objective was to evaluate whether physician feedback accompanied by an action checklist improved diabetes care process measures. Eighty-three physicians in an academic general medicine clinic were provided a single feedback report on the most recent date and result of diabetes care measures (glycosylated hemoglobin [A1c], urine microalbumin, serum creatinine, lipid levels, retinal examination) as well as recent diabetes medication refills with calculated dosing and adherence on 789 patients. An educational session regarding the feedback and adherence information was provided. The physicians were asked to complete a checklist accompanying the feedback on each of their patients, indicating requested actions with respect to follow-up, testing, and counseling. The physicians completed 82% of patient checklists, requesting actions consistent with patient needs on the basis of the feedback. Of the physicians, 93% felt the patient information and intervention format to be useful. The odds of urine microalbumin testing, serum creatinine, lipid profile, A1c, and retinal examination increased in the 6 months after the feedback. The increase was sustained at 1 year only for microalbumin and retinal exams. There was no significant change in refill adherence for the group overall after the feedback, although adherence did improve among patients of physicians attending the educational session. No significant change was noted in lipid or A1c levels during the study period. In conclusion, a simple physician feedback tool with action checklist can be both helpful and popular for improving rates of diabetes care guideline adherence. More complex interventions are likely required to improve diabetes outcomes.

Motorized photoacoustic tomography probe for label-free improvement in image quality

NASA Astrophysics Data System (ADS)

Sangha, Gurneet S.; Hale, Nick H.; Goergen, Craig J.

2018-02-01

One of the challenges in high-resolution in vivo lipid-based photoacoustic tomography (PAT) is improving penetration depth and signal-to-noise ratio (SNR) past subcutaneous fat absorbers. A potential solution is to create optical manipulation techniques to maximize the photon density within a region of interest. Here, we present a motorized PAT probe that is capable of tuning the depth in which light is focused, as well as substantially reducing probe-skin artifacts that can obscure image interpretation. Our PAT system consists of a Nd:YAG laser (Surelite EX, Continuum) coupled with a 40 MHz central frequency ultrasound transducer (Vevo2100, FUJIFILM Visual Sonics). This system allows us to deliver 10 Hz, 5 ns light pulses with fluence of 40 mJ/cm2 to the tissue interest and reconstruct PAT and ultrasound images with axial resolutions of 125 µm and 40 µm, respectively. The motorized PAT holder was validated by imaging a polyethylene-50 tubing embedded polyvinyl alcohol phantom and periaortic fat on apolipoprotein-E deficient mice. We used 1210 nm light for this study, as this wavelength generates PAT signal for both lipids and polyethylene-50 tubes. Ex vivo results showed a 2 mm improvement in penetration depth and in vivo experiments showed an increase in lipid SNR of at least 62%. Our PAT probe also utilizes a 7 μm aluminum filter to prevent in vivo probe-skin reflection artifacts that have been previously resolved using image post-processing techniques. Using this optimized PAT probe, we can direct light to various depths within tissue to improve image quality and prevent reflection artifacts.

Engineering the lipid layer of lipid-PLGA hybrid nanoparticles for enhanced in vitro cellular uptake and improved stability.

PubMed

Hu, Yun; Hoerle, Reece; Ehrich, Marion; Zhang, Chenming

2015-12-01

Lipid-polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a lipid shell, have been intensively examined as delivery systems for cancer drugs, imaging agents, and vaccines. For applications in vaccine particularly, the hybrid NPs need to be able to protect the enclosed antigens during circulation, easily be up-taken by dendritic cells, and possess good stability for prolonged storage. However, the influence of lipid composition on the performance of hybrid NPs has not been well studied. In this study, we demonstrate that higher concentrations of cholesterol in the lipid layer enable slower and more controlled antigen release from lipid-poly(lactide-co-glycolide) acid (lipid-PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher concentrations of cholesterol also promoted in vitro cellular uptake of hybrid NPs, improved the stability of the lipid layer, and protected the integrity of the hybrid structure during long-term storage. However, stabilized hybrid structures of high cholesterol content tended to fuse with each other during storage, resulting in significant size increase and lowered cellular uptake. Additional experiments demonstrated that PEGylation of NPs could effectively minimize fusion-caused size increase after long term storage, leading to improved cellular uptake, although excessive PEGylation will not be beneficial and led to reduced improvement. This paper reports the engineering of the lipid layer that encloses a polymeric nanoparticle, which can be used as a carrier for drug and vaccine molecules for targeted delivery. We demonstrated that the concentration of cholesterol is critical for the stability and uptake of the hybrid nanoparticles by dendritic cells, a targeted cell for the delivery of immune effector molecules. However, we found that hybrid nanoparticles with high cholesterol concentration tend to fuse during storage resulting in larger particles with decreased cellular uptake. This problem is subsequently solved by PEGylating the hybrid nanoparticles. With increased research and clinical applications of lipid-polymer hybrid nanoparticles in drug and vaccine delivery, this work will significantly impact the design of the hybrid nanoparticles for minimized molecule release during circulation and increased bioavailability of the target molecules. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Lipid domains in zwitterionic-anionic lipid mixtures induced by combined effect of monovalent and divalent ions

NASA Astrophysics Data System (ADS)

Xu, Hongcheng; Ganesan, Sai; Matysiak, Silvina

Lipid domain formation is an important process for many cellular processes. In experiment, the effects of Ba2+, Sr2+, Ca2+ and Mg2+ in inducing lateral phase separation in the binary phosphatidylcholine-phosphatidylserine (PC-PS) bilayer are quite different, of which the molecular mechanism remains to be understood. We have explored the effect of monovalent (MI) and divalent (MII) cationic radii on lipid domain formation in mixed zwitterionic-anionic lipid bilayers. We propose a mechanism for the formation of divalent-cation-induced lipid domains based on MD simulations with our Water-Explicit Polarizable MEMbrane (WEPMEM) coarse-grained model, which uses PC as the model for zwitterionic and PS for anionic lipids. Lipid aggregation only occurs with limited range of monovalent and divalent ion sizes in agreement with experimental observations. More ordering and closer packing of the lipids are noted within the domains, which correlate with bilayer thickness, curvature and lipid asymmetry. The results of the simulations reveal that the lipid domain consists of MII-mediated anionic lipid dimer/trimer complexes bridged by monovalent ions MI and provide a stereochemical insight in understanding the experimentally observed calcium-induced phase separation.

mMass 3: a cross-platform software environment for precise analysis of mass spectrometric data.

PubMed

Strohalm, Martin; Kavan, Daniel; Novák, Petr; Volný, Michael; Havlícek, Vladimír

2010-06-01

While tools for the automated analysis of MS and LC-MS/MS data are continuously improving, it is still often the case that at the end of an experiment, the mass spectrometrist will spend time carefully examining individual spectra. Current software support is mostly provided only by the instrument vendors, and the available software tools are often instrument-dependent. Here we present a new generation of mMass, a cross-platform environment for the precise analysis of individual mass spectra. The software covers a wide range of processing tasks such as import from various data formats, smoothing, baseline correction, peak picking, deisotoping, charge determination, and recalibration. Functions presented in the earlier versions such as in silico digestion and fragmentation were redesigned and improved. In addition to Mascot, an interface for ProFound has been implemented. A specific tool is available for isotopic pattern modeling to enable precise data validation. The largest available lipid database (from the LIPID MAPS Consortium) has been incorporated and together with the new compound search tool lipids can be rapidly identified. In addition, the user can define custom libraries of compounds and use them analogously. The new version of mMass is based on a stand-alone Python library, which provides the basic functionality for data processing and interpretation. This library can serve as a good starting point for other developers in their projects. Binary distributions of mMass, its source code, a detailed user's guide, and video tutorials are freely available from www.mmass.org .

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal

PubMed Central

Muñoz, Mario F.; Argüelles, Sandro

2014-01-01

Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown. PMID:24999379

Strategies for Lipid Production Improvement in Microalgae as a Biodiesel Feedstock

PubMed Central

Li, Z. H.; Hiltunen, E.

2016-01-01

In response to the energy crisis, global warming, and climate changes, microalgae have received a great deal of attention as a biofuel feedstock. Due to a high lipid content in microalgal cells, microalgae present as a promising alternative source for the production of biodiesel. Environmental and culturing condition variations can alter lipid production as well as chemical compositions of microalgae. Therefore, application of the strategies to activate lipid accumulation opens the door for lipid overproduction in microalgae. Until now, many original studies regarding the approaches for enhanced microalgal lipid production have been reported in an effort to push forward the production of microalgal biodiesel. However, the current literature demonstrates fragmented information available regarding the strategies for lipid production improvement. From the systematic point of view, the review highlights the main approaches for microalgal lipid accumulation induction to expedite the application of microalgal biodiesel as an alternative to fossil diesel for sustainable environment. Of the several strategies discussed, the one that is most commonly applied is the design of nutrient (e.g., nitrogen, phosphorus, and sulfur) starvation or limitation. Other viable approaches such as light intensity, temperature, carbon dioxide, salinity stress, and metal influence can also achieve enhanced microalgal lipid production. PMID:27725942

Strategies for Lipid Production Improvement in Microalgae as a Biodiesel Feedstock.

PubMed

Zhu, L D; Li, Z H; Hiltunen, E

2016-01-01

In response to the energy crisis, global warming, and climate changes, microalgae have received a great deal of attention as a biofuel feedstock. Due to a high lipid content in microalgal cells, microalgae present as a promising alternative source for the production of biodiesel. Environmental and culturing condition variations can alter lipid production as well as chemical compositions of microalgae. Therefore, application of the strategies to activate lipid accumulation opens the door for lipid overproduction in microalgae. Until now, many original studies regarding the approaches for enhanced microalgal lipid production have been reported in an effort to push forward the production of microalgal biodiesel. However, the current literature demonstrates fragmented information available regarding the strategies for lipid production improvement. From the systematic point of view, the review highlights the main approaches for microalgal lipid accumulation induction to expedite the application of microalgal biodiesel as an alternative to fossil diesel for sustainable environment. Of the several strategies discussed, the one that is most commonly applied is the design of nutrient (e.g., nitrogen, phosphorus, and sulfur) starvation or limitation. Other viable approaches such as light intensity, temperature, carbon dioxide, salinity stress, and metal influence can also achieve enhanced microalgal lipid production.

Synergistic role of solid lipid and porous silica in improving the oral delivery of weakly basic poorly water soluble drugs.

PubMed

Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen; Prestidge, Clive

2017-01-01

Oral absorption of weakly basic drugs (e.g. cinnarizine (CIN)) is limited by their pH dependent precipitation in intestinal conditions. To overcome this challenge, a novel drug delivery system composed of solid lipid and porous silica, namely silica encapsulated solid lipid (SESL) particles, was developed via hot homogenization of melted lipid dispersion, followed by ultra-sonication of the silica stabilized homogenized melted lipid dispersion. Scanning electron microscope (SEM) images of the SESL formulation revealed non-spherical and aggregated hybrid particles, with rough exterior and structured nanoparticles visible on the surface. A 1.5, 2.2 and 7-fold improvement in the dissolution of CIN was observed for the SESL particles, under simulated intestinal non-digesting conditions, in comparison to the drug loaded in solid lipid (CIN-SL) matrix, drug loaded in porous silica (CIN-PS) and pure drug powder. Under simulated intestinal digestive condition, significant improvement in the drug solubilization was reported for the SESL formulation in compared to the individual drug loaded systems i.e. CIN-PS and CIN-SL. Thereby, silica encapsulated solid lipid system provides a promising oral delivery approach for poorly water soluble weakly basic drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems.

PubMed

Aboalnaja, Khaled Omer; Yaghmoor, Soonham; Kumosani, Taha Abdullah; McClements, David Julian

2016-09-01

The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

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

Supramolecular aggregation and organization in peripheral nerve myelin.

PubMed

Pease, D C

1983-09-01

Under certain preparative conditions the lipid bilayers of glutaraldehyde-fixed, PNS myelin demonstrate a marked compartmentalization, which can be augmented by lipid extraction following sectioning. The results are interpreted as indicating a supramolecular domain pattern of arrangement centered upon the transmembrane protein (P0) molecules. The latter are thought to be surrounded by annuli of substantially immobilized phospholipids. In the lamellar planes particular lipids are considered to have a nonrandom distribution. The visualization of bilayer compartmentalization was seen only in negatively stained sections obtained from unembedded or glutaraldehyde-urea-embedded myelin. Lipids were unextracted in the basic preparations except in so far as some unfixed, amphipathic molecules escaped at the trough-fluid interface at the time of sectioning, an observed phenomenon which probably aided in the visualization of the compartmentalization. Visualization was also augmented by surface tension expanding section fragments as they floated on the trough fluid. All stages of transition between well-ordered myelin and dispersed globular units were commonly to be found. Deliberately delipidated myelin exposed more sharply defined and smaller globular units in bilayer regions, but even these are regarded as being supramolecular aggregates including residual lipid annuli around the transmembrane proteins. The addition of cadmium ions as a "fixative" for lecithin seemed to improve the preservation of glutaraldehyde-urea-embedded myelin but was not strictly necessary to reveal its domain structure. A secondary tannic acid fixation was required to process unembedded myelin so as to reveal the fundamental compartmentalization of its lipid bilayers.

Identification of optimum fatty acid extraction methods for two different microalgae Phaeodactylum tricornutum and Haematococcus pluvialis for food and biodiesel applications.

PubMed

Otero, Paz; Saha, Sushanta Kumar; Gushin, Joanne Mc; Moane, Siobhan; Barron, John; Murray, Patrick

2017-07-01

Microalgae have the potential to synthesize and accumulate lipids which contain high value fatty acids intended for nutrition and biodiesel applications. Nevertheless, lipid extraction methods for microalgae cells are not well established and there is not a standard analytical methodology to extract fatty acids from lipid-producing microalgae. In this paper, current lipid extraction procedures employing organic solvents (chloroform/methanol, 2:1 and 1:2, v/v), sodium hypochlorite solution (NaClO), acid-catalysed hot-water extraction and the saponification process [2.5 M KOH/methanol (1:4, v/v)] have been evaluated with two species of microalgae with different types of cell walls. One is a marine diatom, Phaeodactylum tricornutum, and the other a freshwater green microalga, Haematococcus pluvialis. Lipids from all types of extracts were estimated gravimetrically and their fatty acids were quantified by a HPLC equipped with Q-TOF mass spectrometer. Results indicated significant differences both in lipids yield and fatty acids composition. The chloroform and methanol mixture was the most effective extraction solvent for the unsaturated fatty acids such as DPA (C22:05), DHA, (C22:06), EPA (C20:05) and ARA (C20:04). While acid treatments improved the saturated fatty acids (SFAs) yield, especially the short chain SFA, lauric acid (C12:0), whose amount was 64% higher in P. tricornutum and 156% higher in H. pluvialis compared to organic solvent extractions. Graphical abstract ᅟ.

Soybean GmMYB73 promotes lipid accumulation in transgenic plants

PubMed Central

2014-01-01

Background Soybean is one of the most important oil crops. The regulatory genes involved in oil accumulation are largely unclear. We initiated studies to identify genes that regulate this process. Results One MYB-type gene GmMYB73 was found to display differential expression in soybean seeds of different developing stages by microarray analysis and was further investigated for its functions in lipid accumulation. GmMYB73 is a small protein with single MYB repeat and has similarity to CPC-like MYB proteins from Arabidopsis. GmMYB73 interacted with GL3 and EGL3, and then suppressed GL2, a negative regulator of oil accumulation. GmMYB73 overexpression enhanced lipid contents in both seeds and leaves of transgenic Arabidopsis plants. Seed length and thousand-seed weight were also promoted. GmMYB73 introduction into the Arabidopsis try cpc double mutant rescued the total lipids, seed size and thousand-seed weight. GmMYB73 also elevated lipid levels in seeds and leaves of transgenic Lotus, and in transgenic hairy roots of soybean plants. GmMYB73 promoted PLDα1 expression, whose promoter can be bound and inhibited by GL2. PLDα1 mutation reduced triacylglycerol levels mildly in seeds but significantly in leaves of Arabidopsis plants. Conclusions GmMYB73 may reduce GL2, and then release GL2-inhibited PLDα1 expression for lipid accumulation. Manipulation of GmMYB73 may potentially improve oil production in legume crop plants. PMID:24655684

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

Performance of structured lipids incorporating selected phenolic and ascorbic acids.

PubMed

Gruczynska, Eliza; Przybylski, Roman; Aladedunye, Felix

2015-04-15

Conditions applied during frying require antioxidant which is stable at these conditions and provides protection for frying oil and fried food. Novel structured lipids containing nutraceuticals and antioxidants were formed by enzymatic transesterification, exploring canola oil and naturally occurring antioxidants such as ascorbic and selected phenolic acids as substrates. Lipozyme RM IM lipase from Rhizomucor miehei was used as biocatalyst. Frying performance and oxidative stability of the final transesterification products were evaluated. The novel lipids showed significantly improved frying performance compared to canola oil. Oxidative stability assessment of the structured lipids showed significant improvement in resistance to oxidative deterioration compared to original canola oil. Interestingly, the presence of ascorbic acid in an acylglycerol structure protected α-tocopherol against thermal degradation, which was not observed for the phenolic acids. Developed structured lipids containing nutraceuticals and antioxidants may directly affect nutritional properties of lipids also offering nutraceutical ingredients for food formulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lipids and bariatric procedures Part 2 of 2: scientific statement from the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and Obesity Medicine Association (OMA).

PubMed

Bays, Harold; Kothari, Shanu N; Azagury, Dan E; Morton, John M; Nguyen, Ninh T; Jones, Peter H; Jacobson, Terry A; Cohen, David E; Orringer, Carl; Westman, Eric C; Horn, Deborah B; Scinta, Wendy; Primack, Craig

2016-01-01

Bariatric procedures generally improve dyslipidemia, sometimes substantially so. Bariatric procedures also improve other major cardiovascular risk factors. This 2-part Scientific Statement examines the lipid effects of bariatric procedures and reflects contributions from authors representing the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and the Obesity Medicine Association (OMA). Part 1 was published in the Journal of Clinical Lipidology, and reviewed the impact of bariatric procedures upon adipose tissue endocrine and immune factors, adipose tissue lipid metabolism, as well as the lipid effects of bariatric procedures relative to bile acids and intestinal microbiota. This Part 2 reviews: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies, that may occur after bariatric procedures. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

NASA Astrophysics Data System (ADS)

Shen, Jie; Sun, Minjie; Ping, Qineng; Ying, Zhi; Liu, Wen

2010-01-01

The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

PubMed

Lu, Yi; Wu, Qing; Liu, Long-Zhu; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Man-Xiang; Zang, Wei-Jin

2018-04-01

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Can the exercise mode determine lipid profile improvements in obese patients?

PubMed

Romero Moraleda, Blanca; Morencos, Esther; Peinado, Ana Belén; Bermejo, Laura; Gómez Candela, Carmen; Benito, Pedro José

2013-01-01

Unfavorable lipid profile is associated with developed cardiovascular diseases. It is necessary to know the beneficial effects of different mode exercises to improve lipid profile. To investigate, in obese men and women, the effect on lipid profile of hypocaloric diet combined with structured exercise programs or recommendations of physical activity. Ninety six obese subjects (59 women and 61 men; 18 - 50 years; BMI >30 and < 34.9 kg/m(2)) were randomised into four supervised treatment groups: strength training (S; n = 24), endurance training (E; n = 26), combined S + E (SE; n = 24), and and received recommendations of physical activity (PA; n = 22). Energy intake, body composition, training variables (VO(2peak), strength index, dynamometric strength index) and blood lipid profile were recorded at baseline and after 24 weeks of treatment. Blood lipid profile improved in all groups. No statistically significant differences in baseline and posttraining values were observed between groups. HDLCholesterol showed no changes. A decrease in LDLCholesterol values was observed in all groups after the intervention (S: 11.2%, E: 10.8%, SE: 7.9%, PA: 10.8%; p < 0.01). S, E and PA subjects showed decrease in triglycerides (S: 14.9%, E: 15.8%, PA: 15.7%; p < 0.01). Total cholesterol decreased in all groups (S: 8.4%, p < 0.01; E: 8.8%, p < 0.01; SE: 4.9%, p < 0.01; PA: 8.3%, p < 0.05). All protocols proposed in our study improved blood lipid profile in obese people. There were no significant differences about the effect on the lipid profile between the implementation of a structured training protocol with physical activity professional supervision and follow recommendations of physical activity. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

FTIR Spectroscopy for Evaluation and Monitoring of Lipid Extraction Efficiency for Oleaginous Fungi.

PubMed

Forfang, Kristin; Zimmermann, Boris; Kosa, Gergely; Kohler, Achim; Shapaval, Volha

2017-01-01

To assess whether Fourier Transform Infrared (FTIR) spectroscopy could be used to evaluate and monitor lipid extraction processes, the extraction methods of Folch, Bligh and Lewis were used. Biomass of the oleaginous fungi Mucor circinelloides and Mortierella alpina were employed as lipid-rich material for the lipid extraction. The presence of lipids was determined by recording infrared spectra of all components in the lipid extraction procedure, such as the biomass before and after extraction, the water and extract phases. Infrared spectra revealed the incomplete extraction after all three extraction methods applied to M.circinelloides and it was shown that mechanical disruption using bead beating and HCl treatment were necessary to complete the extraction in this species. FTIR spectroscopy was used to identify components, such as polyphosphates, that may have negatively affected the extraction process and resulted in differences in extraction efficiency between M.circinelloides and M.alpina. Residual lipids could not be detected in the infrared spectra of M.alpina biomass after extraction using the Folch and Lewis methods, indicating their complete lipid extraction in this species. Bligh extraction underestimated the fatty acid content of both M.circinelloides and M.alpina biomass and an increase in the initial solvent-to-sample ratio (from 3:1 to 20:1) was needed to achieve complete extraction and a lipid-free IR spectrum. In accordance with previous studies, the gravimetric lipid yield was shown to overestimate the potential of the SCO producers and FAME quantification in GC-FID was found to be the best-suited method for lipid quantification. We conclude that FTIR spectroscopy can serve as a tool for evaluating the lipid extraction efficiency, in addition to identifying components that may affect lipid extraction processes.

FTIR Spectroscopy for Evaluation and Monitoring of Lipid Extraction Efficiency for Oleaginous Fungi

PubMed Central

Zimmermann, Boris; Kosa, Gergely; Kohler, Achim; Shapaval, Volha

2017-01-01

To assess whether Fourier Transform Infrared (FTIR) spectroscopy could be used to evaluate and monitor lipid extraction processes, the extraction methods of Folch, Bligh and Lewis were used. Biomass of the oleaginous fungi Mucor circinelloides and Mortierella alpina were employed as lipid-rich material for the lipid extraction. The presence of lipids was determined by recording infrared spectra of all components in the lipid extraction procedure, such as the biomass before and after extraction, the water and extract phases. Infrared spectra revealed the incomplete extraction after all three extraction methods applied to M.circinelloides and it was shown that mechanical disruption using bead beating and HCl treatment were necessary to complete the extraction in this species. FTIR spectroscopy was used to identify components, such as polyphosphates, that may have negatively affected the extraction process and resulted in differences in extraction efficiency between M.circinelloides and M.alpina. Residual lipids could not be detected in the infrared spectra of M.alpina biomass after extraction using the Folch and Lewis methods, indicating their complete lipid extraction in this species. Bligh extraction underestimated the fatty acid content of both M.circinelloides and M.alpina biomass and an increase in the initial solvent-to-sample ratio (from 3:1 to 20:1) was needed to achieve complete extraction and a lipid-free IR spectrum. In accordance with previous studies, the gravimetric lipid yield was shown to overestimate the potential of the SCO producers and FAME quantification in GC-FID was found to be the best-suited method for lipid quantification. We conclude that FTIR spectroscopy can serve as a tool for evaluating the lipid extraction efficiency, in addition to identifying components that may affect lipid extraction processes. PMID:28118388

APP Function and Lipids: A Bidirectional Link

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Grimm, Heike S.; Hartmann, Tobias

2017-01-01

Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer’s disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals. Interestingly, the observed lipid changes in the brain seem not only to be a consequence of the disease but also modulate Aβ generation. In line with these observations, protective lipids being able to decrease Aβ generation and also potential negative lipids in respect to AD were identified. Mechanistically, Aβ peptides are generated by sequential proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. The α-secretase appears to compete with β-secretase for the initial cleavage of APP, preventing Aβ production. All APP-cleaving secretases as well as APP are transmembrane proteins, further illustrating the impact of lipids on Aβ generation. Beside the pathological impact of Aβ, accumulating evidence suggests that Aβ and the APP intracellular domain (AICD) play an important role in regulating lipid homeostasis, either by direct effects or by affecting gene expression or protein stability of enzymes involved in the de novo synthesis of different lipid classes. This review summarizes the current literature addressing the complex bidirectional link between lipids and AD and APP processing including lipid alterations found in AD post mortem brains, lipids that alter APP processing and the physiological functions of Aβ and AICD in the regulation of several lipid metabolism pathways. PMID:28344547

Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery.

PubMed

Date, Abhijit A; Vador, Nimish; Jagtap, Aarti; Nagarsenker, Mangal S

2011-07-08

To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 °C/60% RH. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

NASA Astrophysics Data System (ADS)

Date, Abhijit A.; Vador, Nimish; Jagtap, Aarti; Nagarsenker, Mangal S.

2011-07-01

Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 °C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month. Indian patent application number 2167/MUM/2008.

Long-duration effect of multi-factor stresses on the cellular biochemistry, oil-yielding performance and morphology of Nannochloropsis oculata

PubMed Central

Wei, Likun; Huang, Xuxiong

2017-01-01

Microalga Nannochloropsis oculata is a promising alternative feedstock for biodiesel. Elevating its oil-yielding capacity is conducive to cost-saving biodiesel production. However, the regulatory processes of multi-factor collaborative stresses (MFCS) on the oil-yielding performance of N. oculata are unclear. The duration effects of MFCS (high irradiation, nitrogen deficiency and elevated iron supplementation) on N. oculata were investigated in an 18-d batch culture. Despite the reduction in cell division, the biomass concentration increased, resulting from the large accumulation of the carbon/energy-reservoir. However, different storage forms were found in different cellular storage compounds, and both the protein content and pigment composition swiftly and drastically changed. The analysis of four biodiesel properties using pertinent empirical equations indicated their progressive effective improvement in lipid classes and fatty acid composition. The variation curve of neutral lipid productivity was monitored with fluorescent Nile red and was closely correlated to the results from conventional methods. In addition, a series of changes in the organelles (e.g., chloroplast, lipid body and vacuole) and cell shape, dependent on the stress duration, were observed by TEM and LSCM. These changes presumably played an important role in the acclimation of N. oculata to MFCS and accordingly improved its oil-yielding performance. PMID:28346505

Optimization of lipase production by solid-state fermentation of olive pomace: from flask to laboratory-scale packed-bed bioreactor.

PubMed

Oliveira, Felisbela; Salgado, José Manuel; Abrunhosa, Luís; Pérez-Rodríguez, Noelia; Domínguez, José M; Venâncio, Armando; Belo, Isabel

2017-07-01

Lipases are versatile catalysts with many applications and can be produced by solid-state fermentation (SSF) using agro-industrial wastes. The aim of this work was to maximize the production of Aspergillus ibericus lipase under SSF of olive pomace (OP) and wheat bran (WB), evaluating the effect on lipase production of C/N ratio, lipids, phenols, content of sugars of substrates and nitrogen source addition. Moreover, the implementation of the SSF process in a packed-bed bioreactor and the improvement of lipase extraction conditions were assessed. Low C/N ratios and high content of lipids led to maximum lipase production. Optimum SSF conditions were achieved with a C/N mass ratio of 25.2 and 10.2% (w/w) lipids in substrate, by the mixture of OP:WB (1:1) and supplemented with 1.33% (w/w) (NH 4 ) 2 SO 4 . Studies in a packed-bed bioreactor showed that the lower aeration rates tested prevented substrate dehydration, improving lipase production. In this work, the important role of Triton X-100 on lipase extraction from the fermented solid substrate has been shown. A final lipase activity of 223 ± 5 U g -1 (dry basis) was obtained after 7 days of fermentation.

Engineering of layered, lipid-encapsulated drug nanoparticles through spray-drying.

PubMed

Sapra, Mahak; Mayya, Y S; Venkataraman, Chandra

2017-06-01

Drug-containing nanoparticles have been synthesized through the spray-drying of submicron droplet aerosols by using matrix materials such as lipids and biopolymers. Understanding layer formation in composite nanoparticles is essential for the appropriate engineering of particle substructures. The present study developed a droplet-shrinkage model for predicting the solid-phase formation of two non-volatile solutes-stearic acid lipid and a set of drugs, by considering molecular volume and solubility. Nanoparticle formation was simulated to define the parameter space of material properties and process conditions for the formation of a layered structure with the preferential accumulation of the lipid in the outer layer. Moreover, lipid-drug demarcation diagrams representing a set of critical values of ratios of solute properties at which the two solutes precipitate simultaneously were developed. The model was validated through the preparation of stearic acid-isoniazid nanoparticles under controlled processing conditions. The developed model can guide the selection of solvents, lipids, and processing conditions such that drug loading and lipid encapsulation in composite nanoparticles are optimized. Copyright © 2017 Elsevier B.V. All rights reserved.

Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice.

PubMed

Federico, Lorenzo; Yang, Liping; Brandon, Jason; Panchatcharam, Manikandan; Ren, Hongmei; Mueller, Paul; Sunkara, Manjula; Escalante-Alcalde, Diana; Morris, Andrew J; Smyth, Susan S

2018-01-01

Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted ceramide and sphingomyelin accumulation during diet-induced adipose tissue expansion, accumulation of the LPP3 substrate sphingosine 1- phosphate, and reduced expression of serine palmitoyl transferase. However, adiposity was unaffected by LPP3 deficiency on standard, high fat diet or Western diets, although Western diet-fed mice with adipocyte LPP3 deficiency exhibited improved glucose tolerance. Our results demonstrate functional compartmentalization of lipid phosphatase activity in adipocytes and identify an unexpected role for LPP3 in the regulation of diet-dependent sphingolipid synthesis that may impact on insulin signaling.

Childhood obesity treatment; Effects on BMI SDS, body composition, and fasting plasma lipid concentrations.

PubMed

Nielsen, Tenna Ruest Haarmark; Fonvig, Cilius Esmann; Dahl, Maria; Mollerup, Pernille Maria; Lausten-Thomsen, Ulrik; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian

2018-01-01

The body mass index (BMI) standard deviation score (SDS) may not adequately reflect changes in fat mass during childhood obesity treatment. This study aimed to investigate associations between BMI SDS, body composition, and fasting plasma lipid concentrations at baseline and during childhood obesity treatment. 876 children and adolescents (498 girls) with overweight/obesity, median age 11.2 years (range 1.6-21.7), and median BMI SDS 2.8 (range 1.3-5.7) were enrolled in a multidisciplinary outpatient treatment program and followed for a median of 1.8 years (range 0.4-7.4). Height and weight, body composition measured by dual-energy X-ray absorptiometry, and fasting plasma lipid concentrations were assessed at baseline and at follow-up. Lipid concentrations (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, and triglycerides (TG)) were available in 469 individuals (264 girls). Linear regressions were performed to investigate the associations between BMI SDS, body composition indices, and lipid concentrations. At baseline, BMI SDS was negatively associated with concentrations of HDL (p = 6.7*10-4) and positively with TG (p = 9.7*10-6). Reductions in BMI SDS were associated with reductions in total body fat percentage (p<2*10-16) and percent truncal body fat (p<2*10-16). Furthermore, reductions in BMI SDS were associated with improvements in concentrations of TC, LDL, HDL, non-HDL, LDL/HDL-ratio, and TG (all p <0.0001). Changes in body fat percentage seemed to mediate the changes in plasma concentrations of TC, LDL, and non-HDL, but could not alone explain the changes in HDL, LDL/HDL-ratio or TG. Among 81 individuals with available lipid concentrations, who increased their BMI SDS, 61% improved their body composition, and 80% improved their lipid concentrations. Reductions in the degree of obesity during multidisciplinary childhood obesity treatment are accompanied by improvements in body composition and fasting plasma lipid concentrations. Even in individuals increasing their BMI SDS, body composition and lipid concentrations may improve.

Childhood obesity treatment; Effects on BMI SDS, body composition, and fasting plasma lipid concentrations

PubMed Central

Fonvig, Cilius Esmann; Dahl, Maria; Mollerup, Pernille Maria; Lausten-Thomsen, Ulrik; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian

2018-01-01

Objective The body mass index (BMI) standard deviation score (SDS) may not adequately reflect changes in fat mass during childhood obesity treatment. This study aimed to investigate associations between BMI SDS, body composition, and fasting plasma lipid concentrations at baseline and during childhood obesity treatment. Methods 876 children and adolescents (498 girls) with overweight/obesity, median age 11.2 years (range 1.6–21.7), and median BMI SDS 2.8 (range 1.3–5.7) were enrolled in a multidisciplinary outpatient treatment program and followed for a median of 1.8 years (range 0.4–7.4). Height and weight, body composition measured by dual-energy X-ray absorptiometry, and fasting plasma lipid concentrations were assessed at baseline and at follow-up. Lipid concentrations (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, and triglycerides (TG)) were available in 469 individuals (264 girls). Linear regressions were performed to investigate the associations between BMI SDS, body composition indices, and lipid concentrations. Results At baseline, BMI SDS was negatively associated with concentrations of HDL (p = 6.7*10−4) and positively with TG (p = 9.7*10−6). Reductions in BMI SDS were associated with reductions in total body fat percentage (p<2*10−16) and percent truncal body fat (p<2*10−16). Furthermore, reductions in BMI SDS were associated with improvements in concentrations of TC, LDL, HDL, non-HDL, LDL/HDL-ratio, and TG (all p <0.0001). Changes in body fat percentage seemed to mediate the changes in plasma concentrations of TC, LDL, and non-HDL, but could not alone explain the changes in HDL, LDL/HDL-ratio or TG. Among 81 individuals with available lipid concentrations, who increased their BMI SDS, 61% improved their body composition, and 80% improved their lipid concentrations. Conclusion Reductions in the degree of obesity during multidisciplinary childhood obesity treatment are accompanied by improvements in body composition and fasting plasma lipid concentrations. Even in individuals increasing their BMI SDS, body composition and lipid concentrations may improve. PMID:29444114

Opportunities for bio-based packaging technologies to improve the quality and safety of fresh and further processed muscle foods.

PubMed

Cutter, Catherine Nettles

2006-09-01

It has been well documented that vacuum or modified atmosphere packaging materials, made from polyethylene- or other plastic-based materials, have been found to improve the stability and safety of raw or further processed muscle foods. However, recent research developments have demonstrated the feasibility, utilization, and commercial application of a variety of bio-based polymers or bio-polymers made from a variety of materials, including renewable/sustainable agricultural commodities, and applied to muscle foods. A variety of these bio-based materials have been shown to prevent moisture loss, drip, reduce lipid oxidation and improve flavor attributes, as well as enhancing the handling properties, color retention, and microbial stability of foods. With consumers demanding more environmentally friendly packaging and a desire for more natural products, bio-based films or bio-polymers will continue to play an important role in the food industry by improving the quality of many products, including fresh or further processed muscle foods.

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.

Wastewater treatment and biodiesel production by Scenedesmus obliquus in a two-stage cultivation process.

PubMed

Álvarez-Díaz, P D; Ruiz, J; Arbib, Z; Barragán, J; Garrido-Pérez, M C; Perales, J A

2015-04-01

The microalga Scenedesmus obliquus was cultured in two cultivation stages: (1) in batch with real wastewater; (2) maintaining the stationary phase with different conditions of CO2, light and salinity according to a factorial design in order to improve the lipid content. The presence of the three factors increased lipid content from 35.8% to 49% at the end of the second stage; CO2 presence presented the highest direct effect increasing lipid content followed by light presence and salt presence. The ω-3 fatty acids content increased with CO2 and light presence acting in isolation, nevertheless, when both factors acted together the interaction effect was negative. The ω-3 eicosapentaenoic acid content of the oil from S. obliquus slightly exceeded the 1% maximum to be used as biodiesel source (EU normative). Therefore, it is suggested the blend with other oils or the selective extraction of the ω-3 fatty acids from S. obliquus oil. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biotechnological potential of Synechocystis salina co-cultures with selected microalgae and cyanobacteria: Nutrients removal, biomass and lipid production.

PubMed

Gonçalves, Ana L; Pires, José C M; Simões, Manuel

2016-01-01

Cultivation of microalgae and cyanobacteria has been the focus of several research studies worldwide, due to the huge biotechnological potential of these photosynthetic microorganisms. However, production of these microorganisms is still not economically viable. One possible alternative to improve the economic feasibility of the process is the use of consortia between microalgae and/or cyanobacteria. In this study, Chlorella vulgaris, Pseudokirchneriella subcapitata and Microcystis aeruginosa were co-cultivated with Synechocystis salina to evaluate how dual-species cultures can influence biomass and lipid production and nutrients removal. Results have shown that the three studied consortia achieved higher biomass productivities than the individual cultures. Additionally, nitrogen and phosphorus consumption rates by the consortia provided final concentrations below the values established by European Union legislation for these nutrients. In the case of lipid productivities, higher values were determined when S. salina was co-cultivated with P. subcapitata and M. aeruginosa. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of structured triglycerides on the kinetic stability of total nutrient admixtures.

PubMed

Balogh, Judit; Bubenik, Júlia; Dredán, Judit; Csempesz, Ferenc; Kiss, Dorottya; Zelkó, Romána

2005-10-05

The physical stability of two types of total parenteral nutrient (TPN) admixtures was studied as a function of storage time and temperature. One of them contained only structured triglycerides and the other exclusively long-chain triglycerides as lipid components. Droplet size of the mixtures was followed by photon correlation spectroscopy for 10 days. Zeta potential and dynamic surface tension measurements were carried out to evaluate the possible changes in the charge and interfacial surface tension of the emulsion droplets during the storage. pH values were monitored in order to follow the possible decomposition processes in the course of storage. Droplet size of emulsions prepared with lipids containing exclusively long-chain triglycerides showed remarkable increase after 4 days of storage in contrast with that of the mixtures containing structured lipids. The obtained results indicate that besides the advantageous metabolic effects of structured triglycerides, their application is recommended to improve the physical stability of TPN admixtures.

Mass production and size control of lipid-polymer hybrid nanoparticles through controlled microvortices

PubMed Central

Kim, YongTae; Chung, Bomy Lee; Ma, Mingming; Mulder, Willem J. M.; Fayad, Zahi A.; Farokhzad, Omid C.; Langer, Robert

2012-01-01

Lipid-polymer hybrid (LPH) nanoparticles can deliver a wide range of therapeutic compounds in a controlled manner. LPH nanoparticle syntheses using microfluidics improve the mixing process, but are restricted by a low throughput. In this study we present a pattern-tunable microvortex platform that allows mass production and size control of LPH nanoparticles with superior reproducibility and homogeneity. We demonstrate that by varying flow rates (i.e. Reynolds number (30∼150)) we can control the nanoparticle size (30∼170nm) with high productivity (∼3g/hour) and low polydispersity (∼0.1). Our approach may contribute to efficient development and optimization of a wide range of multicomponent nanoparticles for medical imaging and drug delivery. PMID:22716029

A Mathematical Model of Neutral Lipid Content in terms of Initial Nitrogen Concentration and Validation in Coelastrum sp. HA-1 and Application in Chlorella sorokiniana

PubMed Central

Zhao, Yue; Liu, Zhiyong; Liu, Chenfeng; Hu, Zhipeng

2017-01-01

Microalgae are considered to be a potential major biomass feedstock for biofuel due to their high lipid content. However, no correlation equations as a function of initial nitrogen concentration for lipid accumulation have been developed for simplicity to predict lipid production and optimize the lipid production process. In this study, a lipid accumulation model was developed with simple parameters based on the assumption protein synthesis shift to lipid synthesis by a linear function of nitrogen quota. The model predictions fitted well for the growth, lipid content, and nitrogen consumption of Coelastrum sp. HA-1 under various initial nitrogen concentrations. Then the model was applied successfully in Chlorella sorokiniana to predict the lipid content with different light intensities. The quantitative relationship between initial nitrogen concentrations and the final lipid content with sensitivity analysis of the model were also discussed. Based on the model results, the conversion efficiency from protein synthesis to lipid synthesis is higher and higher in microalgae metabolism process as nitrogen decreases; however, the carbohydrate composition content remains basically unchanged neither in HA-1 nor in C. sorokiniana. PMID:28194424

Exploring Triacylglycerol Biosynthetic Pathway in Developing Seeds of Chia (Salvia hispanica L.): A Transcriptomic Approach

PubMed Central

Rupwate, Sunny D.; Rajasekharan, Ram; Srinivasan, Malathi

2015-01-01

Chia (Salvia hispanica L.), a member of the mint family (Lamiaceae), is a rediscovered crop with great importance in health and nutrition and is also the highest known terrestrial plant source of heart-healthy omega-3 fatty acid, alpha linolenic acid (ALA). At present, there is no public genomic information or database available for this crop, hindering research on its genetic improvement through genomics-assisted breeding programs. The first comprehensive analysis of the global transcriptome profile of developing Salvia hispanica L. seeds, with special reference to lipid biosynthesis is presented in this study. RNA from five different stages of seed development was extracted and sequenced separately using the Illumina GAIIx platform. De novo assembly of processed reads in the pooled transcriptome using Trinity yielded 76,014 transcripts. The total transcript length was 66,944,462 bases (66.9 Mb), with an average length of approximately 880 bases. In the molecular functions category of Gene Ontology (GO) terms, ATP binding and nucleotide binding were found to be the most abundant and in the biological processes category, the metabolic process and the regulation of transcription-DNA-dependent and oxidation-reduction process were abundant. From the EuKaryotic Orthologous Groups of proteins (KOG) classification, the major category was “Metabolism” (31.97%), of which the most prominent class was ‘carbohydrate metabolism and transport’ (5.81% of total KOG classifications) followed by ‘secondary metabolite biosynthesis transport and catabolism’ (5.34%) and ‘lipid metabolism’ (4.57%). A majority of the candidate genes involved in lipid biosynthesis and oil accumulation were identified. Furthermore, 5596 simple sequence repeats (SSRs) were identified. The transcriptome data was further validated through confirmative PCR and qRT-PCR for select lipid genes. Our study provides insight into the complex transcriptome and will contribute to further genome-wide research and understanding of chia. The identified novel UniGenes will facilitate gene discovery and creation of genomic resource for this crop. PMID:25875809

Avanti lipid tools: connecting lipids, technology, and cell biology.

