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Sample records for modeling lipid accumulation

  1. Quercetin improves insulin resistance and hepatic lipid accumulation in vitro in a NAFLD cell model

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    LI, XIULI; Wang, Rong; Zhou, Na; Wang, XiaoHui; Liu, Qingyan; Bai, Yuqin; BAI, YIN; Liu, Zhijie; YANG, HUIMING; ZOU, JIHONG; Wang, Hongxia; SHI, TIEWEI

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases in the absence of significant alcohol consumption. The aim of this study was to investigate the effect of quercetin on insulin resistance and lipid metabolic abnormalities in free fatty acid (FFA)- and insulin-induced HepG2 cell model of NAFLD, and to determine the possible underlying mechanism. Quercetin markedly improves hepatic lipid accumulation and decreases the levels of triglyceride (TG). The lipid-lower...

  2. A Linear Programming Approach for Modeling and Simulation of Growth and Lipid Accumulation of Phaeodactylum tricornutum

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    Clemens Posten

    2013-10-01

    Full Text Available The unicellular microalga Phaeodactylum tricornutum exhibits the ability to accumulate triacylglycerols to a high specific content when nutrients are limited in the culture medium. Therefore, the organism is a promising candidate for biodiesel production. Mathematical modeling can substantially contribute to process development and optimization of algae cultivation on different levels. In our work we describe a linear programming approach to model and simulate the growth and storage molecule accumulation of P. tricornutum. The model is based on mass and energy balances and shows that the organism realizes the inherent drive for maximization of energy to biomass conversion and growth. The model predicts that under nutrient limiting conditions both storage carbohydrates and lipids are synthesized simultaneously but at different rates. The model was validated with data gained from batch growth experiments.

  3. Statistical analysis and modeling of pelletized cultivation of Mucor circinelloides for microbial lipid accumulation.

    Science.gov (United States)

    Xia, Chunjie; Wei, Wei; Hu, Bo

    2014-04-01

    Microbial oil accumulation via oleaginous fungi has some potential benefits because filamentous fungi can form pellets during cell growth and these pellets are easier to harvest from the culture broth than individual cells. This research studied the effect of various culture conditions on the pelletized cell growth of Mucor circinelloides and its lipid accumulation. The results showed that cell pelletization was positively correlated to biomass accumulation; however, pellet size was negatively correlated to the oil content of the fungal biomass, possibly due to the mass transfer barriers generated by the pellet structure. How to control the size of the pellet is the key to the success of the pelletized microbial oil accumulation process.

  4. Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models

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    Youying Zhang

    2017-06-01

    Full Text Available The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d and atorvastatin (15 mg/kg/d via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL for 8 weeks. Xyloketal B significantly improved HFD+HFL-induced hepatic histological lesions and attenuated lipid and glucose accumulation in the blood as well as lipid accumulation in the liver. Xyloketal B increased the expression of CPT1A, and decreased the expression of SREBP-1c and its downstream targeting enzymes such as ACC1, ACL, and FAS. Xyloketal B also significantly reduced lipid accumulation in HepG2 cells treated with free fatty acids (FFAs. These data suggested that xyloketal B has lipid-lowering effects via the SREBP-1c pathway that regulate lipid metabolism. Thus, targeting SREBP-1c activation with xyloketal B may be a promising novel approach for NAFLD treatment.

  5. Comprehensive modeling and investigation of the effect of iron on the growth rate and lipid accumulation of Chlorella vulgaris cultured in batch photobioreactors.

    Science.gov (United States)

    Concas, Alessandro; Steriti, Alberto; Pisu, Massimo; Cao, Giacomo

    2014-02-01

    Recent works have shown that specific strains of microalgae are capable to simultaneously increase their growth rate and lipid content when cultured under suitable concentrations of iron. While these results are promising in view of the exploitation of microalgae for producing biofuels, to the best of our knowledge, no mathematical model capable to describe the effect of iron on lipid accumulation in microalgae, has been so far proposed. A comprehensive mathematical model describing the effect of iron on chlorophyll synthesis, nitrogen assimilation, growth rate and lipid accumulation in a freshwater strain of Chlorella vulgaris is then proposed in this work. Model results are successfully compared with experimental data which confirm the positive effect of growing iron concentrations on lipid productivity of C. vulgaris. Thus, the proposed model might represent a useful tool to optimize iron-based strategies to improve the lipid productivity of microalgal cultures.

  6. Diets enriched in trans-11 vaccenic acid alleviate ectopic lipid accumulation in a rat model of NAFLD and metabolic syndrome.

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    Jacome-Sosa, M Miriam; Borthwick, Faye; Mangat, Rabban; Uwiera, Richard; Reaney, Martin J; Shen, Jianheng; Quiroga, Ariel D; Jacobs, René L; Lehner, Richard; Proctor, Spencer D; Nelson, Randal C

    2014-07-01

    Trans11-18:1 (vaccenic acid, VA) is one of the most predominant naturally occurring trans fats in our food chain and has recently been shown to exert hypolipidemic effects in animal models. In this study, we reveal new mechanism(s) by which VA can alter body fat distribution, energy utilization and dysfunctional lipid metabolism in an animal model of obesity displaying features of the metabolic syndrome (MetS). Obese JCR:LA-cp rats were assigned to a control diet that included dairy-derived fat or the control diet supplemented with 1% VA. VA reduced total body fat (-6%), stimulated adipose tissue redistribution [reduced mesenteric fat (-17%) while increasing inguinal fat mass (29%)] and decreased adipocyte size (-44%) versus control rats. VA supplementation also increased metabolic rate (7%) concomitantly with an increased preference for whole-body glucose utilization for oxidation and increased insulin sensitivity [lower HOMA-IR (-59%)]. Further, VA decreased nonalcoholic fatty liver disease activity scores (-34%) and reduced hepatic (-27%) and intestinal (-39%) triglyceride secretion relative to control diet, while exerting differential transcriptional regulation of SREBP1 and FAS amongst other key genes in the liver and the intestine. Adding VA to dairy fat alleviates features of MetS potentially by remodeling adipose tissue and attenuating ectopic lipid accumulation in a rat model of obesity and MetS. Increasing VA content in the diet (naturally or by fortification) may be a useful approach to maximize the health value of dairy-derived fats.

  7. Cholesterol accumulation in Niemann Pick type C (NPC) model cells causes a shift in APP localization to lipid rafts

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    Kosicek, Marko, E-mail: marko.kosicek@irb.hr [Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia); Malnar, Martina, E-mail: martina.malnar@irb.hr [Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia); Goate, Alison, E-mail: goate@icarus.wustl.edu [Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110 (United States); Hecimovic, Silva, E-mail: silva.hecimovic@irb.hr [Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia)

    2010-03-12

    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 gradient 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.

  8. A genome-scale metabolic model of the lipid-accumulating yeast Yarrowia lipolytica

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    Loira Nicolas

    2012-05-01

    Full Text Available Abstract Background Yarrowia lipolytica is an oleaginous yeast which has emerged as an important microorganism for several biotechnological processes, such as the production of organic acids, lipases and proteases. It is also considered a good candidate for single-cell oil production. Although some of its metabolic pathways are well studied, its metabolic engineering is hindered by the lack of a genome-scale model that integrates the current knowledge about its metabolism. Results Combining in silico tools and expert manual curation, we have produced an accurate genome-scale metabolic model for Y. lipolytica. Using a scaffold derived from a functional metabolic model of the well-studied but phylogenetically distant yeast S. cerevisiae, we mapped conserved reactions, rewrote gene associations, added species-specific reactions and inserted specialized copies of scaffold reactions to account for species-specific expansion of protein families. We used physiological measures obtained under lab conditions to validate our predictions. Conclusions Y. lipolytica iNL895 represents the first well-annotated metabolic model of an oleaginous yeast, providing a base for future metabolic improvement, and a starting point for the metabolic reconstruction of other species in the Yarrowia clade and other oleaginous yeasts.

  9. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

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    Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  10. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

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    Lasrich, Dorothee; Bartelt, Alexander [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au [Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006 (Australia); Heeren, Joerg, E-mail: heeren@uke.de [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  11. A mathematical model for the study of lipid accumulation in oleaginous microorganisms. I. Lipid accumulation during growth of Mucor circinelloides CBS 172-27 on a vegetable oil

    Directory of Open Access Journals (Sweden)

    Aggelis, G.

    1995-06-01

    Full Text Available    The accumulation of lipids In microorganisms cultivated In growth media having as sole carbon and energy source vegetable or animal fat has been an object of research and industrial interest for many years. Interestingly, the accumulated fat often has a composition and structure much different from that of the fat present In the substrate.
       The present work describes a mathematical approach to the accumulation of fat by oleaginous microorganisms growing on medium containing vegetable oil as carbon source. A mathematical model, correlating the accumulation of reserve fat with the growth of microbial population and the available quantity of exocellular fat, is proposed. This model is verified by experimental data taken by cultivation of Mucor circinelloides CBS 172-27 on sunflower oil.
       The proposed model is described by the equation: XL = XLo + Lo(1-e-k2.t– (lnx-lnxo/k1    where XL(mg/l the concentration of reserve lipids at time t(h, XLo(mg/l the concentration of lipid reserves at time t=o, Lo(mg/l the initial concentration of exocellular fat (a t=o, X(mg/l the concentration of fat-free biomass at a given time t and Xo the concentration of fat-free biomass at time t=o; k1 and k2 constants.

       Durante muchos años la acumulación de lípidos en microorganismos desarrollados en medio de cultivo, tomando como única fuente de carbono y energía grasas vegetales o animales, ha sido objeto de investigación e Interés industrial.    Interesadamente, la grasa acumulada tiene a menudo una composición y estructura muy diferente de la que tiene la grasa presente en el sustrato.    El presente trabajo describe una aproximación matemática a la acumulaci

  12. Experimental Models of Foamy Macrophages and Approaches for Dissecting the Mechanisms of Lipid Accumulation and Consumption during Dormancy and Reactivation of Tuberculosis

    Science.gov (United States)

    Santucci, Pierre; Bouzid, Feriel; Smichi, Nabil; Poncin, Isabelle; Kremer, Laurent; De Chastellier, Chantal; Drancourt, Michel; Canaan, Stéphane

    2016-01-01

    Despite a slight decline since 2014, tuberculosis (TB) remains the major deadly infectious disease worldwide with about 1.5 million deaths each year and with about one-third of the population being latently infected with Mycobacterium tuberculosis, the etiologic agent of TB. During primo-infection, the recruitment of immune cells leads to the formation of highly organized granulomas. Among the different cells, one outstanding subpopulation is the foamy macrophage (FM), characterized by the abundance of triacylglycerol-rich lipid bodies (LB). M. tuberculosis can reside in FM, where it acquires, from host LB, the neutral lipids which are subsequently processed and stored by the bacilli in the form of intracytosolic lipid inclusions (ILI). Although host LB can be viewed as a reservoir of nutrients for the pathogen during latency, the molecular mechanisms whereby intraphagosomal mycobacteria interact with LB and assimilate the LB-derived lipids are only beginning to be understood. Past studies have emphasized that these physiological processes are critical to the M. tuberculosis infectious-life cycle, for propagation of the infection, establishment of the dormancy state and reactivation of the disease. In recent years, several animal and cellular models have been developed with the aim of dissecting these complex processes and of determining the nature and contribution of their key players. Herein, we review some of the in vitro and in vivo models which allowed to gain significant insight into lipid accumulation and consumption in M. tuberculosis, two important events that are directly linked to pathogenicity, granuloma formation/maintenance and survival of the tubercle bacillus under non-replicative conditions. We also discuss the advantages and limitations of each model, hoping that this will serve as a guide for future investigations dedicated to persistence and innovative therapeutic approaches against TB. PMID:27774438

  13. Bilirubin Binding to PPARα Inhibits Lipid Accumulation.

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    Stec, David E; John, Kezia; Trabbic, Christopher J; Luniwal, Amarjit; Hankins, Michael W; Baum, Justin; Hinds, Terry D

    2016-01-01

    Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin.

  14. Lipid accumulation in prokaryotic microorganisms from arid habitats.

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

    2017-03-01

    This review shall provide support for the suitability of arid environments as preferred location to search for unknown lipid-accumulative bacteria. Bacterial lipids are attracting more and more attention as sustainable replacement for mineral oil in fuel and plastic production. The development of prokaryotic microorganisms in arid desert habitats is affected by its harsh living conditions. Drought, nutrient limitation, strong radiation, and extreme temperatures necessitate effective adaption mechanisms. Accumulation of storage lipids as energy reserve and source of metabolic water represents a common adaption in desert animals and presumably in desert bacteria and archaea as well. Comparison of corresponding literature resulted in several bacterial species from desert habitats, which had already been described as lipid-accumulative elsewhere. Based on the gathered information, literature on microbial communities in hot desert, cold desert, and humid soil were analyzed on its content of lipid-accumulative bacteria. With more than 50% of the total community size in single studies, hot deserts appear to be more favorable for lipid-accumulative species then humid soil (≤20%) and cold deserts (≤17%). Low bacterial lipid accumulation in cold deserts is assumed to result from the influence of low temperatures on fatty acids and the increased necessity of permanent adaption methods.

  15. Increased placental fatty acid transporter 6 and binding protein 3 expression and fetal liver lipid accumulation in a mouse model of obesity in pregnancy.

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    Díaz, Paula; Harris, Jessica; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-12-15

    Obesity in pregnancy is associated with increased fetal growth and adiposity, which, in part, is determined by transplacental nutrient supply. Trophoblast uptake and intracellular trafficking of lipids are dependent on placental fatty acid transport proteins (FATP), translocase (FAT/CD36), and fatty acid binding proteins (FABP). We hypothesized that maternal obesity in mice leads to increased placental expression of FAT/CD36, FATPs, and FABPs, and lipid accumulation in the fetal liver. C57/BL6J female mice were fed either a control (C; n = 10) or an obesogenic (OB; n = 10) high-fat, high-sugar diet before mating and throughout pregnancy. At E18.5, placentas and fetal livers were collected. Trophoblast plasma membranes (TPM) were isolated from placental homogenates. Expression of FAT/CD36 and FATP (TPM) and FABP (homogenates) was determined by immunoblotting. Gene expression was assessed by RT-quantitative PCR. Sections of fetal livers were stained for Oil Red O, and lipid droplets were quantified. TPM protein expression of FAT/CD36, FATP 2, and FATP 4 was comparable between C and OB groups. Conversely, TPM FATP 6 expression was increased by 35% in OB compared with C placentas without changes in mRNA expression. FABPs 1, 3-5 and PPARγ were expressed in homogenates, and FABP 3 expression increased 27% in OB compared with C placentas; however, no changes were observed in mRNA expression. Lipid droplet accumulation was 10-fold higher in the livers of fetuses from OB compared with C group. We propose that increased lipid transport capacity in obese mice promotes transplacental fatty acid transport and contributes to excess lipid accumulation in the fetal liver.

  16. Ultrastructural and flow cytometric analyses of lipid accumulation in microalgae

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, J.A.; Hand, R.E. Jr.; Mann, R.C.

    1986-12-01

    Lipid accumulation in three species of microalgae was investigated with flow cytometry (FCM) and transmission electron microscopy (TEM). Previous studies using batch cultures of a algae have led to the assumption that lipid accumulation in microalgae is a gradual process requiring at least several days for completion. However, FCM reveals, through changes in the chlorophyll:lipid ratio, that the time span required for individual cells to change metabolic state is short. Simultaneous FCM measurements of chlorophyll and nile red (neutral lipid) fluorescence in individual cells of nitrogen-deficient Isochrysis populations revealed a bimodal population distribution as one stage in the lipid accumulation process. The fact that two discrete populations exist, with few cells in an intermediate stage, suggests rapid response to a liqid trigger. Interpretations of light and electron microscopic observations are consistent with this hypothesis. The time required for an entire population to achieve maximum lipid content is considerably longer than that required for a single cell, due to the variation in response time among cells. In this study high lipid cultures were sometimes obtained by using FCM to separate high lipid cells from the remainder of the population. FCM holds much promise for strain enhancement but considerable developmental work, directed at providing more consistent results, remains to be done. 8 refs., 35 figs.

  17. Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles

    DEFF Research Database (Denmark)

    Vesterdal, Lise K; Danielsen, Pernille H; Folkmann, Janne K

    2014-01-01

    and subsequently incubated for another 18h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid...... single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral......Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3h...

  18. Vascular lipid accumulation, lipoprotein oxidation and macrophage lipid uptake in hypercholesterolemic zebrafish

    Science.gov (United States)

    Stoletov, Konstantin; Fang, Longhou; Choi, Soo-Ho; Hartvigsen, Karsten; Hansen, Lotte F.; Hall, Chris; Pattison, Jennifer; Juliano, Joseph; Miller, Elizabeth R.; Almazan, Felicidad; Crosier, Phil; Witztum, Joseph L.; Klemke, Richard L.; Miller, Yury I.

    2010-01-01

    Lipid accumulation in arteries induces vascular inflammation and atherosclerosis, the major cause of heart attack and stroke in humans. Extreme hyperlipidemia induced in mice and rabbits enables modeling many aspects of human atherosclerosis, but microscopic examination of plaques is possible only postmortem. Here we report that feeding adult zebrafish (Danio rerio) a high-cholesterol diet (HCD) resulted in hypercholesterolemia, remarkable lipoprotein oxidation and fatty streak formation in the arteries. Feeding an HCD supplemented with a fluorescent cholesteryl ester to optically transparent fli1:EGFP zebrafish larvae in which endothelial cells (EC) express GFP, and using confocal microscopy enabled monitoring vascular lipid accumulation and the EC layer disorganization and thickening in a live animal. The HCD feeding also increased leakage of a fluorescent dextran from the blood vessels. Administering ezetimibe significantly diminished the HCD-induced EC layer thickening and improved its barrier function. Feeding HCD to lyz:DsRed2 larvae in which macrophages and granulocytes express DsRed, resulted in the accumulation of fluorescent myeloid cells in the vascular wall. Using a fluorogenic substrate for phospholipase A2 (PLA2), we observed an increased vascular PLA2 activity in live HCD-fed larvae compared to control larvae. Furthermore, by transplanting genetically modified murine cells into HCD-fed larvae, we demonstrated that toll-like receptor-4 (TLR4) was required for efficient in vivo lipid uptake by macrophages. These results suggest that the novel zebrafish model is suitable for studying temporal characteristics of certain inflammatory processes of early atherogenesis and the in vivo function of vascular cells. PMID:19265037

  19. Markers of skeletal muscle mitochondrial function and lipid accumulation are moderately associated with the homeostasis model assessment index of insulin resistance in obese men.

    Directory of Open Access Journals (Sweden)

    Imtiaz A Samjoo

    Full Text Available Lower skeletal muscle mitochondrial oxidative phosphorylation capacity (OXPHOS and intramyocellular lipid (IMCL accumulation have been implicated in the etiology of insulin resistance (IR in obesity. The purpose of this study was to examine the impact of endurance exercise on biochemical and morphological measures of IMCL and mitochondrial content, and their relationship to IR in obese individuals. We examined mitochondrial content (subunit protein abundance and maximal activity of electron transport chain enzymes, IMCL/mitochondrial morphology in both subsarcolemmal (SS and intermyofibrillar (IMF regions by transmission electron microscopy, and intracellular lipid metabolites (diacylglycerol and ceramide in vastus lateralis biopsies, as well as, the homeostasis model assessment index of IR (HOMA-IR prior to and following twelve weeks of an endurance exercise regimen in healthy age- and physical activity-matched lean and obese men. Obese men did not show evidence of mitochondrial OXPHOS dysfunction, disproportionate IMCL content in sub-cellular regions, or diacylglycerol/ceramide accretion despite marked IR vs. lean controls. Endurance exercise increased OXPHOS and mitochondrial size and density, but not number of individual mitochondrial fragments, with moderate improvements in HOMA-IR. Exercise reduced SS IMCL content (size, number and density, increased IMF IMCL content, while increasing IMCL/mitochondrial juxtaposition in both regions. HOMA-IR was inversely associated with SS (r = -0.34; P = 0.051 and IMF mitochondrial density (r = -0.29; P = 0.096, IMF IMCL/mitochondrial juxtaposition (r = -0.30; P = 0.086, and COXII (r = -0.32; P = 0.095 and COXIV protein abundance (r = -0.35; P = 0.052; while positively associated with SS IMCL size (r = 0.28; P = 0.119 and SS IMCL density (r = 0.25; P = 0.152. Our findings suggest that once physical activity and cardiorespiratory fitness have been

  20. Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

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    Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-08-01

    Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

  1. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.

    2016-01-01

    cultures. We first reconstructed a genome-scale metabolic model and used this for integrative analysis of multilevel omics data. Metabolite profiling and lipidomics was used to quantify the cellular physiology, while regulatory changes were measured using RNAseq. Analysis of the data showed that lipid......Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...... accumulation in Y. lipolytica does not involve transcriptional regulation of lipid metabolism but is associated with regulation of amino-acid biosynthesis, resulting in redirection of carbon flux during nitrogen limitation from amino acids to lipids. Lipid accumulation in Y. lipolytica at nitrogen limitation...

  2. Baicalein inhibits lipid accumulation by regulating early adipogenesis and m-TOR signaling.

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    Seo, Min-Jung; Choi, Hyeon-Son; Jeon, Hui-Jeon; Woo, Mi-Seon; Lee, Boo-Yong

    2014-05-01

    Baicalein is a type of flavonoid that originates from Scutellaria baicalensis. In this study, we examined how baicalein inhibits lipid accumulation during adipogenesis in 3T3-L1 cells. Our data show that baicalein inhibited lipid accumulation during adipogenesis in a dose-dependent manner. Baicalein inhibition was limited to the early adipogenic stage. Cell cycle analysis showed that baicalein induced cell cycle arrest in the G0/G1 phase through cyclin downregulation. In addition, baicalein suppressed the mRNA expression of early adipogenic factors leading to downregulation of late adipogenic factors at mRNA and protein levels. Inhibition of adipogenic factors by baicalein was correlated with downregulation of lipid synthetic enzymes. Additionally, baicalein negatively regulated the m-TOR signaling pathway involved in lipid accumulation during adipogenesis, thus inhibiting phosphorylation of m-TOR and p70S6K. In a zebrafish study, baicalein significantly reduced lipid accumulation in Nile Red staining. Consistent with a report using cell lines, mRNA expression of adipogenic factors was decreased in a dose-dependent manner by baicalein. This result reflects a reduction in total triglyceride levels based on a triglyceride assay. Our data suggest that baicalein inhibits lipid accumulation by controlling the cell cycle and m-TOR signaling in 3T3-L1 cells, and its anti-adipogenic effect was found in a zebrafish model.

  3. Dietary Niacin Supplementation Suppressed Hepatic Lipid Accumulation in Rabbits.

    Science.gov (United States)

    Liu, Lei; Li, Chunyan; Fu, Chunyan; Li, Fuchang

    2016-12-01

    An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32) were allocated to two equal treatment groups: Fed basal diet (control) or fed basal diet with additional 200 mg/kg niacin supplementation (niacin). The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p0.05). However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (prabbits.

  4. JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Guang-feng [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Xiao, Di; Gong, Wei-jing [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Hui-xia; Liu, Jun [Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Zhou, Hong-hao [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China)

    2014-03-14

    Highlights: • JAZF1 was significantly upregulated during the differentiation of 3T3-L1 preadipocytes. • JAZF1 overexpression inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes. • JAZF1 overexpression inhibited the expression of SREBP1, ACC, and FAS. • JAZF1 overexpression upregulated the expression of HSL and ATGL. • SREBP1 and JAZF1 could regulate each other in adipocytes. - Abstract: JAZF1 is a newly identified gene with unknown functions. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. Studies have demonstrated that JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear orphan receptor family members are involved in the regulation of lipid metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism. In this study, JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1 inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and significantly inhibited the expression of SREBPl, ACC, and FAS, which were important in lipid synthesis, while upregulating the expression of key enzyme hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory function on the expression of JAZF1. SREBP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes. Therefore, JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. This result suggests that JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders.

  5. Fucoidan from Marine Brown Algae Inhibits Lipid Accumulation

    Directory of Open Access Journals (Sweden)

    Changhyun Roh

    2011-08-01

    Full Text Available In this study, we elucidated the inhibitory effect of fucoidan from marine brown algae on the lipid accumulation in differentiated 3T3-L1 adipocytes and its mechanism. The treatment of fucoidan in a dose-dependent manner was examined on lipid inhibition in 3T3-L1 cells by using Oil Red O staining. Fucoidan showed high lipid inhibition activity at 200 µg/mL concentration (P < 0.001. Lipolytic activity in adipocytes is highly dependent on hormone sensitive lipase (HSL, which is one of the most important targets of lipolytic regulation. Here, we examined the biological response of fucoidan on the protein level of lipolysis pathway. The expressed protein levels of total hormone sensitive lipase (HSL and its activated form, phosphorylated-HSL were significantly increased at concentration of 200 µg/mL fucoidan. Furthermore, insulin-induced 2-deoxy-D-[3H] glucose uptake was decreased up to 51% in fucoidan-treated cells as compared to control. Since increase of HSL and p-HSL expression and decrease of glucose uptake into adipocytes are known to lead to stimulation of lipolysis, our results suggest that fucoidan reduces lipid accumulation by stimulating lipolysis. Therefore, these results suggest that fucoidan can be useful for the prevention or treatment of obesity due to its stimulatory lipolysis.

  6. Lipid body accumulation alters calcium signaling dynamics in immune cells.

    Science.gov (United States)

    Greineisen, William E; Speck, Mark; Shimoda, Lori M N; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J; Turner, Helen

    2014-09-01

    There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcɛRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signaling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcɛRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signaling pathway and its downstream targets.

  7. A mathematical model for the study of lipid accumulation in oleaginous microorganisms. II. Study of cellular lipids of Mucor circinelloides during growth on a vegetable oil

    Directory of Open Access Journals (Sweden)

    Aggelis, G.

    1995-10-01

    Full Text Available Microbial oil production from fatty materials of animal or plant origin has been an object of research and industrial interest for many years. During the process of microbial growth/accumulation of fat reserves, the dominating phenomena that define the composition of endocellular fat are, first, the specific process of incorporation of substrate fatty acids into the microbial cell and, second, the endocellular changes of fatty acids defined by the enzymic capabilities of the microorganism. The fatty acids will either be degraded for growth needs or act as substrate of endocellular biotransformation processes, leading to concentration changes and production of "new" fatty acids which did not previously exist in the substrate.
    The purpose of the present work is to study the endocellular lipids of Mucor circinelloidesCBS 172-27 grown on sunflower oil. The mathematical model, described in part I, was applied in order to investigate the following:
    a. Microorganism specificity in the incorporation of substrate fatty acids.
    b. Microorganism specificity in the degradation of fatty acids present in the reserve fat.
    c. Possibilities of endocellular biotransformations during the microbial growth.
    In conclusion, this work is aimed at developing a quantitative expression of parameters defining the lipid composition of fat reserves. The proposed mathematical model can be used not only for selection of microbial strains having specific enzymic potential but also for substrate selection.

    La producción de aceites microbianos a partir de materiales grasos de origen animal o vegetal ha sido objeto de investigación e interés industrial durante muchos años. En el proceso de crecimiento microbiano/acumulación de reservas grasas, los fenómenos dominantes que definen la composición de grasa endocelular son, primero, el proceso específico de incorporación de ácidos grasos como sustratos en la célula microbiana

  8. Saturating Light Induces Sustained Accumulation of Oil in Plastidal Lipid Droplets in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Goold, Hugh Douglas; Cuiné, Stéphan; Légeret, Bertrand; Liang, Yuanxue; Brugière, Sabine; Auroy, Pascaline; Javot, Hélène; Tardif, Marianne; Jones, Brian; Beisson, Fred; Peltier, Gilles; Li-Beisson, Yonghua

    2016-08-01

    Enriching algal biomass in energy density is an important goal in algal biotechnology. Nitrogen (N) starvation is considered the most potent trigger of oil accumulation in microalgae and has been thoroughly investigated. However, N starvation causes the slow down and eventually the arrest of biomass growth. In this study, we show that exposing a Chlamydomonas reinhardtii culture to saturating light (SL) under a nonlimiting CO2 concentration in turbidostatic photobioreactors induces a sustained accumulation of lipid droplets (LDs) without compromising growth, which results in much higher oil productivity than N starvation. We also show that the polar membrane lipid fraction of SL-induced LDs is rich in plastidial lipids (approximately 70%), in contrast to N starvation-induced LDs, which contain approximately 60% lipids of endoplasmic reticulum origin. Proteomic analysis of LDs isolated from SL-exposed cells identified more than 200 proteins, including known proteins of lipid metabolism, as well as 74 proteins uniquely present in SL-induced LDs. LDs induced by SL and N depletion thus differ in protein and lipid contents. Taken together, lipidomic and proteomic data thus show that a large part of the sustained oil accumulation occurring under SL is likely due to the formation of plastidial LDs. We discuss our data in relation to the different metabolic routes used by microalgae to accumulate oil reserves depending on cultivation conditions. Finally, we propose a model in which oil accumulation is governed by an imbalance between photosynthesis and growth, which can be achieved by impairing growth or by boosting photosynthetic carbon fixation, with the latter resulting in higher oil productivity.

  9. Prion protein accumulation in lipid rafts of mouse aging brain.

    Directory of Open Access Journals (Sweden)

    Federica Agostini

    Full Text Available The cellular form of the prion protein (PrP(C is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C. In old mice, this change favors PrP(C accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C translocation into detergent-resistant membranes (DRMs, we looked at PrP(C compartmentalization in hippocampi from acid sphingomyelinase (ASM knockout (KO mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases.

  10. Regulation of starch and lipid accumulation in a microalga Chlorella sorokiniana.

    Science.gov (United States)

    Li, Tingting; Gargouri, Mahmoud; Feng, Jie; Park, Jeong-Jin; Gao, Difeng; Miao, Chao; Dong, Tao; Gang, David R; Chen, Shulin

    2015-03-01

    Microalgae have attracted growing attention due to their potential in biofuel feedstock production. However, current understanding of the regulatory mechanisms for lipid biosynthesis and storage in microalgae is still limited. This study revealed that the microalga Chlorella sorokiniana showed sequential accumulation of starch and lipids. When nitrogen was replete and/or depleted over a short period, starch was the predominant carbon storage form with basal levels of lipid accumulation. After prolonged nitrogen depletion, lipid accumulation increased considerably, which was partially due to starch degradation, as well as the turnover of primary metabolites. Lipid accumulation is also strongly dependent on the linear electron flow of photosynthesis, peaking at lower light intensities. Collectively, this study reveals a relatively clear regulation pattern of starch and lipid accumulation that is basically controlled by nitrogen levels. The mixotrophic growth of C. sorokiniana shows promise for biofuel production in terms of lipid accumulation in the final biomass.

  11. Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles

    Energy Technology Data Exchange (ETDEWEB)

    Vesterdal, Lise K.; Danielsen, Pernille H.; Folkmann, Janne K.; Jespersen, Line F.; Aguilar-Pelaez, Karin; Roursgaard, Martin; Loft, Steffen; Møller, Peter, E-mail: pemo@sund.ku.dk

    2014-01-15

    Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3 h and subsequently incubated for another 18 h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14 nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a concentration-dependent increase in intracellular lipid content after exposure to CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic acid. Similar results were observed in HepG2 cells after exposure to diesel exhaust particles, fullerenes C{sub 60} or pristine single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3 h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral exposure to 6.4 mg/kg of CB in lean Zucker rats. This was not associated with increased iNOS staining in the liver, indicating that the oral CB exposure was associated with hepatic steatosis rather than steatohepatitis. The lipid accumulation did not seem to be related to increased lipogenesis because there were unaltered gene expression levels in both the HepG2 cells and rat livers. Collectively, exposure to particles is associated with oxidative stress and steatosis in hepatocytes. - Highlights: • Oral exposure to nanosized carbon black was associated with hepatosteatosis in rats. • In vitro studies included carbon black, C{sub 60}, diesel exhaust particles and SWCNTs. • Exposure to particles and free fatty acids increased lipid load in HepG2 cells. • Unaltered

  12. Jiao Tai Wan Attenuates Hepatic Lipid Accumulation in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Zhaoyi Huang

    2013-01-01

    Full Text Available Jiao Tai Wan (JTW, a Chinese herbal formula containing Rhizoma Coptidis and Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of this study was to determine the main components in JTW and to investigate the effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW extract was prepared and the main components were assayed by HPLC. An animal model of diabetes mellitus was established and JTW was administered intragastrically. In the clinical study, diabetic patients with poor glycemic control were treated with JTW. Blood glucose and lipid parameters, liver histology, hepatic triglyceride content and lipogenic gene expression were examined. Our data demonstrated that JTW significantly improved hyperglycemia, hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC and fatty acid synthase (FAS protein expressions, and the up-regulation of AMP-activated protein kinase (AMPK and phosphorylated-ACC (pACC protein expressions in the liver tissues. Diabetic patients also exhibited decreases in their hepatic triglyceride content. The results suggest that JTW attenuates hepatic lipid accumulation in diabetic rats and humans. These beneficial effects are possibly associated with the inhibition of lipogenic gene expression in the liver.

  13. MAB_3551c encodes the primary triacylglycerol synthase involved in lipid accumulation in Mycobacterium abscessus.

    Science.gov (United States)

    Viljoen, Albertus; Blaise, Mickael; de Chastellier, Chantal; Kremer, Laurent

    2016-11-01

    Slow growing pathogenic mycobacteria utilize host-derived lipids and accumulate large amounts of triacylglycerol (TAG) in the form of intracytoplasmic lipid inclusions (ILI), serving as a source of carbon and energy during prolonged infection. Mycobacterium abscessus is an emerging and rapidly growing species capable to induce severe and chronic pulmonary infections. However, whether M. abscessus, like Mycobacterium tuberculosis, possesses the machinery to acquire and store host lipids, remains unaddressed. Herein, we aimed at deciphering the contribution of the seven putative M. abscessus TAG synthases (Tgs) in TAG synthesis/accumulation thanks to a combination of genetic and biochemical techniques and a well-defined foamy macrophage (FM) model along with electron microscopy. Targeted gene deletion and functional complementation studies identified the MAB_3551c product, Tgs1, as the major Tgs involved in TAG production. Tgs1 exhibits a preference for long acyl-CoA substrates and site-directed mutagenesis demonstrated that His144 and Gln145 are essential for enzymatic activity. Importantly, in the lipid-rich intracellular context of FM, M. abscessus formed large ILI in a Tgs1-dependent manner. This supports the ability of M. abscessus to assimilate host lipids and the crucial role of Tgs1 in intramycobacterial TAG production, which may represent important mechanisms for long-term storage of a rich energy supply.

  14. Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    Hella Wobser; Christoph Dorn; Thomas S Weiss; Thomas Amann; Cornelius Bollheimer; Roland Büttner; Jürgen Sc(o)lmerich; Claus Hellerbrand

    2009-01-01

    Despite the initial belief that non-alcoholic fatty liver disease is a benign disorder, it is now recognized that fbrosis progression occurs in a significant number of patients. Furthermore, hepatic steatosis has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of other liver diseases. Here, we established an in vitro model to study the effect of hepatic lipid accumulation on hepatic stellate cells (HSCs), the central mediators of liver fibrogenesis. Primary human hepatocytes were incubated with the saturated fatty acid palmitate to induce intracellular lipid accumulation. Subsequently, human HSCs were incubated with conditioned media (CM) from steatotic or control hepatocytes. Lipid accumulation in hepatocytes induced the release of factors that accelerated the activation and proliferation of HSC, and enhanced their resistance to apoptosis, largely mediated via activation of the PI-3-kinase pathway. Furthermore, CM from steatotic hepatocytes induced the expression of the profibrogenic genes TGF-β, tissue inhibitor of metallo-proteinase-1 (TIMP-1), TIMP-2 and matrix-metallo-proteinase-2, as well as nuclear-factor Κb-dependent MCP-1 expression in HSC. In summary, our in vitro data indicate a potential mechanism for the pathophysiological link between hepatic steatosis and fibrogenesis in vivo. Herewith, this study provides an attractive in vitro model to study the molecular mechanisms of steatosis-induced fibrogenesis, and to identify and test novel targets for antifibrotic therapies in fatty liver disease.

  15. Oleaginous yeasts from Antarctica: Screening and preliminary approach on lipid accumulation.

    Science.gov (United States)

    Viñarta, Silvana C; Angelicola, M Virginia; Barros, J Maximiliano; Fernández, Pablo M; Mac Cormak, Walter; Aybar, Manuel J; de Figueroa, Lucía I C

    2016-12-01

    The capability of 17 Rhodotorula spp. isolated from Antarctica to accumulate intracellular lipids in nitrogen-limited medium was investigated. As results, 10 isolates were selected by Nile red staining, while 12 isolates were selected as oleaginous by analysis of total lipid content (20.4-73%, w/w of dry biomass). The higher lipid production and accumulation was exhibited for six strains belonging to three species of Rhodotorula (Rhodotorula glutinis, Rhodotorula glacialis, and Rhodotorula laryngis). This is the first report where R. laryngis have been identified within oleaginous specie. Lipid accumulation was evaluated comparatively in two nitrogen-limited glucose-based media (MI and MII). MI (low C/N ratio) was more suitable for biomass and lipid production while in MII (high C/N ratio) total lipid content was improved. R. glutinis R4, R. glacialis R15, and R. glutinis R48 showed high lipid concentrations (4.65-6.93 g L(-1) ) and they were able to accumulate large amounts of lipids per gram of biomass (47-77%, w/w). A similar profile in fatty acids composition and content of neutral lipids to vegetable oils was observed, indicating that lipids produced by oleaginous Antarctic yeasts can be considered an alternative feedstock for biodiesel production. Antarctica represents an important source of oleaginous yeasts with adaptive capabilities to accumulate considerable amounts of lipids with biotechnological interest at 15 °C and 25 °C.

  16. THP-1 macrophage lipid accumulation unaffected by fatty acid double bond geometric or positional configuration

    Science.gov (United States)

    Dietary fatty acid type alters atherosclerotic lesion progression and macrophage lipid accumulation. Incompletely elucidated are the mechanisms by which fatty acids differing in double-bond geometric or positional configuration alter arterial lipid accumulation. The objective of this study was to ev...

  17. Novel Genetic Tools to Accelerate Our Understanding of Photosynthesis and Lipid Accumulation

    Science.gov (United States)

    2014-08-20

    understanding of photosynthesis and lipid accumulation Martin C. Jonikas, Ph.D. Carnegie Institution for Science, Department of Plant Biology 260...knowledge of algal lipid metabolism and photosynthesis . Advances in our basic understanding of these processes will facilitate genetic engineering of...algae to improve lipid yields. Currently, one of the greatest roadblocks in the study of algal photosynthesis and lipid metabolism is the slow pace of

  18. The protein and lipid composition of arterial elastin and its relationship to lipid accumulation in the atherosclerotic plaque.

    Science.gov (United States)

    Kramsch, D M; Franzblau, C; Hollander, W

    1971-08-01

    Elastin preparations from intimal layers and the media of normal and atherosclerotic human aortae were analyzed for protein and lipid content. In atherosclerotic aortae, elastin from plaques was compared with elastin from adjacent normal appearing areas of the same aorta. Arterial elastin purified by alkaline extraction appeared to be a protein-lipid complex containing free and ester cholesterol, phospholipids, and triglycerides. The lipid component of normal arterial elastin was small (1-2%). With increasing severity of atherosclerosis, there was a progressive accumulation of lipid in intimal elastin from plaques, reaching a mean lipid content of 37% in severe plaques. The increase in the lipid content of plaque elastic preparations was mainly due to large increases in cholesterol, over 80% of which was cholesteryl ester. This deposition of cholesterol in plaque elastin accounted for 20-34% of the total cholesterol content of the plaque. The increased lipid deposition in plaque elastin was associated with alterations in the amino acid composition of plaque elastin. In elastin from plaque intima, the following polar amino acids were increased significantly: aspartic acid, threonine, serine, glutamic acid, lysine, histidine, and arginine; whereas, cross-linking amino acids: desmosine, isodesmosine, and lysinonorleucine were decreased significantly. The amino acid and lipid composition of elastin from normal appearing aortic areas was comparable to that of normal arterial elastin except for intimal elastin directly adjacent to and medial elastin directly below the most severe plaques.The data indicate that the focal lipid deposition in early atherosclerotic plaques is due to a large extent to lipid accumulations in altered elastin protein of localized intimal areas. Continued lipid deposition in altered elastin appears to contribute substantially to the progressive lipid accumulation in the plaque. The study suggests that elastin of intimal elastic membranes may play

  19. Saline wastewater treatment by Chlorella vulgaris with simultaneous algal lipid accumulation triggered by nitrate deficiency.

    Science.gov (United States)

    Shen, Qiao-Hui; Gong, Yu-Peng; Fang, Wen-Zhe; Bi, Zi-Cheng; Cheng, Li-Hua; Xu, Xin-Hua; Chen, Huan-Lin

    2015-10-01

    Chlorella vulgaris, a marine microalgae strain adaptable to 0-50 g L(-1) of salinity, was selected for studying the coupling system of saline wastewater treatment and lipid accumulation. The effect of total nitrogen (T N) concentration was investigated on algal growth, nutrients removal as well as lipid accumulation. The removal efficiencies of TN and total phosphorus (TP) were found to be 92.2-96.6% and over 99%, respectively, after a batch cultivation of 20 days. To illustrate the response of lipid accumulation to nutrients removal, C. vulgaris was further cultivated in the recycling experiment of tidal saline water within the photobioreactor. The lipid accumulation was triggered upon the almost depletion of nitrate (<5 mg L(-1)), till the final highest lipid content of 40%. The nitrogen conversion in the sequence of nitrate, nitrite, and then to ammonium in the effluents was finally integrated with previous discussions on metabolic pathways of algal cell under nitrogen deficiency.

  20. Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD.

    Directory of Open Access Journals (Sweden)

    Tongshuai Chen

    Full Text Available Cardiac hypertrophy is an adaptive response to pressure, volume stress, and loss of contractile mass from prior infarction. Metabolic changes in cardiac hypertrophy include suppression of fatty acid oxidation and enhancement of glucose utilization, which could result in lipid accumulation in the heart. SIRT3, a mitochondrial NAD+-dependent deacetylase, has been demonstrated to play a crucial role in controlling the acetylation status of many enzymes participating in energy metabolism. However, the role of SIRT3 in the pathogenesis of hypertrophy-related lipid accumulation remains unclear. In this study, hypertrophy-related lipid accumulation was investigated using a mouse cardiac hypertrophy model induced by transverse aortic constriction (TAC. We showed that mice developed heart failure six weeks after TAC. Furthermore, abnormal lipid accumulation and decreased palmitate oxidation rates were observed in the hypertrophic hearts, and these changes were particularly significant in SIRT3-KO mice. We also demonstrated that the short form of SIRT3 was downregulated in wild-type (WT hypertrophic hearts and that this change was accompanied by a higher acetylation level of long-chain acyl CoA dehydrogenase (LCAD, which is a key enzyme participating in fatty acid oxidation. In addition, SIRT3 may play an essential role in attenuating lipid accumulation in the heart through the deacetylation of LCAD.

  1. Markov models for accumulating mutations

    CERN Document Server

    Beerenwinkel, Niko

    2007-01-01

    We introduce and analyze a waiting time model for the accumulation of genetic changes. The continuous time conjunctive Bayesian network is defined by a partially ordered set of mutations and by the rate of fixation of each mutation. The partial order encodes constraints on the order in which mutations can fixate in the population, shedding light on the mutational pathways underlying the evolutionary process. We study a censored version of the model and derive equations for an EM algorithm to perform maximum likelihood estimation of the model parameters. We also show how to select the maximum likelihood poset. The model is applied to genetic data from different cancers and from drug resistant HIV samples, indicating implications for diagnosis and treatment.

  2. Rosehip Extract Inhibits Lipid Accumulation in White Adipose Tissue by Suppressing the Expression of Peroxisome Proliferator-activated Receptor Gamma.

    Science.gov (United States)

    Nagatomo, Akifumi; Nishida, Norihisa; Matsuura, Yoichi; Shibata, Nobuhito

    2013-06-01

    Recent studies have shown that Rosa canina L. and tiliroside, the principal constituent of its seeds, exhibit anti-obesity and anti-diabetic activities via enhancement of fatty acid oxidation in the liver and skeletal muscle. However, the effects of rosehip, the fruit of this plant, extract (RHE), or tiliroside on lipid accumulation in adipocytes have not been analyzed. We investigated the effects of RHE and tiliroside on lipid accumulation and protein expression of key transcription factors in both in vitro and in vivo models. RHE and tiliroside inhibited lipid accumulation in a dose-dependent manner in 3T3-L1 cells. We also analyzed the inhibitory effect of RHE on white adipose tissue (WAT) in high-fat diet (HFD)-induced obesity mice model. Male C57BL/6J mice were fed HFD or HFD supplemented with 1% RHE (HFDRH) for 8 weeks. The HFDRH-fed group gained less body weight and had less visceral fat than the HFD-fed group. Liver weight was significantly lower in the HFDRH-fed group and total hepatic lipid and triglyceride (TG) content was also reduced. A significant reduction in the expression of peroxisome proliferator-activated receptor gamma (PPARγ) was observed in epididymal fat in the HFDRH-fed group, in comparison with controls, through Western blotting. These results suggest that downregulation of PPARγ expression is involved, at least in part, in the suppressive effect of RHE on lipid accumulation in WAT.

  3. Gravimetric enrichment of high lipid and starch accumulating microalgae.

    Science.gov (United States)

    Hassanpour, Morteza; Abbasabadi, Mahsa; Ebrahimi, Sirous; Hosseini, Maryam; Sheikhbaglou, Ahmad

    2015-11-01

    This study presents gravimetric enrichment of mixed culture to screen starch and lipid producing species separately in a sequencing batch reactor. In the enriched starch-producing mixed culture photobioreactor, the starch content at the end of steady state batch became 3.42 times the beginning of depletion. Whereas in the enriched lipid-producing photobioreactor, the lipid content at the end of steady state batch became 3 times the beginning of famine phase. The obtained results revealed that the gravimetric enrichment is a suitable screening method for specific production of storage compounds in none-sterile large-scaled condition.

  4. Cholecalciferol inhibits lipid accumulation by regulating early adipogenesis in cultured adipocytes and zebrafish.

    Science.gov (United States)

    Kim, Joo Hyoun; Kang, Smee; Jung, Yu Na; Choi, Hyeon-Son

    2016-01-15

    Cholecalciferol (CCF) is a common dietary supplement as a precursor of active vitamin D. In the present study, the effect of CCF on lipid accumulation was investigated in adipocyte cells and zebrafish models. CCF effectively inhibited lipid accumulation in both experimental models; this effect was attributed to the CCF-mediated regulation of early adipogenic factors. CCF down-regulated the expressions of CCAAT-enhancer-binding protein-β (C/EBPβ), C/EBPδ, Krueppel-like factor (KLF) 4, and KLF5, while KLF2, a negative adipogenic regulator, was increased by CCF treatment. CCF inhibited cell cycle progression of adipocytes through down-regulation of cyclin A and cyclinD; p-Rb was suppressed by CCF, but p27 was up-regulated with CCF treatment. This CCF-mediated inhibition of cell cycle progression is highly correlated to the inhibitions of extracellular signal-regulated kinase (ERK), serine threonine-specific kinase (AKT), and mammalian target of rapamycin (mTOR). Furthermore, CCF-induced inactivation of acetyl-CoA carboxylase (ACC), a fatty acid synthetic enzyme, with the activation of AMP-activated protein kinase α (AMPKα) was also observed. Consistent with the observations in adipocytes, CCF effectively inhibited lipid accumulation with the down-regulation of adipogenic factors in zebrafish. The present study indicates that CCF showed anti-adipogenic effect in adipocytes and zebrafish, and its inhibitory effect was involved in the regulation of early adipogenic events including cell cycle arrest and activation of AMPKα signaling.

  5. Plant natural products as an anti-lipid droplets accumulation agent

    OpenAIRE

    Wong, Chin Piow; KANEDA, TOSHIO; Morita, Hiroshi

    2014-01-01

    Recently people often suffer from unhealthy energy metabolism balance as they tend to take more energy than required. Normally, excess energy taken in is converted into triglyceride and stored in adipocyte as lipid droplets. Recent studies have suggested that irregular accumulation of triglyceride in adipocyte might be a cause of many metabolic diseases. Thus, the awareness of the detrimental effects on health of excessive lipid droplets accumulation (LDA) has urged the development or finding...

  6. Sirt1 and Sirt6 mediate beneficial effects of rosiglitazone on hepatic lipid accumulation.

    Directory of Open Access Journals (Sweden)

    Soo Jin Yang

    Full Text Available Sirtuin (Sirt, a sensor of the cell metabolic state, regulates glucose and lipid metabolism. The aim of this study was to address whether rosiglitazone (RGZ alters hepatic Sirt1 and whether Sirt1 and/or Sirt6 have a regulatory role in the protective effects of RGZ on hepatocyte steatosis.To investigate the effect of RGZ on hepatic Sirt1, rats were administered with RGZ for 6 weeks. The involvement of Sirt1/6 in the RGZ-mediated effect against hepatic steatosis was evaluated by single or double knockdown of Sirt1 and Sirt6 in a hepatocyte steatosis model.RGZ in vivo increased Sirt1 expression and its activity in rat livers. In a hepatocyte steatosis model, RGZ significantly reduced lipid accumulation and activated the Sirt1/6-LKB1-AMPK pathway. Sirt1 knockdown abolished the effects of RGZ with regard to hepatocyte fat accumulation and the Sirt1/6-LKB1-AMPK pathway, suggesting that Sirt1 is a key regulator of RGZ-mediated metabolic processes. Sirt6 knockdown inhibited the protective effects of RGZ to a lesser extent than Sirt1, and double knockdown of Sirt1/6 showed no synergistic effects.Our results demonstrate that Sirt1/6 are involved in the RGZ-mediated effects on hepatocyte steatosis, and the regulatory effects of Sirt1 and Sirt6 are not synergistic but compensatory for improving hepatocyte steatosis.

  7. Intracellular mechanisms coupled to NPY Y2 and Y5 receptor activation and lipid accumulation in murine adipocytes.

    Science.gov (United States)

    Rosmaninho-Salgado, Joana; Cortez, Vera; Estrada, Marta; Santana, Magda M; Gonçalves, Alexandra; Marques, Ana Patrícia; Cavadas, Cláudia

    2012-12-01

    The formation of adipose tissue is a process that includes the pre-adipocyte proliferation and differentiation to adipocytes that are cells specialized in lipid accumulation. The adipocyte differentiation is a process driven by the coordinated expression of various transcription factors, such as peroxisome proliferator-activated receptor (PPAR-γ). Neuropeptide Y (NPY) induces adipocyte proliferation and differentiation but the NPY receptors and the intracellular pathways involved in these processes are still not clear. In the present work we studied the role of NPY receptors and the intracellular pathways involved in the stimulatory effect of NPY on lipid accumulation. The murine pre-adipocyte cell line, 3T3-L1, was used as a cell model. Adipogenesis was evaluated by quantifying lipid accumulation by Oil red-O assay and by analyzing PPAR-γ expression using the Western blotting assay. Adipocytes were incubated with NPY (100nM) and a decrease on lipid accumulation and PPAR-γ expression was observed in the presence of NPY Y(2) receptor antagonist (BIIE0246, 1μM) or NPY Y(5) antagonist. Furthermore, NPY Y(2) (NPY(3-36), 100nM) or NPY Y(5) (NPY(19-23)(GLY(1), Ser(3), Gln(4), Thr(6), Ala(31), Aib(32), Gln(34)) PP, 100nM) receptor agonists increased lipid accumulation and PPAR-γ expression. We further investigate the intracellular pathways associated with NPY Y(2) and NPY Y(5) receptor activation. Our results show NPY induces PPAR-γ expression and lipid accumulation through NPY Y(2) and NPY Y(5) receptors activation. PKC and PLC inhibitors inhibit lipid accumulation induced by NPY Y(5) receptor agonist. Moreover, our results suggest that lipid accumulation induced by NPY Y(2) receptor activation occurs through PKA, MAPK and PI3K pathways. In conclusion, this study contributes to a step forward on the knowledge of intracellular mechanisms associated with NPY receptors activation on adipocytes and contributes to a better understanding and the development of new

  8. Transformation of lipid bodies related to hydrocarbon accumulation in a green alga, Botryococcus braunii (Race B.

    Directory of Open Access Journals (Sweden)

    Reiko Suzuki

    Full Text Available The colonial microalga Botryococcus braunii accumulates large quantities of hydrocarbons mainly in the extracellular space; most other oleaginous microalgae store lipids in the cytoplasm. Botryococcus braunii is classified into three principal races (A, B, and L based on the types of hydrocarbons. Race B has attracted the most attention as an alternative to petroleum by its higher hydrocarbon contents than the other races and its hydrocarbon components, botryococcenes and methylsqualenes, both can be readily converted into biofuels. We studied race B using fluorescence and electron microscopy, and clarify the stage when extracellular hydrocarbon accumulation occurs during the cell cycle, in a correlation with the behavior and structural changes of the lipid bodies and discussed development of the algal colony. New accumulation of lipids on the cell surface occurred after cell division in the basolateral region of daughter cells. While lipid bodies were observed throughout the cell cycle, their size and inclusions were dynamically changing. When cells began dividing, the lipid bodies increased in size and inclusions until the extracellular accumulation of lipids started. Most of the lipids disappeared from the cytoplasm concomitant with the extracellular accumulation, and then reformed. We therefore hypothesize that lipid bodies produced during the growth of B. braunii are related to lipid secretion. New lipids secreted at the cell surface formed layers of oil droplets, to a maximum depth of six layers, and fused to form flattened, continuous sheets. The sheets that combined a pair of daughter cells remained during successive cellular divisions and the colony increased in size with increasing number of cells.

  9. Exploration of polar lipid accumulation profiles in Euglena gracilis using LipidBlast, an MS/MS spectral library constructed in silico.

    Science.gov (United States)

    Ogawa, Takumi; Furuhashi, Takeshi; Okazawa, Atsushi; Nakai, Rai; Nakazawa, Masami; Kind, Tobias; Fiehn, Oliver; Kanaya, Shigehiko; Arita, Masanori; Ohta, Daisaku

    2014-01-01

    A rapid protocol for polar lipid profiling was applied to Euglena gracilis lipid metabolism by LipidBlast, an MS/MS spectral similarity search tool. The similarity search results suggested anoxia-induced polar lipid metabolism in Euglena characterized by the accumulation of differential lipid classes, carbon chain lengths, and unsaturated bond numbers. The informatics-supported MS spectral search provides an alternative option for global lipid profiling studies.

  10. Neutral lipid accumulation at elevated temperature in conditional mutants of two microalgae species

    DEFF Research Database (Denmark)

    Yao, Shuo; Brandt, Anders Bøving; Egsgaard, Helge

    2012-01-01

    Triacylglycerols, an energy storage compound in microalgae, are known to be accumulated after nitrogen starvation of microalgae cells. Microalgae could be of importance for future biodiesel production due to their fast growth rate and high oil content. In collections of temperature sensitive...... accumulation in microalgae and suggest possibilities for biodiesel production by specific induction of lipid accumulation in miroalgal cultures by cell-cycle inhibition....

  11. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Qin; Sha, Sha; Sun, Lei; Zhang, Jing; Dong, Ming, E-mail: dr_dongming@126.com

    2016-08-05

    The incidence of nonalcoholic fatty liver disease (NAFLD) keeps rising year by year, and NAFLD is rapidly becoming the most common liver disease worldwide. Clinical studies have found that glucagon-like peptide-1 (GLP-1) analogue, liraglutide (LRG), cannot only reduce glucose levels, but also improve hepatic lipase, especially in patients also with type 2 diabetes mellitus (T2DM). In addition, enhancing autophagy decreases lipid accumulation in hepatocytes. The aim of the present study is to explore the effect of LRG on hepatocyte steatosis and the possible role of autophagy. We set up an obesity mouse model with a high-fat diet (HFD) and induced hepatocyte steatosis with free fatty acids (FFA) in human L-O2 cells. LRG and two inhibitors of autophagy, Chloroquine (CQ) and bafilomycin A1 (Baf), were added into each group, respectively. The lipid profiles and morphological modifications of each group were tested. Immunohistochemistry, immunofluorescence staining and transmission electron microscopy (TEM) were used to measure autophagy in this study. The autophagy protein expression of SQSTM1 (P62), and LC3B, along with the signaling pathway proteins of mTOR, phosphorylated mTOR (p-mTOR), AMPK, phosphorylated AMPK (p-AMPK) and Beclin1, were evaluated by western blot. Our results showed that LRG improved hepatocyte steatosis by inducing autophagy, and the AMPK/mTOR pathway is involved. These findings suggest an important mechanism for the positive effects of LRG on hepatic steatosis, and provide new evidence for clinical use of LRG in NAFLD. -- Highlights: •Liraglutide reduces lipid accumulation in hepatic steatosis both in vivo and in vitro. •Autophagy was involved in relieving effects of liraglutide on hepatic steatosis. •AMPK/mTOR pathway was involved in liraglutide-induced autophagy.

  12. Modeling IRA Accumulation and Withdrawals

    OpenAIRE

    Sabelhaus, John

    2000-01-01

    Empirical analysis of IRA accumulation and withdrawal patterns is limited because information about IRA balances and flows is not available for a sample of taxpayers. This paper combines survey data on IRA balances with individual tax return data on IRA flows to study IRA accumulation and withdrawal patterns across cohorts. The analysis shows that IRA rules such as penalties for early withdrawals and minimum distribution requirements have predictable effects on IRA flows. The estimated propen...

  13. Effect of diurnal temperature difference on lipid accumulation and development in Calanus sinicus (Copepoda: Calanoida)

    Science.gov (United States)

    Zhou, Konglin; Sun, Song

    2016-08-01

    Calanus sinicus, the dominant copepod in the Yellow Sea, develops a large oil sac in late spring to prepare for over-summering in the Yellow Sea Cold Water Mass (YSCWM). The lipid accumulation mechanism for the initiation of over-summering is unknown. Here, we cultured C3 copepodites at four constant temperatures (10, 13, 16, and 19°C) and at three temperature regimes that mimicked the temperature variations experienced during diurnal vertical migration (10-13°C, 10-16°C, and 10-19°C) for 18 days to explore the effects of temperature differences on copepod development and lipid accumulation. C. sinicus stored more lipid at low than at high temperatures. A diurnal temperature difference (10-16°C and 10-19°C) promoted greater lipid accumulation (1.9-2.1 times) than a constant temperature of either 16°C or 19°C, by reducing the energy cost at colder temperatures and lengthening copepodite development. Thereafter, the lipid reserve supported gonad development after final molting. Only one male developed in these experiments. This highly female-skewed sex ratio may have been the result of the monotonous microalgae diet fed to the copepodites. This study provides the first evidence that diurnal temperature differences may promote lipid accumulation in C. sinicus, and provides a foundation for future investigations into the mechanisms involved in over-summering in the YSCWM.

  14. Identification and metabolomic analysis of chemical modulators for lipid accumulation in Crypthecodinium cohnii.

    Science.gov (United States)

    Li, Jinghan; Niu, Xiangfeng; Pei, Guangsheng; Sui, Xiao; Zhang, Xiaoqing; Chen, Lei; Zhang, Weiwen

    2015-09-01

    In the study, fourteen chemical modulators from five groups (i.e., auxin, gibberellin, cytokinin, signal transducer and amine) were evaluated for their effects on lipid accumulation in Crypthecodinium cohnii. The results showed that naphthoxyacetic acid (BNOA), 2-chlorodracylicacid, salicylic acid (SA), abscisic acid (ABA) and ethanolamine (ETA), increased lipid accumulation in C. cohnii by 10.00-18.78%. In addition, the combined uses of the above chemicals showed that two combinations, 1.0mg/L SA & 152.7 mg/L ETA and 4.0mg/L BNOA & 152.7 mg/L ETA, increased lipid accumulation by 22.45% and 20.54%, respectively. Moreover, a targeted metabolomic approach was employed to decipher the possible mechanisms responsible for the increased lipid accumulation, and the results showed that the enhanced metabolism in glycolysis and TCA cycle as well as the decreased metabolism in PPP pathway could be important for the stimulatory roles of BNOA & ETA and SA & ETA on lipid accumulation in C. cohnii.

  15. Effect of carbon source on growth and lipid accumulation in Chlorella sorokiniana GXNN01

    Institute of Scientific and Technical Information of China (English)

    QIAO Hongjin; WANG Guangce

    2009-01-01

    Heterotrophic culture of microalgae to develop methods of increasing biomass productivity and storage lipids has brought new insight to commercial biodiesel production. To understand the relationship between heterotrophy and lipid production, the effects of carbon sources on the growth and lipid accumulation of Chlorella sorokiniana GXNN01 was studied. The alga exhibited an increased growth rate in response to the addition of carbon sources, which reached the stationary phase after 48 h at 30°C. In addition, glucose and NaAc had a significant effect on the lipid accumulation during the early-stationary phase. Specifically, the lipid content was 0.237±0.026 g g~(-1) cell dry weight and 0.272±0.041 g L~(-1) when glucose was used as the carbon source, whereas the lipid content reached 0.287±0.018 g g~(-1) cell dry weight and 0.288±0.008 g L~(-1) when NaAc was used as the carbon source. The neutral lipid content was found to first decrease and then increase over time during the growth phase. A glucose concentration of 20 mmol L~(-1) gave the maximal lipid yield and the optimum harvest time was the early-stationary phase.

  16. Dissolved inorganic carbon enhanced growth, nutrient uptake, and lipid accumulation in wastewater grown microalgal biofilms.