PubMed

Sims, Kacee H; Tytler, Ewan M; Tipton, John; Hill, Kasey L; Burgess, Stephen W; Shaw, Walter A

2014-08-01

Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions. Copyright © 2014. Published by Elsevier B.V.

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.

Recent developments of downstream processing for microbial lipids and conversion to biodiesel.

PubMed

Yellapu, Sravan Kumar; Bharti; Kaur, Rajwinder; Kumar, Lalit R; Tiwari, Bhagyashree; Zhang, Xiaolei; Tyagi, Rajeshwar D

2018-05-01

With increasing global population and depleting resources, there is an apparent demand for radical unprecedented innovation to satisfy the basal needs of lives. Hence, non-conventional renewable energy resources like biodiesel have been worked out in past few decades. Biofuel (e.g. Biodiesel) serves to be the most sustainable answer to solve "food vs. fuel crisis". In biorefinery process, lipid extraction from oleaginous microbial lipids is an integral part as it facilitates the release of fatty acids. Direct lipid extraction from wet cell-biomass is favorable in comparison to dry-cell biomass because it eliminates the application of expensive dehydration. However, this process is not commercialized yet, instead, it requires intensive research and development in order to establish robust approaches for lipid extraction that can be practically applied on an industrial scale. This review aims for the critical presentation on cell disruption, lipid recovery and purification to support extraction from wet cell-biomass for an efficient transesterification. Copyright © 2018 Elsevier Ltd. All rights reserved.

Defining Lipid Transport Pathways in Animal Cells

NASA Astrophysics Data System (ADS)

Pagano, Richard E.; Sleight, Richard G.

1985-09-01

A new technique for studying the metabolism and intracellular transport of lipid molecules in living cells based on the use of fluorescent lipid analogs is described. The cellular processing of various intermediates (phosphatidic acid and ceramide) and end products (phosphatidylcholine and phosphatidylethanolamine) in lipid biosynthesis is reviewed and a working model for compartmentalization during lipid biosynthesis is presented.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs.

PubMed

Choi, Kyeong-Ok; Choe, Jaehyeog; Suh, Seokjin; Ko, Sanghoon

2016-05-20

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis

PubMed Central

2017-01-01

Analyzing lipid composition and distribution within the brain is important to study white matter pathologies that present focal demyelination lesions, such as multiple sclerosis. Some lesions can endogenously re-form myelin sheaths. Therapies aim to enhance this repair process in order to reduce neurodegeneration and disability progression in patients. In this context, a lipidomic analysis providing both precise molecular classification and well-defined localization is crucial to detect changes in myelin lipid content. Here we develop a correlated heterospectral lipidomic (HSL) approach based on coregistered Raman spectroscopy, desorption electrospray ionization mass spectrometry (DESI-MS), and immunofluorescence imaging. We employ HSL to study the structural and compositional lipid profile of demyelination and remyelination in an induced focal demyelination mouse model and in multiple sclerosis lesions from patients ex vivo. Pixelwise coregistration of Raman spectroscopy and DESI-MS imaging generated a heterospectral map used to interrelate biomolecular structure and composition of myelin. Multivariate regression analysis enabled Raman-based assessment of highly specific lipid subtypes in complex tissue for the first time. This method revealed the temporal dynamics of remyelination and provided the first indication that newly formed myelin has a different lipid composition compared to normal myelin. HSL enables detailed molecular myelin characterization that can substantially improve upon the current understanding of remyelination in multiple sclerosis and provides a strategy to assess remyelination treatments in animal models. PMID:29392175

Polyoxylglycerides and glycerides: effects of manufacturing parameters on API stability, excipient functionality and processing.

PubMed

Jannin, Vincent; Rodier, Jean-David; Musakhanian, Jasmine

2014-05-15

Lipid-based formulations are a viable option to address modern drug delivery challenges such as increasing the oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs), or sustaining the drug release of molecules intended for chronic diseases. Esters of fatty acids and glycerol (glycerides) and polyethylene-glycols (polyoxylglycerides) are two main classes of lipid-based excipients used by oral, dermal, rectal, vaginal or parenteral routes. These lipid-based materials are more and more commonly used in pharmaceutical drug products but there is still a lack of understanding of how the manufacturing processes, processing aids, or additives can impact the chemical stability of APIs within the drug product. In that regard, this review summarizes the key parameters to look at when formulating with lipid-based excipients in order to anticipate a possible impact on drug stability or variation of excipient functionality. The introduction presents the chemistry of natural lipids, fatty acids and their properties in relation to the extraction and refinement processes. Then, the key parameters during the manufacturing process influencing the quality of lipid-based excipients are provided. Finally, their critical characteristics are discussed in relation with their intended functionality and ability to interact with APIs and others excipients within the formulation. Copyright © 2014. Published by Elsevier B.V.

Enzymatic modification of egg lecithin to improve properties.

PubMed

Asomaning, Justice; Curtis, Jonathan M

2017-04-01

This research studied the enzymatic modification of egg yolk phospholipids and its effect on physicochemical properties. Egg yolk lipids were extracted with food grade ethanol and egg phospholipids (ePL) produced by deoiling with acetone. Vegetable oils were used to interesterify ePL utilizing Lipozyme®: sn-1,3 specific lipase. The enzymatic interesterification resulted in a single phase liquid product, whereas simple blending of the ePL and vegetable oil resulted in a product with two phases. In addition solid fat content decreased by 50% at -10°C and 94% at 35°C when compared with egg yolk lipids extract. A decrease in melting temperature resulted from the interesterification process. Interesterification improved emulsion stability index when used as an emulsifier in oil-in-water emulsion and compared to the native and soy lecithin. Enzyme reusability test showed retention of 63% activity after 10 cycles. Overall, the properties of native egg phospholipids were significantly enhanced in a potentially useful manner through interesterification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing microalgae biorefinery routes for the production of biofuels via hydrothermal liquefaction.

PubMed

López Barreiro, Diego; Samorì, Chiara; Terranella, Giuseppe; Hornung, Ursel; Kruse, Andrea; Prins, Wolter

2014-12-01

The interest in third generation biofuels from microalgae has been rising during the past years. Meanwhile, it seems not economically feasible to grow algae just for biofuels. Co-products with a higher value should be produced by extracting a particular algae fraction to improve the economics of an algae biorefinery. The present study aims at analyzing the influence of two main microalgae components (lipids and proteins) on the composition and quantity of biocrude oil obtained via hydrothermal liquefaction of two strains (Nannochloropsis gaditana and Scenedesmus almeriensis). The algae were liquefied as raw biomass, after extracting lipids and after extracting proteins in microautoclave experiments at different temperatures (300-375°C) for 5 and 15min. The results indicate that extracting the proteins from the microalgae prior to HTL may be interesting to improve the economics of the process while at the same time reducing the nitrogen content of the biocrude oil. Copyright © 2014 Elsevier Ltd. All rights reserved.

Large-scale production of lipoplexes with long shelf-life.

PubMed

Clement, Jule; Kiefer, Karin; Kimpfler, Andrea; Garidel, Patrick; Peschka-Süss, Regine

2005-01-01

The instability of lipoplex formulations is a major obstacle to overcome before their commercial application in gene therapy. In this study, a continuous mixing technique for the large-scale preparation of lipoplexes followed by lyophilisation for increased stability and shelf-life has been developed. Lipoplexes were analysed for transfection efficiency and cytotoxicity in human aorta smooth muscle cells (HASMC) and a rat smooth muscle cell line (A-10 SMC). Homogeneity of lipid/DNA-products was investigated by photon correlation spectroscopy (PCS) and cryotransmission electron microscopy (cryo-TEM). Studies have been undertaken with DAC-30, a composition of 3beta-[N-(N,N'-dimethylaminoethane)-carbamoyl]-cholesterol (DAC-Chol) and dioleylphosphatidylethanolamine (DOPE) and a green fluorescent protein (GFP) expressing marker plasmid. A continuous mixing technique was compared to the small-scale preparation of lipoplexes by pipetting. Individual steps of the continuous mixing process were evaluated in order to optimise the manufacturing technique: lipid/plasmid ratio, composition of transfection medium, pre-treatment of the lipid, size of the mixing device, mixing procedure and the influence of the lyophilisation process. It could be shown that the method developed for production of lipoplexes on a large scale under sterile conditions led to lipoplexes with good transfection efficiencies combined with low cytotoxicity, improved characteristics and long shelf-life.

Impact of biochemical composition on susceptibility of algal biomass to acid-catalyzed pretreatment for sugar and lipid recovery

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

Dong, Tao; Van Wychen, Stefanie; Nagle, Nick

One of the major challenges associated with algal biofuels production in a biorefinery-type setting is improving biomass utilization in its entirety, increasing the process energetic yields and providing economically viable and scalable co-product concepts. We focus on the impact of compositional characteristics of biomass on the susceptibility to pretreatment in order to maximize the valorization of algal biomass conversion for biofuels and bioproducts. The release of monomeric carbohydrates in the aqueous phase and extractability of the lipid fraction was measured based a response surface methodology to find significant explanatory variables and interaction terms. We studied the effect of harvest timingmore » on the conversion yields, using three algal strains; Chlorella vulgaris and Scenedesmus acutus and Nannochloropsis granulata representing three different nutritional metabolic phases. Four cultivation conditions of high (≥ 90 gallon gasoline equivalent/ton biomass) value for a combined sugar- and lipid-based biofuels process were identified. These four conditions represent either mid or late stage harvest cultivation regimes. Lastly, the results indicate that acid pretreatment has potential to be applicable for a vast range of biomass samples to obtain high energy yields, but that the exact conditions and optima are dependent on the strain and likely the starting composition of the biomass.« less

Impact of biochemical composition on susceptibility of algal biomass to acid-catalyzed pretreatment for sugar and lipid recovery

DOE PAGES

Dong, Tao; Van Wychen, Stefanie; Nagle, Nick; ...

2016-06-11

One of the major challenges associated with algal biofuels production in a biorefinery-type setting is improving biomass utilization in its entirety, increasing the process energetic yields and providing economically viable and scalable co-product concepts. We focus on the impact of compositional characteristics of biomass on the susceptibility to pretreatment in order to maximize the valorization of algal biomass conversion for biofuels and bioproducts. The release of monomeric carbohydrates in the aqueous phase and extractability of the lipid fraction was measured based a response surface methodology to find significant explanatory variables and interaction terms. We studied the effect of harvest timingmore » on the conversion yields, using three algal strains; Chlorella vulgaris and Scenedesmus acutus and Nannochloropsis granulata representing three different nutritional metabolic phases. Four cultivation conditions of high (≥ 90 gallon gasoline equivalent/ton biomass) value for a combined sugar- and lipid-based biofuels process were identified. These four conditions represent either mid or late stage harvest cultivation regimes. Lastly, the results indicate that acid pretreatment has potential to be applicable for a vast range of biomass samples to obtain high energy yields, but that the exact conditions and optima are dependent on the strain and likely the starting composition of the biomass.« less

Identification and characterization of lipid metabolism-related microRNAs in the liver of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) by deep sequencing.

PubMed

Tao, Yi-Fan; Qiang, Jun; Yin, Guo-Jun; Xu, Pao; Shi, Qiong; Bao, Jing-Wen

2017-10-01

MicroRNAs (miRNAs) play vital roles in modulating diverse metabolic processes in the liver, including lipid metabolism. Genetically improved farmed tilapia (GIFT, Oreochromis niloticus), an important aquaculture species in China, is susceptible to hepatic steatosis when reared in intensive culture systems. To investigate the miRNAs involved in GIFT lipid metabolism, two hepatic small RNA libraries from high-fat diet-fed and normal-fat diet-fed GIFT were constructed and sequenced using high-throughput sequencing technology. A total of 204 known and 56 novel miRNAs were identified by aligning the sequencing data with known Danio rerio miRNAs listed in miRBase 21.0. Six known miRNAs (miR-30a-5p, miR-34a, miR-145-5p, miR-29a, miR-205-5p, and miR-23a-3p) that were differentially expressed between the high-fat diet and normal-fat diet groups were validated by quantitative real-time PCR. Bioinformatics tools were used to predict the potential target genes of these differentially expressed miRNAs, and Gene Ontology enrichment analysis indicated that these miRNAs may play important roles in diet-induced hepatic steatosis in GIFT. Our results provide a foundation for further studies of the role of miRNAs in tilapia lipid homeostasis regulation, and may help to identify novel targets for therapeutic interventions to reduce the occurrence of fatty liver disease in farmed tilapia. Copyright © 2017. Published by Elsevier Ltd.

Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice.

PubMed

Lin, Chih-Wen; Zhang, Hao; Li, Min; Xiong, Xiwen; Chen, Xi; Chen, Xiaoyun; Dong, Xiaocheng C; Yin, Xiao-Ming

2013-05-01

Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical Changes in Lipids Produced by Thermal Processing.

ERIC Educational Resources Information Center

Nawar, Wassef W.

1984-01-01

Describes heat effects on lipids, indicating that the chemical and physical changes that occur depend on the lipid's composition and conditions of treatment. Thermolytic and oxidation reactions, thermal/oxidative interaction of lipids with other food components and the chemistry of frying are considered. (JN)

Synthesis of Lipidated Proteins.

PubMed

Mejuch, Tom; Waldmann, Herbert

2016-08-17

Protein lipidation is one of the major post-translational modifications (PTM) of proteins. The attachment of the lipid moiety frequently determines the localization and the function of the lipoproteins. Lipidated proteins participate in many essential biological processes in eukaryotic cells, including vesicular trafficking, signal transduction, and regulation of the immune response. Malfunction of these cellular processes usually leads to various diseases such as cancer. Understanding the mechanism of cellular signaling and identifying the protein-protein and protein-lipid interactions in which the lipoproteins are involved is a crucial task. To achieve these goals, fully functional lipidated proteins are required. However, access to lipoproteins by means of standard expression is often rather limited. Therefore, semisynthetic methods, involving the synthesis of lipidated peptides and their subsequent chemoselective ligation to yield full-length lipoproteins, were developed. In this Review we summarize the commonly used methods for lipoprotein synthesis and the development of the corresponding chemoselective ligation techniques. Several key studies involving full-length semisynthetic lipidated Ras, Rheb, and LC3 proteins are presented.

An improved high-throughput Nile red fluorescence assay for estimating intracellular lipids in a variety of yeast species

PubMed Central

Sitepu, I.R.; Ignatia, L.; Franz, A. K.; Wong, D. M.; Faulina, S.A.; Tsui, M.; Kanti, A.; Boundy-Mills, K.

2012-01-01

A rapid and inexpensive method for estimating lipid content of yeasts is needed for screening large numbers of yeasts samples. Nile red is a fluorescent lipophilic dye used for detection and quantification of intracellular lipid droplets in various biological system including algae, yeasts and filamentous fungi. However, a published assay for yeast is affected by variable diffusion across the cell membrane, and variation in the time required to reach maximal fluorescence emission. In this study, parameters that may influence the emission were varied to determine optimal assay conditions. An improved assay with a high-throughput capability was developed that includes the addition of dimethyl sulfoxide (DMSO) solvent to improve cell permeability, elimination of the washing step, the reduction of Nile red concentration, kinetic readings rather than single time-point reading, and utilization of a black 96-well microplate. The improved method was validated by comparison to gravimetric determination of lipid content of a broad variety of ascomycete and basidiomycete yeast species. PMID:22985718

Improved Productivity of Neutral Lipids in Chlorella sp. A2 by Minimal Nitrogen Supply

PubMed Central

Zhu, Junying; Chen, Weixian; Chen, Hui; Zhang, Xin; He, Chenliu; Rong, Junfeng; Wang, Qiang

2016-01-01

Nitrogen starvation is an efficient environmental pressure for increasing lipid accumulation in microalgae, but it could also significantly lower the biomass productivity, resulting in lower lipid productivity. In this study, green alga Chlorella sp. A2 was cultivated by using a minimal nitrogen supply strategy under both laboratory and outdoor cultivation conditions to evaluate biomass accumulation and lipid production. Results showed that minimal nitrogen supply could promote neutral lipid accumulation of Chlorella sp. A2 without a significant negative effect on cell growth. In laboratory cultivation mode, alga cells cultured with 18 mg L−1 d−1 urea addition could generate 74 and 416% (w/w) more neutral lipid productivity than cells cultured with regular BG11 and nitrogen starvation media, respectively. In outdoor cultivation mode, lipid productivity of cells cultured with 18 mg L−1 d−1 urea addition is approximately 10 and 88% higher than the one with regular BG11 and nitrogen starvation media, respectively. Notably, the results of photosynthetic analysis clarified that minimal nitrogen supply reduced the loss of photosynthetic capacity to keep CO2 fixation during photosynthesis for biomass production. The minimal nitrogen supply strategy for microalgae cultivation could promote neutral lipid accumulation without a significant negative effect on cell growth, resulting in a significant improvement in the lipid productivity. PMID:27148237

Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine.

PubMed

Hiel, Sophie; Neyrinck, Audrey M; Rodriguez, Julie; Pachikian, Barbara D; Bouzin, Caroline; Thissen, Jean-Paul; Cani, Patrice D; Bindels, Laure B; Delzenne, Nathalie M

2018-04-25

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 ( Apoc3 , inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.

Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine

PubMed Central

Hiel, Sophie; Rodriguez, Julie; Pachikian, Barbara D.; Thissen, Jean-Paul; Delzenne, Nathalie M.

2018-01-01

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 (Apoc3, inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk. PMID:29693598

Overexpression of malic enzyme (ME) of Mucor circinelloides improved lipid accumulation in engineered Rhodotorula glutinis.

PubMed

Li, Zhi; Sun, Hanxiao; Mo, Xuemei; Li, Xiuying; Xu, Bo; Tian, Peng

2013-06-01

The oleaginous yeast Rhodotorula glutinis has been known to be a potential feedstock for lipid production. In the present study, we investigated the enhancement of expression of malic enzyme (ME; NADP(+) dependent; EC 1.1.1.40) from Mucor circinelloides as a strategy to improve lipid content inside the yeast cells. The 26S rDNA and 5.8S rDNA gene fragments isolated from Rhodotorula glutinis were used for homologous integration of ME gene into R. glutinis chromosome under the control of the constitutively highly expressed gene phosphoglycerate kinase 1 to achieve stable expression. We demonstrated that by increasing the expression of the foreign ME gene in R. glutinis, we successfully improved the lipid content by more than twofold. At the end of lipid accumulation phrase (96 h) in the transformants, activity of ME was increased by twofold and lipid content of the yeast cells was increased from 18.74 % of the biomass to 39.35 %. Simultaneously, there were no significant differences in fatty acid profiles between the wild-type strain and the recombinant strain. Over 94 % of total fatty acids were C16:0, C18:0, C16:1, C18:1, and C18:2. Our results indicated that heterologous expression of NADP(+)-dependent ME involved in fatty acid biosynthesis indeed increased the lipid accumulation in the oleaginous yeast R. glutinis.

Evaluation of lipid extractability after flash hydrolysis of algae

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

Teymouri, Ali; Adams, Kameron J.; Dong, Tao

Microalgae is identified as a promising feedstock for producing renewable liquid transportation fuels; however, lipids extraction from microalgae for downstream processing to biofuels is one of the important challenges for algal based biorefineries. This work aims at evaluating the potential of applying flash hydrolysis (FH) as a chemical-free technique to increase the lipids extractability of algal biomass as well as its integration with the hydrothermal liquefaction (HTL) of microalgae to enhance the biocrude yields and characteristics for fuel production. To this aim, the FH process was performed on three different algal species (Scenedesmus sp., Nannochloropsis sp., and Chlorella vulgaris) atmore » 280 degrees C and 10 s of residence time. Following FH, in addition to the nutrients rich hydrolysate, approximately, 40 wt% of solids containing almost all (>90 wt%) the lipids termed as biofuels intermediates (BI), were recovered. Kinetics study on lipids extractability from the BI and their lipid profile analyses were conducted for each algal species. The results showed that the FH process had significantly enhanced the lipids extractability. For all three algae species, lipid yields from BI were higher than that of the raw algae. Lipid yields of Chlorella vulgaris in the first 15 min were more than five times higher (52.3 +/- 0.8 vs. 10.7 +/- 0.9 wt%) than that of raw algae during n-hexane based solvent extraction. The kinetics of lipids extractability followed a zero-order reaction rate for all wet raw microalgae and the BI of Scenedesmus sp., while the BI recovered from the other two algal species were determined as a second-order reaction. Comparison of fatty acids profiles indicated the contribution of the FH process in saturating fatty acids. Subsequent to lipids extraction, a conventional hydrothermal liquefaction was performed at 350 degrees C and 1 h to compare the biocrude yields from raw versus BI of Chlorella vulgaris microalgae. The results showed that the biocrude yields from the BI and its quality was significantly enhanced post FH than that of raw algae. The FH process was proven to be a viable option for lipid extraction by increasing the extent of recovery and decreasing the extraction time. Its integration with HTL notably impact the biocrude yields and characteristics for fuel production.« less

Evaluation of lipid extractability after flash hydrolysis of algae

DOE PAGES

Teymouri, Ali; Adams, Kameron J.; Dong, Tao; ...

2018-07-01

Microalgae is identified as a promising feedstock for producing renewable liquid transportation fuels; however, lipids extraction from microalgae for downstream processing to biofuels is one of the important challenges for algal based biorefineries. This work aims at evaluating the potential of applying flash hydrolysis (FH) as a chemical-free technique to increase the lipids extractability of algal biomass as well as its integration with the hydrothermal liquefaction (HTL) of microalgae to enhance the biocrude yields and characteristics for fuel production. To this aim, the FH process was performed on three different algal species (Scenedesmus sp., Nannochloropsis sp., and Chlorella vulgaris) atmore » 280 degrees C and 10 s of residence time. Following FH, in addition to the nutrients rich hydrolysate, approximately, 40 wt% of solids containing almost all (>90 wt%) the lipids termed as biofuels intermediates (BI), were recovered. Kinetics study on lipids extractability from the BI and their lipid profile analyses were conducted for each algal species. The results showed that the FH process had significantly enhanced the lipids extractability. For all three algae species, lipid yields from BI were higher than that of the raw algae. Lipid yields of Chlorella vulgaris in the first 15 min were more than five times higher (52.3 +/- 0.8 vs. 10.7 +/- 0.9 wt%) than that of raw algae during n-hexane based solvent extraction. The kinetics of lipids extractability followed a zero-order reaction rate for all wet raw microalgae and the BI of Scenedesmus sp., while the BI recovered from the other two algal species were determined as a second-order reaction. Comparison of fatty acids profiles indicated the contribution of the FH process in saturating fatty acids. Subsequent to lipids extraction, a conventional hydrothermal liquefaction was performed at 350 degrees C and 1 h to compare the biocrude yields from raw versus BI of Chlorella vulgaris microalgae. The results showed that the biocrude yields from the BI and its quality was significantly enhanced post FH than that of raw algae. The FH process was proven to be a viable option for lipid extraction by increasing the extent of recovery and decreasing the extraction time. Its integration with HTL notably impact the biocrude yields and characteristics for fuel production.« less

Lipid catabolism in microalgae.

PubMed

Kong, Fantao; Romero, Ismael Torres; Warakanont, Jaruswan; Li-Beisson, Yonghua

2018-06-01

Lipid degradation processes are important in microalgae because survival and growth of microalgal cells under fluctuating environmental conditions require permanent remodeling or turnover of membrane lipids as well as rapid mobilization of storage lipids. Lipid catabolism comprises two major spatially and temporarily separated steps, namely lipolysis, which releases fatty acids and head groups and is catalyzed by lipases at membranes or lipid droplets, and degradation of fatty acids to acetyl-CoA, which occurs in peroxisomes through the β-oxidation pathway in green microalgae, and can sometimes occur in mitochondria in some other algal species. Here we review the current knowledge on the enzymes and regulatory proteins involved in lipolysis and peroxisomal β-oxidation and highlight gaps in our understanding of lipid degradation pathways in microalgae. Metabolic use of acetyl-CoA products via glyoxylate cycle and gluconeogenesis is also reviewed. We then present the implication of various cellular processes such as vesicle trafficking, cell cycle and autophagy on lipid turnover. Finally, physiological roles and the manipulation of lipid catabolism for biotechnological applications in microalgae are discussed. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Origin of 1/f noise in hydration dynamics on lipid membrane surfaces

PubMed Central

Yamamoto, Eiji; Akimoto, Takuma; Yasui, Masato; Yasuoka, Kenji

2015-01-01

Water molecules on lipid membrane surfaces are known to contribute to membrane stability by connecting lipid molecules and acting as a water bridge. Although water structures and diffusivities near the membrane surfaces have been extensively studied, hydration dynamics on the surfaces has remained an open question. Here we investigate residence time statistics of water molecules on the surface of lipid membranes using all-atom molecular dynamics simulations. We show that hydration dynamics on the lipid membranes exhibits 1/f noise. Constructing a dichotomous process for the hydration dynamics, we find that residence times in each state follow a power-law with exponential cutoff and that the process can be regarded as a correlated renewal process where interoccurrence times are correlated. The results imply that the origin of the 1/f noise in hydration dynamics on the membrane surfaces is a combination of a power-law distribution with cutoff of interoccurrence times of switching events and a long-term correlation between the interoccurrence times. These results suggest that the 1/f noise attributed to the correlated renewal process may contribute to the stability of the hydration layers and lipid membranes. PMID:25743377

Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium.

PubMed

Xia, Dengning; He, Yuan; Li, Qiuxia; Hu, Cunde; Huang, Wei; Zhang, Yunhai; Wan, Feng; Wang, Chi; Gan, Yong

2018-01-10

Pure drug nanoparticles (NPs) represent a promising formulation for improved drug solubility and controlled dissolution velocity. However, limited absorption by the intestinal epithelium remains challenge to their clinical application, and little is known about how these NPs within the cells are transported. To improve cellular uptake and transport of pure nanodrug in cells, here, a lipid covered saquinavir (SQV) pure drug NP (Lipo@nanodrug) was designed by modifying a pure SQV NP (nanodrug) with a phospholipid bilayer. We studied their endocytosis, intracellular trafficking mechanism using Caco-2 cell model. Uptake of Lipo@nanodrug by Caco-2 cells was 1.91-fold greater than that of pure nanodrug via processes involving cell lipid raft. The transcellular transport of Lipo@nanodrug across Caco-2 monolayers was 3.75-fold and 1.92-fold higher than that of coarse crystals and pure nanodrug, respectively. Within cells, Lipo@nanodrug was mainly localized in the endoplasmic reticulum and Golgi apparatus, leading to transcytosis of Lipo@nanodrug across intestinal epithelial cells, whereas pure nanodrug tended to be retained and to dissolve in cell and removed by P-gp-mediated efflux. In rats, the oral bioavailability of the model drug SQV after Lipo@nanodrug administration was 4.29-fold and 1.77-fold greater than after coarse crystal and pure nanodrug administration, respectively. In conclusion, addition of a phospholipid bilayer to pure drug NP increased their cellular uptake and altered their intracellular processing, helping to improve drug transport across intestinal epithelium. To our knowledge, this is the first presentation of the novel phospholipid bilayer covered SQV pure drug NP design, and a mechanistic study on intracellular trafficking in in vitro cell models has been described. The findings provide a new platform for oral delivery of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrodiffusion of lipids on membrane surfaces.

PubMed

Zhou, Y C

2012-05-28

Lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when the random lateral motion is mediated by the electrostatic interactions and membrane curvature. Although the lateral diffusion rates of lipids on membranes of various compositions are measured and the electrostatic free energies of predetermined protein-membrane-lipid systems can be computed, the process of the aggregation and the evolution to the electrostatically favorable states remain largely undetermined. Here we propose an electrodiffusion model, based on the variational principle of the free energy functional, for the self-consistent lateral drift-diffusion of multiple species of charged lipids on membrane surfaces. Finite sizes of lipids are modeled to enforce the geometrical constraint of the lipid concentration on membrane surfaces. A surface finite element method is developed to appropriate the Laplace-Beltrami operators in the partial differential equations of the model. Our model properly describes the saturation of lipids on membrane surfaces, and correctly predicts that the MARCKS peptide can consistently sequester three multivalent phosphatidylinositol 4,5-bisphosphate lipids through its basic amino acid residues, regardless of a wide range of the percentage of monovalent phosphatidylserine in the membrane.

Electrodiffusion of lipids on membrane surfaces

NASA Astrophysics Data System (ADS)

Zhou, Y. C.

2012-05-01

Lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when the random lateral motion is mediated by the electrostatic interactions and membrane curvature. Although the lateral diffusion rates of lipids on membranes of various compositions are measured and the electrostatic free energies of predetermined protein-membrane-lipid systems can be computed, the process of the aggregation and the evolution to the electrostatically favorable states remain largely undetermined. Here we propose an electrodiffusion model, based on the variational principle of the free energy functional, for the self-consistent lateral drift-diffusion of multiple species of charged lipids on membrane surfaces. Finite sizes of lipids are modeled to enforce the geometrical constraint of the lipid concentration on membrane surfaces. A surface finite element method is developed to appropriate the Laplace-Beltrami operators in the partial differential equations of the model. Our model properly describes the saturation of lipids on membrane surfaces, and correctly predicts that the MARCKS peptide can consistently sequester three multivalent phosphatidylinositol 4,5-bisphosphate lipids through its basic amino acid residues, regardless of a wide range of the percentage of monovalent phosphatidylserine in the membrane.

Application of high-salinity stress for enhancing the lipid productivity of Chlorella sorokiniana HS1 in a two-phase process.

PubMed

Kakarla, Ramesh; Choi, Jung-Woon; Yun, Jin-Ho; Kim, Byung-Hyuk; Heo, Jina; Lee, Sujin; Cho, Dae-Hyun; Ramanan, Rishiram; Kim, Hee-Sik

2018-01-01

Increased lipid accumulation of algal cells as a response to environmental stress factors attracted much attention of researchers to incorporate this stress response into industrial algal cultivation process with the aim of enhancing algal lipid productivity. This study applies high-salinity stress condition to a two-phase process in which microalgal cells are initially grown in freshwater medium until late exponential phase and subsequently subjected to high-salinity condition that induces excessive lipid accumulation. Our initial experiment revealed that the concentrated culture of Chlorella sorokiniana HS1 exhibited the intense fluorescence of Nile red at the NaCl concentration of 60 g/L along with 1 g/L of supplemental bicarbonate after 48 h of induction period without significantly compromising cultural integrity. These conditions were further verified with the algal culture grown for 7 days in a 1 L bottle reactor that reached late exponential phase; a 12% increment in the lipid content of harvested biomass was observed upon inducing high lipid accumulation in the concentrated algal culture at the density of 5.0 g DW/L. Although an increase in the sum of carbohydrate and lipid contents of harvested biomass indicated that the external carbon source supplemented during the induction period increased overall carbon assimilation, a decrease in carbohydrate content suggested the potential reallocation of cellular carbon that promoted lipid droplet formation under high-salinity stress. These results thus emphasize that the two-phase process can be successfully implemented to enhance algal lipid productivity by incorporating high-salinity stress conditions into the pre-concentrated sedimentation ponds of industrial algal production system.

An improved high-throughput lipid extraction method for the analysis of human brain lipids.

PubMed

Abbott, Sarah K; Jenner, Andrew M; Mitchell, Todd W; Brown, Simon H J; Halliday, Glenda M; Garner, Brett

2013-03-01

We have developed a protocol suitable for high-throughput lipidomic analysis of human brain samples. The traditional Folch extraction (using chloroform and glass-glass homogenization) was compared to a high-throughput method combining methyl-tert-butyl ether (MTBE) extraction with mechanical homogenization utilizing ceramic beads. This high-throughput method significantly reduced sample handling time and increased efficiency compared to glass-glass homogenizing. Furthermore, replacing chloroform with MTBE is safer (less carcinogenic/toxic), with lipids dissolving in the upper phase, allowing for easier pipetting and the potential for automation (i.e., robotics). Both methods were applied to the analysis of human occipital cortex. Lipid species (including ceramides, sphingomyelins, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserines) were analyzed via electrospray ionization mass spectrometry and sterol species were analyzed using gas chromatography mass spectrometry. No differences in lipid species composition were evident when the lipid extraction protocols were compared, indicating that MTBE extraction with mechanical bead homogenization provides an improved method for the lipidomic profiling of human brain tissue.

Specific Uptake of Lipid-Antibody-Functionalized LbL Microcarriers by Cells.

PubMed

Göse, Martin; Scheffler, Kira; Reibetanz, Uta

2016-11-14

The modular construction of Layer-by-Layer biopolymer microcarriers facilitates a highly specific design of drug delivery systems. A supported lipid bilayer (SLB) contributes to biocompatibility and protection of sensitive active agents. The addition of a lipid anchor equipped with PEG (shielding from opsonins) and biotin (attachment of exchangeable outer functional molecules) enhances the microcarrier functionality even more. However, a homogeneously assembled supported lipid bilayer is a prerequisite for a specific binding of functional components. Our investigations show that a tightly packed SLB improves the efficiency of functional components attached to the microcarrier's surface, as illustrated with specific antibodies in cellular application. Only a low quantity of antibodies is needed to obtain improved cellular uptake rates independent from cell type as compared to an antibody-functionalized loosely packed lipid bilayer or directly assembled antibody onto the multilayer. A fast disassembly of the lipid bilayer within endolysosomes exposing the underlying drug delivering multilayer structure demonstrates the suitability of LbL-microcarriers as a multifunctional drug delivery system.

Informatics and computational strategies for the study of lipids.

PubMed

Yetukuri, Laxman; Ekroos, Kim; Vidal-Puig, Antonio; Oresic, Matej

2008-02-01

Recent advances in mass spectrometry (MS)-based techniques for lipidomic analysis have empowered us with the tools that afford studies of lipidomes at the systems level. However, these techniques pose a number of challenges for lipidomic raw data processing, lipid informatics, and the interpretation of lipidomic data in the context of lipid function and structure. Integration of lipidomic data with other systemic levels, such as genomic or proteomic, in the context of molecular pathways and biophysical processes provides a basis for the understanding of lipid function at the systems level. The present report, based on the limited literature, is an update on a young but rapidly emerging field of lipid informatics and related pathway reconstruction strategies.

The effects of multiple antimicrobial interventions on processing, lipid, textural, instrumental color and sensory characteristics when used in a ground beef patty production system.

PubMed

Jimenez-Villarreal, J R; Pohlman, F W; Johnson, Z B; Brown, A H

2003-11-01

The impact of multiple antimicrobial interventions on ground beef processing, lipid, textural, instrumental color and sensory characteristics were evaluated. Beef trimmings were treated with 0.5% cetylpyridinium chloride followed by 10% trisodium phosphate (CT), 200-ppm chlorine dioxide followed by 0.5% cetylpyridinium chloride (CLC), 200-ppm chlorine dioxide followed by 10% trisodium phosphate (CLT), or 2% lactic acid followed by 0.5% cetylpyridinium chloride (LC) and compared to an untreated control (C). Sensory panelists found LC and CT treatments similar (P>0.05) in grinding ability to C. By day 2 of display, CT, CLT and LC patties were redder (a(∗); P<0.05) than C. Sensory panelists found CT patties redder (P<0.05) than C by day 2 of display. Sensory panelists found CT and CLT juicier than C. Therefore, the use of these multiple antimicrobial intervention agents on beef trimmings may improve sensory characteristics and shelf-life of ground beef patties.

On plate graphite supported sample processing for simultaneous lipid and protein identification by matrix assisted laser desorption ionization mass spectrometry.

PubMed

Calvano, Cosima Damiana; van der Werf, Inez Dorothé; Sabbatini, Luigia; Palmisano, Francesco

2015-05-01

The simultaneous identification of lipids and proteins by matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) after direct on-plate processing of micro-samples supported on colloidal graphite is demonstrated. Taking advantages of large surface area and thermal conductivity, graphite provided an ideal substrate for on-plate proteolysis and lipid extraction. Indeed proteins could be efficiently digested on-plate within 15 min, providing sequence coverages comparable to those obtained by conventional in-solution overnight digestion. Interestingly, detection of hydrophilic phosphorylated peptides could be easily achieved without any further enrichment step. Furthermore, lipids could be simultaneously extracted/identified without any additional treatment/processing step as demonstrated for model complex samples such as milk and egg. The present approach is simple, efficient, of large applicability and offers great promise for protein and lipid identification in very small samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Lipid- and sugar-modified endomorphins: novel targets for the treatment of neuropathic pain

PubMed Central

Varamini, Pegah; Toth, Istvan

2013-01-01

Endomorphins are endogenous opioid peptides that cause potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, endomorphins are poorly suited to clinical applications because of low membrane permeability and a susceptibility to enzymatic degradation. Glycosylation and lipidation have proven to be two of the most robust approaches for the generation of new therapeutic endomorphin derivatives. Conjugation with lipoamino acids (LAA) confers an amphipathic character to the peptide, which improved interaction between the peptide and the lipid bilayer of the cell membranes, increasing permeability. Glycosylation can also improve peptide stability and blood brain barrier (BBB) transport. It is believed that an endocytotic mechanism (transcytosis) is responsible for the systemic delivery of water-soluble glycopeptides. This review discusses the application of glycosylation and lipidation strategies to improve the drug-like properties of endomorphins. Pharmacologically active endomorphin analogs with less adverse effects are also discussed. PMID:24379782

Role of cholesterol and lipid organization in disease

NASA Astrophysics Data System (ADS)

Maxfield, Frederick R.; Tabas, Ira

2005-12-01

Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.

High-throughput simultaneous analysis of RNA, protein, and lipid biomarkers in heterogeneous tissue samples.

PubMed

Reiser, Vladimír; Smith, Ryan C; Xue, Jiyan; Kurtz, Marc M; Liu, Rong; Legrand, Cheryl; He, Xuanmin; Yu, Xiang; Wong, Peggy; Hinchcliffe, John S; Tanen, Michael R; Lazar, Gloria; Zieba, Renata; Ichetovkin, Marina; Chen, Zhu; O'Neill, Edward A; Tanaka, Wesley K; Marton, Matthew J; Liao, Jason; Morris, Mark; Hailman, Eric; Tokiwa, George Y; Plump, Andrew S

2011-11-01

With expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD). We used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured. The quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting. The TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.

Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers.

PubMed

Rizwanullah, Md; Amin, Saima; Ahmad, Javed

2017-01-01

In the present study, rosuvastatin calcium-loaded nanostructured lipid carriers were developed and optimized for improved efficacy. The ROS-Ca-loaded NLC was prepared using melt emulsification ultrasonication technique and optimized by Box-Behnken statistical design. The optimized NLC composed of glyceryl monostearate (solid lipid) and capmul MCM EP (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and tween 80 (1%) as surfactant. The mean particle size, polydispersity index (PDI), zeta potential (ζ) and entrapment efficiency (%) of optimized NLC formulation was observed to be 150.3 ± 4.67 nm, 0.175 ± 0.022, -32.9 ± 1.36 mV and 84.95 ± 5.63%, respectively. NLC formulation showed better in vitro release in simulated intestinal fluid (pH 6.8) than API suspension. Confocal laser scanning showed deeper permeation of formulation across rat intestine compared to rhodamine B dye solution. Pharmacokinetic study on female albino Wistar rats showed 5.4-fold increase in relative bioavailability with NLC compared to API suspension. Optimized NLC formulation also showed significant (p < 0.01) lipid lowering effect in hyperlipidemic rats. Therefore, NLC represents a great potential for improved efficacy of ROS-Ca after oral administration.