    Science.gov (United States)

    Kesaano, Maureen; Gardner, Robert D; Moll, Karen; Lauchnor, Ellen; Gerlach, Robin; Peyton, Brent M; Sims, Ronald C

    2015-03-01

    Microalgal biofilms grown to evaluate potential nutrient removal options for wastewaters and feedstock for biofuels production were studied to determine the influence of bicarbonate amendment on their growth, nutrient uptake capacity, and lipid accumulation after nitrogen starvation. No significant differences in growth rates, nutrient removal, or lipid accumulation were observed in the algal biofilms with or without bicarbonate amendment. The biofilms possibly did not experience carbon-limited conditions because of the large reservoir of dissolved inorganic carbon in the medium. However, an increase in photosynthetic rates was observed in algal biofilms amended with bicarbonate. The influence of bicarbonate on photosynthetic and respiration rates was especially noticeable in biofilms that experienced nitrogen stress. Medium nitrogen depletion was not a suitable stimulant for lipid production in the algal biofilms and as such, focus should be directed toward optimizing growth and biomass productivities to compensate for the low lipid yields and increase nutrient uptake.

  17. TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice.

    Science.gov (United States)

    Jiang, Shiming; Minter, Lindsey Cauthen; Stratton, Sabrina A; Yang, Peirong; Abbas, Hussein A; Akdemir, Zeynep Coban; Pant, Vinod; Post, Sean; Gagea, Mihai; Lee, Richard G; Lozano, Guillermina; Barton, Michelle Craig

    2015-02-01

    Aberrantly high expression of TRIM24 occurs in human cancers, including hepatocellular carcinoma. In contrast, TRIM24 in the mouse is reportedly a liver-specific tumour suppressor. To address this dichotomy and to uncover direct regulatory functions of TRIM24 in vivo, we developed a new mouse model that lacks expression of all Trim24 isoforms, as the previous model expressed normal levels of Trim24 lacking only exon 4. To produce germline-deleted Trim24(dlE1) mice, deletion of the promoter and exon 1 of Trim24 was induced in Trim24(LoxP) mice by crossing with a zona pellucida 3-Cre line for global deletion. Liver-specific deletion (Trim24(hep)) was achieved by crossing with an albumin-Cre line. Phenotypic analyses were complemented by protein, gene-specific and global RNA expression analyses and quantitative chromatin immunoprecipitation. Global loss of Trim24 disrupted hepatic homeostasis in 100% of mice with highly significant, decreased expression of oxidation/reduction, steroid, fatty acid, and lipid metabolism genes, as well as increased expression of genes involved in unfolded protein response, endoplasmic reticulum stress and cell cycle pathways. Trim24(dlE1/dlE1) mice have markedly depleted visceral fat and, like Trim24(hep/hep) mice, spontaneously develop hepatic lipid-filled lesions, steatosis, hepatic injury, fibrosis and hepatocellular carcinoma. TRIM24, an epigenetic co-regulator of transcription, directly and indirectly represses hepatic lipid accumulation, inflammation, fibrosis and damage in the murine liver. Complete loss of Trim24 offers a model of human non-alcoholic fatty liver disease, steatosis, fibrosis and development of hepatocellular carcinoma in the absence of high-fat diet or obesity. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Modified lipoprotein-derived lipid particles accumulate in human stenotic aortic valves.

    Science.gov (United States)

    Lehti, Satu; Käkelä, Reijo; Hörkkö, Sohvi; Kummu, Outi; Helske-Suihko, Satu; Kupari, Markku; Werkkala, Kalervo; Kovanen, Petri T; Oörni, Katariina

    2013-01-01

    In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine -ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis.

  19. Characterization of polysaccharides with marked inhibitory effect on lipid accumulation in Pleurotus eryngii.

    Science.gov (United States)

    Chen, Jingjing; Yong, Yangyang; Xing, Meichun; Gu, Yifan; Zhang, Zhao; Zhang, Shizhu; Lu, Ling

    2013-09-12

    Mushrooms have a great potential for the production of useful bioactive metabolites. To explore the bioactive compounds from edible mushrooms for interfering with the development of macrophage-derived foam cells, which is recognized as the hallmark of early atherosclerosis, eight types of mushrooms polysaccharides had been selected to be tested. Consequently, different mushrooms polysaccharides displayed diverse component profiles. Of polysaccharides that we tested, the Pleurotus eryngii polysaccharide had the strongest inhibitory effect on lipid accumulation. Furthermore, through fractionation of DEAE-52 and Sephadex G-100, the polysaccharide from P. eryngii had been successfully purified and identified. By the analysis of IR, GC, and HPLC, the purified polysaccharide was estimated to be 30-38 kDa for the average molecular weight with the monosaccharide composition mainly composed of D-types of mannose, glucose and galactose. Findings presented in this report firstly provide direct evidence, which links the purified polysaccharide moiety with the biological function in foam-cell model.

  20. miRNA-133a attenuates lipid accumulation via TR4-CD36 pathway in macrophages.

    Science.gov (United States)

    Peng, Xiao-Ping; Huang, Lei; Liu, Zhi-Hong

    2016-08-01

    lipid metabolism is the major causes of atherosclerosis. There is increasing evidence that miR-133a plays an important role in atherosclerosis. However, the regulatory mechanism of miR-133a in macrophages is still unclear. Several lines of evidence indicate that loss of TR4 leads to reduce lipid accumulation in liver and adipose tissues, etc, and lesional macrophages-derived TR4 can greatly increase the foam cell formation through increasing the CD36-mediated the uptake of ox-LDL. Interestingly, computational analysis suggests that TR4 may be a target gene of miR-133a. Here, we examined whether miR-133a regulates TR4 expression in ox-LDL-induced mouse RAW 264.7 macrophages, thereby affecting lipid accumulation. Using ox-LDL-treatment RAW 264.7 macrophages transfected with miR-133a mimics or inhibitors, we have showed that miR-133a can directly regulate the expression of TR4 in RAW 264.7 cells, thereby attenuates CD36-medide lipid accumulation. Furthermore, our studies suggest an additional explanation for the regulatory mechanism of miR-133a regulation to its functional target, TR4 in RAW 264.7 macrophages. Thus, our findings suggest that miR-133a may regulate lipid accumulation in ox-LDL-stimulated RAW 264.7 macrophages via TR4-CD36 pathway.

  1. Effects of calcium, magnesium and sodium chloride in enhancing lipid accumulation in two green microalgae.

    Science.gov (United States)

    Gorain, Prakash Chandra; Bagchi, Sourav Kumar; Mallick, Nirupama

    2013-01-01

    Biodiesel from microalgae has the potential as a sustainable fuel, since some species show exceptionally high lipid accumulation potential under various stresses. Effects of different concentrations of Ca, Mg and NaCl in the growth medium on biomass yield and lipid accumulation of Chlorella vulgaris and Scenedesmus obliquus grown under batch culture mode were investigated. Starvation of Mg showed a marginal rise in lipid content for a short period of time. Ca-starved cultures, however, demonstrated a profound rise in lipid content, i.e. 40% of dry cell wt. (dcw) was recorded against 11.9% control for C. vulgaris and 37% (dcw) against 11.3% for S. obliquus. Under increased concentration of Mg, significant rise in biomass and lipid yield was recorded. Effect of NaCl-induced osmotic stress showed lipid accumulation of approximately 40% (dcw) in both the test algae, whereas the biomass yield was severely affected. The fatty acid profiles under the above stresses were analysed and discussed.

  2. Effect of organic acids on the growth and lipid accumulation of oleaginous yeast Trichosporon fermentans

    Directory of Open Access Journals (Sweden)

    Huang Chao

    2012-01-01

    Full Text Available Abstract Background Microbial lipids have drawn increasing attention in recent years as promising raw materials for biodiesel production, and the use of lignocellulosic hydrolysates as carbon sources seems to be a feasible strategy for cost-effective lipid fermentation with oleaginous microorganisms on a large scale. During the hydrolysis of lignocellulosic materials with dilute acid, however, various kinds of inhibitors, especially large amounts of organic acids, will be produced, which substantially decrease the fermentability of lignocellulosic hydrolysates. To overcome the inhibitory effects of organic acids, it is critical to understand their impact on the growth and lipid accumulation of oleaginous microorganisms. Results In our present work, we investigated for the first time the effect of ten representative organic acids in lignocellulosic hydrolysates on the growth and lipid accumulation of oleaginous yeast Trichosporon fermentans cells. In contrast to previous reports, we found that the toxicity of the organic acids to the cells was not directly related to their hydrophobicity. It is worth noting that most organic acids tested were less toxic than aldehydes to the cells, and some could even stimulate the growth and lipid accumulation at a low concentration. Unlike aldehydes, most binary combinations of organic acids exerted no synergistic inhibitory effects on lipid production. The presence of organic acids decelerated the consumption of glucose, whereas it influenced the utilization of xylose in a different and complicated way. In addition, all the organic acids tested, except furoic acid, inhibited the malic activity of T. fermentans. Furthermore, the inhibition of organic acids on cell growth was dependent more on inoculum size, temperature and initial pH than on lipid content. Conclusions This work provides some meaningful information about the effect of organic acid in lignocellulosic hydrolysates on the lipid production of

  3. Uncoupling of 3T3-L1 gene expression from lipid accumulation during adipogenesis.

    Science.gov (United States)

    Temple, Karla A; Basko, Xheni; Allison, Margaret B; Brady, Matthew J

    2007-02-06

    Adipocyte differentiation comprises altered gene expression and increased triglyceride storage. To investigate the interdependency of these two events, 3T3-L1 cells were differentiated in the presence of glucose or pyruvate. All adipocytic proteins examined were similarly increased between the two conditions. In contrast, 3T3-L1 adipocytes differentiated with glucose exhibited significant lipid accumulation, which was largely suppressed in the presence of pyruvate. Subsequent addition of glucose to the latter cells restored lipid accumulation and acute rates of insulin-stimulated lipogenesis. These data indicate that extracellular energy is required for induction of adipocytic proteins, while only glucose sustained the parallel increase in triglyceride storage.

  4. The deubiquitinase activity of the Salmonella pathogenicity island 2 effector, SseL, prevents accumulation of cellular lipid droplets.

    Science.gov (United States)

    Arena, Ellen T; Auweter, Sigrid D; Antunes, L Caetano M; Vogl, A Wayne; Han, Jun; Guttman, Julian A; Croxen, Matthew A; Menendez, Alfredo; Covey, Scott D; Borchers, Christoph H; Finlay, B Brett

    2011-11-01

    To cause disease, Salmonella enterica serovar Typhimurium requires two type III secretion systems that are encoded by Salmonella pathogenicity islands 1 and 2 (SPI-1 and -2). These secretion systems serve to deliver specialized proteins (effectors) into the host cell cytosol. While the importance of these effectors to promote colonization and replication within the host has been established, the specific roles of individual secreted effectors in the disease process are not well understood. In this study, we used an in vivo gallbladder epithelial cell infection model to study the function of the SPI-2-encoded type III effector, SseL. The deletion of the sseL gene resulted in bacterial filamentation and elongation and the unusual localization of Salmonella within infected epithelial cells. Infection with the ΔsseL strain also caused dramatic changes in host cell lipid metabolism and led to the massive accumulation of lipid droplets in infected cells. This phenotype was directly attributable to the deubiquitinase activity of SseL, as a Salmonella strain carrying a single point mutation in the catalytic cysteine also resulted in extensive lipid droplet accumulation. The excessive buildup of lipids due to the absence of a functional sseL gene also was observed in murine livers during S. Typhimurium infection. These results suggest that SseL alters host lipid metabolism in infected epithelial cells by modifying the ubiquitination patterns of cellular targets.

  5. Nitrogen-deprivation elevates lipid levels in Symbiodinium spp. by lipid droplet accumulation: morphological and compositional analyses.

    Directory of Open Access Journals (Sweden)

    Pei-Luen Jiang

    Full Text Available Stable cnidarian-dinoflagellate (genus Symbiodinium endosymbioses depend on the regulation of nutrient transport between Symbiodinium populations and their hosts. It has been previously shown that the host cytosol is a nitrogen-deficient environment for the intracellular Symbiodinium and may act to limit growth rates of symbionts during the symbiotic association. This study aimed to investigate the cell proliferation, as well as ultrastructural and lipid compositional changes, in free-living Symbiodinium spp. (clade B upon nitrogen (N-deprivation. The cell proliferation of the N-deprived cells decreased significantly. Furthermore, staining with a fluorescent probe, boron dipyrromethane 493/503 (BODIPY 493/503, indicated that lipid contents progressively accumulated in the N-deprived cells. Lipid analyses further showed that both triacylglycerol (TAG and cholesterol ester (CE were drastically enriched, with polyunsaturated fatty acids (PUFA; i.e., docosahexaenoic acid, heneicosapentaenoic acid, and oleic acid became more abundant. Ultrastructural examinations showed that the increase in concentration of these lipid species was due to the accumulation of lipid droplets (LDs, a cellular feature that have previously shown to be pivotal in the maintenance of intact endosymbioses. Integrity of these stable LDs was maintained via electronegative repulsion and steric hindrance possibly provided by their surface proteins. Proteomic analyses of these LDs identified proteins putatively involved in lipid metabolism, signaling, stress response and energy metabolism. These results suggest that LDs production may be an adaptive response that enables Symbiodinium to maintain sufficient cellular energy stores for survival under the N-deprived conditions in the host cytoplasm.

  6. Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

    Energy Technology Data Exchange (ETDEWEB)

    Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei; Nicora, Carrie D.; Fillmore, Thomas L.; Purvine, Samuel O.; Webb-Robertson, Bobbie-Jo; Smith, Richard D.; Baker, Scott E.; Metz, Thomas O.; Nielsen, Jens; Lee, Sang Yup

    2017-06-20

    ABSTRACT

    The yeastYarrowia lipolyticais a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis inY. lipolyticaand identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination ofDGA1overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor.

    IMPORTANCEThe ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeastYarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors

  7. Effect of Nutrient Starvation under High Irradiance on Lipid and Starch Accumulation in Chlorella fusca (Chlorophyta).

    Science.gov (United States)

    Jerez, Celia G; Malapascua, José R; Sergejevová, Magda; Figueroa, Félix L; Masojídek

    2016-02-01

    The effect of nitrogen and sulphur limitation under high irradiance (PAR) was studied in the green microalga Chlorella fusca (Chlorophyta) in order to follow lipid and/or starch accumulation. Growth, biomass composition and the changes in photosynthetic activity (in vivo chlorophyll a fluorescence) were followed in the trials. The full nutrient culture showed high biomass production and starch accumulation at Day 1, when photosynthetic activity was high. Gradual deprivation (no nutrients added) became evident when photosynthesis was significantly suppressed (Day 3 onwards), which entailed a decrease of maximum relative electron transport rate (rETRmax) and increase of non-photochemical quenching (NPQ), accompanied by the onset of lipid accumulation and decline in starch content. In N- and S-starved cultures, rETRmax significantly decreased by Day 3, which caused a substantial drop in biomass production, cell number, biovolume and induction of lipid and starch accumulation. High starch content (45-50 % of DW) was found at the initial stage in full nutrient culture and at the stationary phase in nutrient-starved cultures. By the end of the trial, all treatments showed high lipid content (~30 % of DW). The full nutrient culture had higher biomass yield than starved treatments although starch (~0.2 g L(-1) day(-1)) and lipid (~0.15 g L(-1) day(-1) productivities were fairly similar in all the cultures. Our results showed that we could enrich biomass of C. fusca (% DW) in lipids using a two-stage strategy (a nutrient replete stage followed by gradual nutrient limitation) while under either procedure, N- or S-starvation, both high lipid and starch contents could be achieved.

  8. [Novel mechanism for hepatic lipid accumulation: a physiological role for hepatic PPARγ-fsp27 signal].

    Science.gov (United States)

    Matsusue, Kimihiko

    2012-01-01

    Fat-specific protein 27 (fsp27) was originally isolated by screening for genes specifically expressed in fully differentiated mouse adipocytes. Fsp27 and cell death-inducing DFF45-like effector (CIDE) C, the human homologue of fsp27, belong to the CIDE family. Fsp27, which is highly expressed in mouse white and brown adipose tissues, was recently reported to be a lipid droplet (LD)-binding protein that promotes lipid accumulation in adipocytes. In contrast, we showed that fsp27 was also expressed in the fatty liver of the ob/ob type II diabetes model mouse. The expression of fsp27 was markedly decreased in livers lacking the nuclear receptor peroxisome proliferator-activated receptor γ(PPARγ). A functional PPAR response element site was identified in the fsp27 promoter region. Forced expression of fsp27 in hepatocytes in vitro or in vivo led to increased LD through increased triglyceride levels. The current status of the physiological roles of the PPARγ-fsp27 signal in fatty liver are discussed along with its significance as a factor involved in the development of metabolic disorders.

  9. Sub-chronically exposing mice to a polycyclic aromatic hydrocarbon increases lipid accumulation in their livers.

    Science.gov (United States)

    Jin, Yuanxiang; Miao, Wenyu; Lin, Xiaojian; Wu, Tao; Shen, Hangjie; Chen, Shan; Li, Yanhong; Pan, Qiaoqiao; Fu, Zhengwei

    2014-09-01

    The potential for exposing humans and wildlife to environmental polycyclic aromatic hydrocarbons (PAHs) has increased. Risk assessments describing how PAHs disturb lipid metabolism and induce hepatotoxicity have only received limited attention. In the present study, seven-week-old male ICR mice received intraperitoneal injections of 0, 0.01, 0.1 or 1mg/kg body weight 3-methylcholanthrene (3MC) per week for 10 weeks. A high-fat diet was provided during the exposure. Histopathological lipid accumulation and lipid metabolism-related genes were measured. We observed that sub-chronic 3MC exposure significantly increased lipid droplet and triacylglycerol (TG) levels in the livers. A low dose of 3MC activated the aryl hydrocarbon receptor, which negatively regulated lipid synthesis in the livers. The primary genes including acetyl-CoA carboxylase (Acc), fatty acid synthase (Fas) and stearoyl-CoA desaturase 1 (Scd1) decreased significantly when compared with those in the control group, indicating that de novo fatty acid synthesis in the hepatocytes was significantly inhibited by the sub-chronic 3MC exposure. However, the free fatty acid (FFA) synthesis in the adipose tissue was greatly enhanced by up-regulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and sterol regulatory element binding protein-1c (SREBP1C) and target genes including Acc, Fas and Scd1. The synthesized FFA was released into the blood and then transported into the liver by the up-regulation of Fat and Fatp2, which resulted in the gradual accumulation of lipids in the liver. In conclusion, histological examinations and molecular level analyses highlighted the development of lipid accumulation and confirmed that 3MC significantly impaired lipid metabolism in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Effects of macro and micronutrients on neutral lipid accumulation in oleaginous microalgae

    NARCIS (Netherlands)

    Ghafari, Mohsen; Rashidi, Behzad; Haznedaroglu, Berat Zeki

    2016-01-01

    In this study, effects of key macro and micronutrients on neutral lipid accumulation of six oleaginous microalgae species were investigated. For each nutrient, three different concentrations (0.5×, 1×, and 2×) were tested individually and compared to the most commonly utilized growth medium recip

  11. Effects of macro and micronutrients on neutral lipid accumulation in oleaginous microalgae

    NARCIS (Netherlands)

    Ghafari, Mohsen; Rashidi, Behzad; Haznedaroglu, Berat Zeki

    2016-01-01

    In this study, effects of key macro and micronutrients on neutral lipid accumulation of six oleaginous microalgae species were investigated. For each nutrient, three different concentrations (0.5×, 1×, and 2×) were tested individually and compared to the most commonly utilized growth medium recip

  12. Effects of macro and micronutrients on neutral lipid accumulation in oleaginous microalgae

    NARCIS (Netherlands)

    Ghafari, Mohsen; Rashidi, Behzad; Haznedaroglu, Berat Zeki

    2016-01-01

    In this study, effects of key macro and micronutrients on neutral lipid accumulation of six oleaginous microalgae species were investigated. For each nutrient, three different concentrations (0.5×, 1×, and 2×) were tested individually and compared to the most commonly utilized growth medium

  13. Dietary Protein Affects Gene Expression and Prevents Lipid Accumulation in the Liver in Mice

    NARCIS (Netherlands)

    Schwarz, J.; Tome, D.G.; Baars, A.; Hooiveld, G.J.E.J.; Müller, M.R.

    2012-01-01

    Background and Aims: High protein (HP) diets are suggested to positively modulate obesity and associated increased prevalence of non-alcoholic fatty liver (NAFLD) disease in humans and rodents. The aim of our study was to detect mechanisms by which a HP diet affects hepatic lipid accumulation. Metho

  14. Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

    2013-07-19

    Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

  15. Proteomic analysis of Chlorella vulgaris: Potential targets for enhanced lipid accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Guarnieri, Michael T.; Nag, Ambarish; Yang, Shihui; Pienkos, Philip T.

    2013-11-01

    Oleaginous microalgae are capable of producing large quantities of fatty acids and triacylglycerides. As such, they are promising feedstocks for the production of biofuels and bioproducts. Genetic strain-engineering strategies offer a means to accelerate the commercialization of algal biofuels by improving the rate and total accumulation of microalgal lipids. However, the industrial potential of these organisms remains to be met, largely due to the incomplete knowledgebase surrounding the mechanisms governing the induction of algal lipid biosynthesis. Such strategies require further elucidation of genes and gene products controlling algal lipid accumulation. In this study, we have set out to examine these mechanisms and identify novel strain-engineering targets in the oleaginous microalga, Chlorella vulgaris. Comparative shotgun proteomic analyses have identified a number of novel targets, including previously unidentified transcription factors and proteins involved in cell signaling and cell cycle regulation. These results lay the foundation for strain-improvement strategies and demonstrate the power of translational proteomic analysis.

  16. Non-polar lipids accumulate during storage of transfusion products and do not contribute to the onset of transfusion-related acute lung injury.

    Science.gov (United States)

    Peters, A L; Vervaart, M A T; van Bruggen, R; de Korte, D; Nieuwland, R; Kulik, W; Vlaar, A P J

    2017-01-01

    The accumulation of non-polar lipids arachidonic acid, 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE and 15-HETE during storage of transfusion products may play a role in the onset of transfusion-related acute lung injury (TRALI), a syndrome of respiratory distress after transfusion. We investigated non-polar lipid accumulation in red blood cells (RBCs) stored for 42 days, plasma stored for 7 days at either 4 or 20°C and platelet (PLT) transfusion products stored for 7 days. Furthermore, we investigated whether transfusion of RBCs with increased levels of non-polar lipids induces TRALI in a 'two-hit' human volunteer model. All products were produced following Dutch Blood Bank protocols and are according to European standards. Non-polar lipids were measured with high-performance liquid chromotography followed by mass spectrometry. All non-polar lipids increased in RBCs after 21 days of storage compared to baseline. The non-polar lipid concentration in plasma increased significantly, and the increase was even more pronounced in products stored at 20°C. In platelets, baseline levels of 5-HETE and 15-HETE were higher than in RBCs or plasma. However, the non-polar lipids did not change significantly during storage of PLT products. Infusion of RBCs with increased levels of non-polar lipids did not induce TRALI in LPS-primed human volunteers. We conclude that non-polar lipids accumulate in RBC and plasma transfusion products and that accumulation is temperature dependent. Accumulation of non-polar lipids does not appear to explain the onset of TRALI (Dutch Trial Register - NTR4455). © 2016 International Society of Blood Transfusion.

  17. Photosynthetic light reactions increase total lipid accumulation in carbon-supplemented batch cultures of Chlorella vulgaris.

    Science.gov (United States)

    Woodworth, Benjamin D; Mead, Rebecca L; Nichols, Courtney N; Kolling, Derrick R J

    2015-03-01

    Microalgae are an attractive biofuel feedstock because of their high lipid to biomass ratios, lipid compositions that are suitable for biodiesel production, and the ability to grow on varied carbon sources. While algae can grow autotrophically, supplying an exogenous carbon source can increase growth rates and allow heterotrophic growth in the absence of light. Time course analyses of dextrose-supplemented Chlorella vulgaris batch cultures demonstrate that light availability directly influences growth rate, chlorophyll production, and total lipid accumulation. Parallel photomixotrophic and heterotrophic cultures grown to stationary phase reached the same amount of biomass, but total lipid content was higher for algae grown in the presence of light (an average of 1.90 mg/mL vs. 0.77 mg/mL over 5 days of stationary phase growth).

  18. Lipid accumulation and CO2 utilization of Nannochloropsis oculata in response to CO2 aeration.

    Science.gov (United States)

    Chiu, Sheng-Yi; Kao, Chien-Ya; Tsai, Ming-Ta; Ong, Seow-Chin; Chen, Chiun-Hsun; Lin, Chih-Sheng

    2009-01-01

    In order to produce microalgal lipids that can be transformed to biodiesel fuel, effects of concentration of CO(2) aeration on the biomass production and lipid accumulation of Nannochloropsis oculata in a semicontinuous culture were investigated in this study. Lipid content of N. oculata cells at different growth phases was also explored. The results showed that the lipid accumulation from logarithmic phase to stationary phase of N. oculata NCTU-3 was significantly increased from 30.8% to 50.4%. In the microalgal cultures aerated with 2%, 5%, 10% and 15% CO(2), the maximal biomass and lipid productivity in the semicontinuous system were 0.480 and 0.142 g L(-1)d(-1) with 2% CO(2) aeration, respectively. Even the N. oculata NCTU-3 cultured in the semicontinuous system aerated with 15% CO(2), the biomass and lipid productivity could reach to 0.372 and 0.084 g L(-1)d(-1), respectively. In the comparison of productive efficiencies, the semicontinuous system was operated with two culture approaches over 12d. The biomass and lipid productivity of N. oculata NCTU-3 were 0.497 and 0.151 g L(-1)d(-1) in one-day replacement (half broth was replaced each day), and were 0.296 and 0.121 g L(-1)d(-1) in three-day replacement (three fifth broth was replaced every 3d), respectively. To optimize the condition for long-term biomass and lipid yield from N. oculata NCTU-3, this microalga was suggested to grow in the semicontinuous system aerated with 2% CO(2) and operated by one-day replacement.

  19. The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells

    Science.gov (United States)

    Nunn, Abigail D. G.; Scopigno, Tullio; Pediconi, Natalia; Levrero, Massimo; Hagman, Henning; Kiskis, Juris; Enejder, Annika

    2016-06-01

    Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome.

  20. Lipid accumulation and growth of Chlorella zofingiensis in flat plate photobioreactors outdoors.

    Science.gov (United States)

    Feng, Pingzhong; Deng, Zhongyang; Hu, Zhengyu; Fan, Lu

    2011-11-01

    Culturing microalgae using natural sunlight is an effective way to reduce the cost of microalgae-based biodiesel production. In order to evaluate the feasibility of culturing Chlorella zofingiensis outdoors for biodiesel production, effects of nitrogen limitation and initial cell concentration on growth and lipid accumulation of this alga were investigated in 60 L flat plate photobioreactors outdoors. The highest μmax and biomass productivity obtained was 0.994 day(-1) and 58.4 mg L(-1)day(-1), respectively. The lipid content was much higher (54.5% of dry weight) under nitrogen limiting condition than under nitrogen sufficient condition (27.3%). With the increasing initial cell concentrations, the lipid contents declined, while lipid concentrations and productivities increased. The highest lipid content, lipid concentration, and lipid productivity obtained was 54.5%, 536 mg L(-1) and 22.3 mg L(-1)day(-1), respectively. This study demonstrated that it was possible to culture C. zofingiensis under outdoor conditions for producing biodiesel feedstock.

  1. Quercetin decreases high-fat diet induced bodyweight gain and accumulation of hepatic and circulating lipids in mice

    NARCIS (Netherlands)

    Schothorst, van E.M.; Hoek-van den Hil, E.F.; Keijer, J.

    2014-01-01

    Dietary flavonoids may protect against cardiovascular diseases (CVD). Increased circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. The aim of this study was to investigate the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid

  2. Sources and resources: importance of nutrients, resource allocation, and ecology in microalgal cultivation for lipid accumulation.

    Science.gov (United States)

    Fields, Matthew W; Hise, Adam; Lohman, Egan J; Bell, Tisza; Gardner, Rob D; Corredor, Luisa; Moll, Karen; Peyton, Brent M; Characklis, Gregory W; Gerlach, Robin

    2014-06-01

    Regardless of current market conditions and availability of conventional petroleum sources, alternatives are needed to circumvent future economic and environmental impacts from continued exploration and harvesting of conventional hydrocarbons. Diatoms and green algae (microalgae) are eukaryotic photoautotrophs that can utilize inorganic carbon (e.g., CO2) as a carbon source and sunlight as an energy source, and many microalgae can store carbon and energy in the form of neutral lipids. In addition to accumulating useful precursors for biofuels and chemical feed stocks, the use of autotrophic microorganisms can further contribute to reduced CO2 emissions through utilization of atmospheric CO2. Because of the inherent connection between carbon, nitrogen, and phosphorus in biological systems, macronutrient deprivation has been proven to significantly enhance lipid accumulation in different diatom and algae species. However, much work is needed to understand the link between carbon, nitrogen, and phosphorus in controlling resource allocation at different levels of biological resolution (cellular versus ecological). An improved understanding of the relationship between the effects of N, P, and micronutrient availability on carbon resource allocation (cell growth versus lipid storage) in microalgae is needed in conjunction with life cycle analysis. This mini-review will briefly discuss the current literature on the use of nutrient deprivation and other conditions to control and optimize microalgal growth in the context of cell and lipid accumulation for scale-up processes.

  3. Effect of acetic acid on lipid accumulation by glucose-fed activated sludge cultures

    Energy Technology Data Exchange (ETDEWEB)

    Mondala, Andro; Hernandez, Rafael; French, Todd; McFarland, Linda; Sparks, Darrell; Holmes, William; Haque, Monica

    2012-01-01

    The effect of acetic acid, a lignocellulose hydrolysis by-product, on lipid accumulation by activated sludge cultures grown on glucose was investigated. This was done to assess the possible application of lignocellulose as low-cost and renewable fermentation substrates for biofuel feedstock production. Results: Biomass yield was reduced by around 54% at a 2 g L -1 acetic acid dosage but was increased by around 18% at 10 g L -1 acetic acid dosage relative to the control run. The final gravimetric lipid contents at 2 and 10 g L -1 acetic acid levels were 12.5 + 0.7% and 8.8 + 3.2% w/w, respectively, which were lower than the control (17.8 + 2.8% w/w). However, biodiesel yields from activated sludge grown with acetic acid (5.6 + 0.6% w/w for 2 g L -1 acetic acid and 4.2 + 3.0% w/w for 10 g L -1 acetic acid) were higher than in raw activated sludge (1-2% w/w). The fatty acid profiles of the accumulated lipids were similar with conventional plant oil biodiesel feedstocks. Conclusions: Acetic acid enhanced biomass production by activated sludge at high levels but reduced lipid production. Further studies are needed to enhance acetic acid utilization by activated sludge microorganisms for lipid biosynthesis.