Stability Improvements of DNA Photonic Devices

DTIC Science & Technology

2008-12-20

possible in such areas as photonics, separation process or biomedical materials . Recent research results on DNA-lipid complexes have shown various...onto Teflon- coated glass plate to obtain films by irradiating UV light to cause crosslinking reactions of the Adeka sol-gel materials Clear and...into sol-gel materials or synthetic polymers so that water permeation is prevented by glass or synthetic polymers to stabilize and to keep the optical

Protein Diffusion on Charged Membranes: A Dynamic Mean-Field Model Describes Time Evolution and Lipid Reorganization

PubMed Central

Khelashvili, George; Weinstein, Harel; Harries, Daniel

2008-01-01

As charged macromolecules adsorb and diffuse on cell membranes in a large variety of cell signaling processes, they can attract or repel oppositely charged lipids. This results in lateral membrane rearrangement and affects the dynamics of protein function. To address such processes quantitatively we introduce a dynamic mean-field scheme that allows self-consistent calculations of the equilibrium state of membrane-protein complexes after such lateral reorganization of the membrane components, and serves to probe kinetic details of the process. Applicable to membranes with heterogeneous compositions containing several types of lipids, this comprehensive method accounts for mobile salt ions and charged macromolecules in three dimensions, as well as for lateral demixing of charged and net-neutral lipids in the membrane plane. In our model, the mobility of membrane components is governed by the diffusion-like Cahn-Hilliard equation, while the local electrochemical potential is based on nonlinear Poisson-Boltzmann theory. We illustrate the method by applying it to the adsorption of the anionic polypeptide poly-Lysine on negatively charged lipid membranes composed of binary mixtures of neutral and monovalent lipids, or onto ternary mixtures of neutral, monovalent, and multivalent lipids. Consistent with previous calculations and experiments, our results show that at steady-state multivalent lipids (such as PIP2), but not monovalent lipid (such as phosphatidylserine), will segregate near the adsorbing macromolecules. To address the corresponding diffusion of the adsorbing protein in the membrane plane, we couple lipid mobility with the propagation of the adsorbing protein through a dynamic Monte Carlo scheme. We find that due to their higher mobility dictated by the electrochemical potential, multivalent lipids such as PIP2 more quickly segregate near oppositely charged proteins than do monovalent lipids, even though their diffusion constants may be similar. The segregation, in turn, slows protein diffusion, as lipids introduce an effective drag on the motion of the adsorbate. In contrast, monovalent lipids such as phosphatidylserine only weakly segregate, and the diffusions of protein and lipid remain largely uncorrelated. PMID:18065451

Models of lipid droplets growth and fission in adipocyte cells

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

Boschi, Federico, E-mail: federico.boschi@univr.it; Rizzatti, Vanni; Zamboni, Mauro

Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage. It is well known that excessive accumulation of lipids leads to several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis and atherosclerosis. LDs' size range from fraction to one hundred of micrometers in adipocytes and is related to the lipid content, but their growth is still a puzzling question. It has been suggested that LDs can grow in size due to the fusion process by which a larger LD is obtained by the merging of two smaller LDs, but these events seems to be rare and difficultmore » to be observed. Many other processes are thought to be involved in the number and growth of LDs, like the de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets. Moreover the number and size of LDs are influenced by the catabolism and the absorption or interaction with other organelles. The comprehension of these processes could help in the confinement of the pathologies related to lipid accumulation. In this study the LDs' size distribution, number and the total volume of immature (n=12), mature (n=12, 10-days differentiated) and lipolytic (n=12) 3T3-L1 adipocytes were considered. More than 11,000 LDs were measured in the 36 cells after Oil Red O staining. In a previous work Monte Carlo simulations were used to mimic the fusion process alone between LDs. We found that, considering the fusion as the only process acting on the LDs, the size distribution in mature adipocytes can be obtained with numerical simulation starting from the size distribution in immature cells provided a very high rate of fusion events. In this paper Monte Carlo simulations were developed to mimic the interaction between LDs taking into account many other processes in addition to fusion (de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets) in order to reproduce the LDs growth and we also simulated the catabolism (fission and the decrease through neutral lipid exit from pre-existing droplets) to reproduce their size reduction observed in lipolytic conditions. The results suggest that each single process, considered alone, can not be considered the only responsible for the size variation observed, but more than one of them, playing together, can quite well reproduce the experimental data. - Highlights: The growth and fission of the lipid droplets (LDs) were computationally simulated. To write and test the growth and fission models more than 110,000 LDs were measured. The usual processes considered alone, are not able to justify the experimental data. Some processes, playing together, can explain the growth and fission.« less

Solid lipid nanoparticles release DNA upon endosomal acidification in human embryonic kidney cells.

PubMed

Radaic, A; de Jesus, M B

2018-08-03

Nanotechnology can produce materials with unique features compared to their bulk counterparts, which can be useful for medical applications (i.e. nanomedicine). Among the therapeutic agents used in nanomedicine, small molecules or biomacromolecules, such as proteins or genetic materials, can be designed for disease diagnostics and treatment. To transport these biomacromolecules to the target cells, nanomedicine requires nanocarriers. Solid lipid nanoparticles (SLNs) are among the promising nanocarriers available, because they can be made from biocompatible materials and present high stability (over one year). In addition, upon the binding genetic material, SLNs form SLNplexes. However, little is yet known about how cells process these SLNplexes-in particular, how internalization and endosome acidification affects the transfection mediated by SLNplexes. Therefore, we aim to investigate how these processes affect SLNplex transfection in HEK293T cells. We find that the SLNplex is mainly internalized by clathrin-mediated endocytosis, which is a fast and reliable pathway to transfection, leading to approximately 60% transfection efficiency. Interestingly, upon acidification (below pH 5.0), the SLN seems to release its DNA content, which can be an essential step for SLNplex transfection. The underlying mechanisms described in this work may help improve SLNplex formulations and transfection efficiency. Moreover, these advances can improve the field of nanomedical research and bring new ways to cure diseases.

Effect of combination of chitosan coating and irradiation on physicochemical and functional properties of chicken egg during room-temperature storage

NASA Astrophysics Data System (ADS)

Liu, Xian De; Jang, Aera; Kim, Dong Hun; Lee, Bong Duk; Lee, Mooha; Jo, Cheorun

2009-07-01

The effect of combination of chitosan coating and irradiation on quality and storage stability of shell egg was investigated. Salmonella typhimurium inoculated on eggshell was not detected by irradiation of 2.0 kGy at day 0 and/or chitosan coating (1%, pH 5.0) after 3 days of storage. One-day-old fresh chicken egg was chitosan coated and irradiated at 0, 0.5, 1.0, 1.5 and 2.0 kGy by gamma ray. The egg samples were stored at room temperature for 14 days and the effects of the combination treatment on internal physicochemical and functional properties were investigated. The Haugh unit of egg was decreased by irradiation even at 0.5 kGy. Irradiation increased the lipid oxidation in egg yolk at 2 kGy but the egg with chitosan coating reduced the level of lipid oxidation. Irradiation increased the foaming ability of egg white and decreased viscosity of egg yolk and white. Results suggested that combination of irradiation and chitosan coating can improve safety of shell egg but irradiation treatment may reduce the egg quality for direct consumption. However, an improved functional property for further processing and efficient separation of egg white and yolk can be expected for egg processing industry using irradiation.

Dermal extracellular lipid in birds.

PubMed

Stromberg, M W; Hinsman, E J; Hullinger, R L

1990-01-01

A light and electron microscopic study of the skin of domestic chickens, seagulls, and antarctic penguins revealed abundant extracellular dermal lipid and intracellular epidermal lipid. Dermal lipid appeared ultrastructurally as extracellular droplets varying from less than 1 micron to more than 25 microns in diameter. The droplets were often irregularly contoured, sometimes round, and of relatively low electron density. Processes of fibrocytes were often seen in contact with extracellular lipid droplets. Sometimes a portion of such a droplet was missing, and this missing part appeared to have been "digested away" by the cell process. In places where cells or cell processes are in contact with fact droplets, there are sometimes extracellular membranous whorls or fragments which have been associated with the presence of fatty acids. Occasionally (in the comb) free fat particles were seen in intimate contact with extravasated erythrocytes. Fat droplets were seen in the lumen of small dermal blood and lymph vessels. We suggest that the dermal extracellular lipid originates in the adipocyte layer and following hydrolysis the free fatty acids diffuse into the epidermis. Here they become the raw material for forming the abundant neutral lipid contained in many of the epidermal cells of both birds and dolphins. The heretofore unreported presence and apparently normal utilization of abundant extracellular lipid in birds, as well as the presence of relatively large droplets of neutral lipid in dermal vessels, pose questions which require a thorough reappraisal of present concepts of the ways in which fat is distributed and utilized in the body.

Optimization of odd chain fatty acid production by Yarrowia lipolytica.

PubMed

Park, Young-Kyoung; Dulermo, Thierry; Ledesma-Amaro, Rodrigo; Nicaud, Jean-Marc

2018-01-01

Odd chain fatty acids (odd FAs) have a wide range of applications in therapeutic and nutritional industries, as well as in chemical industries including biofuel. Yarrowia lipolytica is an oleaginous yeast considered a preferred microorganism for the production of lipid-derived biofuels and chemicals. However, it naturally produces negligible amounts of odd chain fatty acids. The possibility of producing odd FAs using Y. lipolytica was investigated. Y. lipolytica wild-type strain was shown able to grow on weak acids; acetate, lactate, and propionate. Maximal growth rate on propionate reached 0.24 ± 0.01 h -1 at 2 g/L, and growth inhibition occurred at concentration above 10 g/L. Wild-type strain accumulated lipids ranging from 7.39 to 8.14% (w/w DCW) depending on the carbon source composition, and odd FAs represented only 0.01-0.12 g/L. We here proved that the deletion of the PHD1 gene improved odd FAs production, which reached a ratio of 46.82% to total lipids. When this modification was transferred to an obese strain, engineered for improving lipid accumulation, further increase odd FAs production reaching a total of 0.57 g/L was shown. Finally, a fed-batch co-feeding strategy was optimized for further increase odd FAs production, which generated 0.75 g/L, the best production described so far in Y. lipolytica . A Y. lipolytica strain able to accumulate high level of odd chain fatty acids, mainly heptadecenoic acid, has been successfully developed. In addition, a fed-batch co-feeding strategy was optimized to further improve lipid accumulation and odd chain fatty acid content. These lipids enriched in odd chain fatty acid can (1) improve the properties of the biodiesel generated from Y. lipolytica lipids and (2) be used as renewable source of odd chain fatty acid for industrial applications. This work paves the way for further improvements in odd chain fatty acids and fatty acid-derived compound production.

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.

Digestible and indigestible carbohydrates: interactions with postprandial lipid metabolism.

PubMed

Lairon, Denis; Play, Barbara; Jourdheuil-Rahmani, Dominique

2007-04-01

The balance between fats and carbohydrates in the human diet is still a matter of very active debate. Indeed, the processing of ordinary mixed meals involves complex processes within the lumen of the upper digestive tract for digestion, in the small intestine mucosa for absorption and resecretion, and in peripheral tissues and in the circulation for final handling. The purpose of this review is to focus on available knowledge on the interactions of digestible or indigestible carbohydrates with lipid and lipoprotein metabolism in the postprandial state. The observations made in humans after test meals are reported and interpreted in the light of recent findings on the cellular and molecular levels regarding possible interplays between carbohydrates and lipid moieties in some metabolic pathways. Digestible carbohydrates, especially readily digestible starches or fructose, have been shown to exacerbate and/or delay postprandial lipemia, whereas some fiber sources can lower it. While interactions between dietary fibers and the process of lipid digestion and absorption have been studied mainly in the last decades, recent studies have shown that dietary carbohydrate moieties (e.g., glucose) can stimulate the intestinal uptake of cholesterol and lipid resecretion. In addition to the well-known glucose/fructose transporters, a number of transport proteins have recently been involved in intestinal lipid processing, whose implications in such interactions are discussed. The potential importance of postprandial insulinemia in these processes is also evaluated in the light of recent findings. The interactions of carbohydrates and lipid moieties in the postprandial state may result from both acute and chronic effects, both at transcriptional and posttranscriptional levels.

Improved Experimental Techniques for Analyzing Nucleic Acid Transport Through Protein Nanopores in Planar Lipid Bilayers

NASA Astrophysics Data System (ADS)

Costa, Justin A.

The translocation of nucleic acid polymers across cell membranes is a fundamental requirement for complex life and has greatly contributed to genomic molecular evolution. The diversity of pathways that have evolved to transport DNA and RNA across membranes include protein receptors, active and passive transporters, endocytic and pinocytic processes, and various types of nucleic acid conducting channels known as nanopores. We have developed a series of experimental techniques, collectively known as "Wicking", that greatly improves the biophysical analysis of nucleic acid transport through protein nanopores in planar lipid bilayers. We have verified the Wicking method using numerous types of classical ion channels including the well-studied chloride selective channel, CLIC1. We used the Wicking technique to reconstitute α-hemolysin and found that DNA translocation events of types A and B could be routinely observed using this method. Furthermore, measurable differences were observed in the duration of blockade events as DNA length and composition was varied, consistent with previous reports. Finally, we tested the ability of the Wicking technology to reconstitute the dsRNA transporter Sid-1. Exposure to dsRNAs of increasing length and complexity showed measurable differences in the current transitions suggesting that the charge carrier was dsRNA. However, the translocation events occurred so infrequently that a meaningful electrophysiological analysis was not possible. Alterations in the lipid composition of the bilayer had a minor effect on the frequency of translocation events but not to such a degree as to permit rigorous statistical analysis. We conclude that in many instances the Wicking method is a significant improvement to the lipid bilayer technique, but is not an optimal method for analyzing transport through Sid-1. Further refinements to the Wicking method might have future applications in high throughput DNA sequencing, DNA computation, and molecular sensing for diagnostics.

Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QbD approach: Characterization and Evaluation of anticancer activity against human breast cancer cell line.

PubMed

Bhatt, Himanshu; Rompicharla, Sri Vishnu Kiran; Komanduri, Neeraja; Shah, Aashma; Paradkar, Sateja; Ghosh, Balaram; Biswas, Swati

2018-05-03

Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in presence of surfactant Poloxamer 188 and evaluated the efficiency of the SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 μg/mL after 24 h treatment. Further, treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microalgal process-monitoring based on high-selectivity spectroscopy tools: status and future perspectives.

PubMed

Podevin, Michael; Fotidis, Ioannis A; Angelidaki, Irini

2018-08-01

Microalgae are well known for their ability to accumulate lipids intracellularly, which can be used for biofuels and mitigate CO 2 emissions. However, due to economic challenges, microalgae bioprocesses have maneuvered towards the simultaneous production of food, feed, fuel, and various high-value chemicals in a biorefinery concept. On-line and in-line monitoring of macromolecules such as lipids, proteins, carbohydrates, and high-value pigments will be more critical to maintain product quality and consistency for downstream processing in a biorefinery to maintain and valorize these markets. The main contribution of this review is to present current and prospective advances of on-line and in-line process analytical technology (PAT), with high-selectivity - the capability of monitoring several analytes simultaneously - in the interest of improving product quality, productivity, and process automation of a microalgal biorefinery. The high-selectivity PAT under consideration are mid-infrared (MIR), near-infrared (NIR), and Raman vibrational spectroscopies. The current review contains a critical assessment of these technologies in the context of recent advances in software and hardware in order to move microalgae production towards process automation through multivariate process control (MVPC) and software sensors trained on "big data". The paper will also include a comprehensive overview of off-line implementations of vibrational spectroscopy in microalgal research as it pertains to spectral interpretation and process automation to aid and motivate development.

Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

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

Malur, Anagha; Huizar, Isham; Wells, Greg

2011-11-18

Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO)more » mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice but improved significantly after lenti-ABCG1 treatment. Data demonstrate that in vivo instillation of lenti-ABCG1 in GM-CSF KO mice is sufficient to restore pulmonary homeostasis by: (1) upregulating ABCG1; (2) reducing intra and extracellular lipids; and (3) improving lung function. Results suggest that the ABCG1 lipid transporter is the key downstream target of GM-CSF-induced PPAR{gamma} necessary for surfactant catabolism.« less

LIQUID: an-open source software for identifying lipids in LC-MS/MS-based lipidomics data.

PubMed

Kyle, Jennifer E; Crowell, Kevin L; Casey, Cameron P; Fujimoto, Grant M; Kim, Sangtae; Dautel, Sydney E; Smith, Richard D; Payne, Samuel H; Metz, Thomas O

2017-06-01

We introduce an open-source software, LIQUID, for semi-automated processing and visualization of LC-MS/MS-based lipidomics data. LIQUID provides users with the capability to process high throughput data and contains a customizable target library and scoring model per project needs. The graphical user interface provides visualization of multiple lines of spectral evidence for each lipid identification, allowing rapid examination of data for making confident identifications of lipid molecular species. LIQUID was compared to other freely available software commonly used to identify lipids and other small molecules (e.g. CFM-ID, MetFrag, GNPS, LipidBlast and MS-DIAL), and was found to have a faster processing time to arrive at a higher number of validated lipid identifications. LIQUID is available at http://github.com/PNNL-Comp-Mass-Spec/LIQUID . jennifer.kyle@pnnl.gov or thomas.metz@pnnl.gov. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

[Lipid synthesis by an acidic acid tolerant Rhodotorula glutinis].

PubMed

Lin, Zhangnan; Liu, Hongjuan; Zhang, Jian'an; Wang, Gehua

2016-03-01

Acetic acid, as a main by-product generated in the pretreatment process of lignocellulose hydrolysis, significantly affects cell growth and lipid synthesis of oleaginous microorganisms. Therefore, we studied the tolerance of Rhodotorula glutinis to acetic acid and its lipid synthesis from substrate containing acetic acid. In the mixed sugar medium containing 6 g/L glucose and 44 g/L xylose, and supplemented with acetic acid, the cell growth was not:inhibited when the acetic acid concentration was below 10 g/L. Compared with the control, the biomass, lipid concentration and lipid content of R. glutinis increased 21.5%, 171% and 122% respectively when acetic acid concentration was 10 g/L. Furthermore, R. glutinis could accumulate lipid with acetate as the sole carbon source. Lipid concentration and lipid yield reached 3.20 g/L and 13% respectively with the initial acetic acid concentration of 25 g/L. The lipid composition was analyzed by gas chromatograph. The main composition of lipid produced with acetic acid was palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, including 40.9% saturated fatty acids and 59.1% unsaturated fatty acids. The lipid composition was similar to that of plant oil, indicating that lipid from oleaginous yeast R. glutinis had potential as the feedstock of biodiesel production. These results demonstrated that a certain concentration of acetic acid need not to be removed in the detoxification process when using lignocelluloses hydrolysate to produce microbial lipid by R. glutinis.

Integrating Cellular and Bioprocess Engineering in the Non-Conventional Yeast Yarrowia lipolytica for Biodiesel Production: A Review

PubMed Central

Xie, Dongming

2017-01-01

As one of the major biofuels to replace fossil fuel, biodiesel has now attracted more and more attention due to its advantages in higher energy density and overall less greenhouse gas generation. Biodiesel (fatty acid alkyl esters) is produced by chemically or enzymatically catalyzed transesterification of lipids from microbial cells, microalgae, oil crops, or animal fats. Currently, plant oils or waste cooking oils/fats remain the major source for biodiesel production via enzymatic route, but the production capacity is limited either by the uncertain supplement of plant oils or by the low or inconsistent quality of waste oils/fats. In the past decades, significant progresses have been made on synthesis of microalgae oils directly from CO2 via a photosynthesis process, but the production cost from any current technologies is still too high to be commercialized due to microalgae’s slow growth rate on CO2, inefficiency in photo-bioreactors, lack of efficient contamination control methods, and high cost in downstream recovery. At the same time, many oleaginous microorganisms have been studied to produce lipids via the fatty acid synthesis pathway under aerobic fermentation conditions, among them one of the most studied is the non-conventional yeast, Yarrowia lipolytica, which is able to produce fatty acids at very high titer, rate, and yield from various economical substrates. This review summarizes the recent research progresses in both cellular and bioprocess engineering in Y. lipolytica to produce lipids at a low cost that may lead to commercial-scale biodiesel production. Specific technologies include the strain engineering for using various substrates, metabolic engineering in high-yield lipid synthesis, cell morphology study for efficient substrate uptake and product formation, free fatty acid formation and secretion for improved downstream recovery, and fermentation engineering for higher productivities and less operating cost. To further improve the economics of the microbial oil-based biodiesel, production of lipid-related or -derived high-value products are also discussed. PMID:29090211

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.

Adsorption of human tear lipocalin to human meibomian lipid films.

PubMed

Millar, Thomas J; Mudgil, Poonam; Butovich, Igor A; Palaniappan, Chendur K

2009-01-01

Tear lipocalin (Tlc) is a major lipid binding protein in tears and is thought to have an important role in stabilizing the Meibomian lipid layer by transferring lipids to it from the aqueous layer or ocular surface, or by adsorbing to it directly. These possible roles have been investigated in vitro using human Tlc. Tlc was purified from human tears by size exclusion chromatography followed by ion exchange chromatography. Three additional samples of the Tlc were prepared by lipidation, delipidation, and relipidation. The lipids extracted from the purified Tlc were analyzed by HPLC-MS followed by fragmentation. Adsorption of these different forms of Tlc to a human Meibomian lipid film spread on the surface of an artificial tear buffer in a Langmuir trough were observed by recording changes in the pressure with time (Pi-T profile) and monitoring the appearance of the film microscopically. These results were compared with similar experiments using a bovine Meibomian lipid film. The results indicated that Tlc binds slowly to a human Meibomian lipid film compared with lysozyme or lactoferrin, even at 37 degrees C. The adsorption of Tlc to a human Meibomian lipid film was very different from its adsorption to a bovine Meibomian lipid film, indicating the nature of the lipids in the film is critical to the adsorption process. Similarly, the different forms of Tlc had quite distinct adsorption patterns, as indicated both by changes in Pi-T profiles and the microscopic appearance of the films. It was concluded that human Tlc was capable of adsorbing to and penetrating into a Meibomian lipid layer, but this process is very complex and depends on both the types of lipids bound to Tlc and the lipid complement comprising the Meibomian lipid film.

Adsorption of Human Tear Lipocalin to Human Meibomian Lipid Films

PubMed Central

Millar, Thomas J.; Mudgil, Poonam; Butovich, Igor A.; Palaniappan, Chendur K.

2009-01-01

Purpose Tear lipocalin (Tlc) is a major lipid binding protein in tears and is thought to have an important role in stabilizing the Meibomian lipid layer by transferring lipids to it from the aqueous layer or ocular surface, or by adsorbing to it directly. These possible roles have been investigated in vitro using human Tlc. Methods Tlc was purified from human tears by size exclusion chromatography followed by ion exchange chromatography. Three additional samples of the Tlc were prepared by lipidation, delipidation, and relipidation. The lipids extracted from the purified Tlc were analyzed by HPLC-MS followed by fragmentation. Adsorption of these different forms of Tlc to a human Meibomian lipid film spread on the surface of an artificial tear buffer in a Langmuir trough were observed by recording changes in the pressure with time (∏-T profile) and monitoring the appearance of the film microscopically. These results were compared with similar experiments using a bovine Meibomian lipid film. Results The results indicated that Tlc binds slowly to a human Meibomian lipid film compared with lysozyme or lactoferrin, even at 37°C. The adsorption of Tlc to a human Meibomian lipid film was very different from its adsorption to a bovine Meibomian lipid film, indicating the nature of the lipids in the film is critical to the adsorption process. Similarly, the different forms of Tlc had quite distinct adsorption patterns, as indicated both by changes in ∏-T profiles and the microscopic appearance of the films. Conclusions It was concluded that human Tlc was capable of adsorbing to and penetrating into a Meibomian lipid layer, but this process is very complex and depends on both the types of lipids bound to Tlc and the lipid complement comprising the Meibomian lipid film. PMID:18757516

Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability.

PubMed

Sun, Jiabei; Bi, Chao; Chan, Hok Man; Sun, Shaoping; Zhang, Qingwen; Zheng, Ying

2013-11-01

The aim of the present study was to blend liquid lipids with solid lipids to encapsulate curcumin in solid lipid nanoparticles (SLNs), thereby improving the dispersibility and chemical stability of curcumin, prolonging its antitumour activity and cellular uptake and enhancing its bioavailability. Curcumin-loaded SLNs (C-SLNs) were prepared by high-pressure homogenisation with liquid lipid Sefsol-218(®). The morphology, stability and release of curcumin in the optimised formulation were investigated. The anti-cancer activity of the formulation was evaluated in MCF-7 cells. Fluorescence spectrophotometry was used to quantify cellular uptake of the drug. The pharmacokinetic profiles of curcumin in SLNs after intravenous administration were studied in rats. Blending Sefsol-218(®) into a lipid matrix reduced the particle size without improving drug loading. An optimised formulation consisting of Dynasan 114(®), Sefsol-218(®), and Pluronic F68(®) (630:70:300, w/w) loaded with 0.8% drug was prepared. This formulation could be dispersed in water with a mean particle size of 152.8 ± 4.7 nm and a 90% entrapment efficiency. Curcumin displayed a two-phase sustained release profile from C-SLNs with improved chemical stability. Compared to the solubilised solution, C-SLNs exhibited prolonged inhibitory activity in cancer cells, as well as time-dependent increases in intracellular uptake. After intravenous administration to rats, the bioavailability of curcumin was increased by 1.25-fold. C-SLNs with improved dispersibility and chemical stability in an aqueous system have been successfully developed. C-SLNs may represent a potentially useful cancer therapeutic curcumin delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Schneider, Teresa; Graeff-Honninger, Simone; French, William Todd

The production of biodiesel has notably increased over the past decade. Currently, plant oil is the main feedstock for biodiesel production, but, due to concerns related to the competition with food production, alternative oil feedstocks have to be found. Oleaginous yeasts are known to produce high amounts of lipids, but no integrated process from microbial fermentation to final biodiesel production has reached commercial realization yet due to economic constraints. Therefore, growth and lipid production of red yeast Rhodotorula glutinis was tested on low-cost substrates, namely, wastewaters from potato, fruit juice, and lettuce processing. Additionally, the production of carotenoids as high-valuemore » by-products was examined. All evaluated wastewaters met the general criteria for microbial lipid production. However, no significant increase in lipid content was observed, probably due to lack of available carbon in wastewaters from fruit juice and lettuce processing, and excess of available nitrogen in potato processing wastewater, respectively. During growth on wastewaters from fruit juice and lettuce processing the carotenoid content increased significantly in the first 48 hours. The relations between carbon content, nitrogen content, and carotenoid production need to be further assessed. For economic viability, lipid and carotenoid production needs to be increased significantly. Lastly, the screening of feedstocks should be extended to other wastewaters.« less

Investigation of flavonoid influence on peroxidation processes intensity in the blood

NASA Astrophysics Data System (ADS)

Navolokin, N. A.; Mudrak, D. A.; Plastun, I. L.; Bucharskaya, A. B.; Agandeeva, K. E.; Ivlichev, A. V.; Tychina, S. A.; Afanasyeva, G. A.; Polukonova, N. V.; Maslyakova, G. N.

2017-03-01

Influence of flavonoids on the intensity of peroxidation processes in the blood is investigated by numerical modeling and by experiment in vivo. As an example we consider the effects of flavonoid-containing extract of Helichrysum arenarium L. with antitumor activity on serum of rats with transplanted liver cancer PC-1. It was found that the content of malondialdehyde, lipid hydroperoxides and average mass molecules were decreased in animals with transplanted liver cancer after intramuscular and oral administration of Helichrysum arenarium L extract in a dose of 1000 mg/mL. The extract reduces the intensity of lipid peroxidation processes in animals. The compound formation possibility of flavonoids and products of lipid peroxidation is investigated by numerical simulations. Using the density functional theory method of molecular modeling, we analyze hydrogen bonds formation and their influence on IR - spectra and structure of molecular complex which is formed due to interaction between flavonoids and products of lipid peroxidation processes on example of naringine and malondialdehyde. We have found that naringine can form a steady molecular complex with malondialdehyde by hydrogen bonds formation. Thus, the application of Helichrysum arenarium L. extract for suppression processes of lipid peroxidation and activation of enzymatic and non-enzymatic antioxidant systems is promising.

The importance of reaching lipid targets: statins and the prevention of atherosclerosis.

PubMed

Schwandt, P

2003-06-01

To help prevent the development of coronary heart disease (CHD), the European and NCEP guidelines have recommended target cholesterol levels for all individuals. Lifestyle changes are advocated for individuals not achieving these targets. Intervention with lipid-modifying agents may be required for patients at high risk of a cardiovascular event and statins are generally recognised as first-line therapy. Unfortunately, large numbers of patients at risk of cardiovascular events are not being treated to the guideline targets. Primary care physicians are in a good position to improve lipid management by assessing risk factors, implementing lipid management strategies, monitoring whether targets are being reached and amending treatment appropriately. Furthermore, by educating and motivating patients,primary care physicians may improve compliance with lifestyle changes and medication. These approaches may help more patients to achieve recommended lipid levels and prevent the development of cardiovascular disease.

Niacin improves renal lipid metabolism and slows progression in chronic kidney disease.

PubMed

Cho, Kyu-hyang; Kim, Hyun-ju; Kamanna, Vaijinath S; Vaziri, Nosratola D

2010-01-01

Mounting evidence points to lipid accumulation in the diseased kidney and its contribution to progression of nephropathy. We recently found heavy lipid accumulation and marked dysregulation of lipid metabolism in the remnant kidneys of rats with chronic renal failure (CRF). Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF. Kidney function, lipid content, and expression of molecules involved in cholesterol and fatty acid metabolism were determined in untreated CRF (5/6 nephrectomized), niacin-treated CRF (50 mg/kg/day in drinking water for 12 weeks) and control rats. CRF resulted in hypertension, proteinuria, renal tissue lipid accumulation, up-regulation of scavenger receptor A1 (SR-A1), acyl-CoA cholesterol acyltransferase-1 (ACAT1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), acyl-CoA carboxylase (ACC), liver X receptor (LXR), ATP binding cassette (ABC) A-1, ABCG-1, and SR-B1 and down-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2, HMG-CoA reductase, PPAR-alpha, fatty acid binding protein (L-FABP), and CPT1A. Niacin therapy attenuated hypertension, proteinuria, and tubulo-interstitial injury, reduced renal tissue lipids, CD36, ChREBP, LXR, ABCA-1, ABCG-1, and SR-B1 abundance and raised PPAR-alpha and L-FABP. Niacin administration improves renal tissue lipid metabolism and renal function and structure in experimental CRF.

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.

Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study.

PubMed

Shah, Nirmal V; Seth, Avinash K; Balaraman, R; Aundhia, Chintan J; Maheshwari, Rajesh A; Parmar, Ghanshyam R

2016-05-01

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.

Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study

PubMed Central

Shah, Nirmal V.; Seth, Avinash K.; Balaraman, R.; Aundhia, Chintan J.; Maheshwari, Rajesh A.; Parmar, Ghanshyam R.

2016-01-01

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 32 factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and −12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX. PMID:27222747

Emerging Research and Clinical Development Trends of Liposome and Lipid Nanoparticle Drug Delivery Systems

PubMed Central

KRAFT, JOHN C.; FREELING, JENNIFER P.; WANG, ZIYAO; HO, RODNEY J. Y.

2014-01-01

Liposomes are spherical-enclosed membrane vesicles mainly constructed with lipids. Lipid nanoparticles are loaded with therapeutics and may not contain an enclosed bilayer. The majority of those clinically approved have diameters of 50–300 nm. The growing interest in nanomedicine has fueled lipid–drug and lipid–protein studies, which provide a foundation for developing lipid particles that improve drug potency and reduce off-target effects. Integrating advances in lipid membrane research has enabled therapeutic development. At present, about 600 clinical trials involve lipid particle drug delivery systems. Greater understanding of pharmacokinetics, biodistribution, and disposition of lipid–drug particles facilitated particle surface hydration technology (with polyethylene glycol) to reduce rapid clearance and provide sufficient blood circulation time for drug to reach target tissues and cells. Surface hydration enabled the liposome-encapsulated cancer drug doxorubicin (Doxil) to gain clinical approval in 1995. Fifteen lipidic therapeutics are now clinically approved. Although much research involves attaching lipid particles to ligands selective for occult cells and tissues, preparation procedures are often complex and pose scale-up challenges. With emerging knowledge in drug target and lipid–drug distribution in the body, a systems approach that integrates knowledge to design and scale lipid–drug particles may further advance translation of these systems to improve therapeutic safety and efficacy. PMID:24338748

Droplet-Based Production of Liposomes

NASA Technical Reports Server (NTRS)

Ackley, Donald E.; Forster, Anita

2009-01-01

A process for making monodisperse liposomes having lipid bilayer membranes involves fewer, simpler process steps than do related prior methods. First, a microfluidic, cross junction droplet generator is used to produce vesicles comprising aqueous solution droplets contained in single layer lipid membranes. The vesicles are collected in a lipid-solvent mix that is at most partially soluble in water and is less dense than is water. A layer of water is dispensed on top of the solvent. By virtue of the difference in densities, the water sinks to the bottom and the solvent floats to the top. The vesicles, which have almost the same density as that of water, become exchanged into the water instead of floating to the top. As there are excess lipids in the solvent solution, in order for the vesicles to remain in the water, the addition of a second lipid layer to each vesicle is energetically favored. The resulting lipid bilayers present the hydrophilic ends of the lipid molecules to both the inner and outer membrane surfaces. If lipids of a second kind are dissolved in the solvent in sufficient excess before use, then asymmetric liposomes may be formed.

Influence of membrane phospholipid composition and structural organization on spontaneous lipid transfer between membranes.

PubMed

Pankov, R; Markovska, T; Antonov, P; Ivanova, L; Momchilova, A

2006-09-01

Investigations were carried out on the influence of phospholipid composition of model membranes on the processes of spontaneous lipid transfer between membranes. Acceptor vesicles were prepared from phospholipids extracted from plasma membranes of control and ras-transformed fibroblasts. Acceptor model membranes with manipulated levels of phosphatidylethanolamine (PE), sphingomyelin and phosphatidic acid were also used in the studies. Donor vesicles were prepared of phosphatidylcholine (PC) and contained two fluorescent lipid analogues, NBD-PC and N-Rh-PE, at a self-quenching concentration. Lipid transfer rate was assessed by measuring the increase of fluorescence in acceptor membranes due to transfer of fluorescent lipid analogues from quenched donor to unquenched acceptor vesicles. The results showed that spontaneous NBD-PC transfer increased upon fluidization of acceptor vesicles. In addition, elevation of PE concentration in model membranes was also accompanied by an increase of lipid transfer to all series of acceptor vesicles. The results are discussed with respect to the role of lipid composition and structural order of cellular plasma membranes in the processes of spontaneous lipid exchange between membrane bilayers.

Lipids in host-pathogen interactions: pathogens exploit the complexity of the host cell lipidome.

PubMed

van der Meer-Janssen, Ynske P M; van Galen, Josse; Batenburg, Joseph J; Helms, J Bernd

2010-01-01

Lipids were long believed to have a structural role in biomembranes and a role in energy storage utilizing cellular lipid droplets and plasma lipoproteins. Research over the last decades has identified an additional role of lipids in cellular signaling, membrane microdomain organization and dynamics, and membrane trafficking. These properties make lipids an attractive target for pathogens to modulate host cell processes in order to allow their survival and replication. In this review we will summarize the often ingenious strategies of pathogens to modify the lipid homeostasis of host cells, allowing them to divert cellular processes. To this end pathogens take full advantage of the complexity of the lipidome. The examples are categorized in generalized and emerging principles describing the involvement of lipids in host-pathogen interactions. Several pathogens are described that simultaneously induce multiple changes in the host cell signaling and trafficking mechanisms. Elucidation of these pathogen-induced changes may have important implications for drug development. The emergence of high-throughput lipidomic techniques will allow the description of changes of the host cell lipidome at the level of individual molecular lipid species and the identification of lipid biomarkers.

Transcriptomic Analysis of the Regulation of Lipid Fraction Migration and Fatty Acid Biosynthesis in Schizochytrium sp.

PubMed

Ren, Lujing; Hu, Xuechao; Zhao, Xiaoyan; Chen, Shenglan; Wu, Yi; Li, Dan; Yu, Yadong; Geng, Lingjun; Ji, Xiaojun; Huang, He

2017-06-15

Schizochytrium sp. is the main source of docosahexaenoic acid-rich oil, which is widely used in food additive and pharmaceutical industry. In this study, using RNA-seq, comparative transcriptomic analyses were performed at four stages of DHA fermentation by Schizochytrium sp to get potential genes related to cell transition from cell growth to lipid accumulation and then to lipid turnover. 1406, 385, 1384 differently expressed genes were identified by comparisons in pairs of S2 vs S1, S3 vs S2 and S4 vs S3. Functional analysis revealed that binding and single-organism process might be involve in the cell transition from cell growth to lipid accumulation while oxidation-reduction process played an important role in the transition from lipid accumulation to lipid turnover. pfaC in the PKS pathway showed higher sensitivity to the environmental change, which might be the key regulator for enhancing PUFA biosynthesis in the future. Some other genes in signal transduction and cell transport were revealed to be related to lipid turnover, which would enrich the current knowledge regarding lipid metabolism and help to enhance the DHA production and enrich different lipid fractions by Schizochytrium in the future.

Worksite wellness: a cholesterol awareness program.

PubMed

Fritsch, Michelle A; Montpellier, Julie; Kussman, Cyra

2009-02-01

A 7-month intervention was undertaken to determine the impact of education and coaching on lifestyle choices and lipid values among employees with hyperlipidemia. Four classes over 2 months at the worksite during work time and two telephone interventions were provided with pre, mid, and post data collection. Total cholesterol and low-density lipoprotein values improved during the intervention. Positive lifestyle changes were made involving exercise and diet. Appropriate physician visits and continuous health care increased. Lipid-based interventions at the worksite can elicit positive changes in lifestyle, appropriate health care use, and improved lipid values.

Lipid determination in bone marrow and mineralized bone tissue: From sample preparation to improved high-performance thin-layer and liquid chromatographic approaches.

PubMed

During, Alexandrine

2017-09-15

In view of their key roles in the bone physiology (e.g., in the biomineralization process) and their potential implication in bone pathologies, an approach to study lipids in situ is needed. The aim of the present paper is to propose an original procedure to characterize lipids in both bone marrow (BM) and mineralized tissue (MT) compartments, taking into consideration sample preparation, lipid extraction and analytical issues, when using small sample size (≤ 0.5g of rat femurs). The potential contamination of the MT by marrow lipids and the poor accessibility of certain lipids from the MT - two major issues in bone handling - were taking care, respectively by performing two cleaning steps after BM removal and by adding a demineralization step to the overall lipid extraction protocol. For lipid analyses, a multi-one-dimensional HP-TLC method was developed to analyze the major neutral and polar lipids at once and showed an excellent resolution (for 15 standards) and a good precision (inter-day RSD<13%). When subjected to the entire "lipid extraction-HP-TLC" protocol, spike recoveries of the standards ranged between 76 and 122%. This HP-TLC method was suitable for lipid determination in both BM and MT [e.g., the MT had 5-times lesser lipids and a lower TG/phospholipid ratio than the BM (P <0.05)], and was quite reliable in term of lipid quantification. The demineralization step allowed to extract additional phosphatidylserine and esterified cholesterol from the MT, suggesting that these two species were associated to the mineralized matrix possibly in relation to their physiological role in the bone. Moreover, a reverse phase HPLC method for fatty acid determination as naphthacyl esters was set up to study fatty acids in bone samples and was used to validate the HP-TLC data. The fatty acid profile of the MT exhibited lower linoleic acid (18:2 n-6) and linolenic acid (18:3 n-3+n-6) levels and higher arachidonic acid (20:4 n-6) and docosahexaenoic acid (22:6 n-3) levels (P<0.05, compared to BM), suggesting that the MT is more metabolically active than the BM in term of long chain fatty acid production. In sum, the present work should contribute to facilitate future studies in the bone lipid field in view to understand better their implication in the marrow fat expansion-associated bone pathologies, such as osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic Analysis of Digestive Physiology Using Fluorescent Phospholipid Reporters

NASA Astrophysics Data System (ADS)

Farber, Steven A.; Pack, Michael; Ho, Shiu-Ying; Johnson, Iain D.; Wagner, Daniel S.; Dosch, Roland; Mullins, Mary C.; Hendrickson, H. Stewart; Hendrickson, Elizabeth K.; Halpern, Marnie E.

2001-05-01

Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. Genetic screening identifies zebrafish mutants, such as fat free, that show normal digestive organ morphology but severely reduced phospholipid and cholesterol processing. Thus, fluorescent lipids provide a sensitive readout of lipid metabolism and are a powerful tool for identifying genes that mediate vertebrate digestive physiology.

Yak milk fat globules from the Qinghai-Tibetan Plateau: Membrane lipid composition and morphological properties.

PubMed

Luo, Jie; Huang, Ziyu; Liu, Hongna; Zhang, Yan; Ren, Fazheng

2018-04-15

Yak milk fat products constitute the base of Qinghai-Tibetan pastoralists' daily food intake. Despite the great importance of fat in processing and pastoralists' health, studies about yak milk fat are scarce. In this study, the lipid composition and the morphological properties of milk fat globule membranes (MFGMs) of yak milk were investigated. The results demonstrated that the yak milk had a higher cholesterol and sphingomyelin content compared to cow milk. In situ structural investigations performed at 25 °C by confocal microscopy showed the presence of lipid domains in yak MFGM, with a larger number and wider size range compared to cow milk. Moreover, the simultaneous localization of glycosylated molecules and polar lipids indicated that glycosylated molecules could be integrated into the lipid domains in yak MFGM. Different characteristics in yak MFGM could be related to the lipid composition and may affect the functions of yak milk lipids during processing and digestion. Copyright © 2017 Elsevier Ltd. All rights reserved.

LipidQC: Method Validation Tool for Visual Comparison to SRM 1950 Using NIST Interlaboratory Comparison Exercise Lipid Consensus Mean Estimate Values.

PubMed

Ulmer, Candice Z; Ragland, Jared M; Koelmel, Jeremy P; Heckert, Alan; Jones, Christina M; Garrett, Timothy J; Yost, Richard A; Bowden, John A

2017-12-19

As advances in analytical separation techniques, mass spectrometry instrumentation, and data processing platforms continue to spur growth in the lipidomics field, more structurally unique lipid species are detected and annotated. The lipidomics community is in need of benchmark reference values to assess the validity of various lipidomics workflows in providing accurate quantitative measurements across the diverse lipidome. LipidQC addresses the harmonization challenge in lipid quantitation by providing a semiautomated process, independent of analytical platform, for visual comparison of experimental results of National Institute of Standards and Technology Standard Reference Material (SRM) 1950, "Metabolites in Frozen Human Plasma", against benchmark consensus mean concentrations derived from the NIST Lipidomics Interlaboratory Comparison Exercise.

Benzocaine loaded solid lipid nanoparticles: Formulation design, in vitro and in vivo evaluation of local anesthetic effect.

PubMed

Basha, Mona; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; El Awdan, Sally; Awad, Gamal

2015-01-01

The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain.

Protective effect of N-acetylcysteine activated carbon release microcapsule on myocardial ischemia-reperfusion injury in rats

PubMed Central

Cai, Zhaobin; Shi, Tingting; Zhuang, Rangxiao; Fang, Hongying; Jiang, Xiaojie; Shao, Yidan; Zhou, Hongping

2018-01-01

With the development of science and technology, and development of artery bypass, methods such as cardiopulmonary cerebral resuscitation have been practiced in recent years. Despite this, some methods fail to promote or recover the function of tissues and organs, and in some cases, may aggravate dysfunction and structural damage to tissues. The latter is typical of ischemia-reperfusion (IR) injury. Lipid peroxidation mediated by free radicals is an important process of myocardial IR injury. Myocardial IR has been demonstrated to induce the formation of large numbers of free radicals in rats, which promotes the peroxidation of lipids within unsaturated fatty acids in the myocardial cell membrane. Markers of lipid peroxidation include malondialdehyde, superoxide dismutase and lactic dehydrogenase. Recent studies have demonstrated that N-acetylcysteine (NAC) is able to dilate blood vessels, prevent oxidative damage, improve immunity, inhibit apoptosis and the inflammatory response and promote glutathione synthesis in cells. NAC also improves the systolic function of myocardial cells and cardiac function, prevents myocardial apoptosis, protects ventricular remodeling and vascular remodeling, reduces opiomelanocortin levels in the serum and increases the content of nitric oxide in the serum, thus improving vascular endothelial function. Therefore, NAC has potent pharmacological activity; however, the relatively fast metabolism of NAC, along with its large clinical dose and low bioavailability, limit its applications. The present study combined NAC with medicinal activated carbons, and prepared N-acetylcysteine activated carbon sustained-release microcapsules (ACNACs) to overcome the limitations of NAC. It was demonstrated that ACNACs exerted greater effective protective effects than NAC alone on myocardial IR injury in rats. PMID:29434769

Reproducible MRI Measurement of Adipose Tissue Volumes in Genetic and Dietary Rodent Obesity Models

PubMed Central

Johnson, David H.; Flask, Chris A.; Ernsberger, Paul R.; Wong, Wilbur C. K.; Wilson, David L.

2010-01-01

Purpose To develop ratio MRI [lipid/(lipid+water)] methods for assessing lipid depots and compare measurement variability to biological differences in lean controls (spontaneously hypertensive rats, SHRs), dietary obese (SHR-DO), and genetic/dietary obese (SHROBs) animals. Materials and Methods Images with and without CHESS water-suppression were processed using a semi-automatic method accounting for relaxometry, chemical shift, receive coil sensitivity, and partial volume. Results Partial volume correction improved results by 10–15%. Over six operators, volume variation was reduced to 1.9 ml from 30.6 ml for single-image-analysis with intensity inhomogeneity. For three acquisitions on the same animal, volume reproducibility was <1%. SHROBs had 6X visceral and 8X subcutaneous adipose tissue than SHRs. SHR-DOs had enlarged visceral depots (3X SHRs). SHROB had significantly more subcutaneous adipose tissue, indicating a strong genetic component to this fat depot. Liver ratios in SHR-DO and SHROB were higher than SHR, indicating elevated fat content. Among SHROBs, evidence suggested a phenotype SHROB* having elevated liver ratios and visceral adipose tissue volumes. Conclusion Effects of diet and genetics on obesity were significantly larger than variations due to image acquisition and analysis, indicating that these methods can be used to assess accumulation/depletion of lipid depots in animal models of obesity. PMID:18821617

Sorptive capacity of membrane lipids, storage lipids, and proteins: a preliminary study of partitioning of organochlorines in lean fish from a PCB-contaminated freshwater lake.

PubMed

Mäenpää, Kimmo; Leppänen, Matti T; Figueiredo, Kaisa; Tigistu-Sahle, Feven; Käkelä, Reijo

2015-01-01

Knowledge on the internal distribution of halogenated organic chemicals (HOCs) would improve our understanding of dose-effect relationships and subsequently improve risk assessment of contaminated sites. Herein, we determine the concentrations of HOCs based on equilibrium partitioning in storage lipids, membrane lipids, and proteins in field-contaminated fish using equilibrium sampling devices. The study shows the importance of protein as a sorptive phase in lean fish. Our results provide a basis for using species-specific equilibrium partitioning coefficients between sorptive tissues and fish internal water as a substitute for K(ow) in, for example, upgrading models that simulate food-chain accumulation of the chemical.

Hybrid lipid-based nanostructures

NASA Astrophysics Data System (ADS)

Dayani, Yasaman

Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and then, using a sonication process, a uniform lipid bilayer that supports the incorporation of membrane proteins is formed. These bilayer-coated carbon nanotubes are highly dispersible and stable in aqueous solution, and they can be used in development of various biosensors and energy producing devices. In the other hybrid nanostructure, the lipid bilayer of a liposome is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using double-stranded DNA (dsDNA) linkers. Release studies shows that nano-size hydrogel-anchored liposomes are exceptionally stable, and they can be used as biomimetic model membranes that mimic the connectivity between the cytoskeleton and the plasma membrane. After lipid bilayer removal, dsDNA linkers can provide programmable nanogels decorated with oligonucleotides with potential sites for further molecular assembly. These stable nanostructures can be useful for oligonucleotide and drug delivery applications. The developed hydrogel-anchored liposomes are exploited for encapsulation and intracellular delivery of therapeutic peptide. Peptides with anti-cancer properties are successfully encapsulated in hydrogel core of pH-sensitive liposomes during rehydration process. Liposomes release their cargo at acidic pH. Confocal microscopy confirms the intracellular delivery of liposomes through an endocytotic pathway.

Mitochondrial lipids in neurodegeneration.

PubMed

Aufschnaiter, Andreas; Kohler, Verena; Diessl, Jutta; Peselj, Carlotta; Carmona-Gutierrez, Didac; Keller, Walter; Büttner, Sabrina

2017-01-01

Mitochondrial dysfunction is a common feature of many neurodegenerative diseases, including proteinopathies such as Alzheimer's or Parkinson's disease, which are characterized by the deposition of aggregated proteins in the form of insoluble fibrils or plaques. The distinct molecular processes that eventually result in mitochondrial dysfunction during neurodegeneration are well studied but still not fully understood. However, defects in mitochondrial fission and fusion, mitophagy, oxidative phosphorylation and mitochondrial bioenergetics have been linked to cellular demise. These processes are influenced by the lipid environment within mitochondrial membranes as, besides membrane structure and curvature, recruitment and activity of different proteins also largely depend on the respective lipid composition. Hence, the interaction of neurotoxic proteins with certain lipids and the modification of lipid composition in different cell compartments, in particular mitochondria, decisively impact cell death associated with neurodegeneration. Here, we discuss the relevance of mitochondrial lipids in the pathological alterations that result in neuronal demise, focussing on proteinopathies.

PEGylated Lipid bilayer coated mesoporous silica nanoparticles for co-delivery of paclitaxel and curcumin: Design, characterization and its cytotoxic effect.

PubMed

Lin, Jiahao; Cai, Qiang; Tang, Yinian; Xu, Yanjun; Wang, Qian; Li, Tingting; Xu, Huihao; Wang, Shuaiyu; Fan, Kai; Liu, Zhongjie; Jin, Yipeng; Lin, Degui

2018-01-30

Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754nm and particle size of 115±15nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10-15nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50mg MSNs, ratio of MSNs to lipid (w/w)=1:1.11, and ratio of lipid to CHO (w/w)=3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48±2.73) %, (30.70±3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect. Copyright © 2017. Published by Elsevier B.V.

[Abnormal of tear lipid layer and recent advances in clinical study of dry eye].

PubMed

Xiao, Xin-Ye; Liu, Zu-Guo

2012-03-01

Dry eye is a common disease in the ophthalmological clinic, which is related to the dysfunction of tear film. The tear film is composed of lipid layer, aqueous layer and mucin layer (or lipid layer, aqueous/mucin layer). The lipid of the outmost layer derived from Meibomian gland and distributed on the tear film after blinking can decrease the evaporation and stabilize the tear film. The thickness, quality, and distribution of lipid layer are impaired in many dry eye patients, hence restoring the physiological function of lipid layer may be crucial for the treatment of this kind of dry eye. The lipid artificial tears manifest great effects on increasing lipid layer thickness, stabilizing tear film, improving Meibomian gland dysfunction, and promoting tear film distribution.

Immobilized lipid-bilayer materials

DOEpatents

Sasaki, Darryl Y.; Loy, Douglas A.; Yamanaka, Stacey A.

2000-01-01

A method for preparing encapsulated lipid-bilayer materials in a silica matrix comprising preparing a silica sol, mixing a lipid-bilayer material in the silica sol and allowing the mixture to gel to form the encapsulated lipid-bilayer material. The mild processing conditions allow quantitative entrapment of pre-formed lipid-bilayer materials without modification to the material's spectral characteristics. The method allows for the immobilization of lipid membranes to surfaces. The encapsulated lipid-bilayer materials perform as sensitive optical sensors for the detection of analytes such as heavy metal ions and can be used as drug delivery systems and as separation devices.

Reversible Nuclear-Lipid-Droplet Morphology Induced by Oleic Acid: A Link to Cellular-Lipid Metabolism

PubMed Central

Lagrutta, Lucía C.; Montero-Villegas, Sandra; Layerenza, Juan P.; Sisti, Martín S.; García de Bravo, Margarita M.

2017-01-01

Neutral lipids—involved in many cellular processes—are stored as lipid droplets (LD), those mainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved in nuclear-lipid homeostasis serving as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signalling pathways as transcription factors and as enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLD constituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population (2–10%) of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles. PMID:28125673

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology.

PubMed

Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Mahmood, Asif; Maheen, Safirah; Afzal, Khurram; Iqbal, Nabila; Andleeb, Mehwish; Abbas, Nazar

2017-12-20

For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

Distinct lipid profiles predict improved glycemic control in obese, nondiabetic patients after a low-caloric diet intervention: the Diet, Obesity and Genes randomized trial.

PubMed

Valsesia, Armand; Saris, Wim Hm; Astrup, Arne; Hager, Jörg; Masoodi, Mojgan

2016-09-01

An aim of weight loss is to reduce the risk of type 2 diabetes (T2D) in obese subjects. However, the relation with long-term glycemic improvement remains unknown. We evaluated the changes in lipid composition during weight loss and their association with long-term glycemic improvement. We investigated the plasma lipidome of 383 obese, nondiabetic patients within a randomized, controlled dietary intervention in 8 European countries at baseline, after an 8-wk low-caloric diet (LCD) (800-1000 kcal/d), and after 6 mo of weight maintenance. After weight loss, a lipid signature identified 2 groups of patients who were comparable at baseline but who differed in their capacities to lose weight and improve glycemic control. Six months after the LCD, one group had significant glycemic improvement [homeostasis model assessment of insulin resistance (HOMA-IR) mean change: -0.92; 95% CI: -1.17, -0.67)]. The other group showed no improvement in glycemic control (HOMA-IR mean change: -0.26; 95% CI: -0.64, 0.13). These differences were sustained for ≥1 y after the LCD. The same conclusions were obtained with other endpoints (Matsuda index and fasting insulin and glucose concentrations). Significant differences between the 2 groups were shown in leptin gene expression in adipose tissue biopsies. Significant differences were also observed in weight-related endpoints (body mass index, weight, and fat mass). The lipid signature allowed prediction of which subjects would be considered to be insulin resistant after 6 mo of weight maintenance [validation's receiver operating characteristic (ROC) area under the curve (AUC): 71%; 95% CI: 62%, 81%]. This model outperformed a clinical data-only model (validation's ROC AUC: 61%; 95% CI: 50%, 71%; P = 0.01). In this study, we report a lipid signature of LCD success (for weight and glycemic outcome) in obese, nondiabetic patients. Lipid changes during an 8-wk LCD allowed us to predict insulin-resistant patients after 6 mo of weight maintenance. The determination of the lipid composition during an LCD enables the identification of nonresponders and may help clinicians manage metabolic outcomes with further intervention, thereby improving the long-term outcome and preventing T2D. This trial was registered at clinicaltrials.gov as NCT00390637. © 2016 American Society for Nutrition.

Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes.

PubMed

Vetrivel, Kulandaivelu S; Cheng, Haipeng; Lin, William; Sakurai, Takashi; Li, Tong; Nukina, Nobuyuki; Wong, Philip C; Xu, Huaxi; Thinakaran, Gopal

2004-10-22

Alzheimer's disease-associated beta-amyloid peptides (Abeta) are generated by the sequential proteolytic processing of amyloid precursor protein (APP) by beta- and gamma-secretases. There is growing evidence that cholesterol- and sphingolipid-rich membrane microdomains are involved in regulating trafficking and processing of APP. BACE1, the major beta-secretase in neurons is a palmitoylated transmembrane protein that resides in lipid rafts. A subset of APP is subject to amyloidogenic processing by BACE1 in lipid rafts, and this process depends on the integrity of lipid rafts. Here we describe the association of all four components of the gamma-secretase complex, namely presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons that fulfill the criteria of lipid rafts. In PS1(-/-)/PS2(-/-) and NCT(-/-) fibroblasts, gamma-secretase components that still remain fail to become detergent-resistant, suggesting that raft association requires gamma-secretase complex assembly. Biochemical evidence shows that subunits of the gamma-secretase complex and three TGN/endosome-resident SNAREs cofractionate in sucrose density gradients, and show similar solubility or insolubility characteristics in distinct non-ionic and zwitterionic detergents, indicative of their co-residence in membrane microdomains with similar protein-lipid composition. This notion is confirmed using magnetic immunoisolation of PS1- or syntaxin 6-positive membrane patches from a mixture of membranes with similar buoyant densities following Lubrol WX extraction or sonication, and gradient centrifugation. These findings are consistent with the localization of gamma-secretase in lipid raft microdomains of post-Golgi and endosomes, organelles previously implicated in amyloidogenic processing of APP.

Association of γ-Secretase with Lipid Rafts in Post-Golgi and Endosome Membranes*

PubMed Central

Vetrivel, Kulandaivelu S.; Cheng, Haipeng; Lin, William; Sakurai, Takashi; Li, Tong; Nukina, Nobuyuki; Wong, Philip C.; Xu, Huaxi; Thinakaran, Gopal

2005-01-01

Alzheimer’s disease-associated β-amyloid peptides (Aβ) are generated by the sequential proteolytic processing of amyloid precursor protein (APP) by β- and γ-secretases. There is growing evidence that cholesterol- and sphingolipid-rich membrane microdomains are involved in regulating trafficking and processing of APP. BACE1, the major γ-secretase in neurons is a palmi-toylated transmembrane protein that resides in lipid rafts. A subset of APP is subject to amyloidogenic processing by BACE1 in lipid rafts, and this process depends on the integrity of lipid rafts. Here we describe the association of all four components of the γ-secretase complex, namely presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons that fulfill the criteria of lipid rafts. In PS1−/−/PS2−/− and NCT−/− fibroblasts, γ-secretase components that still remain fail to become detergent-resistant, suggesting that raft association requires γ-secretase complex assembly. Biochemical evidence shows that subunits of the γ-secretase complex and three TGN/endosome-resident SNAREs cofractionate in sucrose density gradients, and show similar solubility or insolubility characteristics in distinct non-ionic and zwitterionic detergents, indicative of their co-residence in membrane microdomains with similar protein-lipid composition. This notion is confirmed using magnetic immunoisolation of PS1- or syntaxin 6-positive membrane patches from a mixture of membranes with similar buoyant densities following Lubrol WX extraction or sonication, and gradient centrifugation. These findings are consistent with the localization of γ-secretase in lipid raft microdomains of post-Golgi and endosomes, organelles previously implicated in amyloidogenic processing of APP. PMID:15322084

Improved Tumor Targeting of Polymer-based Nanovesicles Using Polymer-Lipid Blends

PubMed Central

Cheng, Zhiliang; Elias, Drew R.; Kamat, Neha P.; Johnston, Eric D.; Poloukhtine, Andrei; Popik, Vladimir; Hammer, Daniel A.; Tsourkas, Andrew

2011-01-01

Block copolymer-based vesicles have recently garnered a great deal of interest as nanoplatforms for drug delivery and molecular imaging applications due to their unique structural properties. These nanovesicles have been shown to direct their cargo to disease sites either through enhanced permeability and retention or even more efficiently via active targeting. Here we show that the efficacy of nanovesicle targeting can be significantly improved when prepared from polymer-lipid blends compared with block copolymer alone. Polymer-lipid hybrid nanovesicles were produced from the aqueous co-assembly of the diblock copolymer, poly(ethylene oxide)-block-polybutadiene (PEO-PBD), and the phospholipid, hydrogenated soy phosphatidylcholine (HSPC). The PEG-based vesicles, 117 nm in diameter, were functionalized with either folic acid or anti-HER2/neu affibodies as targeting ligands to confer specificity for cancer cells. Our results revealed that nanovesicles prepared from polymer-lipid blends led to significant improvement in cell binding compared to nanovesicles prepared from block copolymer alone in both in vitro cell studies and murine tumor models. Therefore, it is envisioned that nanovesicles composed of polymer-lipid blends may constitute a preferred embodiment for targeted drug delivery and molecular imaging applications. PMID:21899335

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.

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.

Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application

PubMed Central

2013-01-01

The interest of the pharmaceutical industry in lipid drug delivery systems due to their prolonged release profile, biocompatibility, reduction of side effects, and so on is already known. However, conventional methods of preparation of these structures for their use and production in the pharmaceutical industry are difficult since these methods are usually multi-step and involve high amount of organic solvent. Furthermore, some processes need extreme conditions, which can lead to an increase of heterogeneity of particle size and degradation of the drug. An alternative for drug delivery system production is the utilization of supercritical fluid technique. Lipid particles produced by supercritical fluid have shown different physicochemical properties in comparison to lipid particles produced by classical methods. Such particles have shown more physical stability and narrower size distribution. So, in this paper, a critical overview of supercritical fluid-based processes for the production of lipid micro- and nanoparticles is given and the most important characteristics of each process are highlighted. PMID:24034341

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis.

PubMed

Schubert, Thomas; Römer, Winfried

2015-11-01

Synthetic membrane systems, such as giant unilamellar vesicles and solid supported lipid bilayers, have widened our understanding of biological processes occurring at or through membranes. Artificial systems are particularly suited to study the inherent properties of membranes with regard to their components and characteristics. This review critically reflects the emerging molecular mechanism of lipid-driven endocytosis and the impact of model membrane systems in elucidating the complex interplay of biomolecules within this process. Lipid receptor clustering induced by binding of several toxins, viruses and bacteria to the plasma membrane leads to local membrane bending and formation of tubular membrane invaginations. Here, lipid shape, and protein structure and valency are the essential parameters in membrane deformation. Combining observations of complex cellular processes and their reconstitution on minimal systems seems to be a promising future approach to resolve basic underlying mechanisms. This article is part of a Special Issue entitled: Mechanobiology. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Production of Biodiesel from Lipid of Phytoplankton Chaetoceros calcitrans through Ultrasonic Method

PubMed Central

Kwangdinata, Raymond; Raya, Indah; Zakir, Muhammad

2014-01-01

A research on production of biodiesel from lipid of phytoplankton Chaetoceros calcitrans through ultrasonic method has been done. In this research, we carried out a series of phytoplankton cultures to determine the optimum time of growth and biodiesel synthesis process from phytoplankton lipids. Process of biodiesel synthesis consists of two steps, that is, isolation of phytoplankton lipids and biodiesel synthesis from those lipids. Oil isolation process was carried out by ultrasonic extraction method using ethanol 96%, while biodiesel synthesis was carried out by transesterification reaction using methanol and KOH catalyst under sonication. Weight of biodiesel yield per biomass Chaetoceros calcitrans is 35.35%. Characterization of biodiesel was well carried out in terms of physical properties which are density and viscosity and chemical properties which are FFA content, saponification value, and iodine value. These values meet the American Society for Testing and Materials (ASTM D6751) standard levels, except for the viscosity value which was 1.14 g·cm−3. PMID:24688372

Aging Increases Susceptibility to High Fat Diet-Induced Metabolic Syndrome in C57BL/6 Mice: Improvement in Glycemic and Lipid Profile after Antioxidant Therapy

PubMed Central

Nunes-Souza, Valéria; César-Gomes, Cheila Juliana; Da Fonseca, Lucas José Sá; Guedes, Glaucevane Da Silva; Smaniotto, Salete; Rabelo, Luíza Antas

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) has been considered a novel component of the metabolic syndrome (MetS), with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD-) induced MetS received apocynin and tempol 50 mg·kg−1/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD. PMID:27057272

Receptor-mediated membrane adhesion of lipid-polymer hybrid (LPH) nanoparticles studied by dissipative particle dynamics simulations

NASA Astrophysics Data System (ADS)

Li, Zhenlong; Gorfe, Alemayehu A.

2014-12-01

Lipid-polymer hybrid (LPH) nanoparticles represent a novel class of targeted drug delivery platforms that combine the advantages of liposomes and biodegradable polymeric nanoparticles. However, the molecular details of the interaction between LPHs and their target cell membranes remain poorly understood. We have investigated the receptor-mediated membrane adhesion process of a ligand-tethered LPH nanoparticle using extensive dissipative particle dynamics (DPD) simulations. We found that the spontaneous adhesion process follows a first-order kinetics characterized by two distinct stages: a rapid nanoparticle-membrane engagement, followed by a slow growth in the number of ligand-receptor pairs coupled with structural re-organization of both the nanoparticle and the membrane. The number of ligand-receptor pairs increases with the dynamic segregation of ligands and receptors toward the adhesion zone causing an out-of-plane deformation of the membrane. Moreover, the fluidity of the lipid shell allows for strong nanoparticle-membrane interactions to occur even when the ligand density is low. The LPH-membrane avidity is enhanced by the increased stability of each receptor-ligand pair due to the geometric confinement and the cooperative effect arising from multiple binding events. Thus, our results reveal the unique advantages of LPH nanoparticles as active cell-targeting nanocarriers and provide some general principles governing nanoparticle-cell interactions that may aid future design of LPHs with improved affinity and specificity for a given target of interest.

Design of lipid-based delivery systems for improving lymphatic transport and bioavailability of delta-tocopherol and nobiletin

NASA Astrophysics Data System (ADS)

Xia, Chunxin

Lymphatic drug transport can confer bioavailability advantage by avoiding the first-pass metabolism normally observed in the portal vein hepatic route. It was reported that long chain lipid-based delivery systems can stimulate the formation of chylomicron and thus promote the lymphatic transport of drugs. In this study, a novel delta-tocopherol (delta-T) loaded Solid Lipid Nanoparticle (SLN) system was developed to investigate its effect on promoting the lymphatic transport of delta-T. The delta-T SLN was prepared with hot melt emulsification method by using glyceryl behenate (compritol RTM888) as the lipid phase and lecithin (PC75) as the emulsifier. Formula configuration, processing condition and loading capacity were carefully optimized. Physicochemical properties (particle size, surface charge, morphology) were also characterized. Moreover, excellent stability of the developed delta-T SLN in the gastrointestinal environment was observed by using an in vitro digestion model. Further investigations of the SLN in stimulating delta-T lymphatic transport were performed on mice without cannulation. Compared with the control group (delta-T corn oil dispersion), much lower delta-T levels in both blood and liver indicated reduced portal vein and hepatic transport of delta-T in the form of SLN. On the other hand, significantly higher concentrations of delta-T were observed in thymus, a major lymphatic tissue, indicating improved lymphatic transport of delta-T with the SLN delivery system. Finally, the far less excreted delta-T level in feces further confirmed improved lymphatic transport and overall bioavailability of delta-T by using SLN system. Nobiletin (NOB), one of most abundant polymethoxyflavones (PMFs) found in Citrus genus, has a low solubility in both water and oil at ambient temperatures. Thus it tends to form crystals when the loading exceeds its saturation level in the carrier system. This character greatly impaired its bioavailability and application. To overcome these problems, an O/W nanoemulsion was developed for NOB delivery with the presence of cremophor EL (a polyethoxylated excipient). The developed formulation can achieve a high NOB loading (0.5 wt%) with significantly reduced crystallinity and excellent physical stability. NOB's bioaccessibility and permeation rate across the enterocytes were demonstrated to be significantly improved by the in vitro digestion model and Caco-2 cell monolayer, respectively. It is thus predictable that NOB's bioavailability can be improved with our developed nanoemulsion formulation.

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes.

PubMed

D'Aquila, Theresa; Hung, Yu-Han; Carreiro, Alicia; Buhman, Kimberly K

2016-08-01

Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, cardiovascular disease, and cancer. Within enterocytes, the digestive products of dietary fat are re-synthesized into triacylglycerol, which is either secreted on chylomicrons or stored within cytoplasmic lipid droplets (CLDs). CLDs were originally thought to be inert stores of neutral lipids, but are now recognized as dynamic organelles that function in multiple cellular processes in addition to lipid metabolism. This review will highlight recent discoveries related to dietary fat absorption with an emphasis on the presence, synthesis, and metabolism of CLDs within this process. Copyright © 2016 Elsevier B.V. All rights reserved.

WE-FG-207B-06: Plaque Composition Measurement with Dual Energy Computed Tomography

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

Wang, C; Ding, H; Malkasian, S

Purpose: To investigate the feasibility of characterizing arterial plaque composition in terms of water, lipid and protein or calcium using dual energy computed tomography. Characterization of plaque composition can potentially help distinguish vulnerable from stable plaques. Methods: Simulations studies were performed by the CT simulator based on ASTRA tomography toolbox. The beam energy for dual energy images was selected to be 80 kVp and 135 kVp. The radiation dose and energy spectrum for the CT simulator were carefully calibrated with respect to a 320-slice CT scanner. A digital chest phantom was constructed using Matlab for calibration and plaque measurement. Puremore » water, lipid, protein or calcium was used for calibration and a mixture of different volume percentages of these materials were used for validation purposes. Non-calcified plaque was simulated using water, lipid and protein with volumetric percentage range of 35%∼65%, 5%∼60% and 5%∼40%, respectively. Calcified plaque was simulated using water, lipid and calcium with volumetric percentage range of 50%∼80%, 8%∼45% and 3%∼13%, respectively. We employed iterative sinogram processing (ISP) to reduce the beam hardening effect in the simulation to improve the decomposition results. Results: The simulated known composition and dual energy decomposition results were in good agreement. Water, lipid and protein (calcium) mixtures were decomposed into water, lipid and protein (calcium) contents. The RMS errors of volumetric percentage for the water, lipid and protein (non-calcified plaque) decomposition, as compared to known values, were estimated to be approximately 5.74%, 2.54%, and 0.95% respectively. The RMS errors of volumetric percentage for the water, lipid and Calcium (calcified plaque) decomposition, as compared to known values, were estimated to be approximately 7.4%, 8.64%, and 0.08% respectively. Conclusion: The results of this study suggest that the dual energy decomposition can potentially be used to quantify the water, lipid, and protein or calcium composition of a plaque with relatively good accuracy. Grant funding from Toshiba Medical Systems and Philips Medical Systems.« less

The physiology of lipid storage and use in reptiles.

PubMed

Price, Edwin R

2017-08-01

Lipid metabolism is central to understanding whole-animal energetics. Reptiles store most excess energy in lipid form, mobilise those lipids when needed to meet energetic demands, and invest lipids in eggs to provide the primary source of energy to developing embryos. Here, I review the mechanisms by which non-avian reptiles store, transport, and use lipids. Many aspects of lipid absorption, transport, and storage appear to be similar to birds, including the hepatic synthesis of lipids from glucose substrates, the transport of triglycerides in lipoproteins, and the storage of lipids in adipose tissue, although adipose tissue in non-avian reptiles is usually concentrated in abdominal fat bodies or the tail. Seasonal changes in fat stores suggest that lipid storage is primarily for reproduction in most species, rather than for maintenance during aphagic periods. The effects of fasting on plasma lipid metabolites can differ from mammals and birds due to the ability of non-avian reptiles to reduce their metabolism drastically during extended fasts. The effect of fasting on levels of plasma ketones is species specific: β-hydroxybutyrate concentration may rise or fall during fasting. I also describe the process by which the bulk of lipids are deposited into oocytes during vitellogenesis. Although this process is sometimes ascribed to vitellogenin-based transport in reptiles, the majority of lipid deposition occurs via triglycerides packaged in very-low-density lipoproteins (VLDLs), based on physiological, histological, biochemical, comparative, and genomic evidence. I also discuss the evidence for non-avian reptiles using 'yolk-targeted' VLDLs during vitellogenesis. The major physiological states - feeding, fasting, and vitellogenesis - have different effects on plasma lipid metabolites, and I discuss the possibilities and potential problems of using plasma metabolites to diagnose feeding condition in non-avian reptiles. © 2016 Cambridge Philosophical Society.

Molecular mechanism for lipid flip-flops.

PubMed

Gurtovenko, Andrey A; Vattulainen, Ilpo

2007-12-06

Transmembrane lipid translocation (flip-flop) processes are involved in a variety of properties and functions of cell membranes, such as membrane asymmetry and programmed cell death. Yet, flip-flops are one of the least understood dynamical processes in membranes. In this work, we elucidate the molecular mechanism of pore-mediated transmembrane lipid translocation (flip-flop) acquired from extensive atomistic molecular dynamics simulations. On the basis of 50 successful flip-flop events resolved in atomic detail, we demonstrate that lipid flip-flops may spontaneously occur in protein-free phospholipid membranes under physiological conditions through transient water pores on a time scale of tens of nanoseconds. While the formation of a water pore is induced here by a transmembrane ion density gradient, the particular way by which the pore is formed is irrelevant for the reported flip-flop mechanism: the appearance of a transient pore (defect) in the membrane inevitably leads to diffusive translocation of lipids through the pore, which is driven by thermal fluctuations. Our findings strongly support the idea that the formation of membrane defects in terms of water pores is the rate-limiting step in the process of transmembrane lipid flip-flop, which, on average, requires several hours. The findings are consistent with available experimental and computational data and provide a view to interpret experimental observations. For example, the simulation results provide a molecular-level explanation in terms of pores for the experimentally observed fact that the exposure of lipid membranes to electric field pulses considerably reduces the time required for lipid flip-flops.

Dietary silymarin supplementation promotes growth performance and improves lipid metabolism and health status in grass carp (Ctenopharyngodon idellus) fed diets with elevated lipid levels.

PubMed

Xiao, Peizhen; Ji, Hong; Ye, Yuantu; Zhang, Baotong; Chen, Yongsheng; Tian, Jingjing; Liu, Pin; Chen, Liqiao; Du, Zhenyu

2017-02-01

This study was carried out to evaluate whether silymarin supplementation influences growth, lipid metabolism, and health status in grass carp fed elevated dietary lipid levels. The juvenile fish (27.43 ± 0.17 g/tail) were fed six isonitrogenous and isocaloric diets in a factorial design containing 0, 100, or 200 mg kg -1 silymarin (SM0, SM100, SM200) associated with either 4 or 8 % lipid level (low lipid, LL, and high lipid, HL, respectively) for 82 days. The results showed that both dietary silymarin supplementation and high lipid level significantly enhanced growth performance (WG, SGR), protein efficiency ratio, and feed utilization. Silymarin supplementation significantly reduced the VSI, hepatic lipid content, and the total bilirubin concentration in the serum. The gallbladdersomatic index displayed higher in the SM100 groups than SM200 groups. Serum total cholesterol content exhibited lower in the SM100 groups than SM0 groups. Meanwhile, significant interactions were shown for hepatic gene expression of HSL and CPT1 by two factors, and SM100 group had higher hepatic gene expression of HSL and CPT1 in fish fed with the HL diets. The SM100 groups up-regulated hepatic gene expressions of HMGCR and CYP7A1 compared with the SM0 groups. Silymarin supplementation notably reduced the elevated serum MDA content induced by HL treatments. Thus, silymarin supplementation markedly promoted growth and protein efficiency, suppressed lipid accumulation, and improved health status in grass carp fed with high-lipid diets, which might be associated with its enhancement of lipolysis and β-oxidation, antioxidant capacity.

Parenteral Nutrition and Lipids.

PubMed

Raman, Maitreyi; Almutairdi, Abdulelah; Mulesa, Leanne; Alberda, Cathy; Beattie, Colleen; Gramlich, Leah

2017-04-14

Lipids have multiple physiological roles that are biologically vital. Soybean oil lipid emulsions have been the mainstay of parenteral nutrition lipid formulations for decades in North America. Utilizing intravenous lipid emulsions in parenteral nutrition has minimized the dependence on dextrose as a major source of nonprotein calories and prevents the clinical consequences of essential fatty acid deficiency. Emerging literature has indicated that there are benefits to utilizing alternative lipids such as olive/soy-based formulations, and combination lipids such as soy/MCT/olive/fish oil, compared with soybean based lipids, as they have less inflammatory properties, are immune modulating, have higher antioxidant content, decrease risk of cholestasis, and improve clinical outcomes in certain subgroups of patients. The objective of this article is to review the history of IVLE, their composition, the different generations of widely available IVLE, the variables to consider when selecting lipids, and the complications of IVLE and how to minimize them.

Parenteral Nutrition and Lipids

PubMed Central

Raman, Maitreyi; Almutairdi, Abdulelah; Mulesa, Leanne; Alberda, Cathy; Beattie, Colleen; Gramlich, Leah

2017-01-01

Lipids have multiple physiological roles that are biologically vital. Soybean oil lipid emulsions have been the mainstay of parenteral nutrition lipid formulations for decades in North America. Utilizing intravenous lipid emulsions in parenteral nutrition has minimized the dependence on dextrose as a major source of nonprotein calories and prevents the clinical consequences of essential fatty acid deficiency. Emerging literature has indicated that there are benefits to utilizing alternative lipids such as olive/soy-based formulations, and combination lipids such as soy/MCT/olive/fish oil, compared with soybean based lipids, as they have less inflammatory properties, are immune modulating, have higher antioxidant content, decrease risk of cholestasis, and improve clinical outcomes in certain subgroups of patients. The objective of this article is to review the history of IVLE, their composition, the different generations of widely available IVLE, the variables to consider when selecting lipids, and the complications of IVLE and how to minimize them. PMID:28420095

Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease.

PubMed

Lin, Yi; Ding, Dongxiao; Huang, Qiansheng; Liu, Qiong; Lu, Haoyang; Lu, Yanyang; Chi, Yulang; Sun, Xia; Ye, Guozhu; Zhu, Huimin; Wei, Jie; Dong, Sijun

2017-09-01

Exposure to Bisphenol A (BPA) has been associated with the development of nonalcoholic fatty liver disease (NAFLD) but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study was designed to explore whether exposure to BPA-triggered abnormal steatosis and lipid accumulation in the liver could be modulated by miR-192. We showed that male post-weaning C57BL/6 mice exposed to 50μg/kg/day of BPA by oral gavage for 90days displayed a NAFLD-like phenotype. In addition, we found in mouse liver and human HepG2 cells that BPA-induced hepatic steatosis and lipid accumulation were associated with decreased expression of miR-192, upregulation of SREBF1 and a series of genes involved in de novo lipogenesis. Downregulation of miR-192 in BPA-exposed hepatocytes could be due to defective pre-miR-192 processing by DROSHA. Using HepG2 cells, we further confirmed that miR-192 directly acted on the 3'UTR of SREBF1, contributing to dysregulation of lipid homeostasis in hepatocytes. MiR-192 mimic and lentivirus-mediated overexpression of miR-192 improved BPA-induced hepatic steatosis by suppressing SREBF1. Lastly, we noted that lipid accumulation was not a strict requirement for developing insulin resistance in mice after BPA treatment. In conclusion, this study demonstrated a novel mechanism in which NAFLD associated with BPA exposure arose from alterations in the miR-192-SREBF1 axis. Copyright © 2017 Elsevier B.V. All rights reserved.

Furosemide Loaded Silica-Lipid Hybrid Microparticles: Formulation Development, in vitro and ex vivo Evaluation.

PubMed

Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar

2015-09-01

The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs.

Furosemide Loaded Silica-Lipid Hybrid Microparticles: Formulation Development, in vitro and ex vivo Evaluation

PubMed Central

Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar

2015-01-01

Purpose: The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. Methods: The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. Results: In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. Conclusion: It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs. PMID:26504763

Tethered bilayer lipid membranes (tBLMs): interest and applications for biological membrane investigations.

PubMed

Rebaud, Samuel; Maniti, Ofelia; Girard-Egrot, Agnès P

2014-12-01

Biological membranes play a central role in the biology of the cell. They are not only the hydrophobic barrier allowing separation between two water soluble compartments but also a supra-molecular entity that has vital structural functions. Notably, they are involved in many exchange processes between the outside and inside cellular spaces. Accounting for the complexity of cell membranes, reliable models are needed to acquire current knowledge of the molecular processes occurring in membranes. To simplify the investigation of lipid/protein interactions, the use of biomimetic membranes is an approach that allows manipulation of the lipid composition of specific domains and/or the protein composition, and the evaluation of the reciprocal effects. Since the middle of the 80's, lipid bilayer membranes have been constantly developed as models of biological membranes with the ultimate goal to reincorporate membrane proteins for their functional investigation. In this review, after a brief description of the planar lipid bilayers as biomimetic membrane models, we will focus on the construction of the tethered Bilayer Lipid Membranes, the most promising model for efficient membrane protein reconstitution and investigation of molecular processes occurring in cell membranes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Occurrence and Importance of Plant Lipids: A Promising Insight into Algae.

PubMed

Halima, Nihed B

2017-01-01

Lipids are biomolecules with interesting structural variability. They are involved in many processes such as the storage of energy, in nutrition and are also of relevance for signal transduction processes, in apoptosis, cell differentiation and phagocytosis, etc. Macroalgae and microalgae are a promising and very diverse group of organisms. These living arganisms inhabit a vaste range of ecosystems from the Antarctic to the Deserts. They account for above half the primary productivity at the base of the food chain because of their multiple nutritional products including, for instance, lipids. Recently, studies on the oleaginous algae encompass their uses for commercial exploitations with applications ranging from human health food, animal feed, aquaculture, nutraceutical, biofuels and others. In this article, updated knowledge of lipids and recent research studies for algae's valorization performed by several authors were reviewed. Special attention was paid to lipids accumulation and their characterization. The selection of the prominent species of algae will be of great importance to satisfy the corresponding valorization process. Patents identified with algal lipids composition, production and application are presented. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficient Exploration of Membrane-Associated Phenomena at Atomic Resolution.

PubMed

Vermaas, Josh V; Baylon, Javier L; Arcario, Mark J; Muller, Melanie P; Wu, Zhe; Pogorelov, Taras V; Tajkhorshid, Emad

2015-06-01

Biological membranes constitute a critical component in all living cells. In addition to providing a conducive environment to a wide range of cellular processes, including transport and signaling, mounting evidence has established active participation of specific lipids in modulating membrane protein function through various mechanisms. Understanding lipid-protein interactions underlying these mechanisms at a sufficiently high resolution has proven extremely challenging, partly due to the semi-fluid nature of the membrane. In order to address this challenge computationally, multiple methods have been developed, including an alternative membrane representation termed highly mobile membrane mimetic (HMMM) in which lateral lipid diffusion has been significantly enhanced without compromising atomic details. The model allows for efficient sampling of lipid-protein interactions at atomic resolution, thereby significantly enhancing the effectiveness of molecular dynamics simulations in capturing membrane-associated phenomena. In this review, after providing an overview of HMMM model development, we will describe briefly successful application of the model to study a variety of membrane processes, including lipid-dependent binding and insertion of peripheral proteins, the mechanism of phospholipid insertion into lipid bilayers, and characterization of optimal tilt angle of transmembrane helices. We conclude with practical recommendations for proper usage of the model in simulation studies of membrane processes.

Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells.

PubMed

K S, Joshy; Sharma, Chandra P; Kalarikkal, Nandakumar; Sandeep, K; Thomas, Sabu; Pothen, Laly A

2016-09-01

Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66±12.22nm and modified solid lipid nanoparticles showed an average size of 265.61±80.44nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. Copyright © 2016 Elsevier B.V. All rights reserved.

Carbon nanotubes for stabilization of nanostructured lipid particles

NASA Astrophysics Data System (ADS)

Gaunt, Nicholas P.; Patil-Sen, Yogita; Baker, Matthew J.; Kulkarni, Chandrashekhar V.

2014-12-01

Carbon nanotubes (CNTs) are increasingly studied for innovative biotechnological applications particularly where they are combined with essential biological materials like lipids. Lipids have been used earlier for enhancing the dispersibility of CNTs in aqueous solutions. Here we report a novel application of CNTs for stabilization of internally self-assembled nanostructured lipid particles of 2-5 μm size. Single-walled (pristine) as well as -OH and -COOH functionalized multi-walled CNTs were employed to produce nanostructured emulsions which stayed stable for months and could be re-dispersed after complete dehydration. Concentrations of CNTs employed for stabilization were very low; moreover CNTs were well-decorated with lipid molecules. These features contribute towards reducing their toxicity and improving biocompatibility for biomedical and pharmaceutical applications. Our approach paves the way for future development of combination therapies employing both CNTs and nanostructured lipid self-assembly together as carriers of different drugs.Carbon nanotubes (CNTs) are increasingly studied for innovative biotechnological applications particularly where they are combined with essential biological materials like lipids. Lipids have been used earlier for enhancing the dispersibility of CNTs in aqueous solutions. Here we report a novel application of CNTs for stabilization of internally self-assembled nanostructured lipid particles of 2-5 μm size. Single-walled (pristine) as well as -OH and -COOH functionalized multi-walled CNTs were employed to produce nanostructured emulsions which stayed stable for months and could be re-dispersed after complete dehydration. Concentrations of CNTs employed for stabilization were very low; moreover CNTs were well-decorated with lipid molecules. These features contribute towards reducing their toxicity and improving biocompatibility for biomedical and pharmaceutical applications. Our approach paves the way for future development of combination therapies employing both CNTs and nanostructured lipid self-assembly together as carriers of different drugs. Electronic supplementary information (ESI) available: Concentration series studies with Raman spectroscopy and small angle X-ray diffraction pattern for dry lipid and dehydrated CNT-lipid particles support the article. See DOI: 10.1039/c4nr05593d

Single Lipid Molecule Dynamics on Supported Lipid Bilayers with Membrane Curvature.