  4. Nitrogen starvation for lipid accumulation in the microalga species Desmodesmus sp.

    Science.gov (United States)

    Rios, L F; Klein, B C; Luz, L F; Maciel Filho, R; Wolf Maciel, M R

    2015-01-01

    Recently, to obtain lipids from microalgae has been the object of extensive research, since it is viewed as a promising feedstock for biodiesel production, especially when compared with crops such as soybean and sunflower, in terms of theoretical performance. The reduction of nutrient availability in culture media, especially nitrogen, stresses the microorganisms and affects cell growth, thus inducing lipid accumulation. This is an interesting step in biodiesel feedstock obtention from microalgae and should be better understood. In this study, four levels of nitrogen concentration in the BG-11 culture medium were evaluated in the growth of the chlorophycean microalga Desmodesmus sp. Both cell growth and lipid content were monitored over 7 days of cultivation, which yielded a final cell density of 33 × 10(6) cells mL(-1) with an initial NaNO3 concentration of 750 mg L(-1) in the medium and a maximum lipid content of 23 % with total nitrogen starvation. It was observed that the microalgae presented high lipid accumulation in the fourth day of cultivation with nitrogen starvation, although with moderate cell growth.

  5. The Effect of Growth Hormone on Lipid Accumulation or Maturation in Adipocytes

    Directory of Open Access Journals (Sweden)

    Yuchao Zhang

    2016-11-01

    Full Text Available Background: Adipogenesis of adipocytes includes two stages: initiation and maturation. Growth hormone (GH secretion is decreased in obese subjects and GH levels are inversely correlated with abdominal fat mass. The effects of growth hormone (GH on lipids accumulation or maturation of adipocytes remains elusive. Methods: In the present study, effect of GH on lipid accumulation in vitro and in vivo was examined. cDNA microarray, quantitative real time-PCR (qPCR and western blotting was used to analyze the expression of genes related to adipocyte lipid accumulation or degradation in pre- or mature 3T3-F442A adipocytes treated with GH and in epididymal adipose tissue of C57BL/6 mice administrated with GH. Level of adiponectin in supernatants of cultured F442A adipocytes was determined by enzyme-linked immune-sorbent assay. Results: We found that in 3T3-F442A especially 6 days post initiation of adipogenesis, GH intervention resulted in decreased expression of adipocyte maturation regulators (C/EBPα, PPARγ and prominent genes related to lipid synthesis such as FAS and FABP, while the expression of UCP1 was markedly enhanced. cDNA microarray analysis and qPCR showed that the expression of SOCS2 and Adipor2 was increased under GH-treatment in mature 3T3-F442A adipocytes. GH treatment increased the mRNA expression of adiponectin and UCP1 in mature adipocytes. The above results were confirmed by in vivo study. Conclusions: GH potentially negatively modulates the maturation and accumulation of lipid in adipocytes.

  6. Nitrogen substituent polarity influences dithiocarbamate-mediated lipid oxidation, nerve copper accumulation, and myelin injury.

    Science.gov (United States)

    Valentine, Holly L; Viquez, Olga M; Amarnath, Kalyani; Amarnath, Venkataraman; Zyskowski, Justin; Kassa, Endalkachew N; Valentine, William M

    2009-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate's nitrogen substituents influences the lipophilicity of the copper complexes that it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury. In the current study, a series of dithiocarbamate-copper complexes differing in their lipophilicity were evaluated for their relative abilities to promote lipid peroxidation determined by malondialdehyde levels generated in an ethyl arachidonate oil-in-water emulsion. In a second component of this study, rats were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate; both generated dithiocarbamate-copper complexes that were lipid- and water-soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord, and liver tissue copper levels were measured by inductively coupled mass spectroscopy to assess the relative abilities of these two dithiocarbamates to promote copper accumulation. Peripheral nerve injury was evaluated using grip strengths, nerve conduction velocities, and morphologic changes at the light microscope level. Additionally, the protein expression levels of glutathione transferase alpha and heme-oxygenase-1 in nerve were determined, and the quantity of protein carbonyls was measured to assess levels of oxidative stress and injury. The data provided evidence that dithiocarbamate-copper complexes are redox active and that the ability of dithiocarbamate complexes to promote lipid peroxidation is correlated to the lipophilicity of the complex. Consistent with neurotoxicity requiring the formation of a lipid-soluble copper complex, significant increases in copper accumulation, oxidative

  7. Influence of NaNO3 concentration and incident light intensity on Nannochloropsis oculata lipid accumulation

    OpenAIRE

    Lara Regina Soccol Gris; Anderson de Campos Paim; Marcelo Farenzena; Jorge Otávio Trierweiler

    2013-01-01

    This study aimed at evaluating the best conditions for lipid accumulation in the marine microalga Nannochloropsis oculata in an airlift photobioreactor. Experiments were carried out following a central composite design with the following variables: temperature (19 to 29°C), sodium nitrate concentration (NaNO3) in the culture medium (f/2) (25 to 125 mg.L-1) and incident light intensity (49 to 140 µE.m-2s-1). The maximum lipid production was 132.4 mg.L-1 under the following conditions: 27°C, Na...

  8. Altered lipid metabolism in a Drosophila model of Friedreich's ataxia.

    Science.gov (United States)

    Navarro, Juan A; Ohmann, Elisabeth; Sanchez, Diego; Botella, José A; Liebisch, Gerhard; Moltó, María D; Ganfornina, María D; Schmitz, Gerd; Schneuwly, Stephan

    2010-07-15

    Friedreich's ataxia (FRDA) is the most common form of autosomal recessive ataxia caused by a deficit in the mitochondrial protein frataxin. Although demyelination is a common symptom in FRDA patients, no multicellular model has yet been developed to study the involvement of glial cells in FRDA. Using the recently established RNAi lines for targeted suppression of frataxin in Drosophila, we were able to study the effects of general versus glial-specific frataxin downregulation. In particular, we wanted to study the interplay between lowered frataxin content, lipid accumulation and peroxidation and the consequences of these effects on the sensitivity to oxidative stress and fly fitness. Interestingly, ubiquitous frataxin reduction leads to an increase in fatty acids catalyzing an enhancement of lipid peroxidation levels, elevating the intracellular toxic potential. Specific loss of frataxin in glial cells triggers a similar phenotype which can be visualized by accumulating lipid droplets in glial cells. This phenotype is associated with a reduced lifespan, an increased sensitivity to oxidative insult, neurodegenerative effects and a serious impairment of locomotor activity. These symptoms fit very well with our observation of an increase in intracellular toxicity by lipid peroxides. Interestingly, co-expression of a Drosophila apolipoprotein D ortholog (glial lazarillo) has a strong protective effect in our frataxin models, mainly by controlling the level of lipid peroxidation. Our results clearly support a strong involvement of glial cells and lipid peroxidation in the generation of FRDA-like symptoms.

  9. Qushi Huayu Decoction Inhibits Hepatic Lipid Accumulation by Activating AMP-Activated Protein Kinase In Vivo and In Vitro

    Directory of Open Access Journals (Sweden)

    Qin Feng

    2013-01-01

    Full Text Available Qushi Huayu Decoction (QHD, a Chinese herbal formula, has been proven effective on alleviating nonalcoholic fatty liver disease (NAFLD in human and rats. The present study was conducted to investigate whether QHD could inhibit hepatic lipid accumulation by activating AMP-activated protein kinase (AMPK in vivo and in vitro. Nonalcoholic fatty liver (NAFL model was duplicated with high-fat diet in rats and with free fatty acid (FFA in L02 cells. In in vivo experimental condition, QHD significantly decreased the accumulation of fatty droplets in livers, lowered low-density lipoprotein cholesterol (LDL-c, alanine aminotransferase (ALT, and aspartate aminotransferase (AST levels in serum. Moreover, QHD supplementation reversed the HFD-induced decrease in the phosphorylation levels of AMPK and acetyl-CoA carboxylase (ACC and decreased hepatic nuclear protein expression of sterol regulatory element-binding protein-1 (SREBP-1 and carbohydrate-responsive element-binding protein (ChREBP in the liver. In in vitro, QHD-containing serum decreased the cellular TG content and alleviated the accumulation of fatty droplets in L02 cells. QHD supplementation reversed the FFA-induced decrease in the phosphorylation levels of AMPK and ACC and decreased the hepatic nuclear protein expression of SREBP-1 and ChREBP. Overall results suggest that QHD has significant effect on inhibiting hepatic lipid accumulation via AMPK pathway in vivo and in vitro.

  10. Nutritional mode influences lipid accumulation in microalgae with the function of carbon sequestration and nutrient supplementation.

    Science.gov (United States)

    Prathima Devi, M; Swamy, Y V; Venkata Mohan, S

    2013-08-01

    Effect of nutritional mode viz., photoautotrophic, photoheterotrophic and photomixotrophic on the biomass growth and lipid productivity of microalgae was studied. Experiments were designed and operated in biphasic mode i.e., growth phase (GP) followed by stress induced starvation phase (SP). Nutritional mode documented marked influence on biomass growth and subsequent lipid productivity. Mixotrophic mode of operation showed higher biomass growth (4.45 mg/ml) during growth phase while higher lipid productivity was observed with nitrogen deprived autotrophic mode (28.2%) followed by heterotrophic (26.1%) and mixotrophic (19.6%) operations. Relative increments in lipid productivities were noticed in SP operation from GP in mixotrophic operation (2.45) followed by autotrophic (2.2) and heterotrophic (2.14) mode of operations. Higher concentrations of chlorophyll b and presence of lipid accumulating species supported the lipid biosynthesis. Algal fatty acid composition varied with function of nutritional modes and depicted eighteen types of saturated (SFA) and unsaturated fatty acids (USFA) with wide fuel and food characteristics.

  11. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages.

    Science.gov (United States)

    Daniel, Jaiyanth; Maamar, Hédia; Deb, Chirajyoti; Sirakova, Tatiana D; Kolattukudy, Pappachan E

    2011-06-01

    Two billion people are latently infected with Mycobacterium tuberculosis (Mtb). Mtb-infected macrophages are likely to be sequestered inside the hypoxic environments of the granuloma and differentiate into lipid-loaded macrophages that contain triacylglycerol (TAG)-filled lipid droplets which may provide a fatty acid-rich host environment for Mtb. We report here that human peripheral blood monocyte-derived macrophages and THP-1 derived macrophages incubated under hypoxia accumulate Oil Red O-staining lipid droplets containing TAG. Inside such hypoxic, lipid-loaded macrophages, nearly half the Mtb population developed phenotypic tolerance to isoniazid, lost acid-fast staining and accumulated intracellular lipid droplets. Dual-isotope labeling of macrophage TAG revealed that Mtb inside the lipid-loaded macrophages imports fatty acids derived from host TAG and incorporates them intact into Mtb TAG. The fatty acid composition of host and Mtb TAG were nearly identical suggesting that Mtb utilizes host TAG to accumulate intracellular TAG. Utilization of host TAG by Mtb for lipid droplet synthesis was confirmed when fluorescent fatty acid-labeled host TAG was utilized to accumulate fluorescent lipid droplets inside the pathogen. Deletion of the Mtb triacylglycerol synthase 1 (tgs1) gene resulted in a drastic decrease but not a complete loss in both radiolabeled and fluorescent TAG accumulation by Mtb suggesting that the TAG that accumulates within Mtb is generated mainly by the incorporation of fatty acids released from host TAG. We show direct evidence for the utilization of the fatty acids from host TAG for lipid metabolism inside Mtb. Taqman real-time PCR measurements revealed that the mycobacterial genes dosR, hspX, icl1, tgs1 and lipY were up-regulated in Mtb within hypoxic lipid loaded macrophages along with other Mtb genes known to be associated with dormancy and lipid metabolism.

  12. Effects of plant growth regulators on the growth and lipid accumulation of Nannochloropsis oculata (droop) Hibberd

    Science.gov (United States)

    Trinh, Cam Tu; Tran, Thanh Huong; Bui, Trang Viet

    2017-09-01

    Nannochloropsis oculata cells were grown in f/2 modified medium of Chiu et al. (2009) supplemented with the plant growth regulators in different concentrations. Lipid accumulation of N. oculata cells was evaluated by using Nile Red dye and Fiji Image J with Analyze Particles. Indole-3-acetic acid (IAA) stimulated the increase of cell density in rapid growth phase (day 6) at high concentration (0.75 mg/L) and in slow growth phase (day 10) at lower concentration (0.50 mg/L). IAA, gibberellic acid (GA3) and zeatin increased content of chlorophyll a, in particular, in f/2 modified medium supplemented with 0.5 mg/L zeatin at the 10th day of culture. Roles of plant growth regulators in growth and lipid accumulation of N. oculata were discussed.

  13. Pyrolytic characteristics of biodiesel prepared from lipids accumulated in diatom cells with growth regulation.

    Science.gov (United States)

    Cheng, Jun; Feng, Jia; Ge, Tingting; Yang, Weijuan; Zhou, Junhu; Cen, Kefa

    2015-08-01

    Dynamic compositions of lipids accumulated in two diatoms Chaetoceros gracilis and Nitzschia closterium cultured with nitrogen and silicon deprivation were studied. It was found that short-chain fatty acids (C14-C16) content was much higher than long-chain fatty acids (C18-C20) content in lipids of two diatoms. The pyrolytic characteristics of biodiesel made from two diatoms and two plant seeds were compared by thermogravimetric analysis. The highest activation energy of 46.68 kJ mol(-1) and the minimum solid residue of 25.18% were obtained in the pyrolysis of biodiesel made from C. gracilis cells, which were cultured with 0.5 mmol L(-1) of nitrogen (no silicon) and accumulated the minimum polyunsaturated fatty acid (C20:5). The pyrolysis residue percentage of C. gracilis biodiesel was lower than that of N. closterium biodiesel and higher than those of plant (Cormus wilsoniana and Pistacia chinensis) biodiesels.

  14. Hydrophytes lack potential to exhibit cadmium stress induced enhancement in lipid peroxidation and accumulation of proline

    Energy Technology Data Exchange (ETDEWEB)

    Dhir, Bhupinder; Sharmila, P.; Saradhi, P. Pardha

    2004-02-10

    Investigations were carried out to evaluate if hydrophytes (viz. Ceratophyllum, Wolffia, and Hydrilla) can be used as markers to assess the level of heavy metal pollution in aquatic bodies. The potential of these hydrophytes for lipid peroxidation and accumulation of proline in response to cadmium (Cd{sup 2+}) pollution was studied. Hydrophytes were raised in artificial pond water (APW) supplemented with various levels of Cd{sup 2+}. Interestingly, unlike mesophytes none of the hydrophytes showed ability to accumulate proline. Infact, in response to Cd{sup 2+} pollution hydrophytes exhibited a decline in proline levels in comparison to controls but mesophytes (viz. Brassica juncea, Vigna radiata and Triticum aestivum) showed progressive increase in the level of proline with increase in the extent of Cd{sup 2+} pollution. Mesophytes showed six to nine-fold increase in the level of proline in response to 1 mM Cd{sup 2+}. The potential of the above hydrophytes for lipid peroxidation was also low under Cd{sup 2+} stress. In contrast, as expected a significant enhancement in the lipid peroxidation was observed in all three mesophytes in response to their exposure to Cd{sup 2+}. About two-fold increase in production of malondialdehyde (a cytotoxic product of lipid peroxidation) was recorded in mesophytes exposed to 1 mM Cd{sup 2+}. However, a decline in chlorophyll (Chl a and Chl b) levels was recorded in response to Cd{sup 2+}pollution both in hydrophytes as well as mesophytes. In summary, hydrophytes neither have potential to accumulate proline nor have ability to accelerate lipid peroxidation under heavy metal stress. This suggests that the adaptive mechanism(s) existing in hydrophytes to tackle heavy metal stress is distinct from that in mesophytes.

  15. Altered lipid accumulation in Nannochloropsis salina CCAP849/3 following EMS and UV induced mutagenesis

    Directory of Open Access Journals (Sweden)

    T.A. Beacham

    2015-09-01

    Full Text Available Microalgae have potential as a chemical feed stock in a range of industrial applications. Nannochloropsis salina was subject to EMS mutagenesis and the highest lipid containing cells selected using fluorescence-activated cell sorting. Assessment of growth, lipid content and fatty acid composition identified mutant strains displaying a range of altered traits including changes in the PUFA content and a total FAME increase of up to 156% that of the wild type strain. Combined with a reduction in growth this demonstrated a productivity increase of up to 76%. Following UV mutagenesis, lipid accumulation of the mutant cultures was elevated to more than 3 fold that of the wild type strain, however reduced growth rates resulted in a reduction in overall productivity. Changes observed are indicative of alterations to the regulation of the omega 6 Kennedy pathway. The importance of these variations in physiology for industrial applications such as biofuel production is discussed.

  16. Uncoupling of 3T3-L1 gene expression from lipid accumulation during adipogenesis

    OpenAIRE

    Temple, Karla A.; Basko, Xheni; Allison, Margaret B.; Brady, Matthew J.

    2007-01-01

    Adipocyte differentiation comprises altered gene expression and increased triglyceride storage. To investigate the interdependency of these two events, 3T3-L1 cells were differentiated in the presence of glucose or pyruvate. All adipocytic proteins examined were similarly increased between the two conditions. In contrast, 3T3-L1 adipocytes differentiated with glucose exhibited significant lipid accumulation, which was largely suppressed in the presence of pyruvate. Subsequent addition of gluc...

  17. Muscle mass loss and intermuscular lipid accumulation were associated with insulin resistance in patients receiving hemodialysis

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-ling; DING Ting-ting; LU Shi; XU Ye; TIAN Jun; HU Wei-feng; ZHANG Jin-yuan

    2013-01-01

    Background An accelerated muscle wasting was the pivotal factor for protein-energy wasting in end stage renal disease.However,very few researches have examined the skeletal muscle quantity and quality in clinical patients.This study investigated the muscle morphologic changes by magnetic resonance imaging (MRI) and analyzed the related factors in hemodialysis patients.Methods Fifty-eight patients receiving maintenance hemodialysis (HD) were investigated and 28 healthy adults with gender and age matched were used as controls (Control).Anthropometry,cytokine factors,and laboratory data were measured.The muscle and intermuscular adipose tissues (IMAT) were analyzed via a Thigh MRI.The bicep samples were observed after HE staining.Homeostatic model assessment of insulin resistance (HOMA-IR) was measured and their association with muscle wasting was analyzed.Results HD patients tended to have a lower protein diet,anthropometry data,and serum albumin,but the C reactive protein and interleukin-6 increased significantly.The MRI showed that HD patients had less muscle mass and a lower muscle/total ratio,but the fat/muscle and IMAT was higher when compared to the Control group.The muscle fiber showed atrophy and fat accumulation in the biceps samples come from the HD patients.Moreover,we found that the HD patients presented with a high level of plasma fasting insulin and increased HOMA-IR which negatively correlated with the muscle/total ratio,but positively with the fat/muscle ratio.Conclusions Muscle wasting presented early before an obvious malnutrition condition emerged in HD patients.The main morphological change was muscle atrophy along with intermuscular lipid accumulation.Insulin resistance was associated with muscle wasting in dialysis patients.

  18. Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6 deficiency in rats.

    Science.gov (United States)

    Kitagawa, Erina; Yamamoto, Tatsuya; Fujishita, Mayuko; Ota, Yuki; Yamamoto, Kohei; Nakagawa, Tomoyuki; Hayakawa, Takashi

    2017-02-01

    We investigated the efficacy of supplementing the diet with choline or betaine in ameliorating lipid accumulation induced by vitamin B6 (B6) deficiency in rat liver. Male Wistar rats were fed a control, B6-deficient, choline-supplemented (2, 4, or 6 g choline bitartrate/kg diet) B6-deficient diet or betaine-supplemented (1, 2, or 4 g betaine anhydrous/kg diet) B6-deficient diet for 35 d; all diets contained 9 g L-methionine (Met)/kg diet. Choline or betaine supplementation attenuated liver lipid deposition and restored plasma lipid profiles to control levels. These treatments restored the disruptions in Met metabolism and the phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio induced by B6 deficiency in liver microsomes. These results suggest that choline and betaine ameliorated liver lipid accumulation induced by B6 deficiency via recovery of Met metabolism and very low-density lipoprotein secretion by restoring the supply of PC derived from PE.

  19. Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line

    Energy Technology Data Exchange (ETDEWEB)

    Miyamae, Yusaku, E-mail: ymiyamae@lif.kyoto-u.ac.jp [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan); Nishito, Yukina; Nakai, Naomi [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan); Nagumo, Yoko; Usui, Takeo [Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki 305-8572 (Japan); Masuda, Seiji; Kambe, Taiho [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan); Nagao, Masaya, E-mail: mnagao@kais.kyoto-u.ac.jp [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan)

    2016-08-12

    Macroautophagy, or autophagy, is a cellular response in which unnecessary cytoplasmic components, including lipids and organelles, are self-degraded. Recent studies closely related autophagy to activation of hepatic stellate cells (HSCs), a process critical in the pathogenesis of liver fibrosis. During HSC activation, cytoplasmic lipid droplets (LDs) are degraded as autophagic cargo, and then cells express fibrogenic genes. Thus, inhibition of autophagy in HSCs is a potential therapeutic approach for attenuating liver fibrosis. We found that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra, induced lipid accumulation, a phenotype associated with quiescent HSCs, through blockade of autophagy in the rat-derived HSC line HSC-T6. Tetrandrine inhibited autophagic flux without affecting lysosomal function. A phenotypic comparison using siRNA knockdown suggested that tetrandrine may target regulators, involved in fusion between autophagosomes and lysosomes (e.g., syntaxin 17). Moreover, perilipin 1, an LD-coated protein, co-localized specifically with LC3, a marker protein for autophagosomes, in tetrandrine-treated HSC-T6 cells. This suggests a potential role for perilipin 1 in autophagy-mediated LD degradation in HSCs. Our results identified tetrandrine as a potential tool for prevention and treatment of HSC activation. - Highlights: • Autophagy is closely related to lipid degradation in hepatic stellate cells. • Tetrandrine (Tet) causes lipid accumulation via blockade of autophagy in HSC-T6 cells. • Tet blocked autophagy without affecting lysosomal function unlike bafilomycin A{sub 1}. • Perilipin 1 was specifically co-localized with LC3 in Tet-treated cells. • Perilipin 1 may play potential roles in autophagy-mediated lipid degradation.

  20. (13)C-metabolic flux analysis of lipid accumulation in the oleaginous fungus Mucor circinelloides.

    Science.gov (United States)

    Zhao, Lina; Zhang, Huaiyuan; Wang, Liping; Chen, Haiqin; Chen, Yong Q; Chen, Wei; Song, Yuanda

    2015-12-01

    The oleaginous fungus Mucor circinelloides is of industrial interest because it can produce high levels of polyunsaturated fatty acid γ-linolenic acid. M. circinelloides CBS 277.49 is able to accumulate less than 15% of cell dry weight as lipids, while M. circinelloides WJ11 can accumulate lipid up to 36%. In order to better understand the mechanisms behind the differential lipid accumulation in these two strains, tracer experiments with (13)C-glucose were performed with the growth of M. circinelloides and subsequent gas chromatography-mass spectrometric detection of (13)C-patterns in proteinogenic amino acids was carried out to identify the metabolic network topology and estimate intracellular fluxes. Our results showed that the high oleaginous strain WJ11 had higher flux of pentose phosphate pathway and malic enzyme, lower flux in tricarboxylic acid cycle, higher flux in glyoxylate cycle and ATP: citrate lyase, together, it might provide more NADPH and substrate acetyl-CoA for fatty acid synthesis.

  1. Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

    Science.gov (United States)

    Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

    2015-01-01

    Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

  2. Proteomic analysis in nitrogen-deprived Isochrysis galbana during lipid accumulation.

    Science.gov (United States)

    Song, Pingping; Li, Ling; Liu, Jianguo

    2013-01-01

    The differentially co-expressed proteins in N-deprived and N-enriched I. galbana were comparatively analyzed by using two dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight-mass spectrometry (MALDI-TOF/TOF-MS) with the aim of better understanding lipid metabolism in this oleaginous microalga. Forty-five of the 900 protein spots showed dramatic changes in N-deprived I. galbana compared with the N-enriched cells. Of these, 36 protein spots were analyzed and 27 proteins were successfully identified. The identified proteins were classified into seven groups by their molecular functions, including the proteins related to energy production and transformation, substance metabolism, signal transduction, molecular chaperone, transcription and translation, immune defense and cytoskeleton. These altered proteins slowed cell growth and photosynthesis of I. galbana directly or indirectly, but at the same time increased lipid accumulation. Eight key enzymes involved in lipid metabolism via different pathways were identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), enolase, aspartate aminotransferase (AST), fumarate hydratase (FH), citrate synthase (CS), O-acetyl-serine lyase (OAS-L) and ATP sulfurylase (ATPS). The results suggested that the glycolytic pathway and citrate transport system might be the main routes for lipid anabolism in N-deprived I. galbana, and that the tricarboxylic acid (TCA) cycle, glyoxylate cycle and sulfur assimilation system might be the major pathways involved in lipid catabolism.

  3. Proteomic analysis in nitrogen-deprived Isochrysis galbana during lipid accumulation.

    Directory of Open Access Journals (Sweden)

    Pingping Song

    Full Text Available The differentially co-expressed proteins in N-deprived and N-enriched I. galbana were comparatively analyzed by using two dimensional electrophoresis (2-DE and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight-mass spectrometry (MALDI-TOF/TOF-MS with the aim of better understanding lipid metabolism in this oleaginous microalga. Forty-five of the 900 protein spots showed dramatic changes in N-deprived I. galbana compared with the N-enriched cells. Of these, 36 protein spots were analyzed and 27 proteins were successfully identified. The identified proteins were classified into seven groups by their molecular functions, including the proteins related to energy production and transformation, substance metabolism, signal transduction, molecular chaperone, transcription and translation, immune defense and cytoskeleton. These altered proteins slowed cell growth and photosynthesis of I. galbana directly or indirectly, but at the same time increased lipid accumulation. Eight key enzymes involved in lipid metabolism via different pathways were identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH, phosphoglycerate kinase (PGK, enolase, aspartate aminotransferase (AST, fumarate hydratase (FH, citrate synthase (CS, O-acetyl-serine lyase (OAS-L and ATP sulfurylase (ATPS. The results suggested that the glycolytic pathway and citrate transport system might be the main routes for lipid anabolism in N-deprived I. galbana, and that the tricarboxylic acid (TCA cycle, glyoxylate cycle and sulfur assimilation system might be the major pathways involved in lipid catabolism.

  4. Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.

    Science.gov (United States)

    Lee, Bonggi; Kwon, Misung; Choi, Jae Sue; Jeong, Hyoung Oh; Chung, Hae Young; Kim, Hyeung-Rak

    2015-12-01

    Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-α by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARα agonist fenofibrate. Consistently, mRNA expression levels of PPARα target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARα and stimulate fatty acid oxidation signaling in adipocytes.

  5. Oxidative stress is a mediator for increased lipid accumulation in a newly isolated Dunaliella salina strain.

    Science.gov (United States)

    Yilancioglu, Kaan; Cokol, Murat; Pastirmaci, Inanc; Erman, Batu; Cetiner, Selim

    2014-01-01

    oxidative stress mediates lipid accumulation. Understanding such relationships may provide guidance for efficient production of algal biodiesels.

  6. Oxidative stress is a mediator for increased lipid accumulation in a newly isolated Dunaliella salina strain.

    Directory of Open Access Journals (Sweden)

    Kaan Yilancioglu

    results also suggest that oxidative stress mediates lipid accumulation. Understanding such relationships may provide guidance for efficient production of algal biodiesels.

  7. Quercetin decreases high-fat diet induced body weight gain and accumulation of hepatic and circulating lipids in mice.

    Science.gov (United States)

    Hoek-van den Hil, E F; van Schothorst, E M; van der Stelt, I; Swarts, H J M; Venema, D; Sailer, M; Vervoort, J J M; Hollman, P C H; Rietjens, I M C M; Keijer, J

    2014-09-01

    Dietary flavonoids may protect against cardiovascular diseases (CVD). Increased circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. The aim of this study was to investigate the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in mice with high-fat diet induced body weight gain and hepatic lipid accumulation. Adult male mice received a 40 energy% high-fat diet without or with supplementation of 0.33 % (w/w) quercetin for 12 weeks. Body weight gain was 29 % lower in quercetin fed mice (p lipid accumulation to 29 % of the amount present in the control mice (p lipid profiling revealed that the supplementation significantly lowered serum lipid levels. Global gene expression profiling of liver showed that cytochrome P450 2b (Cyp2b) genes, key target genes of the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3), were downregulated. Quercetin decreased high-fat diet induced body weight gain, hepatic lipid accumulation and serum lipid levels. This was accompanied by regulation of cytochrome P450 2b genes in liver, which are possibly under transcriptional control of CAR. The quercetin effects are likely dependent on the fat content of the diet.

  8. Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling

    DEFF Research Database (Denmark)

    Zech, Tobias; Ejsing, Christer S.; Gaus, Katharina;

    2009-01-01

    domains were also enriched in plasmenyl phosphatidylethanolamine and phosphatidylserine. Modulating the T-cell lipidome with polyunsaturated fatty acids impaired the plasma membrane condensation at TCR signalling foci and resulted in a perturbed molecular lipid composition. These results correlate...... and saturated phosphatidylcholine species as compared with control plasma membrane fragments. This provides, for the first time, direct evidence that TCR activation domains comprise a distinct molecular lipid composition reminiscent of liquid-ordered raft phases in model membranes. Interestingly, TCR activation...

  9. Roles of Fatty Acid oversupply and impaired oxidation in lipid accumulation in tissues of obese rats.

    Science.gov (United States)

    Oakes, Nicholas D; Kjellstedt, Ann; Thalén, Pia; Ljung, Bengt; Turner, Nigel

    2013-01-01

    To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studied in vivo fatty acid (FA) metabolism in obese (Obese) and lean (Lean) Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-(3)H]-(R)-2-bromopalmitate ((3)H-R-BrP) and [U-(14)C]-palmitate ((14)C-P) FA tracers, respectively. Whole-body FA appearance (R a ) was estimated from plasma (14)C-P kinetics. Whole-body FA oxidation rate (R ox) was assessed using (3)H2O production from (3)H-palmitate infusion, and tissue FA oxidative capacity was evaluated ex vivo. In the basal fasting state Obese had markedly elevated FA levels and R a , associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid, R ox was lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply.

  10. Roles of Fatty Acid Oversupply and Impaired Oxidation in Lipid Accumulation in Tissues of Obese Rats

    Directory of Open Access Journals (Sweden)

    Nicholas D. Oakes

    2013-01-01

    Full Text Available To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studied in vivo fatty acid (FA metabolism in obese (Obese and lean (Lean Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-3H]-(R-2-bromopalmitate (3H-R-BrP and [U-14C]-palmitate (14C-P FA tracers, respectively. Whole-body FA appearance (Ra was estimated from plasma 14C-P kinetics. Whole-body FA oxidation rate (Rox was assessed using 3H2O production from 3H-palmitate infusion, and tissue FA oxidative capacity was evaluated ex vivo. In the basal fasting state Obese had markedly elevated FA levels and Ra, associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid, Rox was lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply.