PubMed

Cheney, Philip P; Weisgerber, Alan W; Feuerbach, Alec M; Knowles, Michelle K

2017-03-15

The plasma membrane is a highly compartmentalized, dynamic material and this organization is essential for a wide variety of cellular processes. Nanoscale domains allow proteins to organize for cell signaling, endo- and exocytosis, and other essential processes. Even in the absence of proteins, lipids have the ability to organize into domains as a result of a variety of chemical and physical interactions. One feature of membranes that affects lipid domain formation is membrane curvature. To directly test the role of curvature in lipid sorting, we measured the accumulation of two similar lipids, 1,2-Dihexadecanoyl- sn -glycero-3-phosphoethanolamine (DHPE) and hexadecanoic acid (HDA), using a supported lipid bilayer that was assembled over a nanopatterned surface to obtain regions of membrane curvature. Both lipids studied contain 16 carbon, saturated tails and a head group tag for fluorescence microscopy measurements. The accumulation of lipids at curvatures ranging from 28 nm to 55 nm radii was measured and fluorescein labeled DHPE accumulated more than fluorescein labeled HDA at regions of membrane curvature. We then tested whether single biotinylated DHPE molecules sense curvature using single particle tracking methods. Similar to groups of fluorescein labeled DHPE accumulating at curvature, the dynamics of single molecules of biotinylated DHPE was also affected by membrane curvature and highly confined motion was observed.

Pushing the lipid envelope: using bio-inspired nanocomposites to understand and exploit lipid membrane limitations

NASA Astrophysics Data System (ADS)

Montano, Gabriel

Lipids serve as the organizing matrix material for biological membranes, the site of interaction of cells with the external environment. . As such, lipids play a critical role in structure/function relationships of an extraordinary number of critical biological processes. In this talk, we will look at bio-inspired membrane assemblies to better understand the roles of lipids in biological systems as well as attempt to generate materials that can mimic and potentially advance upon biological membrane processes. First, we will investigate the response of lipids to adverse conditions. In particular, I will present data that demonstrates the response of lipids to harsh conditions and how such responses can be exploited to generate nanocomposite rearrangements. I will also show the effect of adding the endotoxin lipopolysaccharide (LPS) to lipid bilayer assemblies and describe implications on our understanding of LPS organization in biological systems as well as describe induced lipid modifications that can be exploited to organize membrane composites with precise, two-dimensional geometric control. Lastly, I will describe the use of amphiphilic block copolymers to create membrane nanocomposites capable of mimicking biological systems. In particular, I will describe the use of our polymer-based membranes in creating artificial photosynthetic assemblies that rival biological systems in function in a more flexible, dynamic matrix.

Mass spectrometric profiling of lipids in intestinal tissue from rats fed cereals processed for medical conditions.

PubMed

Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

2016-06-11

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for lipid profiling of intestine tissue sections from rats fed specially processed cereals and rats fed ordinary feed as a control. This cereal is known to increase the activity of antisecretory factor in plasma and the exact mechanism for the activation process at the cellular level is unclear. ToF-SIMS has been used to track food induced changes in lipid content in intestinal tissue sections to gain insight into the possible mechanisms involved. Data from 20 intestine sections belonging to four different rats from each group of control and specially processed cereals-fed rats were obtained using the stage scan macroraster with a lateral resolution of 5 μm. Data were subsequently subjected to orthogonal partial least squares discriminant analysis. The data clearly show that changes of certain lipids are induced by the specially processed cereal feed. Scores plots show a well-defined separation between the two groups. The corresponding loading plots reveal that the groups separate mainly due to changes of vitamin E, phosphocholine, and phosphosphingolipid fragments, and that for the c18:2 fatty acid. The observed changes in lipids might give insight into the working mechanisms of antisecretory factor in the body, and this has been successfully used to understand the working mechanism of specially processed cereal-induced antisecretory factor activation in intestine.

Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

PubMed Central

Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

2014-01-01

Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

PubMed

Cicero, Arrigo F G; Colletti, Alessandro; Bajraktari, Gani; Descamps, Olivier; Djuric, Dragan M; Ezhov, Marat; Fras, Zlatko; Katsiki, Niki; Langlois, Michel; Latkovskis, Gustavs; Panagiotakos, Demosthenes B; Paragh, Gyorgy; Mikhailidis, Dimitri P; Mitchenko, Olena; Paulweber, Bernhard; Pella, Daniel; Pitsavos, Christos; Reiner, Željko; Ray, Kausik K; Rizzo, Manfredi; Sahebkar, Amirhossein; Serban, Maria-Corina; Sperling, Laurence S; Toth, Peter P; Vinereanu, Dragos; Vrablík, Michal; Wong, Nathan D; Banach, Maciej

2017-09-01

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Genome and methylome of the oleaginous diatom Cyclotella cryptica reveal genetic flexibility toward a high lipid phenotype

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

Traller, Jesse C.; Cokus, Shawn J.; Lopez, David A.

Here, improvement in the performance of eukaryotic microalgae for biofuel and bioproduct production is largely dependent on characterization of metabolic mechanisms within the cell. The marine diatom Cyclotella cryptica, which was originally identified in the Aquatic Species Program, is a promising strain of microalgae for large-scale production of biofuel and bioproducts, such as omega-3 fatty acids. As a result, we sequenced the nuclear genome and methylome of this oleaginous diatom to identify the genetic traits that enable substantial accumulation of triacylglycerol. The genome is comprised of highly methylated repetitive sequence, which does not significantly change under silicon starved lipid induction,more » and data further suggests the primary role of DNA methylation is to suppress DNA transposition. Annotation of pivotal glycolytic, lipid metabolism, and carbohydrate degradation processes reveal an expanded enzyme repertoire in C. cryptica that would allow for an increased metabolic capacity toward triacylglycerol production. Identification of previously unidentified genes, including those involved in carbon transport and chitin metabolism, provide potential targets for genetic manipulation of carbon flux to further increase its lipid phenotype. New genetic tools were developed, bringing this organism on a par with other microalgae in terms of genetic manipulation and characterization approaches. Furthermore, functional annotation and detailed cross-species comparison of key carbon rich processes in C. cryptica highlights the importance of enzymatic subcellular compartmentation for regulation of carbon flux, which is often overlooked in photosynthetic microeukaryotes. The availability of the genome sequence, as well as advanced genetic manipulation tools enable further development of this organism for deployment in large-scale production systems.« less

Genome and methylome of the oleaginous diatom Cyclotella cryptica reveal genetic flexibility toward a high lipid phenotype

DOE PAGES

Traller, Jesse C.; Cokus, Shawn J.; Lopez, David A.; ...

2016-11-25

Here, improvement in the performance of eukaryotic microalgae for biofuel and bioproduct production is largely dependent on characterization of metabolic mechanisms within the cell. The marine diatom Cyclotella cryptica, which was originally identified in the Aquatic Species Program, is a promising strain of microalgae for large-scale production of biofuel and bioproducts, such as omega-3 fatty acids. As a result, we sequenced the nuclear genome and methylome of this oleaginous diatom to identify the genetic traits that enable substantial accumulation of triacylglycerol. The genome is comprised of highly methylated repetitive sequence, which does not significantly change under silicon starved lipid induction,more » and data further suggests the primary role of DNA methylation is to suppress DNA transposition. Annotation of pivotal glycolytic, lipid metabolism, and carbohydrate degradation processes reveal an expanded enzyme repertoire in C. cryptica that would allow for an increased metabolic capacity toward triacylglycerol production. Identification of previously unidentified genes, including those involved in carbon transport and chitin metabolism, provide potential targets for genetic manipulation of carbon flux to further increase its lipid phenotype. New genetic tools were developed, bringing this organism on a par with other microalgae in terms of genetic manipulation and characterization approaches. Furthermore, functional annotation and detailed cross-species comparison of key carbon rich processes in C. cryptica highlights the importance of enzymatic subcellular compartmentation for regulation of carbon flux, which is often overlooked in photosynthetic microeukaryotes. The availability of the genome sequence, as well as advanced genetic manipulation tools enable further development of this organism for deployment in large-scale production systems.« less

Lipids from yeasts and fungi: physiology, production and analytical considerations.

PubMed

Athenaki, M; Gardeli, C; Diamantopoulou, P; Tchakouteu, S S; Sarris, D; Philippoussis, A; Papanikolaou, S

2018-02-01

The last years there has been a significant rise in the number of publications in the international literature that deal with the production of lipids by microbial sources (the 'single cell oils; SCOs' that are produced by the so-called 'oleaginous' micro-organisms). In the first part of the present review article, a general overview of the oleaginous micro-organisms (mostly yeasts, algae and fungi) and their potential upon the production of SCOs is presented. Thereafter, physiological and kinetic events related with the production of, mostly, yeast and fungal lipids when sugars and related substrates like polysaccharides, glycerol, etc. (the de novo lipid accumulation process) or hydrophobic substrates like oils and fats (the ex novo lipid accumulation process) were employed as microbial carbon sources, are presented and critically discussed. Considerations related with the degradation of storage lipid that had been previously accumulated inside the cells, are also presented. The interplay of the synthesis of yeast and fungal lipids with other intracellular (i.e. endopolysaccharides) or extracellular (i.e. citric acid) secondary metabolites synthesized is also presented. Finally, aspects related with the lipid extraction and lipidome analysis of the oleaginous micro-organisms are presented and critically discussed. © 2017 The Society for Applied Microbiology.

Phosphatidic acid and neurotransmission

PubMed Central

Raben, Daniel M.; Barber, Casey N.

2016-01-01

Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system. PMID:27671966

LIQUID: an-open source software for identifying lipids in LC-MS/MS-based lipidomics data

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

Kyle, Jennifer E.; Crowell, Kevin L.; Casey, Cameron P.

2017-01-31

We introduce an open-source software, LIQUID, for semi-automated processing and visualization of LC-MS/MS based lipidomics data. LIQUID provides users with the capability to process high throughput data and contains a customizable target library and scoring model per project needs. The graphical user interface provides visualization of multiple lines of spectral evidence for each lipid identification, allowing rapid examination of data for making confident identifications of lipid molecular species.

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

Kosicek, Marko, E-mail: marko.kosicek@irb.hr; Malnar, Martina, E-mail: martina.malnar@irb.hr; Goate, Alison, E-mail: goate@icarus.wustl.edu

It has been suggested that cholesterol may modulate amyloid-{beta} (A{beta}) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD ({beta}-amyloid precursor protein (APP), {beta}-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/A{beta} formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1{sup -/-} cells (NPC cells) and parental CHOwt cells. By sucrose density gradientmore » centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, {gamma}-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards A{beta} occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.« less

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

PubMed

Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

2011-03-01

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

PubMed Central

Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H. G.

2011-01-01

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders. PMID:21062955

Synchronized growth and neutral lipid accumulation in Chlorella sorokiniana FC6 IITG under continuous mode of operation.

PubMed

Kumar, Vikram; Muthuraj, Muthusivaramapandian; Palabhanvi, Basavaraj; Das, Debasish

2016-01-01

Synchronized growth and neutral lipid accumulation with high lipid productivity under mixotrophic growth of the strain Chlorella sorokiniana FC6 IITG was achieved via manipulation of substrates feeding mode and supplementation of lipid elicitors in the growth medium. Screening and optimization of lipid elicitors resulted in lipid productivity of 110.59mgL(-1)day(-1) under the combined effect of lipid inducers sodium acetate and sodium chloride. Fed-batch cultivation of the strain in bioreactor with intermittent feeding of limiting nutrients and lipid inducer resulted in maximum biomass and lipid productivity of 2.08 and 0.97gL(-1)day(-1) respectively. Further, continuous production of biomass with concomitant lipid accumulation was demonstrated via continuous feeding of BG11 media supplemented with lipid inducers sodium acetate and sodium chloride. The improved biomass and lipid productivity in chemostat was found to be 2.81 and 1.27gL(-1)day(-1) respectively operated at a dilution rate of 0.54day(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of an oven drying protocol to improve biodiesel production for an indigenous chlorophycean microalga Scenedesmus sp.

PubMed

Bagchi, Sourav Kumar; Rao, Pavuluri Srinivasa; Mallick, Nirupama

2015-03-01

Drying of wet algal biomass is a major bottleneck in viable commercial production of the microalgal biodiesel. In the present investigation, an oven drying protocol was standardized for drying of wet Scenedesmus biomass at 60, 80 and 100°C with initial sample thickness of 5.0, 7.5 and 10.0mm. The optimum drying temperature was found to be 80°C with a maximum lipid yield of 425.0±5.9mgg(-1) at 15h drying time for 5.0mm thick samples with 0.033kWh power consumption. Partial drying at 80°C up to 10% residual moisture content was efficient showing 93% lipid recovery with 8h drying and a power consumption of 0.017kWh. Scenedesmus biomass was also found to be rich in saturated and mono-unsaturated fatty acids. Thus, the drying protocol demonstrates its suitability to improve the downstream processing of biodiesel production by significantly lowering the power consumption and the drying time. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lipid interactions in breadmaking.

PubMed

Carr, N O; Daniels, N W; Frazier, P J

1992-01-01

Both the natural lipids of flour and added fats are known to play an important role during the production of bread. In this review, the chemical and physical interactions of fat have been assessed in an attempt to explain these technological functions. Particular emphasis has been placed on the "binding" or complexing of lipid by flour proteins during the development of dough. While publications in this field have frequently been contradictory, evidence now indicates that observed lipid binding may involve lipid mesophase transformation and the nonspecific occlusion of lipid phases within the gluten network. The significance of these suggested events has been compared with current theories of lipid function in the breadmaking process.

Lipid-converter, a framework for lipid manipulations in molecular dynamics simulations

PubMed Central

Larsson, Per; Kasson, Peter M.

2014-01-01

Construction of lipid membrane and membrane protein systems for molecular dynamics simulations can be a challenging process. In addition, there are few available tools to extend existing studies by repeating simulations using other force fields and lipid compositions. To facilitate this, we introduce lipidconverter, a modular Python framework for exchanging force fields and lipid composition in coordinate files obtained from simulations. Force fields and lipids are specified by simple text files, making it easy to introduce support for additional force fields and lipids. The converter produces simulation input files that can be used for structural relaxation of the new membranes. PMID:25081234

Phosphatidylcholine Membrane Fusion Is pH-Dependent.

PubMed

Akimov, Sergey A; Polynkin, Michael A; Jiménez-Munguía, Irene; Pavlov, Konstantin V; Batishchev, Oleg V

2018-05-03

Membrane fusion mediates multiple vital processes in cell life. Specialized proteins mediate the fusion process, and a substantial part of their energy is used for topological rearrangement of the membrane lipid matrix. Therefore, the elastic parameters of lipid bilayers are of crucial importance for fusion processes and for determination of the energy barriers that have to be crossed for the process to take place. In the case of fusion of enveloped viruses (e.g., influenza) with endosomal membrane, the interacting membranes are in an acidic environment, which can affect the membrane's mechanical properties. This factor is often neglected in the analysis of virus-induced membrane fusion. In the present work, we demonstrate that even for membranes composed of zwitterionic lipids, changes of the environmental pH in the physiologically relevant range of 4.0 to 7.5 can affect the rate of the membrane fusion notably. Using a continual model, we demonstrated that the key factor defining the height of the energy barrier is the spontaneous curvature of the lipid monolayer. Changes of this parameter are likely to be caused by rearrangements of the polar part of lipid molecules in response to changes of the pH of the aqueous solution bathing the membrane.

Optimization of β-carotene loaded solid lipid nanoparticles preparation using a high shear homogenization technique

NASA Astrophysics Data System (ADS)

Triplett, Michael D.; Rathman, James F.

2009-04-01

Using statistical experimental design methodologies, the solid lipid nanoparticle design space was found to be more robust than previously shown in literature. Formulation and high shear homogenization process effects on solid lipid nanoparticle size distribution, stability, drug loading, and drug release have been investigated. Experimentation indicated stearic acid as the optimal lipid, sodium taurocholate as the optimal cosurfactant, an optimum lecithin to sodium taurocholate ratio of 3:1, and an inverse relationship between mixing time and speed and nanoparticle size and polydispersity. Having defined the base solid lipid nanoparticle system, β-carotene was incorporated into stearic acid nanoparticles to investigate the effects of introducing a drug into the base solid lipid nanoparticle system. The presence of β-carotene produced a significant effect on the optimal formulation and process conditions, but the design space was found to be robust enough to accommodate the drug. β-Carotene entrapment efficiency averaged 40%. β-Carotene was retained in the nanoparticles for 1 month. As demonstrated herein, solid lipid nanoparticle technology can be sufficiently robust from a design standpoint to become commercially viable.

Detergent assisted lipid extraction from wet yeast biomass for biodiesel: A response surface methodology approach.

PubMed

Yellapu, Sravan Kumar; Bezawada, Jyothi; Kaur, Rajwinder; Kuttiraja, Mathiazhakan; Tyagi, Rajeshwar D

2016-10-01

The lipid extraction from the microbial biomass is a tedious and high cost dependent process. In the present study, detergent assisted lipids extraction from the culture of the yeast Yarrowia lipolytica SKY-7 was carried out. Response surface methodology (RSM) was used to investigate the effect of three principle parameters (N-LS concentration, time and temperature) on microbial lipid extraction efficiency % (w/w). The results obtained by statistical analysis showed that the quadratic model fits in all cases. Maximum lipid recovery of 95.3±0.3% w/w was obtained at the optimum level of process variables [N-LS concentration 24.42mg (equal to 48mgN-LS/g dry biomass), treatment time 8.8min and reaction temperature 30.2°C]. Whereas the conventional chloroform and methanol extraction to achieve total lipid recovery required 12h at 60°C. The study confirmed that oleaginous yeast biomass treatment with N-lauroyl sarcosine would be a promising approach for industrial scale microbial lipid recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of three different wastewater sludge and their respective drying processes: Solar, thermal and reed beds - Impact on organic matter characteristics.

PubMed

Collard, Marie; Teychené, Benoit; Lemée, Laurent

2017-12-01

Drying process aims at minimising the volume of wastewater sludge (WWS) before disposal, however it can impact sludge characteristics. Due to its high content in organic matter (OM) and lipids, sludge are mainly valorised by land farming but can also be considered as a feedstock for biodiesel production. As sludge composition is a major parameter for the choice of disposal techniques, the objective of this study was to determine the influence of the drying process. To reach this goal, three sludges obtained from solar, reed beds and thermal drying processes were investigated at the global and molecular scales. Before the drying step the sludges presented similar physico-chemical (OM content, elemental analysis, pH, infrared spectra) characteristics and lipid contents. A strong influence of the drying process on lipids and humic-like substances contents was observed through OM fractionation. Thermochemolysis-GCMS of raw sludge and lipids revealed similar molecular content mainly constituted with steroids and fatty acids. Molecular changes were noticeable for thermal drying through differences in branched to linear fatty acids ratio. Finally the thermal drying induced a weakening of OM whereas the solar drying led to a complexification. These findings show that smooth drying processes such as solar or reed-beds are preferable for amendment production whereas thermal process leads to pellets with a high lipid content which could be considered for fuel production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Domain Formation Induced by the Adsorption of Charged Proteins on Mixed Lipid Membranes

PubMed Central

Mbamala, Emmanuel C.; Ben-Shaul, Avinoam; May, Sylvio

2005-01-01

Peripheral proteins can trigger the formation of domains in mixed fluid-like lipid membranes. We analyze the mechanism underlying this process for proteins that bind electrostatically onto a flat two-component membrane, composed of charged and neutral lipid species. Of particular interest are membranes in which the hydrocarbon lipid tails tend to segregate owing to nonideal chain mixing, but the (protein-free) lipid membrane is nevertheless stable due to the electrostatic repulsion between the charged lipid headgroups. The adsorption of charged, say basic, proteins onto a membrane containing anionic lipids induces local lipid demixing, whereby charged lipids migrate toward (or away from) the adsorption site, so as to minimize the electrostatic binding free energy. Apart from reducing lipid headgroup repulsion, this process creates a gradient in lipid composition around the adsorption zone, and hence a line energy whose magnitude depends on the protein's size and charge and the extent of lipid chain nonideality. Above a certain critical lipid nonideality, the line energy is large enough to induce domain formation, i.e., protein aggregation and, concomitantly, macroscopic lipid phase separation. We quantitatively analyze the thermodynamic stability of the dressed membrane based on nonlinear Poisson-Boltzmann theory, accounting for both the microscopic characteristics of the proteins and lipid composition modulations at and around the adsorption zone. Spinodal surfaces and critical points of the dressed membranes are calculated for several different model proteins of spherical and disk-like shapes. Among the models studied we find the most substantial protein-induced membrane destabilization for disk-like proteins whose charges are concentrated in the membrane-facing surface. If additional charges reside on the side faces of the proteins, direct protein-protein repulsion diminishes considerably the propensity for domain formation. Generally, a highly charged flat face of a macroion appears most efficient in inducing large compositional gradients, hence a large and unfavorable line energy and consequently lateral macroion aggregation and, concomitantly, macroscopic lipid phase separation. PMID:15626713

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

Impact of intermittent fasting on the lipid profile: Assessment associated with diet and weight loss.

PubMed

Santos, Heitor O; Macedo, Rodrigo C O

2018-04-01

Intermittent fasting, whose proposed benefits include the improvement of lipid profile and the body weight loss, has gained considerable scientific and popular repercussion. This review aimed to consolidate studies that analyzed the lipid profile in humans before and after intermittent fasting period through a detailed review; and to propose the physiological mechanism, considering the diet and the body weight loss. Normocaloric and hypocaloric intermittent fasting may be a dietary method to aid in the improvement of the lipid profile in healthy, obese and dyslipidemic men and women by reducing total cholesterol, LDL, triglycerides and increasing HDL levels. However, the majority of studies that analyze the intermittent fasting impacts on the lipid profile and body weight loss are observational based on Ramadan fasting, which lacks large sample and detailed information about diet. Randomized clinical trials with a larger sample size are needed to evaluate the IF effects mainly in patients with dyslipidemia. Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism in apo E(-/-) mice.

PubMed

Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Park, Yong-Bok; Lee, Ki-Teak; Park, Taesun; Choi, Myung-Sook

2009-07-01

The objective of this study was to explicate the effects of feeding low trans structured fat from flaxseed oil (LF) on plasma and hepatic lipid metabolism involved in apo E(-/-) mice. The animals were fed a commercial shortening (CS), commercial low trans fat (CL) and LF diet based on AIN-76 diet (10% fat) for 12 weeks. LF supplementation exerted a significant suppression in hepatic lipid accumulation with the concomitant decrease in liver weight. The LF significantly lowered plasma total cholesterol and free fatty acid whereas it significantly increased HDL-C concentration and the HDL-C/total-C ratio compared to the CS group. Reduction of hepatic lipid levels in the LF group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis, and cholesterol regulating enzyme activity compared to the CS and CL groups. Accordingly, low trans structured fat from flaxseed oil is highly effective for improving hyperlipidemia and hepatic lipid accumulation in apo E(-/-) mice.

Structured triglyceride emulsions in parenteral nutrition.

PubMed

Chambrier, C; Lauverjat, M; Bouletreau, P

2006-08-01

Over the past 3 decades, various concepts for IV fat emulsions (IVFE) have been developed. A randomized, structured-lipid emulsion based on an old technology has recently become available. This structured-lipid emulsion is produced by mixing medium-chain triglycerides and long-chain triglycerides, then allowing hydrolysis to form free fatty acids, followed by random transesterification of the fatty acids into mixed triglyceride molecules. Studies in animals have shown an improvement in nitrogen balance with the use of these lipid emulsions. Only 8 human clinical studies with these products have been performed. The results of these human clinical studies have been less promising than the animal studies; however, an improvement in nitrogen balance and lipid metabolism exceeds results associated with infusion of long-chain triglycerides (LCT) or a physical mixture of long-chain triglycerides and medium-chain triglycerides (LCT-MCT). Structured-lipid emulsion seems to induce less elevation in serum liver function values compared with standard IVFEs. In addition, structured-lipid emulsions have no detrimental effect on the reticuloendothelial system. Further studies are necessary in order to recommend the use of structured-lipid emulsions. The clinical community hopes that chemically defined structured triglycerides will make it possible to determine the distribution of specific fatty acids on a specific position on the glycerol core and therefore obtain specific activity for a specific clinical situation.

Laparoscopic Roux-En-Y Gastric Bypass Improves Lipid Profile and Decreases Cardiovascular Risk: a 5-Year Longitudinal Cohort Study of 1048 Patients.

PubMed

Gero, Daniel; Favre, Lucie; Allemann, Pierre; Fournier, Pierre; Demartines, Nicolas; Suter, Michel

2018-03-01

Dyslipidemia is a known risk factor for cardiovascular (CV) events. The aim of the study was to assess lipid profiles and their impact on CV risk changes in a large patient cohort 5 years after Roux-en-Y gastric bypass (RYGB). All patients who underwent primary RYGB for severe obesity in our two hospitals between January 1999 and December 2009 were included. The Framingham risk score was used. One thousand and forty-eight patients were included, 791 women and 257 men. Five-year complete lipid profile was available for 77% of patients. At 5 years, mean body mass index (BMI) decreased from 45.7 ± 6 to 31 ± 5.8 kg/m 2 (p < 0.001), excess BMI loss (EBMIL) was 72.35 ± 22%, and total body weight loss (TWL) 31.5 ± 9%. Lipid values improved significantly. Total- and LDL-cholesterol levels dropped at 1 year from 5.4 to 4.48 mmol/L and 3.2 to 2.41 mmol/L, respectively, and slightly increased thereafter. Triglyceride levels dropped from 2 to 1.17 mmol/L at 1 year and remained unchanged. HDL levels rose continuously from 1.27 to 1.77 mmol/L at 5 years. Lipid profile improved more in patients with greater weight loss (%EBMIL ≥ 50 or %TWL ≥ 25%). Assuming that all patients were non-smokers and other baseline risk factors (hypertension, diabetes) remained unchanged at 5 years, the amelioration of the lipid profile itself yielded to a 27% reduction of CV risk (p < 0.001). RYGB results in sustained excess weight loss and in amelioration of the lipid profile from the first to fifth postoperative year. This improvement translates into significantly lower CV risk from the first year after surgery.

Health effect of vegetable-based diet: lettuce consumption improves cholesterol metabolism and antioxidant status in the rat.

PubMed

Nicolle, Catherine; Cardinault, Nicolas; Gueux, Elyett; Jaffrelo, Lydia; Rock, Edmond; Mazur, Andrzej; Amouroux, Pierre; Rémésy, Christian

2004-08-01

It is often assumed that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases. Besides epidemiological observations, scientific evidences for their mechanism of action are scarce. In the present study, we investigated the mean term and post-prandial effects of lettuce ingestion on lipid metabolism and antioxidant protection in the rat. Feeding rats a 20% lettuce diet for 3 weeks resulted in a decrease cholesterol LDL/HDL ratio and a marked decrease of liver cholesterol levels (-41%). Concurrently, fecal total steroid excretion increased (+44%) and apparent absorption of dietary cholesterol was significantly depressed (-37%) by the lettuce diet. Lettuce diet also displayed an improvement of vitamin E/TG ratio in plasma and limited lipid peroxidation in heart as evidenced by TBARS. In post-prandial experiment, lettuce intake significantly increased both ascorbic acid and alpha-tocopherol plasma levels which contribute to improve plasma antioxidant capacity within 2 h of consumption. Other lipid-soluble antioxidants (lutein and vitamin E) may also improve the plasma antioxidant capacity. Lettuce consumption increases the total cholesterol end-products excretion and improves antioxidant status due to the richness in antioxidants (vitamins C, E and carotenoids). In our model, lettuce clearly shows a beneficial effect on lipid metabolism and on tissue oxidation. Therefore regular consumption of lettuce should contribute to improve protection against cardiovascular diseases. Copyright 2003 Elsevier Ltd.

Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs.

PubMed

Delacrétaz, Aurélie; Lagares Santos, Patricia; Saigi Morgui, Nuria; Vandenberghe, Frederik; Glatard, Anaïs; Gholam-Rezaee, Mehdi; von Gunten, Armin; Conus, Philippe; Eap, Chin B

2017-12-01

Dyslipidemia represents a major health issue in psychiatry. We determined whether weighted polygenic risk scores (wPRSs) combining multiple single-nucleotide polymorphisms (SNPs) associated with lipid levels in the general population are associated with lipid levels [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides] and/or dyslipidemia in patients receiving weight gain-inducing psychotropic drugs. We also determined whether genetics improve the predictive power of dyslipidemia. The influence of wPRS on lipid levels was firstly assessed in a discovery psychiatric sample (n=332) and was then tested for replication in an independent psychiatric sample (n=140). The contribution of genetic markers to predict dyslipidemia was evaluated in the combined psychiatric sample. wPRSs were significantly associated with the four lipid traits in the discovery (P≤0.02) and in the replication sample (P≤0.03). Patients whose wPRS was higher than the median wPRS had significantly higher LDL, TC, and triglyceride levels (0.20, 0.32 and 0.26 mmol/l, respectively; P≤0.004) and significantly lower HDL levels (0.13 mmol/l; P<0.0001) compared with others. Adding wPRS to clinical data significantly improved dyslipidemia prediction of HDL (P=0.03) and a trend for improvement was observed for the prediction of TC dyslipidemia (P=0.08). Population-based wPRSs have thus significant effects on lipid levels in the psychiatric population. As genetics improved the predictive power of dyslipidemia development, only 24 patients need to be genotyped to prevent the development of one case of HDL hypocholesterolemia. If confirmed by further prospective investigations, the present results could be used for individualizing psychotropic treatment.

Replication of Simulated Prebiotic Amphiphilic Vesicles in a Finite Environment Exhibits Complex Behavior That Includes High Progeny Variability and Competition

PubMed Central

Armstrong, Don L.; Lancet, Doron

2018-01-01

Abstract We studied the simulated replication and growth of prebiotic vesicles composed of 140 phospholipids and cholesterol using our R-GARD (Real Graded Autocatalysis Replication Domain) formalism that utilizes currently extant lipids that have known rate constants of lipid-vesicle interactions from published experimental data. R-GARD normally modifies kinetic parameters of lipid-vesicle interactions based on vesicle composition and properties. Our original R-GARD model tracked the growth and division of one vesicle at a time in an environment with unlimited lipids at a constant concentration. We explore here a modified model where vesicles compete for a finite supply of lipids. We observed that vesicles exhibit complex behavior including initial fast unrestricted growth, followed by intervesicle competition for diminishing resources, then a second growth burst driven by better-adapted vesicles, and ending with a final steady state. Furthermore, in simulations without kinetic parameter modifications (“invariant kinetics”), the initial replication was an order of magnitude slower, and vesicles' composition variability at the final steady state was much lower. The complex kinetic behavior was not observed either in the previously published R-GARD simulations or in additional simulations presented here with only one lipid component. This demonstrates that both a finite environment (inducing selection) and multiple components (providing variation for selection to act upon) are crucial for portraying evolution-like behavior. Such properties can improve survival in a changing environment by increasing the ability of early protocellular entities to respond to rapid environmental fluctuations likely present during abiogenesis both on Earth and possibly on other planets. This in silico simulation predicts that a relatively simple in vitro chemical system containing only lipid molecules might exhibit properties that are relevant to prebiotic processes. Key Words: Phospholipid vesicles—Prebiotic compartments—Prebiotic vesicle competition—Prebiotic vesicle variability. Astrobiology 18, 419–430. PMID:29634319

Bioconcentration factors and lipid solubility

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

Banerjee, S.; Baughman, G.L.

1991-03-01

The log-log relationship between bioconcentration and hydrophobicity breaks down for several medium and high molecular weight solutes that bioconcentrate either to a small extent or not at all. Much of the failure is attributed to the relatively low solubility of these compounds in lipid. Inclusion of a term in octanol solubility (in place of lipid solubility, which is generally unavailable) considerably improves the quality of the relationship (r = 0.95). It is speculated that the octanol solubility term compensates for the relatively low solubility of large compounds in lipid.

Lipids in DDGS

USDA-ARS?s Scientific Manuscript database

Distillers dried grains with soluble (DDGS) are one of the main coproducts of ethanol production from using the dry-grinding process. The lipids from corn or sorghum are not utilized in ethanol production, and are thus concentrated in DDGS. The main lipid components in corn and sorghum DDGS are tr...

Lipid recovery from wet oleaginous microbial biomass for biofuel production: A critical review

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

Dong, Tao; Knoshaug, Eric P.; Pienkos, Philip T.

Biological lipids derived from oleaginous microorganisms are promising precursors for renewable biofuel productions. Direct lipid extraction from wet cell-biomass is favored because it eliminates the need for costly dehydration. However, the development of a practical and scalable process for extracting lipids from wet cell-biomass is far from ready to be commercialized, instead, requiring intensive research and development to understand the lipid accessibility, mechanisms in mass transfer and establish robust lipid extraction approaches that are practical for industrial applications. Furthermore, this paper aims to present a critical review on lipid recovery in the context of biofuel productions with special attention tomore » cell disruption and lipid mass transfer to support extraction from wet biomass.« less

Lipid recovery from wet oleaginous microbial biomass for biofuel production: A critical review

DOE PAGES

Dong, Tao; Knoshaug, Eric P.; Pienkos, Philip T.; ...

2016-06-15

Biological lipids derived from oleaginous microorganisms are promising precursors for renewable biofuel productions. Direct lipid extraction from wet cell-biomass is favored because it eliminates the need for costly dehydration. However, the development of a practical and scalable process for extracting lipids from wet cell-biomass is far from ready to be commercialized, instead, requiring intensive research and development to understand the lipid accessibility, mechanisms in mass transfer and establish robust lipid extraction approaches that are practical for industrial applications. Furthermore, this paper aims to present a critical review on lipid recovery in the context of biofuel productions with special attention tomore » cell disruption and lipid mass transfer to support extraction from wet biomass.« less

Stabilization of polymer lipid complexes prepared with lipids of lactic acid bacteria upon preservation and internalization into eukaryotic cells.

PubMed

Alves, P; Hugo, A A; Szymanowski, F; Tymczyszyn, E E; Pérez, P F; Coelho, J F J; Simões, P N; Gómez-Zavaglia, A

2014-11-01

The physicochemical characterization of polymer liposome complexes (PLCs) prepared with lipids of lactic acid bacteria and poly(N,N-dimethylaminoethyl methacrylate) covalently bound to cholesterol (CHO-PDMAEMA) was carried out in an integrated approach, including their stability upon preservation and incorporation into eukaryotic cells. PLCs were prepared with different polymer:lipid molar ratios (0, 0.05 and 0.10). Zeta potential, particle size distribution and polydispersity index were determined. The optimal polymer:lipid ratio and the stability of both bare liposomes and PLCs were evaluated at 37 °C and at different pHs, as well as after storage at 4 °C, -80 °C and freeze-drying in the presence or absence of trehalose 250 mM. Internalization of PLCs by eukaryotic cells was assessed to give a complete picture of the system. Incorporation of CHO-PDMAEMA onto bacterial lipids (ratio 0.05 and 0.10) led to stabilization at 37 °C and pH 7. A slight decrease of pH led to their strong destabilization. Bacteria PLCs showed to be more stable than lecithin (LEC) PLCs (used for comparison) upon preservation at 4 and -80 °C. The harmful nature of the preservation processes led to a strong decrease in the stability of PLCs, bacterial formulations being more stable than LEC PLCs. The addition of trehalose to the suspension of liposomes stabilized LEC PLC and did not have effect on bacterial PLCs. In vitro studies on Raw 264.7 and Caco-2/TC7 cells demonstrated an efficient incorporation of PLCs into the cells. Preparations with higher stability were the ones that showed a better cell-uptake. The nature of the lipid composition is determinant for the stability of PLCs. Lipids from lactic acid bacteria are composed of glycolipids and phospholipids like cardiolipin and phosphatidylglycerol. The presence of negatively charged lipids strongly improves the interaction with the positively charged CHO-PDMAEMA, thus stabilizing liposomes. In addition, glycolipids and phosphatidylglycerol act as intrinsic protectants of PLCs upon preservation. This particular lipid composition of lactic acid bacteria makes them natural formulations potentially useful as drug delivery systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway

PubMed Central

Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M.

2016-01-01

Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122 regulated hepatic gluconeogenesis and lipid metabolism as promising therapeutic targets for the treatment of T2D. PMID:27011261

Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway.

PubMed

Wei, Shengnan; Zhang, Ming; Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M

2016-01-01

Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122 regulated hepatic gluconeogenesis and lipid metabolism as promising therapeutic targets for the treatment of T2D.

The biocompatibility of carbon hydroxyapatite/β-glucan composite for bone tissue engineering studied with Raman and FTIR spectroscopic imaging.

PubMed

Sroka-Bartnicka, Anna; Kimber, James A; Borkowski, Leszek; Pawlowska, Marta; Polkowska, Izabela; Kalisz, Grzegorz; Belcarz, Anna; Jozwiak, Krzysztof; Ginalska, Grazyna; Kazarian, Sergei G

2015-10-01

The spectroscopic approaches of FTIR imaging and Raman mapping were applied to the characterisation of a new carbon hydroxyapatite/β-glucan composite developed for bone tissue engineering. The composite is an artificial bone material with an apatite-forming ability for the bone repair process. Rabbit bone samples were tested with an implanted bioactive material for a period of several months. Using spectroscopic and chemometric methods, we were able to determine the presence of amides and phosphates and the distribution of lipid-rich domains in the bone tissue, providing an assessment of the composite's bioactivity. Samples were also imaged in transmission using an infrared microscope combined with a focal plane array detector. CaF2 lenses were also used on the infrared microscope to improve spectral quality by reducing scattering artefacts, improving chemometric analysis. The presence of collagen and lipids at the bone/composite interface confirmed biocompatibility and demonstrate the suitability of FTIR microscopic imaging with lenses in studying these samples. It confirmed that the composite is a very good background for collagen growth and increases collagen maturity with the time of the bone growth process. The results indicate the bioactive and biocompatible properties of this composite and demonstrate how Raman and FTIR spectroscopic imaging have been used as an effective tool for tissue characterisation.

Nixtamalization Process Affects Resistant Starch Formation and Glycemic Index of Tamales.

PubMed

Mariscal-Moreno, Rosa María; de Dios Figueroa Cárdenas, Juan; Santiago-Ramos, David; Rayas-Duarte, Patricia; Veles-Medina, José Juan; Martínez-Flores, Héctor Eduardo

2017-05-01

Tamales were prepared with 3 nixtamalization processes (traditional, ecological, and classic) and evaluated for chemical composition, starch properties, and glycemic index. Resistant starch (RS) in tamales increased 1.6 to 3.7 times compared to raw maize. This increment was due to the starch retrogradation (RS3) and amylose-lipid complexes (RS5) formation. Tamales elaborated with classic and ecological nixtamalization processes exhibited the highest total, soluble and insoluble dietary fiber content, and the highest RS content and lower in vivo glycemic index compared to tamales elaborated with traditional nixtamalization process. Thermal properties of tamales showed 3 endotherms: amylopectin retrogradation (42.7 to 66.6 °C), melting of amylose lipid complex type I (78.8 to 105.4), and melting of amylose-lipid complex type II (110.7 to 129.7). Raw maize exhibited X-ray diffraction pattern type A, after nixtamalization and cooking of tamales it changed to V-type polymorph structure, due to amylose-lipid complexes formation. Tamales from ecological nixtamalization processes could represent potential health benefits associated with the reduction on blood glucose response after consumption. © 2017 Institute of Food Technologists®.

Lipid melting and cuticular permeability: new insights into an old problem.

PubMed

Gibbs, Allen G.

2002-04-01

The idea that the physical properties of cuticular lipids affect cuticular permeability goes back over 65 years. This proposal has achieved textbook status, despite controversy and the general lack of direct supporting evidence. Recent work supports the standard model, in which lipid melting results in increased cuticular permeability. Surprisingly, although all species studied to date can synthesize lipids that remain in a solid state at environmental temperatures, partial melting often occurs due to the deposition of lipids with low melting points. This will tend to increase water loss; the benefits may include better dispersal of lipids or other compounds across the cuticle or improved communication via cuticular pheromones. In addition, insects with high melting-point lipids are not necessarily less permeable at low temperatures. One likely reason is variation in lipid properties within the cuticle. Surface lipids differ from one region to another, and biophysical studies of model mixtures suggest the occurrence of phase separation between melted and solid lipid fractions. Lipid phase separation may have important implications for insect water balance and chemical communication.

Comparison across Three Hybrid Lipid-Based Drug Delivery Systems for Improving the Oral Absorption of the Poorly Water-Soluble Weak Base Cinnarizine.

PubMed

Joyce, Paul; Yasmin, Rokhsana; Bhatt, Achal; Boyd, Ben J; Pham, Anna; Prestidge, Clive A

2017-11-06

Three state-of-the-art drug delivery vehicles engineered by nanostructuring lipid colloids within solid particle matrices were fabricated for the oral delivery of the poorly water-soluble, weak base, cinnarizine (CIN). The lipid and solid phase of each formulation was varied to systematically analyze the impact of key material characteristics, such as nanostructure and surface chemistry, on the in vitro and in vivo fate of CIN. The three systems formulated were: silica-stabilized lipid cubosomes (SSLC), silica-solid lipid hybrid (SSLH), and polymer-lipid hybrid (PLH) particles. Significant biopharmaceutical advantages were presented for CIN when solubilized in the polymer (poly(lactic-co-glycolic) acid; PLGA) and lipid phase of PLH particles compared to the lipid phases of SSLC and SSLH particles. In vitro dissolution in simulated intestinal conditions highlighted reduced precipitation of CIN when administered within PLH particles, given by a 4-5-fold improvement in the extent of CIN dissolution compared to the other delivery vehicles. Furthermore, CIN solubilization was enhanced 1.5-fold and 6-fold under simulated fasted state lipid digestion conditions when formulated with PLH particles compared to SSLH and SSLC particles, respectively. In vivo pharmacokinetics correlated well with in vitro solubilization data, whereby oral CIN bioavailability in rats, when encapsulated in the corresponding formulations, increased from SSLC < SSLH < PLH. The pharmacokinetic data obtained throughout this study indicated a synergistic effect between PLGA nanoparticles and lipid droplets in preventing CIN precipitation and thus, enhancing oral absorption. This synergy can be harnessed to efficiently deliver challenging poorly water-soluble, weak bases through oral administration.

Fermented green tea extract alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice.

PubMed

Seo, Dae-Bang; Jeong, Hyun Woo; Cho, Donghyun; Lee, Bum Jin; Lee, Ji Hae; Choi, Jae Young; Bae, Il-Hong; Lee, Sung-Joon

2015-05-01

Obesity is caused by an imbalance between caloric intake and energy expenditure and accumulation of excess lipids in adipose tissues. Recent studies have demonstrated that green tea and its processed products (e.g., oolong and black tea) are introduced to exert beneficial effects on lipid metabolism. Here, we propose that fermented green tea (FGT) extract, as a novel processed green tea, exhibits antiobesity effects. FGT reduced body weight gain and fat mass without modifying food intake. mRNA expression levels of lipogenic and inflammatory genes were downregulated in white adipose tissue of FGT-administered mice. FGT treatment alleviated glucose intolerance and fatty liver symptoms, common complications of obesity. Notably, FGT restored the changes in gut microbiota composition (e.g., the Firmicutes/Bacteroidetes and Bacteroides/Prevotella ratios), which is reported to be closely related with the development of obesity and insulin resistance, induced by high-fat diets. Collectively, FGT improves obesity and its associated symptoms and modulates composition of gut microbiota; thus, it could be used as a novel dietary component to control obesity and related symptoms.

Enhanced lipid productivity and photosynthesis efficiency in a Desmodesmus sp. mutant induced by heavy carbon ions.

PubMed

Hu, Guangrong; Fan, Yong; Zhang, Lei; Yuan, Cheng; Wang, Jufang; Li, Wenjian; Hu, Qiang; Li, Fuli

2013-01-01

The unicellular green microalga Desmodesmus sp. S1 can produce more than 50% total lipid of cell dry weight under high light and nitrogen-limitation conditions. After irradiation by heavy (12)C(6+) ion beam of 10, 30, 60, 90 or 120 Gy, followed by screening of resulting mutants on 24-well microplates, more than 500 mutants were obtained. One of those, named D90G-19, exhibited lipid productivity of 0.298 g L(-1)⋅d(-1), 20.6% higher than wild type, likely owing to an improved maximum quantum efficiency (Fv/Fm) of photosynthesis under stress. This work demonstrated that heavy-ion irradiation combined with high-throughput screening is an effective means for trait improvement. The resulting mutant D90G-19 may be used for enhanced lipid production.

Co-liposomes having anisamide tagged lipid and cholesteryl tryptophan trigger enhanced gene transfection in sigma receptor positive cells.

PubMed

Misra, Santosh K; Moitra, Parikshit; Kondaiah, Paturu; Bhattacharya, Santanu

2016-06-01

Selective gene transfection could be strategy of interest for reducing off-target gene expression and toxicity. In this respect, sigma receptors are found to be over-expressed in many human tumors and liposomal formulations with ability to target these sigma receptors may improve the transfection efficiency to a significant level. To this direction, six novel lipids have been synthesized with different hydrophobic segments such as a long hydrophobic chain or a cholesteryl group and L-tryptophan as the head group. Three of them, Lipid 1, 3 and 5 possessed cationic Me3N(+) moiety at the distal end. In contrast each of the other three Lipid 2, 4 and 6 possessed sigma receptor targeting anisamide group with no cationic charge. Mixing of cationic and anisamide counterparts of the same lipid in a molar ratio of 1:1 produced co-liposomes L-M-1 (Lipid 1+2), L-M-2 (Lipid 3+4) and L-M-3 (Lipid 5+6). These co-liposomes, while keeping the sigma targeting anisamide tag intact, showed good DNA binding and release which were optimized from EB intercalation and gel electrophoresis assays. Inclusion of a zwitterionic, fusogenic natural lipid, DOPE, into the co-liposomes further improved the binding efficiencies of the lipid mixtures with DNA. These co-liposomes having cationic and anisamide lipids and DOPE were highly selective toward sigma positive HEK293 and HEK293T cells compared to the sigma negative HeLa cells. As evidenced from both FACS and luciferase assay, a lipid mixture comprising Lipid 3, 4 and DOPE in a molar ratio of 1:1:1 (L-M-2D1) was the best for transfection of reporter pEGFP-C3 and functional pCEP4-p53 gene plasmids. Anisamide mediated sigma receptor selectivity was further probed by pre-incubating the transfecting cells with lipids possessing anisamide and by quantification of the un-transfected plasmid DNA. Also each formulation was highly non-toxic in the cell lines examined. Copyright © 2016. Published by Elsevier B.V.

Sugar versus fat: elimination of glycogen storage improves lipid accumulation in Yarrowia lipolytica.

PubMed

Bhutada, Govindprasad; Kavšcek, Martin; Ledesma-Amaro, Rodrigo; Thomas, Stéphane; Rechberger, Gerald N; Nicaud, Jean-Marc; Natter, Klaus

2017-05-01

Triacylglycerol (TAG) and glycogen are the two major metabolites for carbon storage in most eukaryotic organisms. We investigated the glycogen metabolism of the oleaginous Yarrowia lipolytica and found that this yeast accumulates up to 16% glycogen in its biomass. Assuming that elimination of glycogen synthesis would result in an improvement of lipid accumulation, we characterized and deleted the single gene coding for glycogen synthase, YlGSY1. The mutant was grown under lipogenic conditions with glucose and glycerol as substrates and we obtained up to 60% improvement in TAG accumulation compared to the wild-type strain. Additionally, YlGSY1 was deleted in a background that was already engineered for high lipid accumulation. In this obese background, TAG accumulation was also further increased. The highest lipid content of 52% was found after 3 days of cultivation in nitrogen-limited glycerol medium. Furthermore, we constructed mutants of Y. lipolytica and Saccharomyces cerevisiae that are deleted for both glycogen and TAG synthesis, demonstrating that the ability to store carbon is not essential. Overall, this work showed that glycogen synthesis is a competing pathway for TAG accumulation in oleaginous yeasts and that deletion of the glycogen synthase has beneficial effects on neutral lipid storage. © FEMS 2017.

Can fish oil supplementation and physical training improve oxidative metabolism in aged rat hearts?

PubMed

da Silva Pedroza, Anderson Apolonio; Lopes, Andréia; Mendes da Silva, Rosângela F; Braz, Glauber Ruda; Nascimento, Luciana P; Ferreira, Diorginis Soares; dos Santos, Ângela Amâncio; Batista-de-Oliveira-Hornsby, Manuella; Lagranha, Claudia J

2015-09-15

It is well known that in the aging process a variety of physiological functions such as cardiac physiology and energy metabolism decline. Imbalance in production and elimination of reactive oxygen species (ROS) may induce oxidative stress. Research shows that oxidative stress is an important factor in the aging process. Studies suggest that ɷ-3 polyunsaturated fatty acids (PUFAs) and moderate physical exercise modulate the ROS system. Therefore, the present study aimed to investigate whether ɷ-3 present in fish oil supplementation coupled with moderate physical training could improve antioxidant and metabolic enzymes in the hearts of adult and aged rats and, if these effects could be associated to glycemia, plasma lipid profile or murinometric parameters. Adult (weighing 315.1±9.3g) and aged rats (weighing 444.5±11.8g) exercised and receive fish oil supplementation for 4weeks. Then they were used to evaluate murinometric parameters, fasting glucose and lipid profile. After this, their hearts were collected to measure the levels of malondialdehyde (MDA), antioxidant enzyme activity (superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx) and oxidative metabolism marker (citrate synthase-CS activity). Fish oil supplementation increases HDL concentration and activity of CAT and CS. Moreover, physical training coupled with fish oil supplementation induces additional effects on SOD, GPx and CS activity mainly in aged rats. Our data suggest that combined treatment in aged rat hearts improves the antioxidant capacities and metabolic enzyme that can prevent the deleterious effects of aging. Copyright © 2015. Published by Elsevier Inc.

New insights on glucosylated lipids: metabolism and functions.

PubMed

Ishibashi, Yohei; Kohyama-Koganeya, Ayako; Hirabayashi, Yoshio

2013-09-01

Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Exploring the specific features of interfacial enzymology based on lipase studies.

PubMed

Aloulou, Ahmed; Rodriguez, Jorge A; Fernandez, Sylvie; van Oosterhout, Dirk; Puccinelli, Delphine; Carrière, Frédéric

2006-09-01

Many enzymes are active at interfaces in the living world (such as in the signaling processes at the surface of cell membranes, digestion of dietary lipids, starch and cellulose degradation, etc.), but fundamental enzymology remains largely focused on the interactions between enzymes and soluble substrates. The biochemical and kinetic characterization of lipolytic enzymes has opened up new paths of research in the field of interfacial enzymology. Lipases are water-soluble enzymes hydrolyzing insoluble triglyceride substrates, and studies on these enzymes have led to the development of specific interfacial kinetic models. Structure-function studies on lipases have thrown light on the interfacial recognition sites present in the molecular structure of these enzymes, the conformational changes occurring in the presence of lipids and amphiphiles, and the stability of the enzymes present at interfaces. The pH-dependent activity, substrate specificity and inhibition of these enzymes can all result from both "classical" interactions between a substrate or inhibitor and the active site, as well as from the adsorption of the enzymes at the surface of aggregated substrate particles such as oil drops, lipid bilayers or monomolecular lipid films. The adsorption step can provide an alternative target for improving substrate specificity and developing specific enzyme inhibitors. Several data obtained with gastric lipase, classical pancreatic lipase, pancreatic lipase-related protein 2 and phosphatidylserine-specific phospholipase A1 were chosen here to illustrate these specific features of interfacial enzymology.

Lipid characterization of individual porcine oocytes by dual mode DESI-MS and data fusion.

PubMed

Pirro, Valentina; Oliveri, Paolo; Ferreira, Christina Ramires; González-Serrano, Andrés Felipe; Machaty, Zoltan; Cooks, Robert Graham

2014-10-27

The development of sensitive measurements to analyze individual cells is of relevance to elucidate specialized roles or metabolic functions of each cell under physiological and pathological conditions. Lipids play multiple and critical roles in cellular functions and the application of analytical methods in the lipidomics area is of increasing interest. In this work, in vitro maturation of porcine oocytes was studied. Two independent sources of chemical information (represented by mass spectra in the positive and negative ion modes) from single oocytes (immature oocytes, 24-h and 44-h in vitro matured oocytes) were acquired by using desorption electrospray ionization-mass spectrometry (DESI-MS). Low and mid-level data fusion strategies are presented with the aim of better exploring the large amount of chemical information contained in the two mass spectrometric lipid profiles. Data were explored by principal component analysis (PCA) within the two multi-block approaches to include information on free fatty acids, phospholipids, cholesterol-related molecules, di- and triacylglycerols. After data fusion, clearer differences among immature and in vitro matured porcine oocytes were observed, which provide novel information regarding lipid metabolism throughout oocyte maturation. In particular, changes in TAG composition, as well as increase in fatty acid metabolism and membrane complexity were evidenced during the in vitro maturation process. This information can assist the improvement of in vitro embryo production for porcine species. Copyright © 2014 Elsevier B.V. All rights reserved.

Carotenoid stability during production and storage of tomato juice made from tomatoes with diverse pigment profiles measured by infrared spectroscopy.

PubMed

Rubio-Diaz, Daniel E; Santos, Alejandra; Francis, David M; Rodriguez-Saona, Luis E

2010-08-11

Chemical changes in carotenoids and lipids were studied during production and storage of canned tomato juice using ATR infrared spectroscopy and HPLC. Samples from 10 groups of tomatoes with different carotenoid profiles were analyzed fresh, after hot-break and screening, after canning, and at five different time points during 1 year of storage. An apparent increase of carotenoids was observed after hot-break due to improved extraction efficiency. This increase was accompanied by some degree of lipid oxidation and carotenoid isomerization. Canning produced the most intense changes in the lipid profile with breakdown of triglycerides ( approximately 1743 cm(-1)), formation of fatty acids ( approximately 1712 cm(-1)), and degradation and isomerization of trans-carotenoids ( approximately 960 and approximately 3006 cm(-1)). Isomerization was corroborated by the relative increase of HPLC areas corresponding to carotenoid cis isomers. Canning reduced trans-lycopene, trans-delta-carotene, trans-beta-carotene, and trans-lutein by 30, 34, 43, and 67%, respectively. HPLC data indicate that canning causes a drastic reduction of tetra-cis-lycopene and promotes its isomerization to other geometric forms, including all-trans-lycopene. Infrared spectra of tomato juice lipid fractions correlated well with the number of days in storage (SECV < 11 days, r values > 0.99), demonstrating continuous degradation of lipids. Results demonstrated that individual carotenoids and their isomeric forms behave differently during production and storage of canned tomato juice. Information collected by infrared spectroscopy complemented well that of HPLC, providing marker bands to further the understanding of chemical changes taking place during processing and storage of tomato juice.

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

Keith, Dove; Finlay, Liam; Butler, Judy

Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve thesemore » results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.« less

Specially-Made Lipid-Based Assemblies for Improving Transmembrane Gene Delivery: Comparison of Basic Amino Acid Residue Rich Periphery.

PubMed

Jiang, Qian; Yue, Dong; Nie, Yu; Xu, Xianghui; He, Yiyan; Zhang, Shiyong; Wagner, Ernst; Gu, Zhongwei

2016-06-06

Cationic lipid based assemblies provide a promising platform for effective gene condensation into nanosized particles, and the peripheral properties of the assemblies are vital for complexation and interaction with physical barriers. Here, we report three cationic twin head lipids, and each of them contains a dioleoyl-glutamate hydrophobic tail and a twin polar head of lysine, arginine, or histidine. Such lipids were proven to self-assemble in aqueous solution with well-defined nanostructures and residual amino-, guanidine-, or imidazole-rich periphery, showing strong buffering capacity and good liquidity. The assemblies with arginine (RL) or lysine (KL) periphery exhibited positive charges (∼+35 mV) and complete condensation of pDNA into nanosized complexes (∼120 nm). In contrast, assemblies composed of histidine-rich lipids (HL) showed relatively low cationic electric potential (∼+10 mV) and poor DNA binding ability. As expected, the designed RL assemblies with guanidine-rich periphery enhanced the in vitro gene transfection up to 190-fold as compared with the golden standard PEI25k and Lipofectamine 2000, especially in the presence of serum. Meanwhile, interaction with cell and endo/lysosome membrane also revealed the superiority of RL complexes, that the guanidine-rich surface efficiently promoted transmembrane process in cellular internalization and endosomal disruption. More importantly, RL complexes also succeeded beyond others in vivo with significantly (∼7-fold) enhanced expression in HepG2 tumor xenografts in mice, as well as stronger green fluorescence protein imaging in isolated tumors and tumor frozen sections.

Kdo2-lipid A: structural diversity and impact on immunopharmacology

PubMed Central

Wang, Xiaoyuan; Quinn, Peter J; Yan, Aixin

2015-01-01

3-deoxy-d-manno-octulosonic acid-lipid A (Kdo2-lipid A) is the essential component of lipopolysaccharide in most Gram-negative bacteria and the minimal structural component to sustain bacterial viability. It serves as the active component of lipopolysaccharide to stimulate potent host immune responses through the complex of Toll-like-receptor 4 (TLR4) and myeloid differentiation protein 2. The entire biosynthetic pathway of Escherichia coli Kdo2-lipid A has been elucidated and the nine enzymes of the pathway are shared by most Gram-negative bacteria, indicating conserved Kdo2-lipid A structure across different species. Yet many bacteria can modify the structure of their Kdo2-lipid A which serves as a strategy to modulate bacterial virulence and adapt to different growth environments as well as to avoid recognition by the mammalian innate immune systems. Key enzymes and receptors involved in Kdo2-lipid A biosynthesis, structural modification and its interaction with the TLR4 pathway represent a clear opportunity for immunopharmacological exploitation. These include the development of novel antibiotics targeting key biosynthetic enzymes and utilization of structurally modified Kdo2-lipid A or correspondingly engineered live bacteria as vaccines and adjuvants. Kdo2-lipid A/TLR4 antagonists can also be applied in anti-inflammatory interventions. This review summarizes recent knowledge on both the fundamental processes of Kdo2-lipid A biosynthesis, structural modification and immune stimulation, and applied research on pharmacological exploitations of these processes for therapeutic development. PMID:24838025

Combined LC/MS-platform for analysis of all major stratum corneum lipids, and the profiling of skin substitutes.

PubMed

van Smeden, Jeroen; Boiten, Walter A; Hankemeier, Thomas; Rissmann, Robert; Bouwstra, Joke A; Vreeken, Rob J

2014-01-01

Ceramides (CERs), cholesterol, and free fatty acids (FFAs) are the main lipid classes in human stratum corneum (SC, outermost skin layer), but no studies report on the detailed analysis of these classes in a single platform. The primary aims of this study were to 1) develop an LC/MS method for (semi-)quantitative analysis of all main lipid classes present in human SC; and 2) use this method to study in detail the lipid profiles of human skin substitutes and compare them to human SC lipids. By applying two injections of 10μl, the developed method detects all major SC lipids using RPLC and negative ion mode APCI-MS for detection of FFAs, and NPLC using positive ion mode APCI-MS to analyze CERs and cholesterol. Validation showed this lipid platform to be robust, reproducible, sensitive, and fast. The method was successfully applied on ex vivo human SC, human SC obtained from tape strips and human skin substitutes (porcine SC and human skin equivalents). In conjunction with FFA profiles, clear differences in CER profiles were observed between these different SC sources. Human skin equivalents more closely mimic the lipid composition of human stratum corneum than porcine skin does, although noticeable differences are still present. These differences gave biologically relevant information on some of the enzymes that are probably involved in SC lipid processing. For future research, this provides an excellent method for (semi-)quantitative, 'high-throughput' profiling of SC lipids and can be used to advance the understanding of skin lipids and the biological processes involved. © 2013.

Storage lipids of yeasts: a survey of nonpolar lipid metabolism in Saccharomyces cerevisiae, Pichia pastoris, and Yarrowia lipolytica.

PubMed

Koch, Barbara; Schmidt, Claudia; Daum, Günther

2014-09-01

Biosynthesis and storage of nonpolar lipids, such as triacylglycerols (TG) and steryl esters (SE), have gained much interest during the last decades because defects in these processes are related to severe human diseases. The baker's yeast Saccharomyces cerevisiae has become a valuable tool to study eukaryotic lipid metabolism because this single-cell microorganism harbors many enzymes and pathways with counterparts in mammalian cells. In this article, we will review aspects of TG and SE metabolism and turnover in the yeast that have been known for a long time and combine them with new perceptions of nonpolar lipid research. We will provide a detailed insight into the mechanisms of nonpolar lipid synthesis, storage, mobilization, and degradation in the yeast S. cerevisiae. The central role of lipid droplets (LD) in these processes will be addressed with emphasis on the prevailing view that this compartment is more than only a depot for TG and SE. Dynamic and interactive aspects of LD with other organelles will be discussed. Results obtained with S. cerevisiae will be complemented by recent investigations of nonpolar lipid research with Yarrowia lipolytica and Pichia pastoris. Altogether, this review article provides a comprehensive view of nonpolar lipid research in yeast. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Using fluorescent lipids in live zebrafish larvae: From imaging whole animal physiology to subcellular lipid trafficking.

PubMed

Anderson, J L; Carten, J D; Farber, S A

2016-01-01

Lipids serve essential functions in cells as signaling molecules, membrane components, and sources of energy. Defects in lipid metabolism are implicated in a number of pandemic human diseases, including diabetes, obesity, and hypercholesterolemia. Many aspects of how fatty acids and cholesterol are absorbed and processed by intestinal cells remain unclear and present a hurdle to developing approaches for disease prevention and treatment. Numerous studies have shown that the zebrafish is an excellent model for vertebrate lipid metabolism. In this chapter, we review commercially available fluorescent lipids that can be deployed in live zebrafish to better understand lipid signaling and metabolism. In this chapter, we present criteria one should consider when selecting specific fluorescent lipids for the study of digestive physiology or lipid metabolism in larval zebrafish. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative assessment of various lipid extraction protocols and optimization of transesterification process for microalgal biodiesel production.

PubMed

Mandal, Shovon; Patnaik, Reeza; Singh, Amit Kumar; Mallick, Nirupama

2013-01-01

Biodiesel, using microalgae as feedstocks, is being explored as the most potent form of alternative diesel fuel for sustainable economic development. A comparative assessment of various protocols for microalgal lipid extraction was carried out using five green algae, six blue-green algae and two diatom species treated with different single and binary solvents both at room temperature and using a soxhlet. Lipid recovery was maximum with chloroform-methanol in the soxhlet extractor. Pretreatments ofbiomass, such as sonication, homogenization, bead-beating, lyophilization, autoclaving, microwave treatment and osmotic shock did not register any significant rise in lipid recovery. As lipid recovery using chloroform-methanol at room temperature demonstrated a marginally lower value than that obtained under the soxhlet extractor, on economical point of view, the former is recommended for microalgal total lipid extraction. Transesterification process enhances the quality of biodiesel. Experiments were designed to determine the effects of catalyst type and quantity, methanol to oil ratio, reaction temperature and time on the transesterification process using response surface methodology. Fatty acid methyl ester yield reached up to 91% with methanol:HCl:oil molar ratio of 82:4:1 at 65 degrees C for 6.4h reaction time. The biodiesel yield relative to the weight of the oil was found to be 69%.

Co-generation of microbial lipid and bio-butanol from corn cob bagasse in an environmentally friendly biorefinery process.

PubMed

Cai, Di; Dong, Zhongshi; Wang, Yong; Chen, Changjing; Li, Ping; Qin, Peiyong; Wang, Zheng; Tan, Tianwei

2016-09-01

Biorefinery process of corn cob bagasse was investigated by integrating microbial lipid and ABE fermentation. The effects of NaOH concentration on the fermentations performance were evaluated. The black liquor after pretreatment was used as substrate for microbial lipid fermentation, while the enzymatic hydrolysates of the bagasse were used for ABE fermentation. The results demonstrated that under the optimized condition, the cellulose and hemicellulose in raw material could be effectively utilized. Approximate 87.7% of the polysaccharides were converted into valuable biobased products (∼175.7g/kg of ABE along with ∼36.6g/kg of lipid). At the same time, almost half of the initial COD (∼48.9%) in the black liquor could be degraded. The environmentally friendly biorefinery process showed promising in maximizing the utilization of biomass for future biofuels production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Screening of industrial wastewaters as feedstock for the microbial production of oils for biodiesel production and high-quality pigments

DOE PAGES

Schneider, Teresa; Graeff-Honninger, Simone; French, William Todd; ...

2012-01-01

The production of biodiesel has notably increased over the past decade. Currently, plant oil is the main feedstock for biodiesel production, but, due to concerns related to the competition with food production, alternative oil feedstocks have to be found. Oleaginous yeasts are known to produce high amounts of lipids, but no integrated process from microbial fermentation to final biodiesel production has reached commercial realization yet due to economic constraints. Therefore, growth and lipid production of red yeast Rhodotorula glutinis was tested on low-cost substrates, namely, wastewaters from potato, fruit juice, and lettuce processing. Additionally, the production of carotenoids as high-valuemore » by-products was examined. All evaluated wastewaters met the general criteria for microbial lipid production. However, no significant increase in lipid content was observed, probably due to lack of available carbon in wastewaters from fruit juice and lettuce processing, and excess of available nitrogen in potato processing wastewater, respectively. During growth on wastewaters from fruit juice and lettuce processing the carotenoid content increased significantly in the first 48 hours. The relations between carbon content, nitrogen content, and carotenoid production need to be further assessed. For economic viability, lipid and carotenoid production needs to be increased significantly. Lastly, the screening of feedstocks should be extended to other wastewaters.« less

Photon up-conversion increases biomass yield in Chlorella vulgaris.

PubMed

Menon, Kavya R; Jose, Steffi; Suraishkumar, Gadi K

2014-12-01

Photon up-conversion, a process whereby lower energy radiations are converted to higher energy levels via the use of appropriate phosphor systems, was employed as a novel strategy for improving microalgal growth and lipid productivity. Photon up-conversion enables the utilization of regions of the solar spectrum, beyond the typical photosynthetically active radiation, that are usually wasted or are damaging to the algae. The effects of up-conversion of red light by two distinct sets of up-conversion phosphors were studied in the model microalgae Chlorella vulgaris. Up-conversion by set 1 phosphors led to a 2.85 fold increase in biomass concentration and a 3.2 fold increase in specific growth rate of the microalgae. While up-conversion by set 2 phosphors resulted in a 30% increase in biomass and 12% increase in specific intracellular neutral lipid, while the specific growth rates were comparable to that of the control. Furthermore, up-conversion resulted in higher levels of specific intracellular reactive oxygen species in C. vulgaris. Up-conversion of red light (654 nm) was shown to improve biomass yields in C. vulgaris. In principle, up-conversion can be used to increase the utilization range of the electromagnetic spectrum for improved cultivation of photosynthetic systems such as plants, algae, and microalgae. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of self-assembling nanowires containing electronically active oligothiophenes

NASA Astrophysics Data System (ADS)

Tsai, Wei-Wen

This dissertation discusses the development of conductive one-dimensional nanowires from self-assembling oligothiophene molecules. Self-assembly has been demonstrated to be a promising alternative approach towards high performance, solution processable, and low-cost organic electronics. One of the many challenges in this field is the control of supramolecular morphologies of ordered structures containing pi-conjugated moieties. This research demonstrated several successful strategies to achieve self assembly of conductive nanowires using synergistic interactions combining pi stacking and hydrogen bonding. The first approach used was to develop a hairpin-shaped sexithiophene molecule, which features two arms of the conjugated structure. The diamidocyclohexyl headgroup of this molecule successfully directs the self-assembly from hydrogen bonding among the amides, forming high-aspect-ratio one-dimensional nanowires with well-defined diameters of 3.0 +/- 0.3 nm. The molecular orientation in the nanostructures promotes formation of sexithiophene H and J aggregates that facilitate efficient charge transport. Organic field-effect transistors were fabricated to reveal improved intrinsic hole mobility from films of the nanostructures, 3.46 x 10-6 cm2V-1s-1, which is one order of magnitude higher than films cast from unassembled molecules. Bulk heterojunction solar cells were developed from this molecule and fullerenes utilizing solution-phase fabrication methods. Intimate mix of the molecule and phenyl-C61-butyric acid methyl ester creates structured interfaces for efficient exciton splitting. The charge carrier mobilities of each material are improved by self-assembly in solution and thermal-energy assisted phase separation.The photovoltaic devices achieved the highest open-circuit voltage of 0.62 V, short-circuit current of 1.79 mA/cm2, fill factor of 35%, and power conversion efficiency of 0.48%. Another strategy to one-dimensional nanowires studied here involved the modification of a class of peptide lipids. The tripeptide segments in the molecular structure promote beta-sheet formation in nonpolar organic solvents, which is the main driving force for their self-assembly into 1D nanowires. Left-handed helical nanowires were formed with diameters of 8.9 nm and pitches between 50--150 nm. Substitutions of oligothiophenes lead to unprecedented supercoiling phenomena manifested as the transformation from helical to coiled or curved nanowires. We proposed that the curving of the nanowires is the consequence of relaxation from torsionally strained nanohelices, a process similar to supercoiling of strained DNA double helix. This process is governed by the mismatch in intermolecular distances required for peptide beta-sheets vs. pi-pi interactions of the conjugated segments decorating the periphery of the nanowires. Circular dichroism revealed helical arrangements of the conjugated moieties in these peptide lipids manifesting supercoiling phenomena. Peptide lipids without helical arrangement of the conjugated segments only exhibit helical morphologies. The self-assembly process of peptide lipids also leads to hierarchical assemblies of energetically favored single, double, and triple-helical nanostructures with well-defined dimensions. Self-assembled nanowires from oligothiophene-substituted peptide lipids revealed increased conductivity of 1.39--1.41 x 10-5 S/cm, two orders of magnitude higher than unassembled films and one order of magnitude higher than unsubstituted peptide lipids. The role of the primary beta-helix in controlling supramolecular organization was investigated by varying the chirality of the tripeptide segments, GAA. Four diastereomers of a peptide lipid substituted with p-toluene carboxylates were compared using L or D-alanines. Molecules with all L residues self-assemble into left-handed helical nanofibers with a pitch of 160 +/- 30 nm. Substitution of one or two D-alanines leads to assemblies of cylindrical nanofibers without any twisting, left-handed helices with smaller pitches (40 +/- 6 nm), or aggregates without regular shapes. We believe these effects are steric in nature that changes the beta-sheet sub-structure within the nanofibers. These principles could be utilized as strategies to optimize the morphologies and properties of nanostructures based on these amphiphilic molecules.

Wet and dry extraction of coconut oil: impact on lipid metabolic and antioxidant status in cholesterol coadministered rats.

PubMed

Nevin, K Govindan; Rajamohan, Thankappan

2009-08-01

Because coconut oil extracted by wet process (virgin coconut oil, VCO) is gaining popularity among consumers, this study was conducted to evaluate VCO compared with coconut oil extracted by dry process (copra oil, CO) for their influence on lipid parameters, lipid peroxidation, and antioxidant status in rats coadministered with cholesterol. VCO, CO, and cholesterol were fed in a semi-synthetic diet to 24 male Sprague-Dawley rats for 45 days. After the experimental period, lipid and lipid peroxide levels and antioxidant enzyme activities were observed. Chemical composition and antioxidant properties of the polyphenolic fraction from VCO and CO were also analyzed. The results showed that lipid and lipid peroxide levels were lower in VCO-fed animals than in animals fed either CO or cholesterol alone. Antioxidant enzyme activities in VCO-fed animals were comparable with those in control animals. Although the fatty acid profiles of both oils were similar, a significantly higher level of unsaponifiable components was observed in VCO. Polyphenols from VCO also showed significant radical-scavenging activity compared with those from CO. This study clearly indicates the potential benefits of VCO over CO in maintaining lipid metabolism and antioxidant status. These effects may be attributed in part to the presence of biologically active minor unsaponifiable components.

Phosphatidic acid and neurotransmission.

PubMed

Raben, Daniel M; Barber, Casey N

2017-01-01

Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Formation and mobilization of neutral lipids in the yeast Saccharomyces cerevisiae.

PubMed

Wagner, A; Daum, G

2005-11-01

Since energy storage is a basic metabolic process, the synthesis of neutral lipids occurs in all kingdoms of life. The yeast Saccharomyces cerevisiae, widely accepted as a model eukaryotic cell, contains two classes of neutral lipids, namely STEs (steryl esters) and TAGs (triacylglycerols). TAGs are synthesized through two pathways governed by the acyl-CoA diacylglycerol acyltransferase Dga1p and the phospholipid diacylglycerol acyltransferase Lro1p. STEs are formed by two STE synthases Are1p and Are2p, two enzymes with overlapping function, which also catalyse TAG formation, although to a minor extent. Neutral lipids are stored in the so-called lipid particles and can be utilized for membrane formation under conditions of lipid depletion. For this purpose, storage lipids have to be mobilized by TAG lipases and STE hydrolases. A TAG lipase named Tgl3p was identified as a major yeast TAG hydrolytic enzyme in lipid particles. Recently, a new family of hydrolases was detected which is required for STE mobilization in S. cerevisiae. These enzymes, named Yeh1p, Yeh2p and Tgl1p, are paralogues of the mammalian acid lipase family. The role of these proteins in biosynthesis and mobilization of TAG and STE, and the regulation of these processes will be discussed in this minireview.

Extracts of black and brown rice powders improve hepatic lipid accumulation via the activation of PPARα in obese and diabetic model mice.

PubMed

Felix, Angelina Dr; Takahashi, Nobuyuki; Takahashi, Mami; Katsumata-Tsuboi, Rie; Satoh, Ryo; Soon Hui, Teoh; Miyajima, Katsuhiro; Nakae, Dai; Inoue, Hirofumi; Uehara, Mariko

2017-11-01

Rice powder extract (RPE) from black and brown rice (Oryza sativa L. indica) improves hepatic lipid accumulation in obese and diabetic model mice via peroxisomal fatty acid oxidation. RPE showed PPARα agonistic activity which did not differ between black and brown RPE despite a higher anthocyanin content in black RPE.

Olive Oil: What Are the Health Benefits?

MedlinePlus

... D., L.D. Whitney E, et al. The lipids: Triglycerides, phospholipids, and sterols. In: Understanding Nutrition. 14th ... al. A MUFA-rich diet improves postprandial glucose, lipid and GLP-1 responses in insulin-resistant subjects. ...

Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application

PubMed Central

Naseri, Neda; Valizadeh, Hadi; Zakeri-Milani, Parvin

2015-01-01

Lipid nanoparticles (LNPs) have attracted special interest during last few decades. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two major types of Lipid-based nanoparticles. SLNs were developed to overcome the limitations of other colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles because they have advantages like good release profile and targeted drug delivery with excellent physical stability. In the next generation of the lipid nanoparticle, NLCs are modified SLNs which improve the stability and capacity loading. Three structural models of NLCs have been proposed. These LNPs have potential applications in drug delivery field, research, cosmetics, clinical medicine, etc. This article focuses on features, structure and innovation of LNPs and presents a wide discussion about preparation methods, advantages, disadvantages and applications of LNPs by focusing on SLNs and NLCs. PMID:26504751

Role of organic matter on aggregate stability and related mechanisms through organic amendments

NASA Astrophysics Data System (ADS)

Zaher, Hafida

2010-05-01

To date, only a few studies have tried to simultaneously compare the role of neutral and uronic sugars and lipids on soil structural stability. Moreover, evidence for the mechanisms involved has often been established following wetting of moist aggregates after various pre-treatments thus altering aggregate structure and resulting in manipulations on altered aggregates on which the rapid wetting process may not be involved anymore. To the best of our knowledge, the objective of this work was to study the role of neutral and uronic sugars and lipids in affecting key mechanisms (swelling rate, pressure evolution) involved in the stabilization of soil structure. A long-term incubation study (48-wk) was performed on a clay loam and a silty-clay loam amended with de-inking-secondary sludge mix at three rates (8, 16 and 24 Mg dry matter ha-1), primary-secondary sludge mix at one rate (18 Mg oven-dry ha-1) and composted de-inking sludge at one rate (24 Mg ha-1). Different structural stability indices (stability of moist and dry aggregates, the amount of dispersible clay and loss of soil material following sudden wetting) were measured on a regular basis during the incubation, along with CO2 evolved, neutral and uronic sugar, and lipid contents. During the course of the incubations, significant increases in all stability indices were measured for both soil types. In general, the improvements in stability were proportional to the amount of C added as organic amendments. These improvements were linked to a very intense phase of C mineralization and associated with increases in neutral and uronic sugars as well as lipid contents. The statistical relationships found between the different carbonaceous fractions and stability indices were all highly significant and indicated no clear superiority of one fraction over another. Paper sludge amendments also resulted in significant decreases in maximum internal pressure of aggregate and aggregate swelling following immersion in water, two mechanisms affecting structural stability. Overall, the results suggest that reduction in maximum internal pressure induced by organic amendments most likely resulted from increases in pore surface roughness and pore occlusion rather than by increase in surface wetting angles. This study also supports the view of a non specific action of the lipids, neutral and uronic sugars on aggregate stability to rapid wetting. Key words: soil aggregate stability, polysaccharides, lipids, mechanisms, organic matter

A novel microalgal lipid extraction method using biodiesel (fatty acid methyl esters) as an extractant.

PubMed

Huang, Wen-Can; Park, Chan Woo; Kim, Jong-Duk

2017-02-01

Although microalgae are considered promising renewable sources of biodiesel, the high cost of the downstream process is a significant obstacle in large-scale biodiesel production. In this study, a novel approach for microalgal biodiesel production was developed by using the biodiesel as an extractant. First, wet microalgae with 70% water content were incubated with a mixture of biodiesel/methanol and penetration of the mixture through the cell membrane and swelling of the lipids contained in microalgae was confirmed. Significant increases of lipid droplets were observed by confocal microscopy. Second, the swelled lipid droplets in microalgae were squeezed out using mechanical stress across the cell membrane and washed with methanol. The lipid extraction efficiency reached 68%. This process does not require drying of microalgae or solvent recovery, which the most energy-intensive step in solvent-based biodiesel production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lipids in cell biology: how can we understand them better?

PubMed Central

Muro, Eleonora; Atilla-Gokcumen, G. Ekin; Eggert, Ulrike S.

2014-01-01

Lipids are a major class of biological molecules and play many key roles in different processes. The diversity of lipids is on the same order of magnitude as that of proteins: cells express tens of thousands of different lipids and hundreds of proteins to regulate their metabolism and transport. Despite their clear importance and essential functions, lipids have not been as well studied as proteins. We discuss here some of the reasons why it has been challenging to study lipids and outline technological developments that are allowing us to begin lifting lipids out of their “Cinderella” status. We focus on recent advances in lipid identification, visualization, and investigation of their biophysics and perturbations and suggest that the field has sufficiently advanced to encourage broader investigation into these intriguing molecules. PMID:24925915

Investigation of surface-modified solid lipid nanocontainers formulated with a heterolipid-templated homolipid.

PubMed

Attama, A A; Müller-Goymann, C C

2007-04-04

There is increasing interest in the search for improved drug delivery systems with greater versatility. Consequently, many drug delivery systems have been studied. In this study, surface-modified lipid nanocontainers were formulated with a homolipid from Capra hircus (goat fat) templated with a heterolipid (Phospholipon 90G) which was also the surface modifier. The solid lipid nanocontainers (SLN) were formulated by hot high pressure homogenisation using increasing concentrations of polysorbate 80 as the mobile surfactant. Prior to SLN preparation, the templated homolipid was formulated by fusion to obtain a homogeneous lipid matrix, which was characterized using differential scanning calorimetry (DSC), polarized light microscopy (PLM) and wide angle X-ray diffraction (WAXD) to obtain its thermal and crystal characteristics. Isothermal heat conduction microcalorimetry (IMC) and freeze-fracture transmission electron microscopy (FFTEM) studies were carried out on the templated homolipid and SLN containing 1.0% (w/w) of polysorbate 80 to study their in situ crystallization kinetics and morphology, respectively. The formulated SLN were also subjected to time-resolved DSC, WAXD and particle size analyses for one month. The thermal and crystal characteristics were compared with those of the bulk lipid matrix (templated homolipid). Result of the particle size analysis indicated that the particles size remained roughly within the lower nanometer range after one month. FFTEM micrograph of the lipid matrices revealed lamellar sheets for Phospholipon 90G and layered triglyceride structures for the homolipid and Phospholipon 90G-templated homolipid. FFTEM micrograph of SLN revealed anisometric structures. PLM of the templated homolipid did not show, but goat fat (homolipid) alone showed slight growth in crystals with time. WAXD and DSC studies revealed minor increase in crystallinity of the new lipid matrix after one month and DSC also detected templation of homolipid by the heterolipid noted by the disappearance of the lower melting peak of the homolipid. However, for the SLN, WAXD results showed low crystalline particles while DSC only showed a very little endothermic process after one month of storage at 20 degrees C. The implication of this finding is that progression of the SLN to highly ordered particles over time would not occur. This will be favourable for any incorporated drug as drug expulsion, due to increase in crystallinity, will not occur. Result obtained from analysis of the isothermal crystallization exotherms indicated that the templated homolipid and SLN1 containing 1.0% polysorbate 80 possess similar nucleation mechanisms and growth dimensions different from the pure homolipid. The SLN containing 0.5 and 1.0% polysorbate 80 possessed good properties and could prove to be good delivery systems for drugs for parenteral or ocular administration. The result of this study also shows a method of improving natural lipids for use in particulate drug delivery systems.

Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability

PubMed Central

Narala, Arjun; Veerabrahma, Kishan

2013-01-01

Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism. PMID:26555970

1-Butyl-3-Methyl Imidazolium-based Ionic Liquids Explored as Potential Solvents for Lipid Processing

USDA-ARS?s Scientific Manuscript database

Due to global environmental concerns, there is increasing interest in replacing the volatile solvents currently used to process commodity plant lipids. Room-temperature molten salts are one type of media receiving great attention as a possible replacement of the typical organic solvent. Molten sal...

Lipid Cell Biology: A Focus on Lipids in Cell Division.

PubMed

Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

2018-06-20

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

Major roles for minor bacterial lipids identified by mass spectrometry.

PubMed

Garrett, Teresa A

2017-11-01

Mass spectrometry of lipids, especially those isolated from bacteria, has ballooned over the past two decades, affirming in the process the complexity of the lipidome. With this has come the identification of new and interesting lipid structures. Here is an overview of several novel lipids, from both Gram-negative and Gram-positive bacteria with roles in health and disease, whose structural identification was facilitated using mass spectrometry. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

PubMed

García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

2015-03-30

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of nitrogen depletion and repletion on lipid production in yeast and fungal species

DOE PAGES

Yang, Shihui; Wang, Wei; Wei, Hui; ...