  11. Removal of cephalosporin antibiotics 7-ACA from wastewater during the cultivation of lipid-accumulating microalgae.

    Science.gov (United States)

    Guo, Wan-Qian; Zheng, He-Shan; Li, Shuo; Du, Juan-Shan; Feng, Xiao-Chi; Yin, Ren-Li; Wu, Qing-Lian; Ren, Nan-Qi; Chang, Jo-Shu

    2016-12-01

    The aim of this study is to evaluate the feasibility of using lipid-accumulating microalgae to remove cephalosporin antibiotics 7-amino cephalosporanic acid (7-ACA) from wastewater with the additional benefit of biofuels production. Three isolated microalgal strains (namely, Chlorella sp. Cha-01, Chlamydomonas sp. Tai-03 and Mychonastes sp. YL-02) were cultivated under 7-ACA stress and their biomass productivity, lipid production and N-NO3(-) consumption were monitored. It was found that 7-ACA had slight inhibition effects on the microalgal growth at the ratio of 12.0% (Cha-01), 9.6% (YL-02), 11.7% (Tai-03). However, lipid accumulation in the three microalgae was not influenced by the presence of 7-ACA. The investigation on the 7-ACA removal mechanisms during microalgal growth shows that 7-ACA was mainly removed by microalgae adsorption as well as hydrolysis and photolysis reactions. This study demonstrates that using microalgae to treat antibiotic-containing wastewater is promising due to the potential of simultaneous antibiotic removal and biofuel production. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation

    Directory of Open Access Journals (Sweden)

    Paola Giorni

    2015-09-01

    Full Text Available Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host–pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantly with maize ripening. Oxylipins and phytoceramides changed significantly within the hybrids and decreased with kernel maturation, starting from physiological maturity. Although the correlation between fumonisin accumulation and plant lipid profile is certain, the data collected so far cannot define a cause-effect relationship but open up new perspectives. Therefore, the question—“Does fumonisin alter plant lipidome or does plant lipidome modulate fumonisin accumulation?”—is still open.

  13. Investigation of relationship between lipid and Monascus pigment accumulation by extractive fermentation.

    Science.gov (United States)

    Wang, Bo; Zhang, Xuehong; Wu, Zhenqiang; Wang, Zhilong

    2015-10-20

    Fermented Monascus pigments have been utilized as traditional Chinese medicine and food colorant for thousands of years. Under the limited nitrogen concentration and/or low initial pH 2.5 conditions, it was observed that production of intracellular pigments and accumulation of microbial lipids (high content reaching to approximately 50% in dry cell weight) by edible Monascus anka exhibited a positive correlated relationship. Extractive fermentation in nonionic surfactant micelle aqueous solution selectively exported the intracellular Monascus pigments into its extracellular broth, in which the concentration of intracellular pigments was negligible while the extracellular one was enhanced. The extractive fermentation provides a novel strategy for shifting of the metabolic channeling from intracellular lipid accumulation to Monascus pigment production. High pigment concentration, i.e., approximately 40 AU of extracellular Monascus pigments, was achieved by extractive fermentation at a relatively high nonionic surfactant concentration 10 g/l. This phenomenon might be attributed to the nonionic surfactant micelles acting as pigment reservoirs by biomimetic of intracellular lipids.

  14. Increased FAT/CD36 cycling and lipid accumulation in myotubes derived from obese type 2 diabetic patients.

    Directory of Open Access Journals (Sweden)

    Celine Aguer

    Full Text Available BACKGROUND: Permanent fatty acid translocase (FAT/CD36 relocation has previously been shown to be related to abnormal lipid accumulation in the skeletal muscle of type 2 diabetic patients, however mechanisms responsible for the regulation of FAT/CD36 expression and localization are not well characterized in human skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Primary muscle cells derived from obese type 2 diabetic patients (OBT2D and from healthy subjects (Control were used to examine the regulation of FAT/CD36. We showed that compared to Control myotubes, FAT/CD36 was continuously cycling between intracellular compartments and the cell surface in OBT2D myotubes, independently of lipid raft association, leading to increased cell surface FAT/CD36 localization and lipid accumulation. Moreover, we showed that FAT/CD36 cycling and lipid accumulation were specific to myotubes and were not observed in reserve cells. However, in Control myotubes, the induction of FAT/CD36 membrane translocation by the activation of (AMP-activated protein kinase (AMPK pathway did not increase lipid accumulation. This result can be explained by the fact that pharmacological activation of AMPK leads to increased mitochondrial beta-oxidation in Control cells. CONCLUSION/SIGNIFICANCE: Lipid accumulation in myotubes derived from obese type 2 diabetic patients arises from abnormal FAT/CD36 cycling while lipid accumulation in Control cells results from an equilibrium between lipid uptake and oxidation. As such, inhibiting FAT/CD36 cycling in the skeletal muscle of obese type 2 diabetic patients should be sufficient to diminish lipid accumulation.

  15. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jun [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Ren, Pingping; Zhang, Lin [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Wang, Xing Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Chen, Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Shen, Ying H., E-mail: hyshen@bcm.edu [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States)

    2010-02-26

    Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.

  16. Mitochondria: A crossroads for lipid metabolism defect in neurodegeneration with brain iron accumulation diseases.

    Science.gov (United States)

    Aoun, Manar; Tiranti, Valeria

    2015-06-01

    Neurodegeneration with brain iron accumulation (NBIA) comprises a group of brain iron deposition syndromes that lead to mixed extrapyramidal features and progressive dementia. Exact pathologic mechanism of iron deposition in NBIA remains unknown. However, it is becoming increasingly evident that many neurodegenerative diseases are hallmarked by metabolic dysfunction that often involves altered lipid profile. Among the identified disease genes, four encode for proteins localized in mitochondria, which are directly or indirectly implicated in lipid metabolism: PANK2, CoASY, PLA2G6 and C19orf12. Mutations in PANK2 and CoASY, both implicated in CoA biosynthesis that acts as a fatty acyl carrier, lead, respectively, to PKAN and CoPAN forms of NBIA. Mutations in PLA2G6, which plays a key role in the biosynthesis and remodeling of membrane phospholipids including cardiolipin, lead to PLAN. Mutations in C19orf12 lead to MPAN, a syndrome similar to that caused by mutations in PANK2 and PLA2G6. Although the function of C19orf12 is largely unknown, experimental data suggest its implication in mitochondrial homeostasis and lipid metabolism. Altogether, the identified mutated proteins localized in mitochondria and associated with different NBIA forms support the concept that dysfunctions in mitochondria and lipid metabolism play a crucial role in the pathogenesis of NBIA. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.

  17. Computational Modeling of Lipid Metabolism in Yeast

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    Vera Schützhold

    2016-09-01

    Full Text Available Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes.Here, we present a object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner.The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

  18. Strategic Feeding of Ammonium and Metal Ions for Enhanced GLA-Rich Lipid Accumulation in Cunninghamella bainieri 2A1

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    Shuwahida Shuib

    2014-01-01

    Full Text Available Strategic feeding of ammonium and metal ions (Mg2+, Mn2+, Fe3+, Cu2+, Ca2+, Co2+, and Zn2+ for enhanced GLA-rich lipid accumulation in C. bainieri 2A1 was established. When cultivated in nitrogen-limited medium, the fungus produced up to 30% lipid (g/g biomass with 12.9% (g/g lipid GLA. However, the accumulation of lipid stopped at 48 hours of cultivation although glucose was abundant. This event occurred in parallel to the diminishing activity of malic enzyme (ME, fatty acid synthase (FAS, and ATP citrate lyase (ACL as well as the depletion of metal ions in the medium. Reinstatement of the enzymes activities was achieved by feeding of ammonium tartrate, but no increment in the lipid content was observed. However, increment in lipid content from 32% to 50% (g/g biomass with 13.2% GLA was achieved when simultaneous feeding of ammonium, glucose, and metal ions was carried out. This showed that the cessation of lipid accumulation was caused by diminishing activities of the enzymes as well as depletion of the metal ions in the medium. Therefore, strategic feeding of ammonium and metal ions successfully reinstated enzymes activities and enhanced GLA-rich lipid accumulation in C. bainieri 2A1.

  19. Model parameters for simulation of physiological lipids

    Science.gov (United States)

    McGlinchey, Nicholas

    2016-01-01

    Coarse grain simulation of proteins in their physiological membrane environment can offer insight across timescales, but requires a comprehensive force field. Parameters are explored for multicomponent bilayers composed of unsaturated lipids DOPC and DOPE, mixed‐chain saturation POPC and POPE, and anionic lipids found in bacteria: POPG and cardiolipin. A nonbond representation obtained from multiscale force matching is adapted for these lipids and combined with an improved bonding description of cholesterol. Equilibrating the area per lipid yields robust bilayer simulations and properties for common lipid mixtures with the exception of pure DOPE, which has a known tendency to form nonlamellar phase. The models maintain consistency with an existing lipid–protein interaction model, making the force field of general utility for studying membrane proteins in physiologically representative bilayers. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:26864972

  20. Expression of mouse MGAT in Arabidopsis results in increased lipid accumulation in seeds

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    Anna eEl Tahchy

    2015-12-01

    Full Text Available Worldwide demand for vegetable oil is projected to double within the next thirty years due to increasing food, fuel and industrial requirements. There is therefore great interest in metabolic engineering strategies that boost oil accumulation in plant tissues, however, efforts to date have only achieved levels of storage lipid accumulation in plant tissues far below the benchmark to meet demand. Monoacylglycerol acyltransferase (MGAT is predominantly associated with lipid absorption and resynthesis in the animal intestine where it catalyses monoacylglycerol (MAG to form diacylglycerol (DAG, and then triacylglycerol (TAG. In contrast plant lipid biosynthesis routes do not include MGAT. Rather, DAG and TAG are either synthesized from glycerol-3-phosphate (G-3-P by a series of three subsequent acylation reactions, or originate from phospholipids via an acyl editing pathway. Mouse MGATs 1 and 2 have been shown to increase oil content transiently in Nicotiana benthamiana leaf tissue by 2.6 fold. Here we explore the feasibility of this approach to increase TAG in Arabidopsis thaliana seed. The stable MGAT2 expression resulted in a significant increase in seed oil content by 1.32 fold. We also report evidence of the MGAT2 activity based on in vitro assays. Up to 3.9 fold increase of radiolabelled DAG were produced in seed lysate which suggest that the transgenic MGAT activity can result in DAG re-synthesis by salvaging the MAG product of lipid breakdown. The expression of MGAT2 therefore creates an independent and complementary TAG biosynthesis route to the endogenous Kennedy pathway and other glycerolipid synthesis routes.

  1. Leptin signaling in adipose tissue: role in lipid accumulation and weight gain.

    Science.gov (United States)

    Singh, Prachi; Peterson, Timothy E; Sert-Kuniyoshi, Fatima H; Glenn, Jason A; Davison, Diane E; Romero-Corral, Abel; Pusalavidyasagar, Snigdha; Jensen, Michael D; Somers, Virend K

    2012-08-17

    The link between obesity, hyperleptinemia, and development of cardiovascular disease is not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1-dependent mechanisms. However, the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known. To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans. We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent 8 weeks of overfeeding, during which they gained an average weight of 4.1±1.4 kg, with leptin increases from 7±3.8 to 12±5.7 ng/mL. Weight gain also resulted in changes in adipose tissue caveolin-1 expression, which correlated with increases in leptin (rho=0.79, P=0.01). In cultured human white preadipocytes, leptin increased caveolin-1 expression, which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating human white preadipocytes, which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis. In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intracellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism that may be essential to facilitate adipocyte lipid storage during weight gain.

  2. Telmisartan-induced PPARγ activity attenuates lipid accumulation in VSMCs via induction of autophagy.

    Science.gov (United States)

    Li, Bing-Hu; Liao, Shao-Qiong; Yin, Yan-Wei; Long, Chun-Yan; Guo, Lu; Cao, Xiao-Jie; Liu, Yun; Zhou, Yi; Gao, Chang-Yue; Zhang, Li-Li; Li, Jing-Cheng

    2015-01-01

    Foam cell formation is the hallmark of atherosclerosis. Both telmisartan and autophagy protect against the development of atherosclerosis. However, it has yet to be elucidated whether telmisartan prevents vascular smooth muscle cell (VSMC)-derived foam cell formation. Vascular smooth muscle cells isolated from the thoracic aorta of male C57BL/6J mice were used for this study. To induce foam cell formation, primary VSMCs were incubated in 80 μg/ml oxLDL for 24 h. LC3, beclin-1, PPARγ, AMPK, p-AMPK, mTOR and p-mTOR expression were determined via Western blot. Lipid accumulation was evaluated via oil red O staining and intracellular total cholesterol level measurement. Our study demonstrated that telmisartan dose-dependently increased the expression of beclin-1, the LC3II/LC3I ratio and the quantity of GFP-labeled autophagosomes, displaying a peak effect at 10 μM. In control siRNA-transfected VSMCs, telmisartan (10 μM) decreased lipid droplet accumulation and the total cholesterol level significantly. In contrast, in Atg7 siRNA-transfected VSMCs, telmisartan failed to attenuate lipid accumulation. In addition, telmisartan dose-dependently increased the expression of PPARγ and p-AMPK and decreased the expression of p-mTOR. GW9662 attenuated the telmisartan-induced increase in PPARγ expression, the LC3-II/LC3-I ratio and p-AMPK expression and the telmisartan-induced decrease in p-mTOR expression. Compound C restored mTOR activity and abolished the increase in the LC3-II/LC3-I ratio. Rapamycin significantly reduced p-mTOR expression and increased the LC3-II/LC3-I ratio. In conclusion, this study provides evidence that the chronic pharmacological activation of the PPARγ-mediated autophagy pathway using telmisartan may represent a promising therapeutic strategy for atherosclerosis.

  3. Ultrastructural and flow cytometric analyses of lipid accumulation in microalgae: Annual report, Solar Energy Research Institute, Aquatic Species Program

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, J.A.; Hand, R.E. Jr.; Mann, R.C.

    1986-01-01

    Lipid accumulation in three species of microalgae was investigated with flow cytometry (FCM) and transmission electron microscopy (TEM). Previous studies using batch cultures of algae have led to the assumption that lipid accumulation in microalgae is a gradual process requiring at least several days for completion. However, FCM reveals, through changes in the chlorophyll:lipid ratio, that the time span required for individual cells to change metabolic state is short. Simultaneous FCM measurements of chlorophyll and nile red (neutral lipid) fluorescence in individual cells of nitrogen-deficient Isochrysis populations revealed a bimodal population distribution as one stage in the lipid accumulation process. The fact that two discrete populations exist, with few cells in an intermediate stage, suggests rapid response to a lipid trigger. Interpretations of light and electron microscopic observations are consistent with this hypothesis. The time required for an entire population to achieve maximum lipid content is considerably longer than that required for a single cell, due to the variation in response time among cells. In this study high lipid cultures were sometimes obtained by using FCM to separate high lipid cells from the remainder of the population. FCM holds much promise for strain enhancement but considerable developmental work, directed at providing more consistent results, remains to be done. 8 refs., 33 figs.

  4. Carbon black nanoparticles promote endothelial activation and lipid accumulation in macrophages independently of intracellular ROS production

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Danielsen, Pernille Høgh;

    2014-01-01

    Exposure to nanoparticles (NPs) may cause vascular effects including endothelial dysfunction and foam cell formation, with oxidative stress and inflammation as supposed central mechanisms. We investigated oxidative stress, endothelial dysfunction and lipid accumulation caused by nano-sized carbon...... and WST-1 assays, especially in THP-1 and THP-1a cells. The CB exposure decreased the glutathione (GSH) content in THP-1 and THP-1a cells, whereas GSH was increased in HUVECs. The reactive oxygen species (ROS) production was increased in all cell types after CB exposure. A reduction of the intracellular...

  5. Potential role of multiple carbon fixation pathways during lipid accumulation in Phaeodactylum tricornutum

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    Valenzuela Jacob

    2012-06-01

    Full Text Available Abstract Background Phaeodactylum tricornutum is a unicellular diatom in the class Bacillariophyceae. The full genome has been sequenced (P. tricornutum gene expression profiles during nutrient-deprivation and lipid-accumulation, cell cultures were grown with a nitrate to phosphate ratio of 20:1 (N:P and whole-genome transcripts were monitored over time via RNA-sequence determination. Results The specific Nile Red (NR fluorescence (NR fluorescence per cell increased over time; however, the increase in NR fluorescence was initiated before external nitrate was completely exhausted. Exogenous phosphate was depleted before nitrate, and these results indicated that the depletion of exogenous phosphate might be an early trigger for lipid accumulation that is magnified upon nitrate depletion. As expected, many of the genes associated with nitrate and phosphate utilization were up-expressed. The diatom-specific cyclins cyc7 and cyc10 were down-expressed during the nutrient-deplete state, and cyclin B1 was up-expressed during lipid-accumulation after growth cessation. While many of the genes associated with the C3 pathway for photosynthetic carbon reduction were not significantly altered, genes involved in a putative C4 pathway for photosynthetic carbon assimilation were up-expressed as the cells depleted nitrate, phosphate, and exogenous dissolved inorganic carbon (DIC levels. P. tricornutum has multiple, putative carbonic anhydrases, but only two were significantly up-expressed (2-fold and 4-fold at the last time point when exogenous DIC levels had increased after the cessation of growth. Alternative pathways that could utilize HCO3- were also suggested by the gene expression profiles (e.g., putative propionyl-CoA and methylmalonyl-CoA decarboxylases. Conclusions The results indicate that P. tricornutum continued carbon dioxide reduction when population growth was arrested and different carbon-concentrating mechanisms were used dependent upon exogenous

  6. Effect of green and red light in lipid accumulation and transcriptional profile of genes implicated in lipid biosynthesis in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Gaytán-Luna, Daniel Eugenio; Ochoa-Alfaro, Ana Erika; Rocha-Uribe, Alejandro; Pérez-Martínez, Ana Silvia; Alpuche-Solís, Ángel Gabriel; Soria-Guerra, Ruth Elena

    2016-11-01

    Microalgae have the potential to accumulate triacylglycerols under different light spectra. In this work, Chlamydomonas reinhardtii was grown under white (400-700 nm), red (650 nm), and green (550 nm) lights. According to our results, red light (650 nm) has a positive effect in the microalgae growth and chlorophyll concentration. About the lipid content, the control culture (white light-illuminated) reached a 4.4% of dry cell weight (dcw), whereas the culture grown at 550 nm showed an increase of 1.35-fold in the lipids accumulation (5.96% dcw). Interestingly, the most significant accumulation was found in the culture grown at 650 nm (14.78% dcw) which means 3.36-fold higher with respect to the white light-illuminated culture. The most abundant fatty acids found in lipid extracts obtained from the cultures under different light wavelength were palmitic (C16: 0), oleic (C18: 1n9), stearidonic (C18: 4), and linoleic (C18: 2), which are useful in the biodiesel production. Changes in gene expression in response to different wavelength illuminations were assessed; however, an in-depth analysis of a larger number of genes involved in lipid biosynthesis is necessary to fully explain the highest accumulation of lipids in the culture grown under red light. This approach will be useful to find a sustainable source of lipids for biodiesel production. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1404-1411, 2016.

  7. Effects of puerarin on lipid accumulation and metabolism in high-fat diet-fed mice.

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    Guodong Zheng

    Full Text Available In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD, and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK, carnitine acyltransferase (CAT and hormone-sensitive lipase (HSL were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2 was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases.

  8. The role of alkaline phosphatase in intracellular lipid accumulation in the human hepatocarcinoma cell line, HepG2.

    Science.gov (United States)

    Chirambo, George M; van Niekerk, Chantal; Crowther, Nigel J

    2017-04-01

    Inhibition of tissue non-specific alkaline phosphatase (TNALP) decreases intracellular lipid accumulation in human preadipocytes and the murine preadipocyte cell line, 3T3-L1. Therefore, the current study was performed to determine if TNALP is required for intracellular lipid deposition in the human hepatocyte cell line, HepG2. Intracellular lipid accumulation, TNALP activity and peroxisome proliferator activated receptor (PPAR) γ gene expression were measured in HepG2 and 3T3-L1 cells in the presence and absence of the TNALP inhibitors levamisole and histidine. Sub-cellular TNALP activity was localized using cytochemical analysis. Both PPARγ gene expression and TNALP activity increased during intracellular lipid accumulation in HepG2 and 3T3-L1 cells. Inhibition of TNALP blocked intracellular lipid accumulation but did not alter expression of the PPARγ gene. In HepG2 cells, TNALP co-localized with adipophilin on the lipid droplet membrane. These data suggest a role for TNALP in lipid droplet formation, possibly downstream from PPARγ, within HepG2 and 3T3-L1 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Starch and lipid accumulation in eight strains of six Chlorella species under comparatively high light intensity and aeration culture conditions.

    Science.gov (United States)

    Takeshita, Tsuyoshi; Ota, Shuhei; Yamazaki, Tomokazu; Hirata, Aiko; Zachleder, Vilém; Kawano, Shigeyuki

    2014-04-01

    The microalgae family Chlorella species are known to accumulate starch and lipids. Although nitrogen or phosphorous deficiencies promote starch and lipids formation in many microalgae, these deficiencies also limit their growth and productivity. Therefore, the Chlorellaceae strains were attempted to increase starch and lipids productivity under high-light-intensity conditions (600-μmol photons m(-2)s(-1)). The 12:12-h light-dark (LD) cycle conditions elicited more stable growth than the continuous light (LL) conditions, whereas the starch and lipids yields increased in LL conditions. The amount of starch and lipids per cell increased in Chlorella viscosa and Chlorella vulgaris in sulfur-deficient medium, and long-chain fatty acids with 20 or more carbon atoms accumulated in cells grown in sulfur-deficient medium. Accumulation of starch and lipids was investigated in eight strains. The accumulation was strain-dependent, and varied according to the medium and light conditions. Five of the eight Chlorella strains exhibited similar accumulation patterns.

  10. BRD4 regulates fructose-inducible lipid accumulation-related genes in the mouse liver.

    Science.gov (United States)

    Yamada, Aki; Honma, Kazue; Mochizuki, Kazuki; Goda, Toshinao

    2016-10-01

    Fructose intake induces hepatic steatosis by activating fat synthesis. In this study, we searched for genes that showed acute induction in the livers of mice force-fed with fructose, and examined how this induction is regulated. We identified genes induced at 6h after the fructose force-feeding using a microarray and quantitative real-time RT-PCR. Histone acetylation and an acetylated histone binding protein bromodomain containing (BRD)4 binding around the fructose-inducible genes were examined using a chromatin immunoprecipitation assay. We examined whether (+)-JQ1, an inhibitor of the binding between the BRD4 and acetylated histones, inhibited the expressions of fructose-inducible genes, histone acetylation and BRD4 binding around the genes. We identified upregulated genes related to lipid accumulation, such as Cyp8b1, Dak and Plin5, in mice force-fed with fructose compared with those force-fed with glucose. Acetylation of histones H3 and H4, and BRD4 binding around the transcribed region of those fructose-inducible genes, were enhanced by fructose force-feeding. Meanwhile, (+)-JQ1 treatment reduced expressions of fructose-inducible genes, histone acetylation and BRD4 binding around these genes. Acute induction of genes related to lipid accumulation in the livers of mice force-fed with fructose is associated with the induction of histone acetylation and BRD4 binding around these genes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Light attenuates lipid accumulation while enhancing cell proliferation and starch synthesis in the glucose-fed oleaginous microalga Chlorella zofingiensis.

    Science.gov (United States)

    Chen, Tianpeng; Liu, Jin; Guo, Bingbing; Ma, Xiaonian; Sun, Peipei; Liu, Bin; Chen, Feng

    2015-10-07

    The objective of this study was to investigate the effect of light on lipid and starch accumulation in the oleaginous green algae Chlorella zofingiensis supplemented with glucose. C. zofingiensis, when fed with 30 g/L glucose, synthesized lipids up to 0.531 g/g dry weight; while in the presence of light, the lipid content dropped down to 0.352 g/g dry weight. Lipid yield on glucose was 0.184 g/g glucose, 14% higher than that cultured with light. The light-mediated lipid reduction was accompanied by the down-regulation of fatty acid biosynthetic genes at the transcriptional level. Furthermore, light promoted cell proliferation, starch accumulation, and the starch yield based on glucose. Taken together, light may attenuate lipid accumulation, possibly through the inhibition of lipid biosynthetic pathway, leading to more carbon flux from glucose to starch. This study reveals the dual effects of light on the sugar-fed C. zofingiensis and provides valuable insights into the possible optimization of algal biomass and lipid production by manipulation of culture conditions.

  12. Olive leaf extract from Sicilian cultivar reduced lipid accumulation by inducing thermogenic pathway during adipogenesis

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    Rosa ePalmeri

    2016-05-01

    Full Text Available Olive leaves contain a wide variety of phenolic compounds belonging to phenolic acids, phenolic alcohols, flavonoids and secoiridoids, and include also many other pharmacological active compounds. They could play an important role in human diet and health because of their ability to lower blood pressure, increase coronary arteries blood flow and decrease the risk of cardiovascular diseases. The aim of this study was to investigate the effect of Olive leaf extract (OLE from Sicilian cultivar on adipogenic differentiation of human adipose derived mesenchymal stem cells and its impact on lipid metabolism. We showed that OLE treatment during adipogenic differentiation reduces inflammation, lipid accumulation and induces thermogenesis by activation of uncoupling protein UCP1, SIRT-1, PPARα and Pgc-1α. Furthermore, OLE significantly decreases the expression of molecules involved in adipogenesis and upregulates the expression of mediators involved in thermogenesis and lipid metabolism. Taken together, our results suggest that OLE may promote the brown remodeling of white adipose tissue inducing thermogenesis and improving metabolic homeostasis.

  13. Olive Leaf Extract from Sicilian Cultivar Reduced Lipid Accumulation by Inducing Thermogenic Pathway during Adipogenesis

    Science.gov (United States)

    Palmeri, Rosa; Monteleone, Julieta I.; Spagna, Giovanni; Restuccia, Cristina; Raffaele, Marco; Vanella, Luca; Li Volti, Giovanni; Barbagallo, Ignazio

    2016-01-01

    Olive leaves contain a wide variety of phenolic compounds belonging to phenolic acids, phenolic alcohols, flavonoids, and secoiridoids, and include also many other pharmacological active compounds. They could play an important role in human diet and health because of their ability to lower blood pressure, increase coronary arteries blood flow and decrease the risk of cardiovascular diseases. The aim of this study was to investigate the effect of olive leaf extract (OLE) from Sicilian cultivar on adipogenic differentiation of human adipose derived mesenchymal stem cells and its impact on lipid metabolism. We showed that OLE treatment during adipogenic differentiation reduces inflammation, lipid accumulation and induces thermogenesis by activation of uncoupling protein uncoupling protein 1, sirtuin 1, peroxisome proliferator-activated receptor alpha, and coactivator 1 alpha. Furthermore, OLE significantly decreases the expression of molecules involved in adipogenesis and upregulates the expression of mediators involved in thermogenesis and lipid metabolism. Taken together, our results suggest that OLE may promote the brown remodeling of white adipose tissue inducing thermogenesis and improving metabolic homeostasis. PMID:27303302

  14. Mild pressure induces rapid accumulation of neutral lipid (triacylglycerol) in Chlorella spp.

    Science.gov (United States)

    Praveenkumar, Ramasamy; Kim, Bohwa; Lee, Jiye; Vijayan, Durairaj; Lee, Kyubock; Nam, Bora; Jeon, Sang Goo; Kim, Dong-Myung; Oh, You-Kwan

    2016-11-01

    Effective enhancement of neutral lipid (especially triacylglycerol, TAG) content in microalgae is an important issue for commercialization of microalgal biorefineries. Pressure is a key physical factor affecting the morphological, physiological, and biochemical behaviors of organisms. In this paper, we report a new stress-based method for induction of TAG accumulation in microalgae (specifically, Chlorella sp. KR-1 and Ch. sp. AG20150) by very-short-duration application of mild pressure. Pressure treatments of 10-15bar for 2h resulted in a considerable, ∼55% improvement of the 10-100g/Lcells' TAG contents compared with the untreated control. The post-pressure-treatment increase of cytoplasmic TAG granules was further confirmed by transmission electron microscopy (TEM). Notwithstanding the increased TAG content, the total lipid content was not changed by pressurization, implying that pressure stress possibly induces rapid remodeling/transformation of algal lipids rather than de novo biosynthesis of TAG. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Cardiac remodeling associated with protein increase and lipid accumulation in early-stage chronic kidney disease in rats.

    Science.gov (United States)

    Kuwahara, Mieko; Bannai, Kenji; Segawa, Hiroko; Miyamoto, Ken-ichi; Yamato, Hideyuki

    2014-09-01

    Chronic kidney disease (CKD) is associated with increased risks of cardiovascular morbidity and mortality. Cardiac remodeling including myocardial fibrosis and hypertrophy is frequently observed in CKD patients. In this study, we investigate the mechanism involved in cardiac hypertrophy associated with CKD using a rat model, by morphological and chemical component changes of the hypertrophic and non-hypertrophic hearts. Sprague-Dawley rats were 4/5 nephrectomized (Nx) at 11 weeks of age and assigned to no treatment and treatment with AST-120, which was reported to affect the cardiac damage, at 18 weeks of age. At 26 weeks of age, the rats were euthanized under anesthesia, and biochemical tests as well as analysis of cardiac condition were performed by histological and spectrophotometric methods. Cardiac hypertrophy and CKD were observed in 4/5 Nx rats even though vascular calcification and myocardial fibrosis were not detected. The increasing myocardial protein was confirmed in hypertrophic hearts by infrared spectroscopy. The absorption of amide I and other protein bands in hypertrophic hearts increased at the same position as in normal cardiac absorption. Infrared spectra also showed that lipid accumulation was also detected in hypertrophic heart. Conversely, the absorptions of protein were obviously reduced in the myocardium of non-hypertrophic heart with CKD compared to that of hypertrophic heart. The lipid associated absorption was also decreased in non-hypertrophic heart. Our results suggest that cardiac remodeling associated with relatively early-stage CKD may be suppressed by reducing increased myocardial protein and ameliorating cardiac lipid load.

  16. Phosphorus limitation and starvation effects on cell growth and lipid accumulation in Isochrysis galbana U4 for biodiesel production.

    Science.gov (United States)

    Roopnarain, A; Gray, V M; Sym, S D

    2014-03-01

    The effect of varying levels of phosphorus (P) on Isochrysis galbana U4 growth, pigmentation and lipid accumulation were investigated. A reduction in the P content to 25% of the recommended level for f/2 medium did not lead to declines in cell growth rates or lipid accumulation levels relative to the cultures maintained on medium supplemented with the normal P dose. Evidence suggesting that the recommended P supply in f/2 exceeds the requirements for maximal algal growth has obvious economic implications for the mass production of I. galbana for biodiesel production. When P supply was in excess this species was also found to accumulate intracellular levels of P that exceeded by up to 6 times its P requirements for growth and cell division. The reduction in P concentration to levels below 25% resulted in P starvation stimulated chlorophyll reductions and carotenoid and lipid accumulation in this species.

  17. Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants.