2016-08-29

Although it is well known that low nitrogen stimulates lipid accumulation, especially for algae and some oleaginous yeast, few studies have been conducted in fungal species, especially on the impact of different nitrogen deficiency strategies. In this study, we use two promising consolidated bioprocessing (CBP) candidates to examine the impact of two nitrogen deficiency strategies on lipid production, which are the extensively investigated oleaginous yeast Yarrowia lipolytica, and the commercial cellulase producer Trichoderma reesei. We first utilized bioinformatics approaches to reconstruct the fatty acid metabolic pathway and demonstrated the presence of a triacylglycerol (TAG) biosynthesis pathway in Trichoderma reesei. Wemore » then examined the lipid production of Trichoderma reesei and Y. lipomyces in different media using two nitrogen deficiency strategies of nitrogen natural repletion and nitrogen depletion through centrifugation. Our results demonstrated that nitrogen depletion was better than nitrogen repletion with about 30% lipid increase for Trichoderma reesei and Y. lipomyces, and could be an option to improve lipid production in both oleaginous yeast and filamentous fungal species. The resulting distinctive lipid composition profiles indicated that the impacts of nitrogen depletion on yeast were different from those for fungal species. Under three types of C/N ratio conditions, C16 and C18 fatty acids were the predominant forms of lipids for both Trichoderma reesei and Y. lipolytica. In addition, while the overall fatty acid methyl ester (FAME) profiles of Trichoderma reesei were similar, the overall FAME profiles of Y. lipolytica observed a shift. The fatty acid metabolic pathway reconstructed in this work supports previous reports of lipid production in T. reesei, and provides a pathway for future omics studies and metabolic engineering efforts. Further investigation to identify the genetic targets responsible for the effect of nitrogen depletion on lipid production improvement will facilitate strain engineering to boost lipid production under more optimal conditions for productivity than those required for nitrogen depletion.« less

Comparison of nitrogen depletion and repletion on lipid production in yeast and fungal species

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

Yang, Shihui; Wang, Wei; Wei, Hui

Although it is well known that low nitrogen stimulates lipid accumulation, especially for algae and some oleaginous yeast, few studies have been conducted in fungal species, especially on the impact of different nitrogen deficiency strategies. In this study, we use two promising consolidated bioprocessing (CBP) candidates to examine the impact of two nitrogen deficiency strategies on lipid production, which are the extensively investigated oleaginous yeast Yarrowia lipolytica, and the commercial cellulase producer Trichoderma reesei. We first utilized bioinformatics approaches to reconstruct the fatty acid metabolic pathway and demonstrated the presence of a triacylglycerol (TAG) biosynthesis pathway in Trichoderma reesei. Wemore » then examined the lipid production of Trichoderma reesei and Y. lipomyces in different media using two nitrogen deficiency strategies of nitrogen natural repletion and nitrogen depletion through centrifugation. Our results demonstrated that nitrogen depletion was better than nitrogen repletion with about 30% lipid increase for Trichoderma reesei and Y. lipomyces, and could be an option to improve lipid production in both oleaginous yeast and filamentous fungal species. The resulting distinctive lipid composition profiles indicated that the impacts of nitrogen depletion on yeast were different from those for fungal species. Under three types of C/N ratio conditions, C16 and C18 fatty acids were the predominant forms of lipids for both Trichoderma reesei and Y. lipolytica. In addition, while the overall fatty acid methyl ester (FAME) profiles of Trichoderma reesei were similar, the overall FAME profiles of Y. lipolytica observed a shift. The fatty acid metabolic pathway reconstructed in this work supports previous reports of lipid production in T. reesei, and provides a pathway for future omics studies and metabolic engineering efforts. Further investigation to identify the genetic targets responsible for the effect of nitrogen depletion on lipid production improvement will facilitate strain engineering to boost lipid production under more optimal conditions for productivity than those required for nitrogen depletion.« less

Engineering Aspergillus oryzae A-4 through the Chromosomal Insertion of Foreign Cellulase Expression Cassette to Improve Conversion of Cellulosic Biomass into Lipids

PubMed Central

Shen, Qi; Ma, Junwei; Fu, Jianrong; Zhao, Yuhua

2014-01-01

A genetic modification scheme was designed for Aspergillus oryzae A-4, a natural cellulosic lipids producer, to enhance its lipid production from biomass by putting the spotlight on improving cellulase secretion. Four cellulase genes were separately expressed in A-4 under the control of hlyA promoter, with the help of the successful development of a chromosomal genetic manipulation system. Comparison of cellulase activities of PCR-positive transformants showed that these transformants integrated with celA gene and with celC gene had significantly (p<0.05) higher average FPAase activities than those strains integrated with celB gene and with celD gene. Through the assessment of cellulosic lipids accumulating abilities, celA transformant A2-2 and celC transformant D1-B1 were isolated as promising candidates, which could yield 101%–133% and 35.22%–59.57% higher amount of lipids than the reference strain A-4 (WT) under submerged (SmF) conditions and solid-state (SSF) conditions, respectively. Variability in metabolism associated to the introduction of cellulase gene in A2-2 and D1-B1 was subsequently investigated. It was noted that cellulase expression repressed biomass formation but enhanced lipid accumulation; whereas the inhibitory effect on cell growth would be shielded during cellulosic lipids production owing to the essential role of cellulase in substrate utilization. Different metabolic profiles also existed between A2-2 and D1-B1, which could be attributed to not only different transgene but also biological impacts of different integration. Overall, both simultaneous saccharification and lipid accumulation were enhanced in A2-2 and D1-B1, resulting in efficient conversion of cellulose into lipids. A regulation of cellulase secretion in natural cellulosic lipids producers could be a possible strategy to enhance its lipid production from lignocellulosic biomass. PMID:25251435

Engineering Aspergillus oryzae A-4 through the chromosomal insertion of foreign cellulase expression cassette to improve conversion of cellulosic biomass into lipids.

PubMed

Lin, Hui; Wang, Qun; Shen, Qi; Ma, Junwei; Fu, Jianrong; Zhao, Yuhua

2014-01-01

A genetic modification scheme was designed for Aspergillus oryzae A-4, a natural cellulosic lipids producer, to enhance its lipid production from biomass by putting the spotlight on improving cellulase secretion. Four cellulase genes were separately expressed in A-4 under the control of hlyA promoter, with the help of the successful development of a chromosomal genetic manipulation system. Comparison of cellulase activities of PCR-positive transformants showed that these transformants integrated with celA gene and with celC gene had significantly (p<0.05) higher average FPAase activities than those strains integrated with celB gene and with celD gene. Through the assessment of cellulosic lipids accumulating abilities, celA transformant A2-2 and celC transformant D1-B1 were isolated as promising candidates, which could yield 101%-133% and 35.22%-59.57% higher amount of lipids than the reference strain A-4 (WT) under submerged (SmF) conditions and solid-state (SSF) conditions, respectively. Variability in metabolism associated to the introduction of cellulase gene in A2-2 and D1-B1 was subsequently investigated. It was noted that cellulase expression repressed biomass formation but enhanced lipid accumulation; whereas the inhibitory effect on cell growth would be shielded during cellulosic lipids production owing to the essential role of cellulase in substrate utilization. Different metabolic profiles also existed between A2-2 and D1-B1, which could be attributed to not only different transgene but also biological impacts of different integration. Overall, both simultaneous saccharification and lipid accumulation were enhanced in A2-2 and D1-B1, resulting in efficient conversion of cellulose into lipids. A regulation of cellulase secretion in natural cellulosic lipids producers could be a possible strategy to enhance its lipid production from lignocellulosic biomass.

The fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms improves insulin resistance and hepatic lipid accumulation by modulation of liver adenosine monophosphate-activated protein kinase activity and lipogenic gene expression in high-fat diet-fed obese mice.

PubMed

Saito, Tetsuo; Nishida, Miyako; Saito, Masafumi; Tanabe, Akari; Eitsuka, Takahiro; Yuan, Shi-Hua; Ikekawa, Nobuo; Nishida, Hiroshi

2016-10-01

Obesity-associated insulin resistance is a major risk factor for most metabolic diseases, including dyslipidemia and type 2 diabetes. Acanthopanax senticosus (Rupr. et Maxim.) Harms (Goka) root has been used in traditional Chinese medicine for treatment of diabetes and other conditions; however, little is known about the effects of Goka fruit (GF). Goka fruit is rich in anthocyanin, which has beneficial effects on obesity and insulin resistance via activation of adenosine monophosphate-activated protein kinase (AMPK). We hypothesized that GF can improve obesity-associated insulin resistance. The aim of the present study was to investigate whether GF improves insulin resistance in high-fat diet (HFD)-induced obese mice. High-fat diet mice treated with GF (500 and 1000 mg/kg) for 12 weeks showed an improved glucose tolerance and insulin sensitivity, as well as reduced plasma insulin and liver lipid accumulation. Moreover, GF administration to HFD mice resulted in down-regulation of fatty acid synthase expression and up-regulation of cholesterol 7-alpha-hydroxylase expression in the liver. Notably, AMPK phosphorylation in the liver increased after GF administration. In summary, GF supplementation improved obesity-associated insulin resistance and hepatic lipid accumulation through modulation of AMPK activity and lipid metabolism-associated gene expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Different effects of bariatric surgical procedures on dyslipidemia: a registry-based analysis.

PubMed

Spivak, Hadar; Sakran, Nasser; Dicker, Dror; Rubin, Moshe; Raz, Itamar; Shohat, Tamy; Blumenfeld, Orit

2017-07-01

The scale and variables linked to bariatric surgery's effect on dyslipidemia have not been conclusive. To compare the effect of Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (LAGB) on dyslipidemia SETTING: National bariatric surgery registry. Plasma lipids and associated variables were compared at baseline and 1 year (12±4 mo) after surgery for registry patients with dyslipidemia enrolled from June 2013 to August 2014. The greatest mean total-cholesterol (TC) reduction was observed post-RYGB, 226.7±26.4 to 181.3±30.9 mg/dL (19.9%, n = 208), followed by post-SG, 227.9±24.4 to 206.7±34.2 mg/dL (8.9%, n = 1515; P<.001). Normal TC levels of below 200 mg/dL were achieved by 76% post-RYGB patients compared with 43.5% post-SG patients (odds ratio [OR] = 6.24, 95% confidence interval [CI]: 3.69-10.53) and 25.6% post-LABG patients (OR = 9.66, 95% CI: 4.11-22.67; P<.01). Although equivalent patterns were observed for low-density-lipoprotein cholesterol (LDL), the levels of high-density-lipoprotein cholesterol (HDL) were most improved post-SG, reaching normal levels in 58.1% of SG male patients versus 39.5% of RYGB male patients (OR = 1.56, 95% CI: 1.04-2.35), (P = .02). The lowering of triglyceride levels by approximately 75% was comparable after SG and RYGB procedures. The type of surgery was the strongest independent predictor for all lipid level improvements or remissions. Male sex was an independent predictor for LDL normalization only (OR = 1.88, 95% CI: 1.24-2.85). Excess weight loss offered no meaningful prediction for lipid improvement (OR = 1.01-1.03). Particular types of bariatric surgeries had different effects on dyslipidemia, independent of weight loss. Overall, the RYGB achieved the biggest reduction in plasma lipids (TC and LDL), although SG did affect HDL. Our results could aid in the decision-making process regarding the most appropriate procedure for patients with dyslipidemia. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Raman spectroscopic analysis of human skin tissue sections ex-vivo: evaluation of the effects of tissue processing and dewaxing

NASA Astrophysics Data System (ADS)

Ali, Syed M.; Bonnier, Franck; Tfayli, Ali; Lambkin, Helen; Flynn, Kathleen; McDonagh, Vincent; Healy, Claragh; Clive Lee, T.; Lyng, Fiona M.; Byrne, Hugh J.

2013-06-01

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections and the effects of tissue processing. Both hand and thigh sections of human cadavers were analyzed in their unprocessed and formalin-fixed, paraffin-processed (FFPP), and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum (SC), intermediate underlying epithelium, and dermal layers for sections from both anatomical sites. The SC is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that of the dermis is dominated by the characteristics of collagen. For a given anatomical site, little difference in layer structure and biochemistry is observed between samples from different cadavers. However, the hand and thigh sections are consistently differentiated for all cadavers, largely based on lipidic profiles. In dewaxed FFPP samples, while the SC, intermediate, and dermal layers are clearly differentiated by KMCA of Raman maps of tissue sections, the lipidic contributions to the spectra are significantly reduced, with the result that respective skin layers from different anatomical sites become indistinguishable. While efficient at removing the fixing wax, the tissue processing also efficiently removes the structurally similar lipidic components of the skin layers. In studies of dermatological processes in which lipids play an important role, such as wound healing, dewaxed samples are therefore not appropriate. Removal of the lipids does however accentuate the spectral features of the cellular and protein components, which may be more appropriate for retrospective analysis of disease progression and biochemical analysis using tissue banks.

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.

Vesicle solubilization by bile salts: comparison of macroscopic theory and simulation.

PubMed

Haustein, M; Wahab, M; Mögel, H-J; Schiller, P

2015-04-14

Lipid metabolism is accompanied by the solubilization of lipid bilayer membranes by bile salts. We use Brownian dynamics simulations to study the solubilization of model membranes and vesicles by sodium cholate. The solubilization pathways of small and large vesicles are found to be different. Both results for small and large vesicles can be compared with predictions of a macroscopic theoretical description. The line tension of bilayer edges is an important parameter in the solubilization process. We propose a simple method to determine the line tension by analyzing the shape fluctuations of planar membrane patches. Macroscopic mechanical models provide a reasonable explanation for processes observed when a spherical vesicle consisting of lipids and adsorbed bile salt molecules is transformed into mixed lipid-bile salt micelles.

Can we improve the nutritional quality of meat?

PubMed

Scollan, Nigel D; Price, Eleri M; Morgan, Sarah A; Huws, Sharon A; Shingfield, Kevin J

2017-11-01

The nutritional value of meat is an increasingly important factor influencing consumer preferences for poultry, red meat and processed meat products. Intramuscular fat content and composition, in addition to high quality protein, trace minerals and vitamins are important determinants of nutritional value. Fat content of meat at retail has decreased substantially over the past 40 years through advances in animal genetics, nutrition and management and changes in processing techniques. Evidence of the association between diet and the incidence of human non-communicable diseases has driven an interest in developing production systems for lowering total SFA and trans fatty acid (TFA) content and enrichment of n-3 PUFA concentrations in meat and meat products. Typically, poultry and pork has a lower fat content, containing higher PUFA and lower TFA concentrations than lamb or beef. Animal genetics, nutrition and maturity, coupled with their rumen microbiome, are the main factors influencing tissue lipid content and relative proportions of SFA, MUFA and PUFA. Altering the fatty acid (FA) profile of lamb and beef is determined to a large extent by extensive plant and microbial lipolysis and subsequent microbial biohydrogenation of dietary lipid in the rumen, and one of the major reasons explaining the differences in lipid composition of meat from monogastrics and ruminants. Nutritional strategies can be used to align the fat content and FA composition of poultry, pork, lamb and beef with Public Health Guidelines for lowering the social and economic burden of chronic disease.

Lipids in the cell: organisation regulates function.

PubMed

Santos, Ana L; Preta, Giulio

2018-06-01

Lipids are fundamental building blocks of all cells and play important roles in the pathogenesis of different diseases, including inflammation, autoimmune disease, cancer, and neurodegeneration. The lipid composition of different organelles can vary substantially from cell to cell, but increasing evidence demonstrates that lipids become organised specifically in each compartment, and this organisation is essential for regulating cell function. For example, lipid microdomains in the plasma membrane, known as lipid rafts, are platforms for concentrating protein receptors and can influence intra-cellular signalling. Lipid organisation is tightly regulated and can be observed across different model organisms, including bacteria, yeast, Drosophila, and Caenorhabditis elegans, suggesting that lipid organisation is evolutionarily conserved. In this review, we summarise the importance and function of specific lipid domains in main cellular organelles and discuss recent advances that investigate how these specific and highly regulated structures contribute to diverse biological processes.

Effect of tension and curvature on the chemical potential of lipids in lipid aggregates.

PubMed

Grafmüller, Andrea; Lipowsky, Reinhard; Knecht, Volker

2013-01-21

Understanding the factors that influence the free energy of lipids in bilayer membranes is an essential step toward understanding exchange processes of lipids between membranes. In general, both lipid composition and membrane geometry can affect lipid exchange rates between bilayer membranes. Here, the free energy change ΔG(des) for the desorption of dipalmitoyl-phosphatidylcholine (DPPC) lipids from different lipid aggregates has been computed using molecular dynamics simulations and umbrella sampling. The value of ΔG(des) is found to depend strongly on the local properties of the aggregate, in that both tension and curvature lead to an increase in ΔG(des). A detailed analysis shows that the increased desorption free energy for tense bilayers arises from the increased conformational entropy of the lipid tails, which reduces the favorable component -TΔS(L) of the desorption free energy.

Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice.

PubMed

Shu, Run-Zhe; Zhang, Feng; Wang, Fang; Feng, De-Chun; Li, Xi-Hua; Ren, Wei-Hua; Wu, Xiao-Lin; Yang, Xue; Liao, Xiao-Dong; Huang, Lei; Wang, Zhu-Gang

2009-09-01

Liver regeneration is a very complex and well-orchestrated process associated with signaling cascades involving cytokines, growth factors, and metabolic pathways. Adiponectin is an adipocytokine secreted by mature adipocytes, and its receptors are widely distributed in many tissues, including the liver. Adiponectin has direct actions in the liver with prominent roles to improve hepatic insulin sensitivity, increase fatty acid oxidation, and decrease inflammation. To test the hypothesis that adiponectin is required for normal progress of liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and adiponectin-null mice. Compared to wild-type mice, adiponectin-null mice displayed decreased liver mass regrowth, impeded hepatocyte proliferation, and increased hepatic lipid accumulation. Gene expression analysis revealed that adiponectin regulated the gene transcription related to lipid metabolism. Furthermore, the suppressed hepatocyte proliferation was accompanied with reduced signal transducer and activator of transcription protein 3 (STAT3) activity and enhanced suppressor of cytokine signaling 3 (Socs3) transcription. In conclusion, adiponectin-null mice exhibit impaired liver regeneration and increased hepatic steatosis. Increased expression of Socs3 and subsequently reduced activation of STAT3 in adiponectin-null mice may contribute to the alteration of the liver regeneration capability and hepatic lipid metabolism after PH.

A novel culture medium designed for the simultaneous enhancement of biomass and lipid production by Chlorella vulgaris UTEX 26.

PubMed

Ramírez-López, Citlally; Chairez, Isaac; Fernández-Linares, Luis

2016-07-01

A novel culture medium to enhance the biomass and lipid production simultaneously by Chlorella vulgaris UTEX 26 was designed in three stages of optimization. Initially, a culture medium was inferred applying the response surface method to adjust six factors [NaNO3, NH4HCO3, MgSO4·7H2O, KH2PO4, K2HPO4 and (NH4)2HPO4], which were selected on the basement of BBM (Bold's Basal Medium) and HAMGM (Highly Assimilable Minimal Growth Medium) culture media. Afterwards, the nitrogen source compound was optimized to reduce both, ammonium and nitrate concentrations. As result of the optimization process, the proposed culture medium improved 40% the biomass (0.73gL(-1)) compared with the BBM medium and 85% the lipid concentration (281mgL(-1)), with respect to HAMGM medium. Some culture media components concentrations were reduced up to 50%. Gas chromatography analysis revealed that C16:0, C18:0, C18:1, C18:2 and C18:3 were the major fatty acids produced by C. vulgaris UTEX 26. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thermal phase transition behavior of lipid layers on a single human corneocyte cell.

PubMed

Imai, Tomohiro; Nakazawa, Hiromitsu; Kato, Satoru

2013-09-01

We have improved the selected area electron diffraction method to analyze the dynamic structural change in a single corneocyte cell non-invasively stripped off from human skin surface. The improved method made it possible to obtain reliable diffraction images to trace the structural change in the intercellular lipid layers on a single corneocyte cell during heating from 24°C to 100°C. Comparison of the results with those of synchrotron X-ray diffraction experiments on human stratum corneum sheets revealed that the intercellular lipid layers on a corneocyte cell exhibit essentially the same thermal phase transitions as those in a stratum corneum sheet. These results suggest that the structural features of the lipid layers are well preserved after the mechanical stripping of the corneocyte cell. Moreover, electron diffraction analyses of the thermal phase transition behaviors of the corneocyte cells that had the lipid layers with different distributions of orthorhombic and hexagonal domains at 24°C suggested that small orthorhombic domains interconnected with surrounding hexagonal domains transforms in a continuous manner into new hexagonal domains. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems.

PubMed

Gurram, A K; Deshpande, P B; Kar, S S; Nayak, Usha Y; Udupa, N; Reddy, M S

2015-01-01

Pharmaceutical research is focused in designing novel drug delivery systems to improve the bioavailability of poorly water soluble drugs. Self-microemulsifying drug delivery systems, one among the lipid-based dosage forms were proven to be promising in improving the oral bioavailability of such drugs by enhancing solubility, permeability and avoiding first-pass metabolism via enhanced lymphatic transport. Further, they have been successful in avoiding both inter and intra individual variations as well as the dose disproportionality. Aqueous insoluble drugs, in general, show greater solubility in lipid based excipients, and hence they are formulated as lipid based drug delivery systems. The extent of solubility of a hydrophobic drug in lipid excipients i.e. oil, surfactant and co-surfactant (components of self-microemulsifying drug delivery systems) greatly affects the drug loading and in producing stable self-microemulsifying drug delivery systems. The present review highlighted the influence of physicochemical factors and structural features of the hydrophobic drug on its solubility in lipid excipients and an attempt was made to explore the role of each component of self-microemulsifying drug delivery systems in the formation of stable microemulsion upon dilution.

Lipid production of microalga Chlorella sorokiniana CY1 is improved by light source arrangement, bioreactor operation mode and deep-sea water supplements.

PubMed

Chen, Chun-Yen; Chang, Hsin-Yueh

2016-03-01

Microalgae-based biodiesel has been recognized as a sustainable and promising alternative to fossil diesel. High lipid productivity of microalgae is required for economic production of biodiesel from microalgae. This study was undertaken to enhance the growth and oil accumulation of an indigenous microalga Chlorella sorokiniana CY1 by applying engineering strategies using deep-sea water as the medium. First, the microalga was cultivated using LED as the immersed light source, and the results showed that the immersed LED could effectively enhance the oil/lipid content and final microalgal biomass concentration to 53.8% and 2.5 g/l, respectively. Next, the semi-batch photobioreactor operation with deep-sea water was shown to improve lipid content and microalgal growth over those from using batch and continuous cultures under similar operating conditions. The optimal replacement ratio was 50%, resulting in an oil/lipid content and final biomass concentration of 61.5% and 2.8 g/l, respectively. A long-term semi-batch culture utilizing 50%-replaced medium was carried out for four runs. The final biomass concentration and lipid productivity were 2.5 g/L and 112.2 mg/L/d, respectively. The fatty acid composition of the microalgal lipids was predominant by palmitic acid, stearic acid, oleic acid and linoleic acid, and this lipid quality is suitable for biodiesel production. This demonstrates that optimizing light source arrangement, bioreactor operation and deep-sea water supplements could effectively promote the lipid production of C. sorokiniana CY1 for the applications in microalgae-based biodiesel industry. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lipid Profiling of the Arabidopsis Hypersensitive Response Reveals Specific Lipid Peroxidation and Fragmentation Processes: Biogenesis of Pimelic and Azelaic Acid1[C][W

PubMed Central

Zoeller, Maria; Stingl, Nadja; Krischke, Markus; Fekete, Agnes; Waller, Frank; Berger, Susanne; Mueller, Martin J.

2012-01-01

Lipid peroxidation (LPO) is induced by a variety of abiotic and biotic stresses. Although LPO is involved in diverse signaling processes, little is known about the oxidation mechanisms and major lipid targets. A systematic lipidomics analysis of LPO in the interaction of Arabidopsis (Arabidopsis thaliana) with Pseudomonas syringae revealed that LPO is predominantly confined to plastid lipids comprising galactolipid and triacylglyceride species and precedes programmed cell death. Singlet oxygen was identified as the major cause of lipid oxidation under basal conditions, while a 13-lipoxygenase (LOX2) and free radical-catalyzed lipid oxidation substantially contribute to the increase upon pathogen infection. Analysis of lox2 mutants revealed that LOX2 is essential for enzymatic membrane peroxidation but not for the pathogen-induced free jasmonate production. Despite massive oxidative modification of plastid lipids, levels of nonoxidized lipids dramatically increased after infection. Pathogen infection also induced an accumulation of fragmented lipids. Analysis of mutants defective in 9-lipoxygenases and LOX2 showed that galactolipid fragmentation is independent of LOXs. We provide strong in vivo evidence for a free radical-catalyzed galactolipid fragmentation mechanism responsible for the formation of the essential biotin precursor pimelic acid as well as of azelaic acid, which was previously postulated to prime the immune response of Arabidopsis. Our results suggest that azelaic acid is a general marker for LPO rather than a general immune signal. The proposed fragmentation mechanism rationalizes the pathogen-induced radical amplification and formation of electrophile signals such as phytoprostanes, malondialdehyde, and hexenal in plastids. PMID:22822212

Lipid profiling of the Arabidopsis hypersensitive response reveals specific lipid peroxidation and fragmentation processes: biogenesis of pimelic and azelaic acid.

PubMed

Zoeller, Maria; Stingl, Nadja; Krischke, Markus; Fekete, Agnes; Waller, Frank; Berger, Susanne; Mueller, Martin J

2012-09-01

Lipid peroxidation (LPO) is induced by a variety of abiotic and biotic stresses. Although LPO is involved in diverse signaling processes, little is known about the oxidation mechanisms and major lipid targets. A systematic lipidomics analysis of LPO in the interaction of Arabidopsis (Arabidopsis thaliana) with Pseudomonas syringae revealed that LPO is predominantly confined to plastid lipids comprising galactolipid and triacylglyceride species and precedes programmed cell death. Singlet oxygen was identified as the major cause of lipid oxidation under basal conditions, while a 13-lipoxygenase (LOX2) and free radical-catalyzed lipid oxidation substantially contribute to the increase upon pathogen infection. Analysis of lox2 mutants revealed that LOX2 is essential for enzymatic membrane peroxidation but not for the pathogen-induced free jasmonate production. Despite massive oxidative modification of plastid lipids, levels of nonoxidized lipids dramatically increased after infection. Pathogen infection also induced an accumulation of fragmented lipids. Analysis of mutants defective in 9-lipoxygenases and LOX2 showed that galactolipid fragmentation is independent of LOXs. We provide strong in vivo evidence for a free radical-catalyzed galactolipid fragmentation mechanism responsible for the formation of the essential biotin precursor pimelic acid as well as of azelaic acid, which was previously postulated to prime the immune response of Arabidopsis. Our results suggest that azelaic acid is a general marker for LPO rather than a general immune signal. The proposed fragmentation mechanism rationalizes the pathogen-induced radical amplification and formation of electrophile signals such as phytoprostanes, malondialdehyde, and hexenal in plastids.

Understanding the interaction of block copolymers with DMPC lipid bilayer using coarse-grained molecular dynamics simulations.

PubMed

Hezaveh, Samira; Samanta, Susruta; De Nicola, Antonio; Milano, Giuseppe; Roccatano, Danilo

2012-12-13

In this paper, we present a computational model of the adsorption and percolation mechanism of poloxamers (poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) triblock copolymers) across a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer. A coarse-grained model was used to cope with the long time scale of the percolation process. The simulations have provided details of the interaction mechanism of Pluronics with lipid bilayer. In particular, the results have shown that polymer chains containing a PPO block with a length comparable to the DMPC bilayer thickness, such as P85, tends to percolate across the lipid bilayer. On the contrary, Pluronics with a shorter PPO chain, such as L64 and F38, insert partially into the membrane with the PPO block part while the PEO blocks remain in water on one side of the lipid bilayer. The percolation of the polymers into the lipid tail groups reduces the membrane thickness and increases the area per lipid. These effects are more evident for P85 than L64 or F38. Our findings are qualitatively in good agreement with published small-angle X-ray scattering experiments that have evidenced a thinning effect of Pluronics on the lipid bilayer as well as the role of the length of the PPO block on the permeation process of the polymer through the lipid bilayer. Our theoretical results complement the experimental data with a detailed structural and dynamic model of poloxamers at the interface and inside the lipid bilayer.

Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus.

PubMed

Alshehry, Zahir H; Mundra, Piyushkumar A; Barlow, Christopher K; Mellett, Natalie A; Wong, Gerard; McConville, Malcolm J; Simes, John; Tonkin, Andrew M; Sullivan, David R; Barnes, Elizabeth H; Nestel, Paul J; Kingwell, Bronwyn A; Marre, Michel; Neal, Bruce; Poulter, Neil R; Rodgers, Anthony; Williams, Bryan; Zoungas, Sophia; Hillis, Graham S; Chalmers, John; Woodward, Mark; Meikle, Peter J

2016-11-22

Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes mellitus or cardiovascular disease. Lipidomics enables the assessment of hundreds of lipid species as potential markers for disease risk. Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionization-tandem mass spectrometry on a case-cohort (n=3779) subset from the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year follow-up period. Multivariable models combining traditional risk factors with lipid species were optimized with the Akaike information criteria. C statistics and NRIs were calculated within a 5-fold cross-validation framework. Sphingolipids, phospholipids (including lyso- and ether- species), cholesteryl esters, and glycerolipids were associated with future cardiovascular events and cardiovascular death. The addition of 7 lipid species to a base model (14 traditional risk factors and medications) to predict cardiovascular events increased the C statistic from 0.680 (95% confidence interval [CI], 0.678-0.682) to 0.700 (95% CI, 0.698-0.702; P<0.0001) with a corresponding continuous NRI of 0.227 (95% CI, 0.219-0.235). The prediction of cardiovascular death was improved with the incorporation of 4 lipid species into the base model, showing an increase in the C statistic from 0.740 (95% CI, 0.738-0.742) to 0.760 (95% CI, 0.757-0.762; P<0.0001) and a continuous net reclassification index of 0.328 (95% CI, 0.317-0.339). The results were validated in a subcohort with type 2 diabetes mellitus (n=511) from the LIPID trial (Long-Term Intervention With Pravastatin in Ischemic Disease). The improvement in the prediction of cardiovascular events, above traditional risk factors, demonstrates the potential of plasma lipid species as biomarkers for cardiovascular risk stratification in diabetes mellitus. URL: https://clinicaltrials.gov. Unique identifier: NCT00145925. © 2016 American Heart Association, Inc.

Process strategies for high titers of lipid production by oleaginous yeasts in undetoxified hydrolyzates of lignocellulosic biomass

USDA-ARS?s Scientific Manuscript database

Oleaginous yeasts can accumulate up to 70% of cell biomass as lipid, predominantly as triacylglycerols. Yeast lipid fatty acid profiles have been reported to be similar to that of vegetable oils and consist primarily of oleic, palmitic, stearic, and linoleic acids. This capability provides the oppor...

Process strategies to maximize lipid accumulations of novel yeast in acid and base treated hydrolyzates

USDA-ARS?s Scientific Manuscript database

Oleaginous yeasts can accumulate up to 70% of cell biomass as lipids, predominantly as triacylglycerols. Yeast lipid fatty acid profiles have been reported to be similar to that of vegetable oils and consist primarily of oleic, palmitic, stearic, and linoleic acids. This capability provides the oppo...

Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options.

PubMed

Serban, Maria-Corina; Banach, Maciej; Mikhailidis, Dimitri P

2016-01-01

A residual risk of morbidity and mortality from cardiovascular (CV) disease remains despite statin therapy. This situation has generated an interest in finding novel approaches of combining statins with other lipid-lowering agents, or finding new lipid and non-lipid targets, such as triglycerides, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, cholesterol ester transfer protein (CETP), lipoprotein (a), fibrinogen or C-reactive protein. The recent results from the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated an incremental clinical benefit when ezetimibe, a non-statin agent, was added to simvastatin therapy. The results from IMPROVE-IT revalidated the concept that low-density lipoprotein cholesterol (LDL-C) levels are a clinically relevant treatment goal. This trial also suggested that further decrease of LDL-C levels (53 vs. 70 mg/dl; 1.4 vs. 1.8 mmol/l) was more beneficial in lowering CV events. This "even lower is even better" evidence for LDL-C levels may influence future guidelines and the use of new drugs. Furthermore, these findings make ezetimibe a more realistic option to treat patients with statin intolerance or those who cannot achieve LDL-C targets with statin monotherapy.

Effect of Thermal Processing towards Lipid Oxidation and Non-enzymatic Browning Reactions of Antartic Krill (Euphausia superba) Meal.

PubMed

Liu, Yanzi; Cong, Peixu; Li, Beijia; Song, Yu; Liu, Yanjun; Xu, Jie; Xue, Changhu

2018-04-13

Antarctic krill is a huge source of biomass and prospective high-quality lipid source. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), nutritionally important lipid components with poor oxidative stability, were used as markers of oxidation during thermal processing of Antarctic krill (Euphausia superba) meal by evaluating the lipolysis, lipid oxidation, and non-enzymatic browning reactions. Liquid chromatography-mass spectrometry of the phospholipids (PLs) and the main oxidation products of free fatty acids (FFAs) and phosphatidylcholine (PC) was effective for evaluating the oxidation of EPA and DHA. During boiling, oxidation of EPA and DHA in the FFA and PC fractions and hydrolysis of the fatty acids at the sn-2 position of the PLs were predominant. The changes in PC during drying were mainly attributed to the oxidation of EPA and DHA. Heat treatment increased the oxidation products and concentration of hydrophobic pyrrole owing to pyrrolization between phosphatidylethanolamine (PE) and the lipid oxidation products. The lipid oxidation level of Antarctic krill increased after drying, owing to prolonged heating under the severe conditions. This article is protected by copyright. All rights reserved.

Lipoidal labellar secretions in Maxillaria ruiz & pav. (Orchidaceae).

PubMed

Davies, K L; Turner, M P; Gregg, A

2003-03-01

The labella of Maxillaria acuminata Lindl., M. cerifera Barb. Rodr. and M. notylioglossa Rchb.f., all members of the M. acuminata alliance, produce a viscid wax-like secretion. Histochemical analysis revealed that the chemical composition of the secretion is similar in all three species, consisting largely of lipid and protein. Light microscopy and low-vacuum scanning electron microscopy were used to investigate the secretory process. In a fourth taxon, M. cf. notylioglossa, transmission electron microscopy showed that lipid bodies are associated with smooth endoplasmic reticulum or occur as plastoglobuli within plastids. Lipid bodies vary in appearance and this may reflect differences in chemical composition. They become associated with the plasmalemma and eventually accumulate between the latter and the cell wall. The wall contains no pits or ectodesmata, and it is speculated that lipid passes through the wall as small lipid moieties before eventually reassembling to form lipid globules on the external surface of the cuticle. These globules are able to coalesce forming extensive viscid areas on the labellum. The possible significance of this process to pollination is discussed.

Lipoidal Labellar Secretions in Maxillaria Ruiz & Pav. (Orchidaceae)

PubMed Central

DAVIES, K. L.; TURNER, M. P.; GREGG, A.

2003-01-01

The labella of Maxillaria acuminata Lindl., M. cerifera Barb. Rodr. and M. notylioglossa Rchb.f., all members of the M. acuminata alliance, produce a viscid wax‐like secretion. Histochemical analysis revealed that the chemical composition of the secretion is similar in all three species, consisting largely of lipid and protein. Light microscopy and low‐vacuum scanning electron microscopy were used to investigate the secretory process. In a fourth taxon, M. cf. notylioglossa, transmission electron microscopy showed that lipid bodies are associated with smooth endoplasmic reticulum or occur as plastoglobuli within plastids. Lipid bodies vary in appearance and this may reflect differences in chemical composition. They become associated with the plasmalemma and eventually accumulate between the latter and the cell wall. The wall contains no pits or ectodesmata, and it is speculated that lipid passes through the wall as small lipid moieties before eventually reassembling to form lipid globules on the external surface of the cuticle. These globules are able to coalesce forming extensive viscid areas on the labellum. The possible significance of this process to pollination is discussed. PMID:12588723

Intraduodenal infusion of cyanidin-3-glucoside transiently promotes triglyceride excretion into bile in rats.

PubMed

Hashimoto, Naoto; Han, Kyu-Ho; Fukushima, Michihiro

2017-02-01

Flavonoids purportedly have a role in improving lipid metabolism. In our preliminary study, highly concentrated flavonoid metabolites appeared in bile juice in rats, which also contains various lipids. Biliary flavonoid metabolites generally have amphiphilic properties, may influence lipid solubility, and possibly contribute to the improvement of dyslipidemia. However, the influence of biliary flavonoid metabolites on the biliary lipid profile is not well known. Therefore, we hypothesized that the amphiphilic property of biliary flavonoid metabolites alters biliary lipid profiles. To estimate the influence of flavonoids on the biliary lipid profile, we laparotomized rats under anesthesia, intraduodenally injected them with cyanidin-3-glucoside chloride (C3G) or quercetin, and analyzed their biliary metabolite concentrations for 2 hours. Concentrations of C3G and quercetin metabolites peaked at 30 minutes after the injection; those of quercetin were 6 to 10 times higher than those of C3G throughout the sampling period up to 2 hours. Biliary triglyceride (TG) concentrations were higher in the C3G group at 30 and 45 minutes; biliary cholesterol and phospholipid concentrations were lower in the quercetin group at 30 minutes than those in the control group. Hepatic TG content after the 2-hour sampling was lower in the C3G group than in the control group. These results suggest that C3G, but not quercetin, may transiently promote TG excretion into bile, with a reduction in hepatic TG content. This C3G effect may be involved in improvement of TG metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

PubMed Central

López-Malo, María; García-Ríos, Estéfani; Chiva, Rosana; Guillamon, José M.

2014-01-01

Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 - 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1, LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must. PMID:28357215

[Achievement of low-density lipoprotein cholesterol therapeutic goal in lipid and vascular risk units of the Spanish Arteriosclerosis Society].

PubMed

Pedro-Botet, Juan; Mostaza, José M; Pintó, Xavier; Banegas, José R

2013-01-01

To evaluate low-density lipoprotein-cholesterol (LDLc) goal achievement among dyslipidemic patients treated in lipid and vascular risk units of the Spanish Society of Arteriosclerosis (SEA). The LDLc goal was based on the 2007 European guidelines for cardiovascular prevention. Observational, longitudinal, retrospective, multicenter national study that included consecutive patients of both sexes over 18 years of age referred for dyslipidemia and cardiovascular risk. Information was collected from medical records corresponding to two visits in the lipid unit. We included 1,828 patients from 43 lipid units. In the initial visit, 846 (46.3%) patients were on lipid lowering drug treatment. On the follow-up there was a significant increase in the use of cholesterol-lowering agents, except for a decrease in the use of nicotinic acid. 65.3% of patients with vascular disease and 50.4% with diabetes achieved an LDLc level <100mg/dL. Overall, 44.7% of patients achieved the LDLc goal and the predictors in the multivariate analysis were age, waist circumference, diabetes and the presence of vascular disease. Dyslipidemic patients referred to SEA lipid units have improved LDLc goal achievement after follow-up compared with data reported from previous studies in other health care settings. This improvement was associated with a substantial increase in the prescription of statins, both in monotherapy and combined with ezetimibe. There is still a wide room for improvement in the effectiveness of hypercholesterolemia treatment. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature.

PubMed

López-Malo, María; García-Ríos, Estéfani; Chiva, Rosana; Guillamon, José M

2014-10-29

Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 - 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1 , LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.

Insights into the complex association of bovine factor Va with acidic-lipid-containing synthetic membranes.

PubMed Central

Cutsforth, G A; Koppaka, V; Krishnaswamy, S; Wu, J R; Mann, K G; Lentz, B R

1996-01-01

The mechanism of binding of blood coagulation cofactor factor Va to acidic-lipid-containing membranes has been addressed. Binding isotherms were generated at room temperature using the change in fluorescence anisotropy of pyrene-labeled bovine factor Va to detect binding to sonicated membrane vesicles containing either bovine brain phosphatidylserine (PS) or 1,2-dioleoyl-3-sn-phosphatidylglycerol (DOPG) in combination with 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC). The composition of the membranes was varied from 0 to 40 mol% for PS/POPC and from 0 to 65 mol % for DOPG/POPC membranes. Fitting the data to a classical Langmuir adsorption model yielded estimates of the dissociation constant (Kd) and the stoichiometry of binding. The values of Kd defined in this way displayed a maximum at low acidic lipid content but were nearly constant at intermediate to high fractions of acidic lipid. Fitting the binding isotherms to a two-process binding model (nonspecific adsorption in addition to binding of acidic lipids to sites on the protein) suggested a significant acidic-lipid-independent binding affinity in addition to occupancy of three protein sites that bind PS in preference to DOPG. Both analyses indicated that interaction of factor Va with an acidic-lipid-containing membrane is much more complex than those of factor Xa or prothrombin. Furthermore, a change in the conformation of bound pyrene-labeled factor Va with surface concentration of acidic lipid was implied by variation of both the saturating fluorescence anisotropy and the binding parameters with the acidic lipid content of the membrane. Finally, the results cannot support the contention that binding occurs through nonspecific adsorption to a patch or domain of acidic lipids in the membrane. Factor Va is suggested to associate with membranes by a complex process that includes both acidic-lipid-specific and acidic-lipid-independent sites and a protein structure change induced by occupancy of acidic-lipid-specific sites on the factor Va molecule. Images FIGURE 5 PMID:8744332

Metastable Prepores in Tension-Free Lipid Bilayers

NASA Astrophysics Data System (ADS)

Ting, Christina L.; Awasthi, Neha; Müller, Marcus; Hub, Jochen S.

2018-03-01

The formation and closure of aqueous pores in lipid bilayers is a key step in various biophysical processes. Large pores are well described by classical nucleation theory, but the free-energy landscape of small, biologically relevant pores has remained largely unexplored. The existence of small and metastable "prepores" was hypothesized decades ago from electroporation experiments, but resolving metastable prepores from theoretical models remained challenging. Using two complementary methods—atomistic simulations and self-consistent field theory of a minimal lipid model—we determine the parameters for which metastable prepores occur in lipid membranes. Both methods consistently suggest that pore metastability depends on the relative volume ratio between the lipid head group and lipid tails: lipids with a larger head-group volume fraction (or shorter saturated tails) form metastable prepores, whereas lipids with a smaller head-group volume fraction (or longer unsaturated tails) form unstable prepores.

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.

Development of Clickable Monophosphoryl Lipid A Derivatives toward Semisynthetic Conjugates with Tumor-Associated Carbohydrate Antigens.

PubMed

Ziaco, Marcello; Górska, Sabina; Traboni, Serena; Razim, Agnieszka; Casillo, Angela; Iadonisi, Alfonso; Gamian, Andrzej; Corsaro, Maria Michela; Bedini, Emiliano

2017-12-14

A semisynthetic strategy to obtain monophosphoryl lipid A derivatives equipped with clickable (azide, alkyne, double bond, or thiol precursor) moieties, starting from the native lipid A isolated from Escherichia coli, is presented. These lipid A derivatives can be conjugated with other interesting biomolecules, such as tumor-associated carbohydrate antigens (TACAs). In this way, the immunostimulant activity of monophosphoryl lipid A can significantly improve the immunogenicity of TACAs, thus opening access to potential self-adjuvant anticancer vaccine candidates. A monophosphoryl lipid A-Thomson-Friedenreich (TF) antigen conjugate was obtained to demonstrate the feasibility of this methodology, which stands as a valuable, rapid, and scalable alternative to the highly complex approaches of total synthesis recently reported to the same aim. A preliminary evaluation of the immunological activity of this conjugate as well as of other semisynthetic lipid A derivatives was also reported.

Biochemical and physicochemical analysis of fish protein isolate recovered from red snapper (Lutjanus sp.) by-product using isoelectric solubilization/precipitation method

NASA Astrophysics Data System (ADS)

Pramono, H.; Pujiastuti, D. Y.; Sahidu, A. M.

2018-04-01

The effect of acid- and alkali-process on biochemical and physicochemical characteristics of fish protein isolate from red snapper (Lutjanus sp) by-product was evaluated. Protein recovered by alkali process (16.79%) was higher compared to acid process (13.75%). Reduction of lipid content and total volatile basic nitrogen (TVB-N) exhibited in both treatments indicated both process improved fish protein isolate recovered from red snapper by-product. In addition, the increasing of water holding capacity and oil binding capacity were observed. However, high peroxide value of fish protein isolate was showed in both treatment. This finding indicated that acid and alkali process can be used as a useful method to recover proteins from red snapper by-product. Alkali process gave a protein isolate with better overall quality compared to acid process.

Metabolism. Part III: Lipids.

ERIC Educational Resources Information Center

Bodner, George M.

1986-01-01

Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

Life-Cycle Assessment of Biodiesel Produced from Grease Trap Waste.

PubMed

Hums, Megan E; Cairncross, Richard A; Spatari, Sabrina

2016-03-01

Grease trap waste (GTW) is a low-quality waste material with variable lipid content that is an untapped resource for producing biodiesel. Compared to conventional biodiesel feedstocks, GTW requires different and additional processing steps for biodiesel production due to its heterogeneous composition, high acidity, and high sulfur content. Life-cycle assessment (LCA) is used to quantify greenhouse gas emissions, fossil energy demand, and criteria air pollutant emissions for the GTW-biodiesel process, in which the sensitivity to lipid concentration in GTW is analyzed using Monte Carlo simulation. The life-cycle environmental performance of GTW-biodiesel is compared to that of current GTW disposal, the soybean-biodiesel process, and low-sulfur diesel (LSD). The disposal of the water and solid wastes produced from separating lipids from GTW has a high contribution to the environmental impacts; however, the impacts of these processed wastes are part of the current disposal practice for GTW and could be excluded with consequential LCA system boundaries. At lipid concentrations greater than 10%, most of the environmental metrics studied are lower than those of LSD and comparable to soybean biodiesel.

Lipid Metabolism, Apoptosis and Cancer Therapy

PubMed Central

Huang, Chunfa; Freter, Carl

2015-01-01

Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy. PMID:25561239

A Review on The Bioconversion of Lignin to Microbial Lipid with Oleaginous Rhodococcus opacus

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

Mahan, Kristina M.; Le, Rosemary K.; Yuan, Joshua

Rhodococcus opacus produces intracellular lipids from the biodegradation of lignocellulosic biomass. These lipids can be used to produce biofuels that could potentially replace petroleum-derived chemicals. Some current studies are focusing on deconstructing lignin through efficient and cost-effective pretreatment methods and improving microbial lipid titers. Furthermore, R. opacus can reach high levels of oleaginicity (>80%) when grown on glucose and other aromatic model compounds but intracellular lipid production is much lower on complex recalcitrant lignin substrates. Our review will discuss recent advances in studying R. opacus lignin degradation by exploring different pretreatment methods, increasing lignin solubility, enriching for low molecular weightmore » lignin compounds and laccase supplementation.« less

A Review on The Bioconversion of Lignin to Microbial Lipid with Oleaginous Rhodococcus opacus

DOE PAGES

Mahan, Kristina M.; Le, Rosemary K.; Yuan, Joshua; ...

2017-06-29

Rhodococcus opacus produces intracellular lipids from the biodegradation of lignocellulosic biomass. These lipids can be used to produce biofuels that could potentially replace petroleum-derived chemicals. Some current studies are focusing on deconstructing lignin through efficient and cost-effective pretreatment methods and improving microbial lipid titers. Furthermore, R. opacus can reach high levels of oleaginicity (>80%) when grown on glucose and other aromatic model compounds but intracellular lipid production is much lower on complex recalcitrant lignin substrates. Our review will discuss recent advances in studying R. opacus lignin degradation by exploring different pretreatment methods, increasing lignin solubility, enriching for low molecular weightmore » lignin compounds and laccase supplementation.« less

Examination of the skin barrier repair/wound healing process using a living skin equivalent model and matrix-assisted laser desorption-ionization-mass spectrometry imaging.

PubMed

Lewis, E E L; Barrett, M R T; Freeman-Parry, L; Bojar, R A; Clench, M R

2018-04-01

Examination of the skin barrier repair/wound healing process using a living skin equivalent (LSE) model and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to identify lipids directly involved as potential biomarkers. These biomarkers may be used to determine whether an in vivo wound is going to heal for example if infected. An in vitro LSE model was wounded with a scalpel blade and assessed at day 4 post-wounding by histology and MALDI-MSI. Samples were sectioned at wound site and were either formalin-fixed paraffin-embedded (FFPE) for histology or snapped frozen (FF) for MSI analysis. The combination of using an in vitro wounded skin model with MSI allowed the identification of lipids involved in the skin barrier repair/wound healing process. The technique was able to highlight lipids directly in the wound site and distinguish differences in lipid distribution between the epidermis and wound site. This novel method of coupling an in vitro LSE with MSI allowed in-depth molecular analysis of the skin barrier repair/wound healing process. The technique allowed the identification of lipids directly involved in the skin barrier repair/wound healing process, indicating these biomarkers may be potentially be used within the clinic. These biomarkers will help to determine, which stage of the skin barrier repair/wound healing process the wound is in to provide the best treatment. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Nanostructured lipid system as a strategy to improve the anti-Candida albicans activity of Astronium sp.

PubMed Central

Bonifácio, Bruna Vidal; Ramos, Matheus Aparecido dos Santos; da Silva, Patrícia Bento; Negri, Kamila Maria Silveira; de Oliveira Lopes, Érica; de Souza, Leonardo Perez; Vilegas, Wagner; Pavan, Fernando Rogério; Chorilli, Marlus; Bauab, Taís Maria

2015-01-01

The genus Astronium (Anacardiaceae) includes species, such as Astronium fraxinifolium, Astronium graveolens, and Astronium urundeuva, which possess anti-inflammatory, anti-ulcerogenic, healing, and antimicrobial properties. Nanostructured lipid systems are able to potentiate the action of plant extracts, reducing the required dose and side effects and improving antimicrobial activity. This work aims to evaluate a nanostructured lipid system that was developed as a strategy to improve the anti-Candida albicans activity of hydroethanolic extracts of stems and leaves from Astronium sp. The antifungal activity against C. albicans (ATCC 18804) was evaluated in vitro by a microdilution technique. In addition to the in vitro assays, the Astronium sp. that showed the best antifungal activity and selectivity index was submitted to an in vivo assay using a model of vulvovaginal candidiasis infection. In these assays, the extracts were either used alone or were incorporated into the nanostructured lipid system (comprising 10% oil phase, 10% surfactant, and 80% aqueous phase). The results indicated a minimal inhibitory concentration of 125.00 µg/mL before incorporation into the nanostructured system; this activity was even more enhanced when this extract presented a minimal inhibitory concentration of 15.62 µg/mL after its incorporation. In vivo assay dates showed that the nanostructure-incorporated extract of A. urundeuva leaves was more effective than both the unincorporated extract and the antifungal positive control (amphotericin B). These results suggest that this nanostructured lipid system can be used in a strategy to improve the in vitro and in vivo anti-C. albicans activity of hydroethanolic extracts of Astronium sp. PMID:26300640

Design and characterization of Amoitone B-loaded nanostructured lipid carriers for controlled drug release.

PubMed

Luan, Jingjing; Zhang, Dianrui; Hao, Leilei; Li, Caiyun; Qi, Lisi; Guo, Hejian; Liu, Xinquan; Zhang, Qiang

2013-11-01

Amoitone B, a novel compound chemically synthesized as the analogue of cytosporone B, has been proved to own superior affinity with Nur77 than its parent compound and exhibit notable anticancer activity. However, its application is seriously restricted due to the water-insolubility and short biological half-time. The aim of this study was to construct an effective delivery system for Amoitone B to realize sustained release, thus prolong drug circulation time in body and improve the bioavailability. Nanostructured lipid carriers (NLC) act as a new type of colloidal drug delivery system, which offer the advantages of improved drug loading and sustained release. Amoitone B-loaded NLC (AmB-NLC) containing glyceryl monostearate (GMS) and various amounts of medium chain triglycerides (MCT) were successfully prepared by emulsion-evaporation and low temperature-solidification technology with a particle size of about 200 nm and a zeta potential value of about -20 mV. The results of X-ray diffraction and DSC analysis showed amorphous crystalline state of Amoitone B in NLC. Furthermore, the drug entrapment efficacy (EE) was improved compared with solid lipid nanoparticles (SLN). The EE range was from 71.1% to 84.7%, enhanced with the increase of liquid lipid. In vitro drug release studies revealed biphasic drug release patterns with burst release initially and prolonged release afterwards and the release was accelerated with augment of liquid lipid. These results demonstrated that AmB-NLC could be a promising delivery system to control drug release and improve loading capacity, thus prolong drug action time in body and enhance the bioavailability.

Exploring lipids with nonlinear optical microscopy in multiple biological systems

NASA Astrophysics Data System (ADS)

Alfonso-Garcia, Alba

Lipids are crucial biomolecules for the well being of humans. Altered lipid metabolism may give rise to a variety of diseases that affect organs from the cardiovascular to the central nervous system. A deeper understanding of lipid metabolic processes would spur medical research towards developing precise diagnostic tools, treatment methods, and preventive strategies for reducing the impact of lipid diseases. Lipid visualization remains a complex task because of the perturbative effect exerted by traditional biochemical assays and most fluorescence markers. Coherent Raman scattering (CRS) microscopy enables interrogation of biological samples with minimum disturbance, and is particularly well suited for label-free visualization of lipids, providing chemical specificity without compromising on spatial resolution. Hyperspectral imaging yields large datasets that benefit from tailored multivariate analysis. In this thesis, CRS microscopy was combined with Raman spectroscopy and other label-free nonlinear optical techniques to analyze lipid metabolism in multiple biological systems. We used nonlinear Raman techniques to characterize Meibum secretions in the progression of dry eye disease, where the lipid and protein contributions change in ratio and phase segregation. We employed similar tools to examine lipid droplets in mice livers aboard a spaceflight mission, which lose their retinol content contributing to the onset of nonalcoholic fatty-liver disease. We also focused on atherosclerosis, a disease that revolves around lipid-rich plaques in arterial walls. We examined the lipid content of macrophages, whose variable phenotype gives rise to contrasting healing and inflammatory activities. We also proposed new label-free markers, based on lifetime imaging, for macrophage phenotype, and to detect products of lipid oxidation. Cholesterol was also detected in hepatitis C virus infected cells, and in specific strains of age-related macular degeneration diseased cells by spontaneous Raman spectroscopy. We used synthesized highly-deuterated cholesterol to track its compartmentalization in adrenal cells, revealing heterogeneous lipid droplet content. These examples illustrate the potential of label-free nonlinear optical microscopy for unveiling complex physiological processes by direct visualization of lipids. Detailed image analysis and combined microscopy modalities will continue to reveal and quantify fundamental biology that will support the advance of biomedicine.

A survey of useful salt additives in matrix-assisted laser desorption/ionization mass spectrometry and tandem mass spectrometry of lipids: introducing nitrates for improved analysis.

PubMed

Griffiths, Rian L; Bunch, Josephine

2012-07-15

Matrix-assisted laser desorption/ionization (MALDI) is a powerful technique for the direct analysis of lipids in complex mixtures and thin tissue sections, making it an extremely attractive method for profiling lipids in health and disease. Lipids are readily detected as [M+H](+), [M+Na](+) and [M+K](+) ions in positive ion MALDI mass spectrometry (MS) experiments. This not only decreases sensitivity, but can also lead to overlapping m/z values of the various adducts of different lipids. Additives can be used to promote formation of a particular adduct, improving sensitivity, reducing spectral complexity and enhancing structural characterization in collision-induced dissociation (CID) experiments. Li(+), Na(+), K(+), Cs(+) and NH(4)(+) cations were considered as a range of salt types (acetates, chlorides and nitrates) incorporated into DHB matrix solutions at concentrations between 5 and 80 mM. The study was extended to evaluate the effect of these additives on CID experiments of a lipid standard, after optimization of collision energy parameters. Experiments were performed on a hybrid quadrupole time-of-flight (QqTOF) instrument. The systematic evaluation of new and existing additives in MALDI-MS and MS/MS of lipids demonstrated the importance of additive cation and anion choice and concentration for tailoring spectral results. The recommended choice of additive depends on the desired outcomes of the experiment to be performed (MS or MS/MS). Nitrates are found to be particularly useful additives for lipid analysis. Copyright © 2012 John Wiley & Sons, Ltd.

Aronia melanocarpa Extract Ameliorates Hepatic Lipid Metabolism through PPARγ2 Downregulation

PubMed Central

Kim, Jung-Hee; Lee, Eun Byul; Hur, Wonhee; Kwon, Oh-Joo; Park, Hyoung-Jin; Yoon, Seung Kew

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Studies have demonstrated that anthocyanin-rich foods may improve hyperlipidemia and ameliorate hepatic steatosis. Here, effects of Aronia melanocarpa (AM), known to be rich of anthocyanins, on hepatic lipid metabolism and adipogenic genes were determined. AM was treated to C57BL/6N mice fed with high fat diet (HFD) or to FL83B cells treated with free fatty acid (FFA). Changes in levels of lipids, enzymes and hormones were observed, and expressions of adipogenic genes involved in hepatic lipid metabolism were detected by PCR, Western blotting and luciferase assay. In mice, AM significantly reduced the body and liver weight, lipid accumulation in the liver, and levels of biochemical markers such as fatty acid synthase, hepatic triglyceride and leptin. Serum transaminases, indicators for hepatocyte injury, were also suppressed, while superoxide dismutase activity and liver antioxidant capacity were significantly increased. In FL83B cells, AM significantly reduced FFA-induced lipid droplet accumulation. Protein synthesis of an adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2) was inhibited in vivo. Furthermore, transcriptional activity of PPARγ2 was down-regulated in vitro, and mRNA expression of PPARγ2 and its downstream target genes, adipocyte protein 2 and lipoprotein lipase were down-regulated by AM both in vitro and in vivo. These results show beneficial effects of AM against hepatic lipid accumulation through the inhibition of PPARγ2 expression along with improvements in body weight, liver functions, lipid profiles and antioxidant capacity suggesting the potential therapeutic efficacy of AM on NAFLD. PMID:28081181

Aronia melanocarpa Extract Ameliorates Hepatic Lipid Metabolism through PPARγ2 Downregulation.

PubMed

Park, Chung-Hwa; Kim, Jung-Hee; Lee, Eun Byul; Hur, Wonhee; Kwon, Oh-Joo; Park, Hyoung-Jin; Yoon, Seung Kew

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Studies have demonstrated that anthocyanin-rich foods may improve hyperlipidemia and ameliorate hepatic steatosis. Here, effects of Aronia melanocarpa (AM), known to be rich of anthocyanins, on hepatic lipid metabolism and adipogenic genes were determined. AM was treated to C57BL/6N mice fed with high fat diet (HFD) or to FL83B cells treated with free fatty acid (FFA). Changes in levels of lipids, enzymes and hormones were observed, and expressions of adipogenic genes involved in hepatic lipid metabolism were detected by PCR, Western blotting and luciferase assay. In mice, AM significantly reduced the body and liver weight, lipid accumulation in the liver, and levels of biochemical markers such as fatty acid synthase, hepatic triglyceride and leptin. Serum transaminases, indicators for hepatocyte injury, were also suppressed, while superoxide dismutase activity and liver antioxidant capacity were significantly increased. In FL83B cells, AM significantly reduced FFA-induced lipid droplet accumulation. Protein synthesis of an adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2) was inhibited in vivo. Furthermore, transcriptional activity of PPARγ2 was down-regulated in vitro, and mRNA expression of PPARγ2 and its downstream target genes, adipocyte protein 2 and lipoprotein lipase were down-regulated by AM both in vitro and in vivo. These results show beneficial effects of AM against hepatic lipid accumulation through the inhibition of PPARγ2 expression along with improvements in body weight, liver functions, lipid profiles and antioxidant capacity suggesting the potential therapeutic efficacy of AM on NAFLD.

Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles.

PubMed

Noriega-Peláez, Eddy Kei; Mendoza-Muñoz, Néstor; Ganem-Quintanar, Adriana; Quintanar-Guerrero, David

2011-02-01

The essential aim of this article is to prepare solid lipid nanoparticles (SLNs) by emulsification and solvent displacement method and to determine the best process conditions to obtain submicron particles. The emulsification and solvent displacement method is a modification of the well-known emulsification-diffusion method, but without dilution of the system. The extraction of the partially water-miscible solvent from the emulsion globules is carried out under reduced pressure, which causes the diffusion of the solvent toward the external phase, with subsequent lipid aggregation in particles whose size will depend on the process conditions. The critical variables affecting the process, such as stirring rate, the proportion of phases in the emulsion, and the amount of stabilizer and lipid, were evaluated and optimized. By this method, it was possible to obtain a high yield of solids in the dispersion for the lipids evaluated (Compritol(®) ATO 888, Geleol(®), Gelucire(®) 44/14, and stearic acid). SLNs of up to ∼20 mg/mL were obtained for all lipids evaluated. A marked reduction in size, between 500 and 2500 rpm, was seen, and a transition from micro- to nanometric size was observed. The smaller particle sizes obtained were 113 nm for Compritol(®) ATO 888, 70 nm for Gelucire(®) 44/14, 210 nm for Geleol(®), and 527 nm for stearic acid, using a rotor-stator homogenizer (Ultra-Turrax(®)) at 16,000 rpm. The best phase ratio (organic/aqueous) was 1 : 2. The process proposed in this study is a new alternative to prepare SLNs with technological potential.

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

Biodiesel production by direct transesterification of microalgal biomass with co-solvent.

PubMed

Zhang, Yan; Li, Ya; Zhang, Xu; Tan, Tianwei

2015-11-01

In this study, a direct transesterification process using 75% ethanol and co-solvent was studied to reduce the energy consumption of lipid extraction process and improve the conversion yield of the microalgae biodiesel. The addition of a certain amount of co-solvent (n-hexane is most preferable) was required for the direct transesterification of microalgae biomass. With the optimal reaction condition of n-hexane to 75% ethanol volume ratio 1:2, mixed solvent dosage 6.0mL, reaction temperature 90°C, reaction time 2.0h and catalyst volume 0.6mL, the direct transesterification process of microalgal biomass resulted in a high conversion yield up to 90.02±0.55wt.%. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lipids and lipid binding proteins: a perfect match.

PubMed

Glatz, Jan F C

2015-02-01

Lipids serve a great variety of functions, ranging from structural components of biological membranes to signaling molecules affecting various cellular functions. Several of these functions are related to the unique physico-chemical properties shared by all lipid species, i.e., their hydrophobicity. The latter, however, is accompanied by a poor solubility in an aqueous environment and thus a severe limitation in the transport of lipids in aqueous compartments such as blood plasma and the cellular soluble cytoplasm. Specific proteins which can reversibly and non-covalently associate with lipids, designated as lipid binding proteins or lipid chaperones, greatly enhance the aqueous solubility of lipids and facilitate their transport between tissues and within tissue cells. Importantly, transport of lipids across biological membranes also is facilitated by specific (membrane-associated) lipid binding proteins. Together, these lipid binding proteins determine the bio-availability of their ligands, and thereby markedly influence the subsequent processing, utilization, or signaling effect of lipids. The bio-availability of specific lipid species thus is governed by the presence of specific lipid binding proteins, the affinity of these proteins for distinct lipid species, and the presence of competing ligands (including pharmaceutical compounds). Recent studies suggest that post-translational modifications of lipid binding proteins may have great impact on lipid-protein interactions. As a result, several levels of regulation exist that together determine the bio-availability of lipid species. This short review discusses the significance of lipid binding proteins and their potential application as targets for therapeutic intervention. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Holt, Allison M; Standaert, Robert F; Jubb, Aaron M

Biological membranes, formed primarily by the self-assembly of complex mixtures of phospholipids, provide a structured scaffold for compartmentalization and structural processes in living cells. The specific physical properties of phospholipid species present in a given membrane play a key role in mediating these processes. Phosphatidylethanolamine (PE), a zwitterionic lipid present in bacterial, yeast, and mammalian cell membranes, is exceptional. In addition to undergoing the standard lipid polymorphic transition between the gel and liquid-crystalline phase, it can also assume an unusual polymorphic state, the inverse hexagonal phase (HII). Divalent cations are among the factors that drive the formation of the HIImore » phase, wherein the lipid molecules form stacked tubular structures by burying the hydrophilic head groups and exposing the hydrophobic tails to the bulk solvent. Most biological membranes contain a lipid species capable of forming the HII state suggesting that such lipid polymorphic structural states play an important role in structural biological processes such as membrane fusion. In this study, the interactions between Mg2+ and biomimetic bacterial cell membranes composed of PE and phosphatidylglycerol (PG) were probed using differential scanning calorimetry (DSC), small-angle x-ray scattering (SAXS), and fluorescence spectroscopy. The lipid phase transitions were examined at varying ratios of PE to PG and upon exposure to physiologically relevant concentrations of Mg2+. An understanding of these basic interactions enhances our understanding of membrane dynamics and how membrane-mediated structural changes may occur in vivo.« less

Investigating Hydrophilic Pores in Model Lipid Bilayers using Molecular Simulations: Correlating Bilayer Properties with Pore Formation Thermodynamics

PubMed Central

Hu, Yuan; Sinha, Sudipta Kumar

2015-01-01

Cell-penetrating and antimicrobial peptides show remarkable ability to translocate across physiological membranes. Along with factors such as electric potential induced-perturbations of membrane structure and surface tension effects, experiments invoke pore-like membrane configurations during the solute transfer process into vesicles and cells. The initiation and formation of pores are associated with a non-trivial free energy cost, thus necessitating consideration of the factors associated with pore formation and attendant free energetics. Due to experimental and modeling challenges related to the long timescales of the translocation process, we use umbrella-sampling molecular dynamics simulations with a lipid-density based order parameter to investigate membrane pore-formation free energy employing Martini coarse-grained models. We investigate structure and thermodynamic features of the pore in 18 lipids spanning a range of head-groups, charge states, acyl chain lengths and saturation. We probe the dependence of pore-formation barriers on area per lipid, lipid bilayer thickness, membrane bending rigidities in three different lipid classes. The pore formation free energy in pure bilayers and peptide translocating scenarios are significantly coupled with bilayer thickness. Thicker bilayers require more reversible work to create pores. Pore formation free energy is higher in peptide-lipid systems relative to the peptide-free lipid systems due to penalties to maintain solvation of charged hydrophilic solutes within the membrane environment. PMID:25614183

Investigating Hydrophilic Pores in Model Lipid Bilayers Using Molecular Simulations: Correlating Bilayer Properties with Pore-Formation Thermodynamics.

PubMed

Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

2015-06-23

Cell-penetrating and antimicrobial peptides show a remarkable ability to translocate across physiological membranes. Along with factors such as electric-potential-induced perturbations of membrane structure and surface tension effects, experiments invoke porelike membrane configurations during the solute transfer process into vesicles and cells. The initiation and formation of pores are associated with a nontrivial free-energy cost, thus necessitating a consideration of the factors associated with pore formation and the attendant free energies. Because of experimental and modeling challenges related to the long time scales of the translocation process, we use umbrella sampling molecular dynamics simulations with a lipid-density-based order parameter to investigate membrane-pore-formation free energy employing Martini coarse-grained models. We investigate structure and thermodynamic features of the pore in 18 lipids spanning a range of headgroups, charge states, acyl chain lengths, and saturation. We probe the dependence of pore-formation barriers on the area per lipid, lipid bilayer thickness, and membrane bending rigidities in three different lipid classes. The pore-formation free energy in pure bilayers and peptide translocating scenarios are significantly coupled with bilayer thickness. Thicker bilayers require more reversible work to create pores. The pore-formation free energy is higher in peptide-lipid systems than in peptide-free lipid systems due to penalties to maintain the solvation of charged hydrophilic solutes within the membrane environment.

Study of supported bilayer lipid membranes for use in chemo-electric energy conversion via active proton transport

NASA Astrophysics Data System (ADS)

Sarles, Stephen A.; Sundaresan, Vishnu B.; Leo, Donald J.

2007-09-01

Bilayer lipid membranes (BLMs) have been studied extensively due to functional and structural similarities to cell membranes, fostering research to understand ion-channel protein functions, measure bilayer mechanical properties, and identify self-assembly mechanisms. BLMs have traditionally been formed across single pores in substrates such as PTFE (Teflon). The incorporation of ion-channel proteins into the lipid bilayer enables the selective transfer of ions and fluid through the BLM. Processes of this nature have led to the measurement of ion current flowing across the lipid membrane and have been used to develop sensors that signal the presence of a particular reactant (glucose, urea, penicillin), improve drug recognition in cells, and develop materials capable of creating chemical energy from light. Recent research at Virginia Tech has shown that the incorporation of proton transporters in a supported BLM formed across an array of pores can convert chemical energy available in the adenosine triphosphate (ATP) into electricity. Experimental results from this work show that the system-named Biocell-is capable of developing 2µW/cm2 of membrane area with 15μl of ATPase. Efforts to increase the power output and conversion efficiency of this process while moving toward a packaged device present a unique engineering problem. The bilayer, as host to the active proton transporters, must therefore be formed evenly across a porous substrate, remain stable and yet fluid-like for protein interaction, and exhibit a large seal resistance. This article presents the ongoing work to characterize the Biocell using impedance analysis. Electrical impedance spectroscopy (EIS) is used to study the effect of adding ATPase proteins to POPS:POPE bilayer lipid membranes and correlate structural changes evident in the impedance data to the energy-conversion capability of various partial and whole Biocell assemblies. The specific membrane resistance of a pure BLM drops from 40-120kΩ•cm2 to only a few hundred Ω•cm2 upon reconstitution of ATPase proteins. Power characterization indicates that ATP hydrolysis may result in charging of the silver-silver chloride electrodes.

Nanointaglio fabrication of optical lipid multilayer diffraction gratings with applications in biosensing

NASA Astrophysics Data System (ADS)

Lowry, Troy Warren

The dynamic self-organization of lipids in biological systems is a highly regulated process that enables the compartmentalization of living systems at microscopic and nanoscopic levels. Exploiting the self-organization and innate biofunctionality of lyotropic liquid crystalline phospholipids, a novel nanofabrication process called "nanointaglio" was invented in order to rapidly and scalably integrate lipid nanopatterns onto the surface. The work presented here focuses on using nanointaglio fabricated lipid diffraction micro- and nanopatterns for the development of new sensing and bioactivity studies. The lipids are patterned as diffraction gratings for sensor functionality. The lipid multilayer gratings operate as nanomechanical sensor elements that are capable of transducing molecular binding to fluid lipid multilayers into optical signals in a label free manner due to shape changes in the lipid nanostructures. To demonstrate the label free detection capabilities, lipid nanopatterns are shown to be suitable for the integration of chemically different lipid multilayer gratings into a sensor array capable of distinguishing vapors by means of an optical nose. Sensor arrays composed of six different lipid formulations are integrated onto a surface and their optical response to three different vapors (water, ethanol and acetone) in air as well as pH under water is monitored as a function of time. Principal component analysis of the array response results in distinct clustering, indicating the suitability of the arrays for distinguishing these analytes. Importantly, the nanointaglio process used is capable of producing lipid gratings out of different materials with sufficiently uniform heights for the fabrication of an optical nose. A second main application is demonstrated for the study of membrane binding proteins. Although in vitro methods for assaying the catalytic activity of individual enzymes are well established, quantitative methods for assaying the kinetics of supramolecular remodeling such as vesicle formation from planar lipid bilayers or multilayers are needed to understand cellular self-organization. Presented next is a nanointaglio based method for quantitative measurements of lipid-protein interactions and its suitability for quantifying the membrane binding, inflation, and budding activity of the membrane-remodeling protein Sar1. Optical diffraction gratings composed of lipids are printed on surfaces using nanointaglio, resulting in lipid multilayer gratings. Exposure of lipid multilayer gratings to Sar1 results in the inflation of lipid multilayers into unilamellar structures, the kinetics of which can be detected in a label-free manner by monitoring the diffraction of white light through an optical microscope. Local variations in lipid multilayer volume on the surface can be used to vary substrate availability in a microarray format, allowing kinetic and thermodynamic data to be obtained from a single experiment without the need for varying enzyme concentration. A quantitative model is developed and fits to the data allow measurements of both binding affinity (KD) and kinetics (kon and koff). Importantly, this assay is uniquely capable of quantifying membrane remodeling. Upon Sar1 induced inflation of single bilayers from surface supported multilayers, the semi-cylindrical grating lines are observed to remodel into semi-spherical buds when a critical radius of curvature equal to 300 nm is reached, which is explained in terms of a Rayleigh type instability.

The potential role of IDEAL MRI for identification of lipids and hemorrhage in carotid artery plaques.

PubMed

Khosa, Faisal; Clough, Rachel E; Wang, Xiaoen; Madhuranthakam, Ananth J; Greenman, Robert L

2018-06-01

Hemorrhage and lipid deposits contribute to instability in atherosclerotic plaques. Unstable carotid artery plaques can lead to cerebral ischemic events. While MRI studies have shown the ability to identify plaque components, the identification of hemorrhage and lipids has proven to be problematic. The purpose of this study was to quantitatively evaluate the potential of the MRI fat/water separation method known as iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL) to complement and improve existing methods for the identification of hemorrhage and lipids in carotid artery plaques. Fifteen asymptomatic subjects with 50-79% stenosis of at least one carotid artery were enrolled. Hemorrhage and lipid components within carotid plaques were identified using previously published criteria based on the multiple contrast-weighted (MCW) method (3D Time-of-Flight (3D-TOF), T1-Weighted (T1W) and T2-Weighted (T2W)). The hemorrhage:muscle, lipid:muscle and intra-plaque lipid:hemorrhage signal intensity ratios (SIR) and contrast to noise ratios (CNR) were measured on MCW and compared to IDEAL black-blood images. No differences were found between any of the MCW methods for any of the SIRs measured. The IDEAL Fat images had higher lipid:muscle and lipid/hemorrhage SIRs (p<0.001) compared to IDEAL Water and all MCW image sequence types. The mean values of IDEAL Fat hemorrhage:muscle SIR and CNR were nearly unity (1.1±0.6) and nearly zero (0.1±1.1), respectively. The IDEAL Water imaging was not significantly different than any of the MCW methods for any of the SIRs or for the hemorrhage:muscle CNR of 3D-TOF, while its CNRs were significantly higher than IDEAL Fat lipid:muscle (p<0.05) and lipid:hemorrhage (p<0.001) and all MCW methods (p<0.001). The addition of IDEAL Water and Fat imaging to the MCW method shows potential to improve the identification of hemorrhage and lipid structures in carotid artery plaques. Copyright © 2017 Elsevier Inc. All rights reserved.

Trifunctional lipid probes for comprehensive studies of single lipid species in living cells

PubMed Central

Nadler, André; Haberkant, Per; Kirkpatrick, Joanna; Schifferer, Martina; Stein, Frank; Hauke, Sebastian; Porter, Forbes D.; Schultz, Carsten

2017-01-01

Lipid-mediated signaling events regulate many cellular processes. Investigations of the complex underlying mechanisms are difficult because several different methods need to be used under varying conditions. Here we introduce multifunctional lipid derivatives to study lipid metabolism, lipid−protein interactions, and intracellular lipid localization with a single tool per target lipid. The probes are equipped with two photoreactive groups to allow photoliberation (uncaging) and photo–cross-linking in a sequential manner, as well as a click-handle for subsequent functionalization. We demonstrate the versatility of the design for the signaling lipids sphingosine and diacylglycerol; uncaging of the probe for these two species triggered calcium signaling and intracellular protein translocation events, respectively. We performed proteomic screens to map the lipid-interacting proteome for both lipids. Finally, we visualized a sphingosine transport deficiency in patient-derived Niemann−Pick disease type C fibroblasts by fluorescence as well as correlative light and electron microscopy, pointing toward the diagnostic potential of such tools. We envision that this type of probe will become important for analyzing and ultimately understanding lipid signaling events in a comprehensive manner. PMID:28154130

Multilateral approach on enhancing economic viability of lipid production from microalgae: A review.

PubMed

Shin, Ye Sol; Choi, Hong Il; Choi, Jin Won; Lee, Jeong Seop; Sung, Young Joon; Sim, Sang Jun

2018-06-01

Microalgae have been rising as a feedstock for biofuel in response to the energy crisis. Due to a high lipid content, composed of fatty acids favorable for the biodiesel production, microalgae are still being investigated as an alternative to biodiesel. Environmental factors and process conditions can alternate the quality and the quantity of lipid produced by microalgae, which can be critical for the overall production of biodiesel. To maximize both the lipid content and the biomass productivity, it is necessary to start with robust algal strains and optimal physio-chemical properties of the culture environment in combination with a novel culture system. These accumulative approaches for cost reduction can take algal process one step closer in achieving the economic feasibility. Copyright © 2018 Elsevier Ltd. All rights reserved.

Role of macromolecules in the safety of use of body wash cosmetics.

PubMed

Bujak, Tomasz; Wasilewski, Tomasz; Nizioł-Łukaszewska, Zofia

2015-11-01

One of the most challenging problems related to the use of surfactants in body wash cosmetics is their potential to cause skin irritations. Surfactants can bind with proteins, remove lipids from the epidermal surface, contribute to the disorganization of liquid crystal structures in the intercellular lipids, and interact with living skin cells. These processes can lead to skin irritations and allergic reactions, and impair the epidermal barrier function. The present study is an attempt to assess the effect of polymers and hydrolysed proteins present in the formulations of model body wash cosmetics on product properties. Special attention was given to the safety of use of this product type. The study examined three macromolecules: polyvinylpyrrolidone (PVP), hydrolysed wheat protein (HWP) and polyvinylpyrrolidone/hydrolysed wheat protein crosspolymer (PVP/HWP). The addition of the substances under study was found to improve the foaming properties of body wash cosmetics, increase their stability during storage, and contribute significantly to an improvement in the safety of product use by reducing the irritant potential. The strongest ability to reduce the skin irritation potential was determined for the formula enriched with the PVP/HWP crosspolymer. Copyright © 2015 Elsevier B.V. All rights reserved.

Continuous selection pressure to improve temperature acclimation of Tisochrysis lutea

PubMed Central

Grimaud, Ghjuvan; Rumin, Judith; Bougaran, Gaël; Talec, Amélie; Gachelin, Manon; Boutoute, Marc; Pruvost, Eric; Bernard, Olivier; Sciandra, Antoine

2017-01-01

Temperature plays a key role in outdoor industrial cultivation of microalgae. Improving the thermal tolerance of microalgae to both daily and seasonal temperature fluctuations can thus contribute to increase their annual productivity. A long term selection experiment was carried out to increase the thermal niche (temperature range for which the growth is possible) of a neutral lipid overproducing strain of Tisochrysis lutea. The experimental protocol consisted to submit cells to daily variations of temperature for 7 months. The stress intensity, defined as the amplitude of daily temperature variations, was progressively increased along successive selection cycles. Only the amplitude of the temperature variations were increased, the daily average temperature was kept constant along the experiment. This protocol resulted in a thermal niche increase by 3°C (+16.5%), with an enhancement by 9% of the maximal growth rate. The selection process also affected T. lutea physiology, with a feature generally observed for ‘cold-temperature’ type of adaptation. The amount of total and neutral lipids was significantly increased, and eventually productivity was increased by 34%. This seven month selection experiment, carried out in a highly dynamic environment, challenges some of the hypotheses classically advanced to explain the temperature response of microalgae. PMID:28902878

Understanding the effect of particle size and processing on almond lipid bioaccessibility through microstructural analysis: from mastication to faecal collection

USDA-ARS?s Scientific Manuscript database

We have previously reported on the low lipid bioaccessibility from almond seeds during digestion in the upper gastrointestinal tract (GIT). In the present study, we quantified the lipid released during artificial mastication from four almond meals: natural raw almonds (NA), roasted almonds (RA), roa...

Production of solid lipid submicron particles for protein delivery using a novel supercritical gas-assisted melting atomization process.

PubMed

Salmaso, Stefano; Elvassore, Nicola; Bertucco, Alberto; Caliceti, Paolo

2009-02-01

A supercritical carbon dioxide micronization technique based on gas-assisted melting atomization has been designed to prepare protein-loaded solid lipid submicron particles. The supercritical process was applied to homogeneous dispersions of insulin in lipid mixtures: (1) tristearin, Tween-80, phosphatidylcholine and 5 kDa PEG (1:0.1:0.9:1 and 1:0.1:0.9:2 weight ratio); and (2) tristearin, dioctyl sulfosuccinate and phosphatidylcholine (1:1:0.5 weight ratio). Optimized process conditions yielded dry nonagglomerated powders with high product recovery (70%, w/w). Dynamic light scattering and transmission electron microscopy showed that two size fractions of particles, with 80-120 and 200-400 nm diameters, were produced. In all final products, dimethylsulfoxide used to prepare the insulin/lipid mixture was below 20 ppm. Protein encapsulation efficiency increased up to 80% as the DMSO content in the insulin/lipid mixture increased. Compared to the particles without PEG, the polymer-containing particles dispersed rapidly in water, and the dispersions were more stable under centrifugation as less than 20% of suspended particles precipitated after extensive centrifugation. In vitro, the protein was slowly released from the formulation without PEG, while a burst and faster release were obtained from the formulations containing PEG. Subcutaneous injection to diabetic mice of insulin extracted from the particles showed that the supercritical process did not impair the protein hypoglycemic activity.

Downstream Processing of Synechocystis for Biofuel Production

NASA Astrophysics Data System (ADS)

Sheng, Jie

Lipids and free fatty acids (FFA) from cyanobacterium Synechocystis can be used for biofuel (e.g. biodiesel or renewable diesel) production. In order to utilize and scale up this technique, downstream processes including culturing and harvest, cell disruption, and extraction were studied. Several solvents/solvent systems were screened for lipid extraction from Synechocystis. Chloroform + methanol-based Folch and Bligh & Dyer methods were proved to be "gold standard" for small-scale analysis due to their highest lipid recoveries that were confirmed by their penetration of the cell membranes, higher polarity, and stronger interaction with hydrogen bonds. Less toxic solvents, such as methanol and MTBE, or direct transesterification of biomass (without preextraction step) gave only slightly lower lipid-extraction yields and can be considered for large-scale application. Sustained exposure to high and low temperature extremes severely lowered the biomass and lipid productivity. Temperature stress also triggered changes of lipid quality such as the degree of unsaturation; thus, it affected the productivities and quality of Synechocystis-derived biofuel. Pulsed electric field (PEF) was evaluated for cell disruption prior to lipid extraction. A treatment intensity > 35 kWh/m3 caused significant damage to the plasma membrane, cell wall, and thylakoid membrane, and it even led to complete disruption of some cells into fragments. Treatment by PEF enhanced the potential for the low-toxicity solvent isopropanol to access lipid molecules during subsequent solvent extraction, leading to lower usage of isopropanol for the same extraction efficiency. Other cell-disruption methods also were tested. Distinct disruption effects to the cell envelope, plasma membrane, and thylakoid membranes were observed that were related to extraction efficiency. Microwave and ultrasound had significant enhancement of lipid extraction. Autoclaving, ultrasound, and French press caused significant release of lipid into the medium, which may increase solvent usage and make medium recycling difficult. Production of excreted FFA by mutant Synechocystis has the potential of reducing the complexity of downstream processing. Major problems, such as FFA precipitation and biodegradation by scavengers, account for FFA loss in operation. Even a low concentration of FFA scavengers could consume FFA at a high rate that outpaced FFA production rate. Potential strategies to overcome FFA loss include high pH, adsorptive resin, and sterilization techniques.

Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

PubMed

Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

2012-10-01

Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.