    Science.gov (United States)

    Cai, Yingqi; McClinchie, Elizabeth; Price, Ann; Nguyen, Thuy N; Gidda, Satinder K; Watt, Samantha C; Yurchenko, Olga; Park, Sunjung; Sturtevant, Drew; Mullen, Robert T; Dyer, John M; Chapman, Kent D

    2017-07-01

    Fat storage-inducing transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. Here, we tested the function of FIT2 in plant cells by ectopically expressing mouse (Mus musculus) FIT2 in Nicotiana tabacum suspension-cultured cells, Nicotiana benthamiana leaves and Arabidopsis thaliana plants. Confocal microscopy indicated that the expression of FIT2 dramatically increased the number and size of LDs in leaves of N. benthamiana and Arabidopsis, and lipidomics analysis and mass spectrometry imaging confirmed the accumulation of neutral lipids in leaves. FIT2 also increased seed oil content by ~13% in some stable, overexpressing lines of Arabidopsis. When expressed transiently in leaves of N. benthamiana or suspension cells of N. tabacum, FIT2 localized specifically to the ER and was often concentrated at certain regions of the ER that resembled ER-LD junction sites. FIT2 also colocalized at the ER with other proteins known to be involved in triacylglycerol biosynthesis or LD formation in plants, but not with ER resident proteins involved in electron transfer or ER-vesicle exit sites. Collectively, these results demonstrate that mouse FIT2 promotes LD accumulation in plants, a surprising functional conservation in the context of a plant cell given the apparent lack of FIT2 homologues in higher plants. These results suggest also that FIT2 expression represents an effective synthetic biology strategy for elaborating neutral lipid compartments in plant tissues for potential biofuel or bioproduct purposes. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  18. Production of fungal lipids : kinetic modeling and process design

    NARCIS (Netherlands)

    Meeuwse, P.

    2011-01-01

    Finding alternatives for fossil fuels is currently urgent. One of the new processes in this field is the production of biodiesel from lipids accumulated by microorganisms. Some yeasts and fungi accumulate lipids when a component needed for growth, usually the N-source, is limiting while the C-source

  19. Effects of chronic sugar consumption on lipid accumulation and autophagy in the skeletal muscle.

    Science.gov (United States)

    De Stefanis, Daniela; Mastrocola, Raffaella; Nigro, Debora; Costelli, Paola; Aragno, Manuela

    2017-02-01

    In recent years, the increasing consumption of soft drinks containing high-fructose corn syrup or sucrose has caused a rise in fructose intake, which has been related to the epidemic of metabolic diseases. As fructose and glucose intake varies in parallel, it is still unclear what the effects of the increased consumption of the two single sugars are. In the present study, the impact of chronic consumption of glucose or fructose on skeletal muscle of healthy mice was investigated. C57BL/6J male mice received water (C), 15 % fructose (ChF) or 15 % glucose (ChG) to drink for up to 7 months. Lipid metabolism and markers of inflammation and autophagy were assessed in gastrocnemius muscle. Increased body weight and gastrocnemius muscle mass, as well as circulating glucose, insulin, and lipid plasma levels were observed in sugar-drinking mice. Although triglycerides increased in the gastrocnemius muscle of both ChF and ChG mice (+32 and +26 %, vs C, respectively), intramyocellular lipids accumulated to a significantly greater extent in ChF than in ChG animals (ChF +10 % vs ChG). Such perturbations were associated with increased muscle interleukin-6 levels (threefold of C) and with the activation of autophagy, as demonstrated by the overexpression of LC3B-II (ChF, threefold and ChG, twofold of C) and beclin-1 (ChF, sevenfold and ChG, tenfold of C). The present results suggest that intramyocellular lipids and the pro-inflammatory signaling could contribute to the onset of insulin resistance and lead to the induction of autophagy, which could be an adaptive response to lipotoxicity.

  20. β2-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice.

    Science.gov (United States)

    Shi, Yun; Shu, Zhen-Ju; Xue, Xiaoling; Yeh, Chih-Ko; Katz, Michael S; Kamat, Amrita

    2016-06-01

    Catecholamines acting through β-adrenergic receptors (β(1)-, β(2)-, β(3)-AR subtypes) modulate important biological responses in various tissues. Our previous studies suggest a role for increased hepatic β-AR-mediated signaling during aging as a mediator of hepatic steatosis, liver glucose output, and insulin resistance in rodents. In the current study, we have utilized β(2)-AR knockout (KO) and wildtype (WT) control mice to define further the role of β(2)-AR signaling during aging on lipid and glucose metabolism. Our results demonstrate for the first time that age-related increases in hepatic triglyceride accumulation and body weight are attenuated upon β(2)-AR ablation. Although no differences in plasma triglyceride, non-esterified fatty acids or insulin levels were detected between old WT and KO animals, an age-associated increase in hepatic expression of lipid homeostasis regulator Cidea was significantly reduced in old KO mice. Interestingly, we also observed a shift from reduced glucose tolerance in young adult KO animals to significantly improved glucose tolerance in old KO when compared to age-matched WT mice. These results provide evidence for an important role played by β(2)-ARs in the regulation of lipid and glucose metabolism during aging. The effect of β(2)-AR ablation on caloric intake during aging is currently not known and requires investigation. Future studies are also warranted to delineate the β(2)-AR-mediated mechanisms involved in the control of lipid and glucose homeostasis, especially in the context of a growing aging population. Published by Elsevier Inc.

  1. Major Lipid Body Protein: A Conserved Structural Component of Lipid Body Accumulated during Abiotic Stress in S. quadricauda CASA-CC202

    Directory of Open Access Journals (Sweden)

    Arumugam Muthu

    2016-11-01

    Full Text Available Abiotic stress in oleaginous microalgae enhances lipid accumulation and is stored in a specialised organelle called lipid droplets (LDs. Both the LDs and body are enriched with major lipid droplet protein (MLDP. It serves as a major structural component and also plays a key role in recruiting other proteins and enzymes involved in lipid body maturation. In the present study, the presence of MLDP was detected in two abiotic stress condition namely nitrogen starvation and salt stress condition. Previous research reveals that nitrogen starvation enhances lipid accumulation. Therefore, the effect of salt on growth, biomass yield, and fatty acid profile is studied in detail. The specific growth rate of S. quadricauda under the salt stress of 10mM concentration is about 0.174μ and in control, the SGR is 0.241μ. An increase in the doubling time of the cells shows that the rate of cell division decreases during salt stress (2.87–5.17. The dry biomass content also decreased drastically at 50mM salt-treated cells (129mg/L compared to control (236mg/L on the day 20. The analysis of fatty acid composition also revealed that there is a 20% decrease in the saturated fatty acid level and 19.9% increment in monounsaturated fatty acid level, which makes salt-mediated lipid accumulation as a suitable biodiesel precursor.

  2. The influence of an antitumor lipid - erucylphosphocholine - on artificial lipid raft system modeled as Langmuir monolayer.

    Science.gov (United States)

    Wnętrzak, Anita; Łątka, Kazimierz; Makyła-Juzak, Katarzyna; Zemla, Joanna; Dynarowicz-Łątka, Patrycja

    2015-01-01

    Outer layer of cellular membrane contains ordered domains enriched in cholesterol and sphingolipids, called 'lipid rafts', which play various biological roles, i.e., are involved in the induction of cell death by apoptosis. Recent studies have shown that these domains may constitute binding sites for selected drugs. For example alkylphosphocholines (APCs), which are new-generation antitumor agents characterized by high selectivity and broad spectrum of activity, are known to have their molecular targets located at cellular membrane and their selective accumulation in tumor cells has been hypothesized to be linked with the alternation of biophysical properties of lipid rafts. To get a deeper insight into this issue, interactions between representative APC: erucylphosphocholine, and artificial lipid raft system, modeled as Langmuir monolayer (composed of cholesterol and sphingomyelin mixed in 1:2 proportion) were investigated. The Langmuir monolayer experiments, based on recording surface pressure-area isotherms, were complemented with Brewster angle microscopy results, which enabled direct visualization of the monolayers structure. In addition, the investigated monolayers were transferred onto solid supports and studied with AFM. The interactions between model raft system and erucylphosphocholine were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with ΔG(exc) function). The obtained results indicate that erucylphosphocholine introduced to raft-mimicking model membrane causes fluidizing effect and weakens the interactions between cholesterol and sphingomyelin, which results in phase separation at high surface pressures. This leads to the redistribution of cholesterol molecules in model raft, which confirms the results observed in biological studies.

  3. Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

    Directory of Open Access Journals (Sweden)

    Qi Huang

    2017-05-01

    Full Text Available Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK and silent information regulator 1 (sirt1. Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD and glucose tolerance.

  4. Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

    Directory of Open Access Journals (Sweden)

    Marta Moya

    Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

  5. Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-Regulated in Nonalcoholic Fatty Liver

    Science.gov (United States)

    Moya, Marta; Benet, Marta; Guzmán, Carla; Tolosa, Laia; García-Monzón, Carmelo; Pareja, Eugenia; Castell, José Vicente; Jover, Ramiro

    2012-01-01

    Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. PMID:22238690

  6. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  7. Potential role of multiple carbon fixation pathways during lipid accumulation in Phaeodactylum tricornutum.

    Science.gov (United States)

    Valenzuela, Jacob; Mazurie, Aurelien; Carlson, Ross P; Gerlach, Robin; Cooksey, Keith E; Peyton, Brent M; Fields, Matthew W

    2012-06-06

    Phaeodactylum tricornutum is a unicellular diatom in the class Bacillariophyceae. The full genome has been sequenced (over time via RNA-sequence determination. The specific Nile Red (NR) fluorescence (NR fluorescence per cell) increased over time; however, the increase in NR fluorescence was initiated before external nitrate was completely exhausted. Exogenous phosphate was depleted before nitrate, and these results indicated that the depletion of exogenous phosphate might be an early trigger for lipid accumulation that is magnified upon nitrate depletion. As expected, many of the genes associated with nitrate and phosphate utilization were up-expressed. The diatom-specific cyclins cyc7 and cyc10 were down-expressed during the nutrient-deplete state, and cyclin B1 was up-expressed during lipid-accumulation after growth cessation. While many of the genes associated with the C3 pathway for photosynthetic carbon reduction were not significantly altered, genes involved in a putative C4 pathway for photosynthetic carbon assimilation were up-expressed as the cells depleted nitrate, phosphate, and exogenous dissolved inorganic carbon (DIC) levels. P. tricornutum has multiple, putative carbonic anhydrases, but only two were significantly up-expressed (2-fold and 4-fold) at the last time point when exogenous DIC levels had increased after the cessation of growth. Alternative pathways that could utilize HCO3- were also suggested by the gene expression profiles (e.g., putative propionyl-CoA and methylmalonyl-CoA decarboxylases). The results indicate that P. tricornutum continued carbon dioxide reduction when population growth was arrested and different carbon-concentrating mechanisms were used dependent upon exogenous DIC levels. Based upon overall low gene expression levels for fatty acid synthesis, the results also suggest that the build-up of precursors to the acetyl-CoA carboxylases may play a more significant role in TAG synthesis rather than the actual enzyme levels of

  8. Models of lipid droplets growth and fission in adipocyte cells

    Energy Technology Data Exchange (ETDEWEB)

    Boschi, Federico, E-mail: federico.boschi@univr.it [Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona (Italy); Rizzatti, Vanni; Zamboni, Mauro [Department of Medicine, Geriatric Section, University of Verona, Piazzale Stefani 1, 37126 Verona (Italy); Sbarbati, Andrea [Department of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona (Italy)

    2015-08-15

    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 difficult 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

  9. Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters.

    Science.gov (United States)

    Dimastrogiovanni, Giorgio; Córdoba, Marlon; Navarro, Isabel; Jáuregui, Olga; Porte, Cinta

    2015-08-01

    This work investigates the suitability of the rainbow trout liver cell line (RTL-W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL-W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish.

  10. Induction of DKK1 by ox-LDL negatively regulates intracellular lipid accumulation in macrophages.

    Science.gov (United States)

    Zhang, Yu; Ge, Cheng; Wang, Lin; Liu, Xinxin; Chen, Yifei; Li, Mengmeng; Zhang, Mei

    2015-01-01

    Dickkopf1 (DKK1), a canonical Wnt/β-catenin pathway antagonist, is closely associated with cardiovascular disease and adipogenesis. We performed an in vitro study to determine whether oxidized low-density lipoprotein (ox-LDL) increased the expression of DKK1 in macrophages and whether β-catenin and liver X receptor α (LXRα) were involved in this regulation. Induction of DKK1 expression by ox-LDL decreased the level of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) via a Wnt/β-catenin pathway and increased ATP-binding cassette transporter A/G1 (ABCA/G1) levels via a signal transducer and activator of transcription 3 (STAT3) pathway. Lower LOX-1 and higher ABCA/G1 levels inhibited cholesterol loading in macrophages. In conclusion, ox-LDL may induce DKK1 expression in macrophages to inhibit the accumulation of lipids through a mechanism that involves downregulation of LOX-1-mediated lipid uptake and upregulation of ABCA/G1-dependent cholesterol efflux.

  11. Apolipoprotein O expression in mouse liver enhances hepatic lipid accumulation by impairing mitochondrial function.

    Science.gov (United States)

    Tian, Feng; Wu, Chen-Lu; Yu, Bi-Lian; Liu, Ling; Hu, Jia-Rui

    2017-09-09

    Apolipoprotein O (ApoO) was recently observed in the cellular mitochondrial inner membrane, which plays a role in mitochondrial function and is associated with myocardiopathy. Empirical information on the physiological functions of apoO is therefore limited. In this study, we aimed to elucidate the effect of apoO on hepatic fatty acid metabolism. An adenoviral vector expressing hApoO was constructed and introduced into chow diet and high-fat diet induced mice and the L02 human hepatoma cell line. High levels of hApoO mRNA and protein were detected in the liver, and the expression of lipid metabolism genes was significantly altered compared with negative controls. The liver function indices (serum ALT and AST) were clearly elevated, and the ultrastructure of cellular mitochondria was distinctly altered in the liver after apoO overexpression. Further, mitochondrial membrane potential decreased with hApoO treatment in L02 cells. These results establish a link between apoO and lipid accumulation and could suggest a new pathway for regulating non-alcoholic fatty liver disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. H-rev107 Regulates Cytochrome P450 Reductase Activity and Increases Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Fu-Ming Tsai

    Full Text Available H-rev107 is a member of the HREV107 type II tumor suppressor gene family and acts as a phospholipase to catalyze the release of fatty acids from glycerophospholipid. H-rev107 has been shown to play an important role in fat metabolism in adipocytes through the PGE2/cAMP pathway, but the detailed molecular mechanism underlying H-rev107-mediated lipid degradation has not been studied. In this study, the interaction between H-rev107 and cytochrome P450 reductase (POR, which is involved in hepatic lipid content regulation, was determined by yeast two-hybrid screen and confirmed by using in vitro pull down assays and immunofluorescent staining. The expression of POR in H-rev107-expressing cells enhanced the H-rev107-mediated release of arachidonic acid. However, H-rev107 inhibited POR activity and relieved POR-mediated decreased triglyceride content in HtTA and HeLa cervical cells. The inhibitory effect of H-rev107 will be abolished when POR-expressing cells transfected with PLA2-lacking pH-rev107 or treated with PLA2 inhibitor. Silencing of H-rev107 using siRNA resulted in increased glycerol production and reversion of free fatty acid-mediated growth suppression in Huh7 hepatic cells. In summary, our results revealed that H-rev107 is also involved in lipid accumulation in liver cells through the POR pathway via its PLA2 activity.

  13. Application of high-content image analysis for quantitatively estimating lipid accumulation in oleaginous yeasts with potential for use in biodiesel production.

    Science.gov (United States)

    Capus, Aurélie; Monnerat, Marianne; Ribeiro, Luiz Carlos; de Souza, Wanderley; Martins, Juliana Lopes; Sant'Anna, Celso

    2016-03-01

    Biodiesel from oleaginous microorganisms is a viable substitute for a fossil fuel. Current methods for microorganism lipid productivity evaluation do not analyze lipid dynamics in single cells. Here, we described a high-content image analysis (HCA) as a promising strategy for screening oleaginous microorganisms for biodiesel production, while generating single-cell lipid dynamics data in large cell density. Rhodotorula slooffiae yeast were grown in standard (CTL) or lipid trigger medium (LTM), and lipid droplet (LD) accumulation was analyzed in deconvolved confocal microscopy images of cells stained with the lipophilic fluorescent Nile red (NR) dye using automated cell and LD segmentation. The 'vesicle segmentation' method yielded valid morphometric results for limited lipid accumulation in smaller LDs (CTL samples) and for high lipid accumulation in larger LDs (LTM samples), and detected LD localization changes. Thus, HCA can be used to analyze the lipid accumulation patterns likely to be encountered in screens for biodiesel production.

  14. SF-1 deficiency causes lipid accumulation in Leydig cells via suppression of STAR and CYP11A1.

    Science.gov (United States)

    Hatano, Megumi; Migita, Toshiro; Ohishi, Tomokazu; Shima, Yuichi; Ogawa, Yoshihiro; Morohashi, Ken-Ichirou; Hasegawa, Yukihiro; Shibasaki, Futoshi

    2016-11-01

    Genetic mutations of steroidogenic factor 1 (also known as Ad4BP or Nr5a1) have increasingly been reported in patients with 46,XY disorders of sex development (46,XY disorders of sex development). However, because the phenotype of 46,XY disorders of sex development with a steroidogenic factor 1 mutation is wide-ranging, its precise diagnosis remains a clinical problem. We previously reported the frequent occurrence of lipid accumulation in Leydig cells among patients with 46,XY disorders of sex development with a steroidogenic factor 1 mutation, an observation also reported by other authors. To address the mechanism of lipid accumulation in this disease, we examined the effects of steroidogenic factor 1 deficiency on downstream targets of steroidogenic factor 1 in in vitro and in vivo. We found that lipid accumulation in Leydig cells was enhanced after puberty in heterozygous steroidogenic factor 1 knockout mice compared with wild-type mice, and was accompanied by a significant decrease in steroidogenic acute regulatory protein and CYP11A1 expression. In mouse Leydig cell lines, steroidogenic factor 1 knockdown induced a remarkable accumulation of neutral lipids and cholesterol with reduced androgen levels. Steroidogenic factor 1 knockdown reduced the expression of steroidogenic acute regulatory protein and CYP11A1, both of which are transcriptional targets of steroidogenic factor 1 and key molecules for steroidogenesis from cholesterol in the mitochondria. Knockdown of either steroidogenic acute regulatory protein or CYP11A1 also induced lipid accumulation, and knockdown of both had an additive effect. Our data suggested that lipid accumulation in the Leydig cells of the 46,XY disorders of sex development phenotype with a steroidogenic factor 1 mutation is due, at least in part, to the suppression of steroidogenic acute regulatory protein and CYP11A1, and a resulting increase in unmetabolized cholesterol.

  15. Weight restoration on a high carbohydrate refeeding diet promotes rapid weight regain and hepatic lipid accumulation in female anorexic rats.

    Science.gov (United States)

    Giles, Erin D; Hagman, Jennifer; Pan, Zhaoxing; MacLean, Paul S; Higgins, Janine A

    2016-01-01

    There is currently no standard clinical refeeding diet for the treatment of anorexia nervosa (AN). To provide the most efficacious AN clinical care, it is necessary to define the metabolic effects of current refeeding diets. An activity-based model of anorexia nervosa (AN) was used in female rats. AN was induced over 7d by timed access to low fat (LF) diet with free access to a running wheel. Plasma hormones/metabolites and body composition were assessed at baseline, AN diagnosis (day 0), and following 28d of refeeding on LF diet. Energy balance and expenditure were measured via continuous indirect calorimetry on days -3 to +3. AN induction caused stress as indicated by higher levels of corticosterone versus controls (p weight gain during refeeding was higher in AN rats than controls (p = 0.0188), despite lower overall energy intake (p weight as controls. It is possible that liver lipid accumulation was caused by overfeeding of carbohydrate suggesting that a lower carbohydrate, higher fat diet may be beneficial during AN treatment. To test whether such a diet would be accepted clinically, we conducted a study in adolescent female AN patients which showed equivalent palatability and acceptability for LF and moderate fat diets. In addition, this diet was feasible to provide clinically during inpatient treatment in this population. Refeeding a LF diet to restore body weight in female AN rats caused depressed TEE and REE which facilitated rapid regain. However, this weight gain was metabolically unhealthy as it resulted in elevated lipid accumulation in the liver. It is necessary to investigate the use of other diets, such as lower carbohydrate, moderate fat diets, in pre-clinical models to develop the optimal clinical refeeding diets for AN.

  16. Effect of high glucose on the expression of CD36 and lipid accumulation in THP-1 macrophages

    Institute of Scientific and Technical Information of China (English)

    谭玉林

    2014-01-01

    Objective To investigate the effect of high glucose on regulating the expression of CD36 and lipid accumulation in THP-1 macrophages.Methods THP-1 macrophages were incubated with different concentrations of D-glucose(5.6,11,20,30 and 35 mmol/L),50 mg/L oxidized low density lipoprotein(ox-LDL),50 mg/L oxLDL+20 mmol/L D-glucose for 24 h.Total cholesterol content in THP-1 macrophages was determined by high performance liquid chromatography,the lipid accumulation was detected by oil red O stain.CD36 mRNA and

  17. Advanced glycation end products (AGEs) increase renal lipid accumulation: a pathogenic factor of diabetic nephropathy (DN).

    Science.gov (United States)

    Yuan, Yang; Sun, Hong; Sun, Zilin

    2017-06-28

    Advanced glycation end products (AGEs) are pathogenic factors of diabetic nephropathy (DN), causing renal damage in various ways. The aim of this study is to investigate the ectopic lipid accumulation caused by AGEs in human renal tubular epithelial cell line (HK-2) cells and the kidney of type 2 diabetic rats. In vivo study, diabetes was induced in male Sprague-Dawley rats through intraperitoneal injection of high-fat/high-sucrose diet and low-dose streptozocin (STZ). Two weeks after STZ injection, the diabetic rats were randomly divided into two groups, namely, untreated diabetic and Aminoguanidine Hydrochloride (AG, an AGEs formation inhibitor)-treated (100 mg/Kg/day, i.g., for 8 weeks) group. In vitro study, according to the different treatments, HK-2 were divided into 6 groups. Intracellular cholesterol content was assessed by Oil Red O staining and cholesterol enzymatic assay. Expression of mRNA and protein of molecules controlling cholesterol homeostasis in the treated cells was examined by real-time quantitative PCR and western blotting, respectively. SREBP cleavage-activating protein (SCAP) translocation was detected by confocal microscopy. Here we found Nε-(carboxymethyl) lysine (CML, a member of the AGEs family) increased Oil Red O staining and intracellular cholesterol ester (CE) in HK-2 cells; Anti-RAGE (AGEs receptor) reduced lipid droplets and the CE level. A strong staining of Oil Red O was also found in the renal tubules of the diabetic rats, which could be alleviated by AG. CML upregulated both mRNA and protein expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), LDL receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2) and SCAP, which were inhibited by anti-RAGE. The upregulation of these molecules in the kidney of the diabetic rats was also ameliorated by AG. Furthermore, AG reduced serum and renal CML deposition, and improved urine protein and u-NGAL in type 2 diabetic rats. Overall, these results

  18. Inhibitory effect of Piper betel leaf extracts on copper-mediated LDL oxidation and oxLDL-induced lipid accumulation via inducing reverse cholesterol transport in macrophages.

    Science.gov (United States)

    Ma, Gwo-Chin; Wu, Pei-Fang; Tseng, Hsien-Chun; Chyau, Charng-Cherng; Lu, Hsiu-Chin; Chou, Fen-Pi

    2013-12-15

    Piper betel leaf (PBL) has the biological capabilities of detoxification and can work as an anti-inflammatory agent and an anti-oxidant. In this study, we evaluated the anti-oxidative activity of the extract of Piper betel leaves (PBLs) on the basis of Cu(2+)-mediated oxidation, and its ability to prevent foam cell formation in a model for oxidised low density lipoprotein (oxLDL)-induced lipid accumulation in macrophages. Our data demonstrated that PBLs were able to inhibit LDL oxidation in vitro and are able to reduce the lipid accumulation in macrophages. We showed the underlying mechanisms to be the following: PBLs up-regulated the protein levels of the class A and class B scavenger receptors, the membrane lipid transporter ABCA1, and its upstream regulator Liver X receptor (LXR) in the macrophages exposed to oxLDL. The results suggested that PBLs activated the reverse cholesterol transport mechanism to enhance the metabolism of the oxLDL that could prevent both lipid accumulation and foam cell formation and further minimise the possible damage of vessels caused by the oxLDL.

  19. Measurement of Lipid Droplet Accumulation Kinetics in Chlamydomonas reinhardtii Using Seoul-Fluor

    Directory of Open Access Journals (Sweden)

    Noo Li Jeon

    2013-10-01

    Full Text Available Alternative energy resources have become an important issue due to the limited stocks of petroleum-based fuel. Microalgae, a source of renewable biodiesel, use solar light to convert CO2 into lipid droplets (LDs. Quantification of LDs in microalgae is required for developing and optimizing algal bioprocess engineering. However, conventional quantification methods are both time and labor-intensive and difficult to apply in high-throughput screening systems. LDs in plant and mammalian cells can be visualized by staining with various fluorescence probes such as the Nile Red, BODIPY, and Seoul-Fluor (SF series. This report describes the optimization of LD staining in Chlamydomonas reinhardtii with SF probes via systematic variations of dye concentration, staining time, temperature, and pH. A protocol for quantitative measurement of accumulation kinetics of LDs in C. reinhardtii was developed using a spectrofluorimeter and the accuracy of LD size measurement was confirmed by transmission electron microscopy (TEM. Our results indicate that our spectrofluorimeter-based measurement approach can monitor kinetics of intracellular LDs (in control and nitrogen-source-starved Chlamydomonas reinhardtii accumulation that has not been possible in the case of conventional imaging-based methods. Our results presented here confirmed that an SF44 can be a powerful tool for in situ monitoring and tracking of intracellular LDs formation.

  20. Chronic Insulin Exposure Induces ER Stress and Lipid Body Accumulation in Mast Cells at the Expense of Their Secretory Degranulation Response.

    Directory of Open Access Journals (Sweden)

    William E Greineisen

    Full Text Available Lipid bodies (LB are reservoirs of precursors to inflammatory lipid mediators in immunocytes, including mast cells. LB numbers are dynamic, increasing dramatically under conditions of immunological challenge. We have previously shown in vitro that insulin-influenced lipogenic pathways induce LB biogenesis in mast cells, with their numbers attaining steatosis-like levels. Here, we demonstrate that in vivo hyperinsulinemia resulting from high fat diet is associated with LB accumulation in murine mast cells and basophils. We characterize the lipidome of purified insulin-induced LB, and the shifts in the whole cell lipid landscape in LB that are associated with their accumulation, in both model (RBL2H3 and primary mast cells. Lipidomic analysis suggests a gain of function associated with LB accumulation, in terms of elevated levels of eicosanoid precursors that translate to enhanced antigen-induced LTC4 release. Loss-of-function in terms of a suppressed degranulation response was also associated with LB accumulation, as were ER reprogramming and ER stress, analogous to observations in the obese hepatocyte and adipocyte. Taken together, these data suggest that chronic insulin elevation drives mast cell LB enrichment in vitro and in vivo, with associated effects on the cellular lipidome, ER status and pro-inflammatory responses.

  1. Transcript level coordination of carbon pathways during silicon starvation-induced lipid accumulation in the diatom Thalassiosira pseudonana.

    Science.gov (United States)

    Smith, Sarah R; Glé, Corine; Abbriano, Raffaela M; Traller, Jesse C; Davis, Aubrey; Trentacoste, Emily; Vernet, Maria; Allen, Andrew E; Hildebrand, Mark

    2016-05-01

    Diatoms are one of the most productive and successful photosynthetic taxa on Earth and possess attributes such as rapid growth rates and production of lipids, making them candidate sources of renewable fuels. Despite their significance, few details of the mechanisms used to regulate growth and carbon metabolism are currently known, hindering metabolic engineering approaches to enhance productivity. To characterize the transcript level component of metabolic regulation, genome-wide changes in transcript abundance were documented in the model diatom Thalassiosira pseudonana on a time-course of silicon starvation. Growth, cell cycle progression, chloroplast replication, fatty acid composition, pigmentation, and photosynthetic parameters were characterized alongside lipid accumulation. Extensive coordination of large suites of genes was observed, highlighting the existence of clusters of coregulated genes as a key feature of global gene regulation in T. pseudonana. The identity of key enzymes for carbon metabolic pathway inputs (photosynthesis) and outputs (growth and storage) reveals these clusters are organized to synchronize these processes. Coordinated transcript level responses to silicon starvation are probably driven by signals linked to cell cycle progression and shifts in photophysiology. A mechanistic understanding of how this is accomplished will aid efforts to engineer metabolism for development of algal-derived biofuels.

  2. SIRT1-metabolite binding histone macroH2A1.1 protects hepatocytes against lipid accumulation

    Science.gov (United States)

    Pazienza, Valerio; Borghesan, Michela; Mazza, Tommaso; Sheedfar, Fareeba; Panebianco, Concetta; Williams, Roger; Mazzoccoli, Gianluigi; Andriulli, Angelo; Nakanishi, Tomoko; Vinciguerra, Manlio

    2014-01-01

    Non-alcoholic-fatty-liver-disease (NAFLD) encompasses conditions associated to fat deposition in the liver, which are generally deteriorated during the aging process. MacroH2A1, a variant of histone H2A, is a key transcriptional regulator involved in tumorigenic processes and cell senescence, and featuring two alternatively splicing isoforms, macroH2A1.1 and macroH2A1.2. MacroH2A1.1 binds with high affinity O-acetyl ADP ribose, a small metabolite produced by the reaction catalysed by NAD+-dependent deacetylase SIRT1, whereas macroH2A1.2 is unable to do so. The functional significance of this binding is unknown. We previously reported that the hepatic levels of macroH2A1.1 and macroH2A1.2 are differentially expressed in mice models of NAFLD. Here we show that over-expression of macroH2A1.1, but not of macroH2A1.2, is able to protect hepatocytes against lipid accumulation. MacroH2A1.1 over-expressing cells display ameliorated glucose metabolism, reduced expression of lipidogenic genes and fatty acids content. SIRT1/macroH2A1.1-dependent epigenetic regulation of lipid metabolism may be relevant to NAFLD development. PMID:24473773

  3. Impacts of CO2 concentration on growth, lipid accumulation, and carbon-concentrating-mechanism-related gene expression in oleaginous Chlorella.

    Science.gov (United States)

    Fan, Jianhua; Xu, Hui; Luo, Yuanchan; Wan, Minxi; Huang, Jianke; Wang, Weiliang; Li, Yuanguang

    2015-03-01

    Biodiesel production by microalgae with photosynthetic CO2 biofixation is thought to be a feasible way in the field of bioenergy and carbon emission reduction. Knowledge of the carbon-concentrating mechanism plays an important role in improving microalgae carbon fixation efficiency. However, little information is available regarding the dramatic changes of cells suffered upon different environmental factors, such as CO2 concentration. The aim of this study was to investigate the growth, lipid accumulation, carbon fixation rate, and carbon metabolism gene expression under different CO2 concentrations in oleaginous Chlorella. It was found that Chlorella pyrenoidosa grew well under CO2 concentrations ranging from 1 to 20 %. The highest biomass and lipid productivity were 4.3 g/L and 107 mg/L/day under 5 % CO2 condition. Switch from high (5 %) to low (0.03 %, air) CO2 concentration showed significant inhibitory effect on growth and CO2 fixation rate. The amount of the saturated fatty acids was increased obviously along with the transition. Low CO2 concentration (0.03 %) was suitable for the accumulation of saturated fatty acids. Reducing the CO2 concentration could significantly decrease the polyunsaturated degree in fatty acids. Moreover, the carbon-concentrating mechanism-related gene expression revealed that most of them, especially CAH2, LCIB, and HLA3, had remarkable change after 1, 4, and 24 h of the transition, which suggests that Chlorella has similar carbon-concentrating mechanism with Chlamydomonas reinhardtii. The findings of the present study revealed that C. pyrenoidosa is an ideal candidate for mitigating CO2 and biodiesel production and is appropriate as a model for mechanism research of carbon sequestration.

  4. Atomic force microscopy of model lipid membranes.

    Science.gov (United States)

    Morandat, Sandrine; Azouzi, Slim; Beauvais, Estelle; Mastouri, Amira; El Kirat, Karim

    2013-02-01

    Supported lipid bilayers (SLBs) are biomimetic model systems that are now widely used to address the biophysical and biochemical properties of biological membranes. Two main methods are usually employed to form SLBs: the transfer of two successive monolayers by Langmuir-Blodgett or Langmuir-Schaefer techniques, and the fusion of preformed lipid vesicles. The transfer of lipid films on flat solid substrates offers the possibility to apply a wide range of surface analytical techniques that are very sensitive. Among them, atomic force microscopy (AFM) has opened new opportunities for determining the nanoscale organization of SLBs under physiological conditions. In this review, we first focus on the different protocols generally employed to prepare SLBs. Then, we describe AFM studies on the nanoscale lateral organization and mechanical properties of SLBs. Lastly, we survey recent developments in the AFM monitoring of bilayer alteration, remodeling, or digestion, by incubation with exogenous agents such as drugs, proteins, peptides, and nanoparticles.

  5. The "lipid accumulation product" performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison

    Directory of Open Access Journals (Sweden)

    Kahn Henry S

    2005-09-01

    Full Text Available Abstract Background Body mass index (BMI, kg/m2 may not be the best marker for estimating the risk of obesity-related disease. Consistent with physiologic observations, an alternative index uses waist circumference (WC and fasting triglycerides (TG concentration to describe lipid overaccumulation. Methods The WC (estimated population minimum 65 cm for men and 58 cm for women and TG concentration from the third National Health and Nutrition Examination Survey (N = 9,180, statistically weighted to represent 100.05 million US adults were used to compute a "lipid accumulation product" [LAP = (WC-65 × TG for men and (WC-58 × TG for women] and to describe the population distribution of LAP. LAP and BMI were compared as categorical variables and as log-transformed continuous variables for their ability to identify adverse levels of 11 cardiovascular risk factors. Results Nearly half of the represented population was discordant for their quartile assignments to LAP and BMI. When 23.54 million with ordinal LAP quartile > BMI quartile were compared with 25.36 million with ordinal BMI quartile > LAP quartile (regression models adjusted for race-ethnicity and sex the former had more adverse risk levels than the latter (p 0.1. As continuous variables, LAP provided a consistently more adverse beta coefficient (slope than BMI for nine cardiovascular risk variables (p 0.2. Conclusion LAP (describing lipid overaccumulation performed better than BMI (describing weight overaccumulation for identifying US adults at cardiovascular risk. Compared to BMI, LAP might better predict the incidence of cardiovascular disease, but this hypothesis needs prospective testing.

  6. Replacing Fish Oil with Vegetable Oils in Salmon Feed Increases Hepatic Lipid Accumulation and Reduces Insulin Sensitivity in Mice

    DEFF Research Database (Denmark)

    Midtbø, Lisa Kolden

    %) of FO with different vegetable oils (VOs); rape seed oil (WDRO), olive oil (WD-OO) or soybean oil (WD-SO). These diets were given to C57BL/6J mice, and mice had higher hepatic lipid accumulation and lower insulin sensitivity when given WD-SO compared with WD-FO. Mice given WD-SO had higher hepatic...

  7. Angiotensinogen gene silencing reduces markers of inflammation and lipid accumulation in adipocytes

    Directory of Open Access Journals (Sweden)

    Wenting eXin

    2013-03-01

    Full Text Available Inflammatory adipokines secreted from adipose tissue are major contributors to obesity-associated inflammation and other metabolic dysfunctions. We and others have recently documented the contribution of adipose tissue renin-angiotensin system (RAS to the pathogenesis of obesity, inflammation and insulin resistance. We hypothesized that adipocyte-derived angiotensinogen (Agt plays a critical role in adipogenesis and/or lipogenesis as well as inflammation. This was tested using 3T3-L1 adipocytes, stably transfected with Agt-shRNA or scrambled Sc-shRNAcas a control. Transfected preadipocytes were differentiated and used to investigate the role of adipose Agt through microarray and PCR analyses and adipokine profiling. As expected, Agt gene silencing significantly reduced the expression of Agt and its hormone product angiotensin II (Ang II, as well as lipid accumulation in 3T3-L1 adipocytes. Microarray studies identified several genes involved in lipid metabolism and inflammatory pathways which were down-regulated by Agt gene inactivation, such as glycerol-3-phosphate dehydrogenase 1 (Gpd1, serum amyloid A 3 (Saa3, nucleotide-binding oligomerization domain containing 1 (Nod1 and signal transducer and activator of transcription 1 (Stat1. Mouse adipogenesis PCR arrays revealed lower expression levels of adipogenic/lipogenic genes such as peroxisome proliferator activated receptor gamma (Pparg, sterol regulatory element binding transcription factor 1 (Srebf1, adipogenin (Adig, and fatty acid binding protein 4 (Fabp4. Further, silencing of Agt gene significantly lowered expression of pro-inflammatory adipokines including interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, and monocyte chemotactic protein-1 (MCP-1. In conclusion, this study directly demonstrates critical effects of Agt in adipocyte metabolism and inflammation and further support a potential role for adipose Agt in the pathogenesis of obesity-associated metabolic alterations.

  8. Physiological characterization of lipid accumulation and in vivo ester formation in Gordonia sp. KTR9.

    Science.gov (United States)

    Eberly, Jed O; Ringelberg, David B; Indest, Karl J

    2013-02-01

    Previous work has demonstrated the feasibility of in vivo biodiesel synthesis in Escherichia coli, however, ethyl ester formation was dependent on an external fatty acid feedstock. In contrast to E. coli, actinomycetes may be ideal organisms for direct biodiesel synthesis because of their capacity to synthesize high levels of triacylglcerides (TAGs). In this study, we investigated the physiology and associated TAG accumulation along with the in vivo ability to catalyze ester formation from exogenous short chain alcohol sources in Gordonia sp. KTR9, a strain that possesses a large number of genes dedicated to fatty acid and lipid biosynthesis. Total lipid fatty acids content increased by 75 % and TAG content increased by 50 % under nitrogen starvation conditions in strain KTR9. Strain KTR9 tolerated the exogenous addition of up to 4 % methanol, 4 % ethanol and 2 % propanol in the media. Increasing alcohol concentrations resulted in a decrease in the degree of saturation of recovered fatty acid alcohol esters and a slight increase in the fatty acid chain length. A linear dose dependency in fatty alcohol ester synthesis was observed in the presence of 0.5-2 % methanol and ethanol compared to control KTR9 strains grown in the absence of alcohols. An inspection of the KTR9 genome revealed the presence of several putative wax ester synthase/acyl-coenzyme A : diacylglycerol acyltransferase (WS/DGAT) enzymes, encoded by atf gene homologs, that may catalyze the in vivo synthesis of fatty acid esters from short chain alcohols. Collectively, these results indicate that Gordonia sp. KTR9 may be a suitable actinomycete host strain for in vivo biodiesel synthesis.

  9. Green microalga Scenedesmus acutus grown on municipal wastewater to couple nutrient removal with lipid accumulation for biodiesel production.

    Science.gov (United States)

    Sacristán de Alva, Manuel; Luna-Pabello, Víctor M; Cadena, Erasmo; Ortíz, Edgar

    2013-10-01

    The green microalga Scenedesmus acutus was cultivated in two different municipal wastewater discharges (pre- and post-treated), and was compared to a culture medium with basic nutrients (20% of N, P, K), in order to study the simultaneous potential of nutrient removal and lipid accumulation ability. The highest level of nutrient removal was found in the pretreated wastewater discharge (achieving a high removal of phosphorus [66%] and organic nitrogen [94%]). Likewise, better results on biomass productivity and lipid accumulation were found in cultures using pretreated wastewater compared to enriched medium, obtaining 79.9 mg/L, and 280 mg/L, respectively. Since the best results were found in pretreated wastewater, the biodiesel preparation was performed using said medium at small-scale. After cultivation, 249.4 mg/L of biodiesel were obtained. According to this analysis, S. acutus could be used for wastewater treatment producing biomass with a suitable content of lipids, convenient for biodiesel production.

  10. Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kai Connie [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-01

    Oxidative stress and lipid accumulation play important roles in alcohol-induced liver injury. Previous reports showed that, in livers of nuclear factor erythroid 2-related factor 2 (Nrf2)-activated mice, genes involved in antioxidant defense are induced, whereas genes involved in lipid biosynthesis are suppressed. To investigate the role of Nrf2 in ethanol-induced hepatic alterations, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation, were treated with ethanol (5 g/kg, po). Blood and liver samples were collected 6 h thereafter. Ethanol increased alanine aminotransferase and lactate dehydrogenase activities as well as thiobarbituric acid reactive substances in serum of Nrf2-null and wild-type mice, but not in Nrf2-enhanced mice. After ethanol administration, mitochondrial glutathione concentrations decreased markedly in Nrf2-null mice but not in Nrf2-enhanced mice. H{sub 2}DCFDA staining of primary hepatocytes isolated from the four genotypes of mice indicates that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. Ethanol increased serum triglycerides and hepatic free fatty acids in Nrf2-null mice, and these increases were blunted in Nrf2-enhanced mice. In addition, the basal mRNA and nuclear protein levels of sterol regulatory element-binding protein 1(Srebp-1) were decreased with graded Nrf2 activation. Ethanol further induced Srebp-1 mRNA in Nrf2-null mice but not in Nrf2-enhanced mice. In conclusion, Nrf2 activation prevented alcohol-induced oxidative stress and accumulation of free fatty acids in liver by increasing genes involved in antioxidant defense and decreasing genes involved in lipogenesis. -- Highlights: ► Ethanol depleted mitochondrial GSH in Nrf2-null mice but not in Keap1-KD mice. ► Ethanol increased ROS in hepatocytes isolated from Nrf2-null and wild

  11. mTORC1 signalling mediates PI3K-dependent large lipid droplet accumulation in Drosophila ovarian nurse cells

    Directory of Open Access Journals (Sweden)

    Lawrence B. Mensah

    2017-05-01

    Full Text Available Insulin and insulin-like growth factor signalling (IIS, which is primarily mediated by the PI3-kinase (PI3K/PTEN/Akt kinase signalling cassette, is a highly evolutionarily conserved pathway involved in co-ordinating growth, development, ageing and nutrient homeostasis with dietary intake. It controls transcriptional regulators, in addition to promoting signalling by mechanistic target of rapamycin (mTOR complex 1 (mTORC1, which stimulates biosynthesis of proteins and other macromolecules, and drives organismal growth. Previous studies in nutrient-storing germline nurse cells of the Drosophila ovary showed that a cytoplasmic pool of activated phosphorylated Akt (pAkt controlled by Pten, an antagonist of IIS, cell-autonomously regulates accumulation of large lipid droplets in these cells at late stages of oogenesis. Here, we show that the large lipid droplet phenotype induced by Pten mutation is strongly suppressed when mTor function is removed. Furthermore, nurse cells lacking either Tsc1 or Tsc2, which negatively regulate mTORC1 activity, also accumulate large lipid droplets via a mechanism involving Rheb, the downstream G-protein target of TSC2, which positively regulates mTORC1. We conclude that elevated IIS/mTORC1 signalling is both necessary and sufficient to induce large lipid droplet formation in late-stage nurse cells, suggesting roles for this pathway in aspects of lipid droplet biogenesis, in addition to control of lipid metabolism.

  12. Fatty acid rich effluent from acidogenic biohydrogen reactor as substrate for lipid accumulation in heterotrophic microalgae with simultaneous treatment.

    Science.gov (United States)

    Venkata Mohan, S; Prathima Devi, M

    2012-11-01

    Acid-rich effluent generated from acidogenic biohydrogen production process was evaluated as substrate for lipid synthesis by integrating with heterotrophic cultivation of mixed microalgae. Experiments were performed both with synthetic volatile fatty acids (SVFA) and fermented fatty acids (FFA) from biohydrogen producing reactor. Fatty acid based platform evidenced significant influence on algal growth as well as lipid accumulation by the formation of triglycerides through fatty acid synthesis. Comparatively FFA documented higher biomass and lipid productivity (1.42mg/ml (wet weight); 26.4%) than SVFAs ((HAc+HBu+HPr), 0.60mg/ml; 23.1%). Lipid profiles varied with substrates and depicted 18 types of saturated and unsaturated fatty acids with wide fuel and food characteristics. The observed higher concentrations of Chl b over Chl a supports the biosynthesis of triacylglycerides. Microalgae diversity visualized the presence of lipid accumulating species viz., Scenedesmus sp. and Chlorella sp. Integration of microalgae cultivation with biohydrogen production showed lipid productivity for biodiesel production along with additional treatment.

  13. Self-assembly models for lipid mixtures

    Science.gov (United States)

    Singh, Divya; Porcar, Lionel; Butler, Paul; Perez-Salas, Ursula

    2006-03-01

    Solutions of mixed long and short (detergent-like) phospholipids referred to as ``bicelle'' mixtures in the literature, are known to form a variety of different morphologies based on their total lipid composition and temperature in a complex phase diagram. Some of these morphologies have been found to orient in a magnetic field, and consequently bicelle mixtures are widely used to study the structure of soluble as well as membrane embedded proteins using NMR. In this work, we report on the low temperature phase of the DMPC and DHPC bicelle mixture, where there is agreement on the discoid structures but where molecular packing models are still being contested. The most widely accepted packing arrangement, first proposed by Vold and Prosser had the lipids completely segregated in the disk: DHPC in the rim and DMPC in the disk. Using data from small angle neutron scattering (SANS) experiments, we show how radius of the planar domain of the disks is governed by the effective molar ratio qeff of lipids in aggregate and not the molar ratio q (q = [DMPC]/[DHPC] ) as has been understood previously. We propose a new quantitative (packing) model and show that in this self assembly scheme, qeff is the real determinant of disk sizes. Based on qeff , a master equation can then scale the radii of disks from mixtures with varying q and total lipid concentration.

  14. The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma.

    Science.gov (United States)

    Renga, Barbara; Francisci, Daniela; Carino, Adriana; Marchianò, Silvia; Cipriani, Sabrina; Chiara Monti, Maria; Del Sordo, Rachele; Schiaroli, Elisabetta; Distrutti, Eleonora; Baldelli, Franco; Fiorucci, Stefano

    2015-10-15

    Liver disease is the second most common cause of mortality in HIV-infected persons. Exactly how HIV infection per se affects liver disease progression is unknown. Here we have investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in HepG2 cells upon stimulation with the HIV matrix protein p17. This viral protein regulated mRNA expression of some NRs among which LXRα and its transcriptional co-activator MED1 were highly induced at mRNA level. Dissection of p17 downstream intracellular pathway demonstrated that p17 mediated activation of Jak/STAT signaling is responsible for the promoter dependent activation of LXR. The treatment of both HepG2 as well as primary hepatocytes with HIV p17 results in the transcriptional activation of LXR target genes (SREBP1c and FAS) and lipid accumulation. These effects are lost in HepG2 cells pre-incubated with a serum from HIV positive person who underwent a vaccination with a p17 peptide as well as in HepG2 cells pre-incubated with the natural LXR antagonist gymnestrogenin. These results suggest that HIV p17 affects NRs and their related signal transduction thus contributing to the progression of liver disease in HIV infected patients.

  15. Methamphetamine absorption by skin lipids: accumulated mass, partition coefficients, and the influence of fatty acids.

    Science.gov (United States)

    Parker, K; Morrison, G

    2016-08-01

    Occupants of former methamphetamine laboratories, often residences, may experience increased exposure through the accumulation of the methamphetamine in the organic films that coat skin and indoor surfaces. The objectives of this study were to determine equilibrium partition coefficients of vapor-phase methamphetamine with artificial sebum (AS-1), artificial sebum without fatty acids (AS-2), and real skin surface films, herein called skin oils. Sebum and skin oil-coated filters were exposed to vapor-phase methamphetamine at concentrations ranging from 8 to 159 ppb, and samples were analyzed for exposure time periods from 2 h to 60 days. For a low vapor-phase methamphetamine concentration range of ~8-22 ppb, the equilibrium partition coefficient for AS-1 was 1500 ± 195 μg/g/ppb. For a high concentration range of 98-112 ppb, the partition coefficient was lower, 459 ± 80 μg/g/ppb, suggesting saturation of the available absorption capacity. The low partition coefficient for AS-2 (33 ± 6 μg/g/ppb) suggests that the fatty acids in AS-1 and skin oil are responsible for much high partition coefficients. We predict that the methamphetamine concentration in skin lipids coating indoor surfaces can exceed recommended surface remediation standards even for air concentrations well below 1 ppb.

  16. Absence of cardiac lipid accumulation in transgenic mice with heart-specific HSL overexpression.

    Science.gov (United States)

    Suzuki, J; Shen, W J; Nelson, B D; Patel, S; Veerkamp, J H; Selwood, S P; Murphy, G M; Reaven, E; Kraemer, F B

    2001-10-01

    Hormone-sensitive lipase (HSL) hydrolyzes triglyceride (TG) in adipose tissue. HSL is also expressed in heart. To explore the actions of cardiac HSL, heart-specific, tetracycline (Tc)-controlled HSL-overexpressing mice were generated. Tc-responsive element-HSL transgenic (Tg) mice were generated and crossed with myosin heavy chain (MHC)alpha-tTA Tg mice, which express the Tc-responsive transactivator (tTA) in the heart. The double-Tg mice (MHC-HSL) were maintained with doxycycline (Dox) to suppress Tg HSL. Upon removal of Dox, cardiac HSL activity and protein increased 12- and 8-fold, respectively, and the expression was heart specific. Although cardiac TG content increased twofold in control mice after an overnight fast, it did not increase in HSL-induced mice. Electron microscopy showed numerous lipid droplets in the myocardium of fasted control mice, whereas fasted HSL-induced mice showed virtually no droplets. Microarray analysis showed altered expression of cardiac genes for fatty acid oxidation, transcription factors, signaling molecules, cytoskeletal proteins, and histocompatibility antigens in HSL-induced mice. Thus cardiac HSL plays a role in controlling accumulation of triglyceride droplets and can affect the expression of a number of cardiac genes.

  17. Small Molecule-Induced Complement Factor D (Adipsin) Promotes Lipid Accumulation and Adipocyte Differentiation.

    Science.gov (United States)

    Song, No-Joon; Kim, Suji; Jang, Byung-Hyun; Chang, Seo-Hyuk; Yun, Ui Jeong; Park, Ki-Moon; Waki, Hironori; Li, Dean Y; Tontonoz, Peter; Park, Kye Won

    2016-01-01

    Adipocytes are differentiated by various transcriptional cascades integrated on the master regulator, Pparγ. To discover new genes involved in adipocyte differentiation, preadipocytes were treated with three newly identified pro-adipogenic small molecules and GW7845 (a Pparγ agonist) for 24 hours and transcriptional profiling was analyzed. Four genes, Peroxisome proliferator-activated receptor γ (Pparγ), human complement factor D homolog (Cfd), Chemokine (C-C motif) ligand 9 (Ccl9), and GIPC PDZ Domain Containing Family Member 2 (Gipc2) were induced by at least two different small molecules but not by GW7845. Cfd and Ccl9 expressions were specific to adipocytes and they were altered in obese mice. Small hairpin RNA (shRNA) mediated knockdown of Cfd in preadipocytes inhibited lipid accumulation and expression of adipocyte markers during adipocyte differentiation. Overexpression of Cfd promoted adipocyte differentiation, increased C3a production, and led to induction of C3a receptor (C3aR) target gene expression. Similarly, treatments with C3a or C3aR agonist (C4494) also promoted adipogenesis. C3aR knockdown suppressed adipogenesis and impaired the pro-adipogenic effects of Cfd, further suggesting the necessity for C3aR signaling in Cfd-mediated pro-adipogenic axis. Together, these data show the action of Cfd in adipogenesis and underscore the application of small molecules to identify genes in adipocytes.

  18. Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood.

    Science.gov (United States)

    Baars, Annemarie; Oosting, Annemarie; Engels, Eefje; Kegler, Diane; Kodde, Andrea; Schipper, Lidewij; Verkade, Henkjan J; van der Beek, Eline M

    2016-06-01

    Epidemiological studies have demonstrated protective effects of breast-feeding on childhood obesity. Differences between human milk and infant milk formula (IMF) in dietary lipid structure may contribute to this effect. In our mouse model, feeding a diet containing large lipid droplets coated with phospholipids (PL) (Nuturis®; PL of milk fat globule membrane (MFGM) fraction origin) in early life protected against excessive body fat accumulation following a diet challenge in adult life. We now set out to determine the relevance of increased droplet size and/or MFGM lipid droplet coating to the observed anti-obesogenic effects in adult life. From day 16 to 42, male mouse pups were exposed to diets with small (S) or large (L) lipid droplets (0·3 v. 2·9 µm average mode diameter, respectively), either without MFGM or with MFGM coating around the lipid droplet, resulting in four groups: S (control diet), L, Scoating and Lcoating (Nuturis® IMF diet). Mice were subsequently challenged with a Western-style diet until dissection at postnatal day 98. A non-challenged group served as reference (REF). We repeatedly determined body composition between postnatal day 42 and 98. At day 98 plasma and gene expression measurements were performed. Only the Nuturis® IMF diet (Lcoating) in early life containing MFGM-coated large lipid droplets reduced body fat mass to a level comparable with the REF group. These data support the notion that the structural aspects of lipids in human milk, for example, both lipid droplet size as well as the MFGM coating, may contribute to its reported protective effect against obesity in later life.

  19. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  20. Heterotrophic growth and lipid accumulation of Chlorella protothecoides in whey permeate, a dairy by-product stream, for biofuel production.

    Science.gov (United States)

    Espinosa-Gonzalez, Isabel; Parashar, Archana; Bressler, David C

    2014-03-01

    This study proposes a novel alternative for the utilization of whey permeate, a by-product stream from the dairy industry, as the feedstock for the biomass and lipid production of the microalgae Chlorella protothecoides. Glucose and galactose from the pre-hydrolyzed whey permeate were used as main carbon sources in a base mineral media for establishing batch and fed batch cultures. Batch cultures reached a biomass production of 9.1±0.2g/L with a total lipid accumulation of 42.0±6.6% (dry weight basis), while in the fed batch cultures 17.2±1.3g/L of biomass with 20.5±0.3% lipid accumulation (dry weight basis) were obtained. A third strategy for the direct utilization of whey permeate was investigated by simultaneous saccharification and fermentation (SSF), wherein, 7.3±1.3g/L of biomass with 49.9±3.3% lipid accumulation (dry weight basis) was obtained in batch mode using immobilized enzyme. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Effects of Trophic Modes, Carbon Sources, and Salinity on the Cell Growth and Lipid Accumulation of Tropic Ocean Oilgae Strain Desmodesmus sp. WC08.

    Science.gov (United States)

    Zhao, Zhenyu; Ma, Shasha; Li, Ang; Liu, Pinghuai; Wang, Meng

    2016-10-01

    The effects of trophic modes, carbon sources, and salinity on the growth and lipid accumulation of a marine oilgae Desmodesmus sp. WC08 in different trophic cultures were assayed by single factor experiment based on the blue-green algae medium (BG-11). The results implied that biomass and lipid accumulation culture process were optimized depending on the tophic modes, sorts, and concentration of carbon sources and salinity in the cultivation. There was no significant difference in growth or lipid accumulation with Na2CO3 amendment or NaHCO3 amendment. However, Na2CO3 amendment did enhance the biomass and lipid accumulation to some extent. The highest Desmodesmus sp. WC08 biomass and lipid accumulation was achieved in the growth medium with photoautotrophic cultivation, 0.08 g L(-1) Na2CO3 amendment and 15 g L(-1) sea salt, respectively.

  2. Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood.

    Science.gov (United States)

    Oosting, Annemarie; Kegler, Diane; Wopereis, Harm J; Teller, Inga C; van de Heijning, Bert J M; Verkade, Henkjan J; van der Beek, Eline M

    2012-10-01

    In addition to contemporary lifestyle factors that contribute to the increased obesity prevalence worldwide, early nutrition is associated with sustained effects on later life obesity. We hypothesized that physical properties of dietary lipids contribute to this nutritional programming. We developed a concept infant formula (IMF) with large, phospholipid-coated lipid droplets (Nuturis; Danone Research, Paris, France) and investigated its programming effect on metabolic phenotype later in life. Male C57Bl/6j mice were fed a control formula (Control IMF) or Nuturis (Concept IMF) diet between postnatal day (PN)16 and PN42. All mice were subsequently fed a Western-style diet (WSD) until PN126. Body composition was monitored repeatedly by dual-energy X-ray absorptiometry between PN42 and PN126. Concept IMF slightly increased lean body mass as compared with Control IMF at PN42 but did not affect fat mass. Upon 84 d of WSD feeding, the Concept IMF group showed reduced fat accumulation as compared with Control IMF. In addition, fasting plasma leptin, resistin, glucose, and lipids were significantly lower in the Concept IMF group. Large phospholipid-coated lipid droplets in young mice reduced fat accumulation and improved metabolic profile in adulthood. These data emphasize that physical properties of early dietary lipids contribute to metabolic programming.

  3. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.

    Science.gov (United States)

    Erb, Samuel J; Schappi, Jeffrey M; Rasenick, Mark M

    2016-09-16

    Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics.

  4. Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation.

    Science.gov (United States)

    Lee, Hui-Young; Lee, Jae Sung; Alves, Tiago; Ladiges, Warren; Rabinovitch, Peter S; Jurczak, Michael J; Choi, Cheol Soo; Shulman, Gerald I; Samuel, Varman T

    2017-08-01

    We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute infusion of a lipid emulsion. RC-fed MCAT mice were similar to littermate wild-type (WT) mice. However, HFD-fed MCAT mice were protected from diet-induced insulin resistance. In contrast, an acute lipid infusion caused muscle insulin resistance in both MCAT and WT mice. ROS production was decreased in both HFD-fed and lipid-infused MCAT mice and cannot explain the divergent response in insulin action. MCAT mice had subtly increased energy expenditure and muscle fat oxidation with decreased intramuscular diacylglycerol (DAG) accumulation, protein kinase C-θ (PKCθ) activation, and impaired insulin signaling with HFD. In contrast, the insulin resistance with the acute lipid infusion was associated with increased muscle DAG content in both WT and MCAT mice. These studies suggest that altering muscle mitochondrial ROS production does not directly alter the development of lipid-induced insulin resistance. However, the altered energy balance in HFD-fed MCAT mice protected them from DAG accumulation, PKCθ activation, and impaired muscle insulin signaling. © 2017 by the American Diabetes Association.

  5. Accumulation of Oxidized Low-Density Lipoprotein in Psoriatic Skin and Changes of Plasma Lipid Levels in Psoriatic Patients

    Directory of Open Access Journals (Sweden)

    Nilgun Solak Tekin

    2007-01-01

    Full Text Available Background. Psoriasis is a chronic inflammatory skin disease characterized by an accelerated turnover of epidermal cells and an incomplete differentiation in epidermis with lesion. However, the exact etiology of psoriasis is unknown. Abnormalities in essential fatty acid metabolism, free radical generation, lipid peroxidation, and release of lymphokines have been proposed. Objective. Our purpose was to evaluate the plasma lipids and oxidized low-density lipoprotein accumulation in psoriatic skin lesion in order to ascertain the possible participation of oxidative stress and oxidative modification of lipids in pathogenesis of psoriasis. Methods. The study group included 84 patients with psoriasis, and 40 sex- and age-matched healthy volunteers. Blood lipid profile was determined. Psoriatic and nonlesional skin samples of psoriatic patients were evaluated for the presence of oxidized low-density lipoprotein by using an immune-fluorescent staining method. Results. The mean levels of lipids (total cholesterol, triglyceride, and LDL cholesterol in patients with psoriasis were found to be significantly higher than those of healthy subjects. Psoriatic skins were shown positive oxidized low-density lipoprotein staining. There was no staining in nonlesional skin samples of the same individuals. Conclusion. Lipid peroxidation mediated by free radicals is believed to be one of the important causes of cell membrane destruction and cell damage. This study shows for the first time the accumulation of oxidized low-density lipoprotein in psoriatic skin lesion. We believe that accumulation of ox-LDL in psoriatic skin may have an important role in the immune-inflammatory events that result in progressive skin damage.

  6. Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice.

    Science.gov (United States)

    Zhang, Xiaoyu; Qin, Juliang; Zhao, Yihan; Shi, Jueping; Lan, Rong; Gan, Yunqiu; Ren, Hua; Zhu, Bing; Qian, Min; Du, Bing

    2016-04-01

    The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated glucose and insulin tolerance in KD-fed diabetic mice was found, although the body weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of adipose tissue in KD mice was greater than in the other groups. The KD diet resulted in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover, the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed significant changes in several key genes such as sterol regulatory element-binding protein, fibroblast growth factor 21, and peroxisome proliferator-activated receptor α, which are all important in metabolism. In summary, KD ameliorates glucose and insulin tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and hepatic steatosis were observed, which should be considered carefully in the long-term application of KD.

  7. Muscle-specific deletion of signal transducer and activator of transcription 5 augments lipid accumulation in skeletal muscle and liver of mice in response to high-fat diet.

    Science.gov (United States)

    Baik, Myunggi; Lee, Mi Sun; Kang, Hyeok Joong; Park, Seung Ju; Piao, Min Yu; Nguyen, Trang Hoa; Hennighausen, Lothar

    2017-03-01

    Growth hormone (GH) controls liver metabolism through the transcription factor signal transducer and activator of transcription 5 (STAT5). However, it remains to be fully understood to what extent other GH/STAT5 target tissues contribute to lipid and glucose metabolism. This question was now addressed in muscle-specific STAT5 knockout (STAT5 MKO) mice model. Changes in lipid and glucose metabolism were investigated at physiological and molecular levels in muscle and liver tissues of STAT5 MKO mice under normal diet or high-fat diet (HFD) conditions. STAT5 MKO mice exhibited an increased intramyocellular lipid (IMCL) accumulation in the quadriceps in HFD group. Decreased lipolytic hormone-sensitive lipase transcript levels may contribute to the increased IMCL accumulation in STAT5 MKO mice. STAT5 MKO induced hepatic lipid accumulation without deregulated STAT5 signaling. The upregulation of lipoprotein lipase and Cd36 mRNA levels, an increased trend of very low-density lipoprotein receptor mRNA levels, and elevated circulating concentrations of free fatty acid, triglyceride, and total cholesterol support the increase in hepatic lipid accumulation. STAT5 MKO in conjunction with a HFD deregulated both lipid and glucose metabolism in skeletal muscle, and this deregulation induced hepatic fat accumulation via increased circulating glucose, FFA, and TG concentrations. Our study emphasizes that muscle-specific STAT5 signaling is important for balancing lipid and glucose metabolism in peripheral tissues, including muscle and liver and that the deregulation of local STAT5 signaling augments HFD-induced lipid accumulation in both muscle and liver.

  8. Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells

    DEFF Research Database (Denmark)

    Pasarica, Magdalena; Mashtalir, Nazar; McAllister, Emily J

    2008-01-01

    , the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly...... and the accumulation of its extracellular fraction. hASC from subjects harboring Ad-36 DNA in their adipose tissue due to natural infection had significantly greater ability to differentiate compared with Ad-36 DNA-negative counterparts, which offers a proof of concept. Thus, Ad-36 has the potential to induce...

  9. Multiscale Modeling of Supported Lipid Bilayers

    Science.gov (United States)

    Hoopes, Matthew I.; Xing, Chenyue; Faller, Roland

    Cell membranes consist of a multitude of lipid molecules that serve as a framework for the even greater variety of membrane associated proteins [1-4]. As this highly complex (nonequilibrium) system cannot easily be understood and studied in a controlled way, a wide variety of model systems have been devised to understand the dynamics, structure, and thermodynamics in biological membranes. One such model system is a supported lipid bilayer (SLB), a two-dimensional membrane suspended on a surface. SLBs have been realized to be manageable experimentally while reproducing many of the key features of real biological membranes [5,6]. One of the main advantages of supported bilayers is the physical stability due to the solid support that enables a wide range of surface characterization techniques not available to free or unsupported membranes. As SLBs maintain some of the crucial structural and dynamic properties of biological membranes, they provide an important bridge to natural systems. In order to mimic cell membranes reliably, certain structural and dynamic features have to be reliably reproduced in the artificially constructed lipid bilayers. SLBs should display lateral mobility as in living cells, because many membrane activities involve transport, recruitment, or assembly of specific components. It is also critical for membranes to exhibit the correct thermodynamic phase, namely, a fluid lipid bilayer, to respond to environmental stress such as temperature and pressure changes [7]. There are several ways to fabricate supported lipid bilayers (SLBs) on planar substrates. One can use vesicle fusion on solid substrates [5,8-10] as well as Langmuir-Blodgett deposition [11,12]. Proteoliposome adsorption and subsequent membrane formation on a mica surface was first demonstrated by Brian and McConnell [13]. Because of its simplicity and reproducibility, this is one of the most common approaches to prepare supported membranes. A diverse range of different solid substrates

  10. Suppressive effects of the flavonoids quercetin and luteolin on the accumulation of lipid rafts after signal transduction via receptors.

    Science.gov (United States)

    Kaneko, Masahiro; Takimoto, Hiroaki; Sugiyama, Tsuyoshi; Seki, Yoko; Kawaguchi, Kiichiro; Kumazawa, Yoshio

    2008-01-01

    Quercetin (QUER) and luteolin (LUTE) are dietary flavonoids capable of regulating the production of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). However, their mechanisms of action are not fully understood. In lipopolysaccharide-triggered (LPS)-triggered signaling via Toll-like receptor 4 (TLR4), QUER and LUTE suppresses not only the degradation of the inhibitor of kappaB (IkappaB), with resultant activation of nuclear factor-kappaB (NF-kappaB), but also the phosphorylation of p38 and Akt in bone marrow-derived macrophages that have been stimulated with LPS. We report here that, in TNF-alpha-induced signaling, QUER and LUTE significantly suppressed the production of IL-6 and activation of NF-kappaB. Accumulation of lipid rafts, the initial step in the signaling pathway, was significantly inhibited when macrophages were treated with QUER or with LUTE prior to exposure to LPS. Similarly, the accumulation of lipid rafts was inhibited by the flavonoids when B cells were activated via the membrane IgM and when T cells were activated via CD3. In contrast, QUER and LUTE did not inhibit the activation of phorbol myristate acetate-induced NF-kappaB in macrophages. Our observations suggest that QUER and LUTE interact with receptors on the cell surface and suppress the accumulation of lipid rafts that occurs downstream of the activation of the receptors.

  11. Reduction of lipid accumulation in white adipose tissues by Cassia tora (Leguminosae) seed extract is associated with AMPK activation.

    Science.gov (United States)

    Tzeng, Thing-Fong; Lu, Hung-Jen; Liou, Shorong-Shii; Chang, Chia Ju; Liu, I-Min

    2013-01-15

    Natural herbal medications may be one answer to the worldwide epidemic of obesity. This study examines the effects of Cassia seed ethanol extract (CSEE) upon lipid accumulation in white adipose tissue (WAT). CSEE exhibited a significant concentration-dependent decrease in the intracellular accumulation of trigycerides in 3T3-L1 adipocytes. After being fed a high-fat diet (HFD) for 2 weeks, rats were fed CSEE (100, 200 or 300 mg/kg) once daily for 8 weeks. CSEE caused dose-related reductions in body weight gain (as well as plasma lipid levels and epididymal WAT sizes in HFD-fed rats). CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element-binding protein 1 and fatty acid synthase protein levels in epididymal WAT of HFD-fed rats. CSEE could attenuate lipid accumulation in WAT via AMPK signaling pathway activation.

  12. Loss of L-FABP, SCP-2/SCP-x, or both induces hepatic lipid accumulation in female mice.

    Science.gov (United States)

    Martin, Gregory G; Atshaves, Barbara P; Landrock, Kerstin K; Landrock, Danilo; Schroeder, Friedhelm; Kier, Ann B

    2015-08-15

    Although roles for both sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) and liver fatty acid binding protein (L-FABP) have been proposed in hepatic lipid accumulation, individually ablating these genes has been complicated by concomitant alterations in the other gene product(s). For example, ablating SCP2/SCP-x induces upregulation of L-FABP in female mice. Therefore, the impact of ablating SCP-2/SCP-x (DKO) or L-FABP (LKO) individually or both together (TKO) was examined in female mice. Loss of SCP-2/SCP-x (DKO, TKO) more so than loss of L-FABP alone (LKO) increased hepatic total lipid and total cholesterol content, especially cholesteryl ester. Hepatic accumulation of nonesterified long chain fatty acids (LCFA) and phospholipids occurred only in DKO and TKO mice. Loss of SCP-2/SCP-x (DKO, TKO) increased serum total lipid primarily by increasing triglycerides. Altered hepatic level of proteins involved in cholesterol uptake, efflux, and/or secretion was observed, but did not compensate for the loss of L-FABP, SCP-2/SCP-x or both. However, synergistic responses were not seen with the combinatorial knock out animals-suggesting that inhibiting SCP-2/SCP-x is more correlative with hepatic dysfunction than L-FABP. The DKO- and TKO-induced hepatic accumulation of cholesterol and long chain fatty acids shared significant phenotypic similarities with non-alcoholic fatty liver disease (NAFLD).

  13. Fatty Acid Transport Protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity

    Science.gov (United States)

    Saini, Nipun; Black, Paul N.; Montefusco, David; DiRusso, Concetta C.

    2015-01-01

    The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC50 8–11μM) and prevented palmitate-mediated lipid accumulation and cell death in cell lines that are models for intestines, liver, muscle and pancreas. In adipocytes, uptake inhibition was less effective (IC50 58μM). Inhibition was specific for long chain fatty acids and was ineffective toward medium chain fatty acids, which are transported by diffusion. Kinetic analysis of Grassofermata-dependent FA transport inhibition verified a non-competitive mechanism. By comparison with Grassofermata, several atypical antipsychotic drugs previously implicated as inhibitors of FA uptake were ineffectual. In mice Grassofermata decreased absorption of 13C-oleate demonstrating its potential as a therapeutic agent. PMID:26284975

  14. Physiological and molecular analysis of carbon source supplementation and pH stress-induced lipid accumulation in the marine diatom Phaeodactylum tricornutum.

    Science.gov (United States)

    Mus, Florence; Toussaint, Jean-Paul; Cooksey, Keith E; Fields, Matthew W; Gerlach, Robin; Peyton, Brent M; Carlson, Ross P

    2013-04-01

    A detailed physiological and molecular analysis of lipid accumulation under a suite of conditions including nitrogen limitation, alkaline pH stress, bicarbonate supplementation, and organic acid supplementation was performed on the marine diatom Phaeodactylum tricornutum. For all tested conditions, nitrogen limitation was a prerequisite for lipid accumulation and the other culturing strategies only enhanced accumulation highlighting the importance of compounded stresses on lipid metabolism. Volumetric lipid levels varied depending on condition; the observed rankings from highest to lowest were for inorganic carbon addition (15 mM bicarbonate), organic acid addition (15 carbon mM acetate), and alkaline pH stress (pH 9.0). For all lipid-accumulating cultures except acetate supplementation, a common series of physiological steps were observed. Upon extracellular nitrogen exhaustion, culture growth continued for approximately 1.5 cell doublings with decreases in specific protein and photosynthetic pigment content. As nitrogen limitation arrested cell growth, carbohydrate content decreased with a corresponding increase in lipid content. Addition of the organic carbon source acetate appeared to activate alternative metabolic pathways for lipid accumulation. Molecular level data on more than 50 central metabolism transcripts were measured using real-time PCR. Analysis of transcripts suggested the central metabolism pathways associated with bicarbonate transport, carbonic anhydrases, and C4 carbon fixations were important for lipid accumulation. Transcriptomic data also suggested that repurposing of phospholipids may play a role in lipid accumulation. This study provides a detailed physiological and molecular-level foundation for improved understanding of diatom nutrient cycling and contributes to a metabolic blueprint for controlling lipid accumulation in diatoms.

  15. Maternal Diabetes Leads to Unphysiological High Lipid Accumulation in Rabbit Preimplantation Embryos

    NARCIS (Netherlands)

    Schindler, Maria; Pendzialek, Mareike; Santos, Alexander Navarrete; Ploesch, Torsten; Seyring, Stefanie; Guerke, Jacqueline; Haucke, Elisa; Knelangen, Julia Miriam; Fischer, Bernd; Santos, Anne Navarrete

    2014-01-01

    According to the "developmental origin of health and disease" hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation devel

  16. Maternal Diabetes Leads to Unphysiological High Lipid Accumulation in Rabbit Preimplantation Embryos

    NARCIS (Netherlands)

    Schindler, Maria; Pendzialek, Mareike; Santos, Alexander Navarrete; Ploesch, Torsten; Seyring, Stefanie; Guerke, Jacqueline; Haucke, Elisa; Knelangen, Julia Miriam; Fischer, Bernd; Santos, Anne Navarrete

    According to the "developmental origin of health and disease" hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation

  17. Role of salt inducible kinase 1 in high glucose-induced lipid accumulation in HepG2 cells and metformin intervention.

    Science.gov (United States)

    Zhang, Yue; Takemori, Hiroshi; Wang, Chang; Fu, JiaHui; Xu, MingWang; Xiong, Liang; Li, NingXu; Wen, XiuYing

    2017-03-15

    To investigate the roles of salt inducible kinase (SIK1) in high glucose-induced triglyceride accumulation in human hepatoma HepG2 cells as well as in the molecular mechanism by which metformin, a drug to treat diabetes, suppresses high glucose-induced lipogenesis. A cell model for high glucose-induced hepatic steatosis was prepared by exposing HepG2 cells to high glucose (25mmol) in the absence or presence of metformin (0.5mmol). Intracellular triglycerides were visualized by Oil Red O and measured using a triglyceride assay kit. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. SIK1 overexpression in HepG2 cells was achieved by transient transfection, and the mRNA and protein levels of SIK1 and lipogenic factors were measured using a reverse transcription-polymerase chain reaction and western blotting, respectively. Lipid accumulation in HepG2 cells was obvious after treatment with high glucose for 24h. In response to high glucose, SIK1 expression was negatively correlated with that of lipogenic factors and lipid accumulation in HepG2 cells. We observed that overexpression of SIK1, or treatment with metformin, suppressed lipogenesis, even in high glucose conditions. Furthermore, treatment with metformin upregulated SIK1 mRNA and protein levels, as well as the active form of SIK1. SIK1 plays a vital role in high glucose-induced lipid accumulation, and metformin suppresses lipogenesis via the induction and activation of SIK1. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jung Hwan [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Lee, Yoo Jeong [Division of Metabolic Disease, Center for Biomedical Sciences, National Institutes of Health, Cheongwon-gun, Chungbuk 363-951 (Korea, Republic of); Kim, Hyo Jung; Choi, Hyeonjin [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Choi, Yoonjeong; Seok, Jo Woon [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Kim, Jae-woo, E-mail: japol13@yuhs.ac [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2015-05-08

    Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans. - Highlights: • PPARγ promotes MGAT1 expression in human primary hepatocytes. • PPARγ directly regulates MGAT1 promoter activity. • Human MGAT1 promoter has at least two PPARγ-binding elements. • Inhibition of MGAT1 expression attenuates hepatic lipid accumulation in humans.

  19. Proteomics analysis for enhanced lipid accumulation in oleaginous Chlorella vulgaris under a heterotrophic-Na⁺ induction two-step regime.

    Science.gov (United States)

    Li, Yuqin; Mu, Jinxiu; Chen, Di; Xu, Hua; Han, Fangxin; Feng, Bo; Zeng, Hongyan

    2015-05-01

    A heterotrophic-Na(+) induction (HNI) two-step regime was developed to enhance lipid accumulation in oleaginous Chlorella vulgaris. C. vulgaris was cultivated heterotrophically to a biomass of 7.8 g l(-1) in 120 h. The cells were re-suspended in fresh media supplemented with 0.5 M NaCl followed by 12 h growth to accumulate lipid to 53.4 % (w/w). The lipid productivity (625 mg l(-1) day(-1)) achieved with HNI was better than that using heterotrophy alone (405 mg l(-1) day(-1)). To promote possible applications of HNI strategy in other microalgal species, the lipid triggers and potential molecular pathways associated with lipid biosynthesis were investigated. Malic enzyme and acyl-CoA-binding protein were key metabolic checkpoints found to modulate lipid biosynthesis in cells. These results provide the foundation to develop high-lipid engineering miroalgae for industrialization of biodiesel.

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

    Energy Technology Data Exchange (ETDEWEB)

    Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

    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) 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

  1. Lipid accumulation in overweight type 2 diabetic subjects: relationships with insulin sensitivity and adipokines.

    Science.gov (United States)

    Sambataro, Maria; Perseghin, Gianluca; Lattuada, Guido; Beltramello, Giampietro; Luzi, Livio; Pacini, Giovanni

    2013-06-01

    Adipokines are known to play a fundamental role in the etiology of obesity, that is, in the impaired balance between increased feeding and decreased energy expenditure. While the adipokine-induced changes of insulin resistance in obese diabetic and nondiabetic subjects are well known, the possible role of fat source in modulating insulin sensitivity (IS) remains controversial. The aim of our study was to explore in overweight type 2 diabetic patients (T2DM) with metabolic syndrome IS in different energy storage conditions (basal and dynamic) for relating it to leptin and adiponectin. Sixteen T2DM (5/11 F/M; 59 ± 2 years; 29.5 ± 1.1 kg/m(2)) and 16 control (CNT 5/11; 54 ± 2; 29.1 ± 1.0) underwent an oral glucose tolerance test. Fasting IS was measured by QUICKI, while the dynamic one with OGIS. The insulinogenic index (IGI) described beta cell function. Also, the lipid accumulation product parameter (LAP) was assessed. LAP accounts for visceral abdominal fat and triglycerides, and it is known to be related to IS. Possible interrelationships between LAP and adipokines were explored. In T2DM and CNT, adiponectin (7.4 ± 0.5 vs. 7.8 ± 0.9 μg/mL), leptin (13.3 ± 3.0 vs. 12.4 ± 2.6 ng/mL), and QUICKI (0.33 ± 0.01 vs. 0.33 ± 0.01) were not different (P > 0.40), at variance with OGIS (317 ± 11 vs. 406 ± 13 mL/min/m(2); P = 0.006) and IGI (0.029 ± 0.005 vs. 0.185 ± 0.029 × 10(3) pmolI/mmolG; P = 0.00001). LAP was 85 ± 15 cm × mg/dL in T2DM and 74 ± 10 in CNT (P > 0.1), correlated with OGIS in all subjects (R = -0.42, P = 0.02) and QUICKI (R = -0.56, P = 0.025) in T2DM. Leptin correlated with QUICKI (R = -0.45, P = 0.009), and adiponectin correlated with OGIS (R = 0.43, P = 0.015). In overweight T2DM, insulin sensitivity in basal condition appears to be multifaceted with respect to the dynamic one, because it should be more fat-related. Insulin sensitivity appears to be incompletely described by functions of fasting glucose and insulin values alone and the

  2. An accumulator model of semantic interference

    NARCIS (Netherlands)

    van Maanen, Leendert; van Rijn, Hedderik

    2007-01-01

    To explain latency effects in picture-word interference tasks, cognitive models need to account for both interference and stimulus onset asynchrony (SOA) effects. As opposed to most models of picture-word interference, which model the time course during the task in a ballistic manner, the RACE model

  3. Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract.

    Science.gov (United States)

    Müller, C; Gardemann, A; Keilhoff, G; Peter, D; Wiswedel, I; Schild, L

    2012-03-15

    Hepatocytes of a primary cell culture that are exposed to high glucose, insulin, and linoleic (LA) acid concentration respond with lipid accumulation, oxidative stress up to cell death. Such alterations are typically found in patients with non-alcoholic fatty liver disease (NAFLD). We used this cellular model to study the effect of an ethanolic Gynostemma pentaphyllum (GP) extract in NAFLD. When hepatocytes were cultured in the presence of high insulin, glucose, and LA concentration the extract completely protected the cells from cell death. In parallel, the extract prevented accumulation of triglycerides (TGs) and cholesterol as well as oxidative stress. Our data further demonstrate that GP stimulates the production of nitric oxide (NO) in hepatocytes and affects the molecular composition of the mitochondrial phospholipid cardiolipin (CL). We conclude that GP is able to protect hepatocytes from cell death, lipid accumulation, and oxidative stress caused by diabetic-like metabolism and lipotoxicity. Therefore, GP could be beneficial for patients with diabetes mellitus and NAFLD. Copyright © 2012 Elsevier GmbH. All rights reserved.

  4. Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation.

    Science.gov (United States)

    Yu, Jung Hwan; Lee, Yoo Jeong; Kim, Hyo Jung; Choi, Hyeonjin; Choi, Yoonjeong; Seok, Jo Woon; Kim, Jae-woo

    2015-05-08

    Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans.

  5. Swertiamarin ameliorates oleic acid induced lipid accumulation and oxidative stress by attenuating gluconeogenesis and lipogenesis in hepatic steatosis.

    Science.gov (United States)

    Patel, Tushar P; Rawal, Komal; Soni, Sanket; Gupta, Sarita

    2016-10-01

    Swertiamarin, a bitter secoiridoid glycoside, is an antidiabetic drug with lipid lowering activity meliorates insulin resistance in Type 2 Diabetes condition. Therefore, the study was designed to explore the antioxidant and hypolipidemic activity of swertiamarin in ameliorating NAFLD caused due to hepatic lipid accumulation, inflammation and insulin resistance. Steatosis was induced in HepG2 cells by supplementing 1mM oleic acid (OA) for 24h which was marked by significant accumulation of lipid droplets. This was determined by Oil Red O (ORO) staining and triglyceride accumulation. Swertiamarin (25μg/ml) decreased triglyceride content by 2 folds and effectively reduced LDH release (50%) activity by protecting membrane integrity thus, preventing apoptosis evidenced by reduced cleavage of Caspase 3 and PARP1. We observed that swertiamarin significantly increased the expressions of major insulin signaling proteins like Insulin receptor (IR), PI(3)K, pAkt with concomitant reduction in p307 IRS-1. AMPK was activated by swertiamarin action, thus restoring insulin sensitivity in hepatocytes. In addition, qPCR results confirmed OA up-regulated Sterol Regulatory Element Binding Protein (SREBP)-1c and fatty acid synthase (FAS), resulting in increased fatty acid synthesis. Swertiamarin effectively modulated PPAR-α, a major potential regulator of carbohydrate metabolism which, in turn, decreased the levels of the gluconeogenic enzyme PEPCK, further restricting hepatic glucose production and fatty acid synthesis. Cumulatively, swertiamarin targets potential metabolic regulators AMPK and PPAR-α, through which it regulates hepatic glycemic burden, fat accumulation, insulin resistance and ROS in hepatic steatosis which emphasizes clinical significance of swertiamarin in regulating metabolism and as a suitable candidate for treating NAFLD.

  6. Effect of nitrogen source on growth and lipid accumulation in Scenedesmus abundans and Chlorella ellipsoidea.

    Science.gov (United States)

    González-Garcinuño, Álvaro; Tabernero, Antonio; Sánchez-Álvarez, José Ma; Martin del Valle, Eva M; Galán, Miguel A

    2014-12-01

    Discovering microalgae strains containing a high lipid yield and adequate fatty acid composition is becoming a crucial fact in algae-oil factories. In this study, two unknown strains, named Scenedesmus abundans and Chlorella ellipsoidea, have been tested for their response to different nitrogen sources, in order to determine its influence in the production of lipids. For S. abundans, autotrophic culture with ammonium nitrate offers the maximum lipid yield, obtaining up to 3.55 mg L(-1) d(-1). For C. ellipsoidea, heterotrophic culture with ammonium nitrate has been shown to be the best condition, reaching a lipid production of 9.27 mg L(-1) d(-1). Moreover, fatty acid composition obtained from these cultures meets international biodiesel standards with an important amount of C18:1, achieving 70% of total fatty acids and thus representing a potential use of these two strains at an industrial scale.

  7. Improving cell growth and lipid accumulation in green microalgae Chlorella sp. via UV irradiation.

    Science.gov (United States)

    Liu, Shuyu; Zhao, Yueping; Liu, Li; Ao, Xiyong; Ma, Liyan; Wu, Minghong; Ma, Fang

    2015-04-01

    Microalgae with high biomass and high lipid content are the ideal feedstock for biodiesel production. To obtain such microalgae, ultraviolet (UV) irradiation was applied to Chlorella sp. to induce mutagenesis. The growth characteristics, total nitrogen (TN), and biochemical compositions of the control and UV mutation strains were analyzed. Compared to the control strain, the biomass for the UV mutation strain was 7.6 % higher and it presented a higher growth rate. The lipid content of the UV mutation strain showed different levels of increase and reached the maximum value of 28.1 % on day 15. Furthermore, the lipid productivity of the UV mutation strain showed a desired increase. The nitrogen consumption and Acetyl-CoA carboxylase (ACC) activity contributed to the lipid production by UV. All these results indicate that UV mutagenesis is an efficient method to improve probability for using Chlorella sp. as the potential raw material for biodiesel production.

  8. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  9. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  10. Accumulation of hydroxyl lipids and 4-hydroxy-2-hexenal in live fish infected with fish diseases.

    Science.gov (United States)

    Tanaka, Ryusuke; Shigeta, Kazuhiro; Sugiura, Yoshimasa; Hatate, Hideo; Matsushita, Teruo

    2014-04-01

    Hydroxy lipids (L-OH) and 4-hydroxy-2-hexenal (HHE) levels as well as other parameters such as lipid level, lipid class, fatty acid composition, and other aldehydes levels in the liver of diseased fish were investigated. Although significant differences in lipid level, lipid class, fatty acid composition, and other aldehyde levels were not always observed between normal and diseased fish, L-OH and HHE levels were significantly higher in the liver of the diseased fish than in that of the normal fish cultured with the same feeds under the same conditions. In the liver of puffer fish (Fugu rubripes) infected with Trichodina, L-OH and HHE levels significantly increased from 25.29±5.04 to 47.70 ± 5.27 nmol/mg lipid and from 299.79±25.25 to 1,184.40±60.27 nmol/g tissue, respectively. When the levels of HHE and other aldehydes in the liver of the normal and diseased puffer fish were plotted, a linear relationship with a high correlation coefficient was observed between HHE and propanal (r2=0.9447). Increased L-OH and HHE levels in the liver of the diseased fish and a high correlation between HHE and propanal in the liver of the normal and diseased fish were also observed in flat fish (Paralichthys olivaceus) infected with streptococcus, yellowtail (Seriola quinqueradiata) infected with jaundice, and amberjack (S. purpurascens) infected with Photobacterium damselae subsp. piscicida.

  11. Clusterin: full-length protein and one of its chains show opposing effects on cellular lipid accumulation

    Science.gov (United States)

    Matukumalli, Suvarsha Rao; Tangirala, Ramakrishna; Rao, C. M.

    2017-01-01

    Proteins, made up of either single or multiple chains, are designed to carry out specific biological functions. We found an interesting example of a two-chain protein where administration of one of its chains leads to a diametrically opposite outcome than that reported for the full-length protein. Clusterin is a highly glycosylated protein consisting of two chains, α- and β-clusterin. We have investigated the conformational features, cellular localization, lipid accumulation, in vivo effects and histological changes upon administration of recombinant individual chains of clusterin. We demonstrate that recombinant α- and β-chains exhibit structural and functional differences and differ in their sub-cellular localization. Full-length clusterin is known to lower lipid levels. In contrast, we find that β-chain-treated cells accumulate 2-fold more lipid than controls. Interestingly, α-chain-treated cells do not show such increase. Rabbits injected with β-chain, but not α-chain, show ~40% increase in weight, with adipocyte hypertrophy, liver and kidney steatosis. Many, sometimes contrasting, roles are ascribed to clusterin in obesity, metabolic syndrome and related conditions. Our findings of differential localization and activities of individual chains of clusterin should help in understanding better the roles of clusterin in metabolism. PMID:28120874

  12. β Common Receptor Mediates Erythropoietin-Conferred Protection on OxLDL-Induced Lipid Accumulation and Inflammation in Macrophages

    Directory of Open Access Journals (Sweden)

    Tzong-Shyuan Lee

    2015-01-01

    Full Text Available Erythropoietin (EPO, the key factor for erythropoiesis, also protects macrophage foam cells from lipid accumulation, yet the definitive mechanisms are not fully understood. β common receptor (βCR plays a crucial role in the nonhematopoietic effects of EPO. In the current study, we investigated the role of βCR in EPO-mediated protection in macrophages against oxidized low-density lipoprotein- (oxLDL- induced deregulation of lipid metabolism and inflammation. Here, we show that βCR expression was mainly in foamy macrophages of atherosclerotic aortas from apolipoprotein E-deficient mice. Results of confocal microscopy and immunoprecipitation analyses revealed that βCR was colocalized and interacted with EPO receptor (EPOR in macrophages. Inhibition of βCR activation by neutralizing antibody or small interfering RNA (siRNA abolished the EPO-conferred protection in oxLDL-induced lipid accumulation. Furthermore, EPO-promoted cholesterol efflux and upregulation of ATP-binding cassette (ABC transporters ABCA1 and ABCG1 were prevented by pretreatment with βCR neutralizing antibody or βCR siRNA. Additionally, blockage of βCR abrogated the EPO-conferred anti-inflammatory action on oxLDL-induced production of macrophage inflammatory protein-2. Collectively, our findings suggest that βCR may play an important role in the beneficial effects of EPO against oxLDL-elicited dysfunction of macrophage foam cells.

  13. Kinetic modeling of growth and lipid body induction in Chlorella pyrenoidosa under heterotrophic conditions.

    Science.gov (United States)

    Sachdeva, Neha; Kumar, G Dinesh; Gupta, Ravi Prakash; Mathur, Anshu Shankar; Manikandan, B; Basu, Biswajit; Tuli, Deepak Kumar

    2016-10-01

    The aim of the present work was to develop a mathematical model to describe the biomass and (total) lipid productivity of Chlorella pyrenoidosa NCIM 2738 under heterotrophic conditions. Biomass growth rate was predicted by Droop's cell quota model, while changes observed in cell quota (utilization) under carbon excess conditions were used for the modeling and predicting the lipid accumulation rate. The model was simulated under non-limiting (excess) carbon and limiting nitrate concentration and validated with experimental data for the culture grown in batch (flask) mode under different nitrate concentrations. The present model incorporated two modes (growth and stressed) for the prediction of endogenous lipid synthesis/induction and aimed to predict the effect and response of the microalgae under nutrient starvation (stressed) conditions. MATLAB and Genetic Algorithm were employed for the prediction and validation of the model parameters.

  14. Anthocyanins and phenolic acids from a wild blueberry (Vaccinium angustifolium) powder counteract lipid accumulation in THP-1-derived macrophages

    DEFF Research Database (Denmark)

    Del Bo', Cristian; Cao, Yi; Roursgaard, Martin

    2016-01-01

    PURPOSE: Blueberries are a rich source of anthocyanins (ACNs) and phenolic acids (PA), which are hypothesized to protect against development of atherosclerosis. The present study examined the effect of an ACN- and PA-rich fractions, obtained from a wild blueberry powder, on the capacity...... to counteract lipid accumulation in macrophages derived from monocytic THP-1 cells. In addition, we tested the capacity of pure ACNs and their metabolites to alter lipid accumulation. METHODS: THP-1-derived macrophages were incubated with fatty acids (500 μM oleic/palmitic acid, 2:1 ratio) and different...... concentrations (from 0.05 to 10 μg mL(-1)) of ACN- and PA-rich fractions, pure ACN standards (malvidin, delphinidin and cyanidin 3-glucoside), and metabolites (syringic, gallic and protocatechuic acids). Lipid accumulation was quantified with the fluorescent dye Nile red. RESULTS: Lipid accumulation was reduced...

  15. Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet.

    Science.gov (United States)

    Xu, Li; Huang, Danping; Hu, Qiaolin; Wu, Jing; Wang, Yizhen; Feng, Jie

    2015-06-28

    To assess the effects of betaine on hepatic lipid accumulation and investigate the underlying mechanism, thirty-two male Sprague-Dawley rats weighing 100 (sd 2·50) g were divided into four groups, and started on one of four treatments: basal diet, basal diet with betaine administration, high-fat diet and high-fat diet with betaine administration. The results showed that no significant difference of body weight was found among experimental groups. Compared with high-fat diet-fed rats, a betaine supplementation decreased (Pbetaine-homocysteine methyltransferase concentration [corrected] as well as its mRNA abundance and lecithin level were found increased (Pbetaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (Pbetaine administration in high-fat diet-fed rats elevated (Pbetaine administration in high-fat diet group; meanwhile the gene expression of hepatic AMP-activated protein kinase was increased (Pbetaine administration enhanced hepatic lipid export and fatty acid oxidation in high-fat diet-fed rats, thus effectively alleviating fat accumulation in the liver.

  16. Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis.

    Science.gov (United States)

    Janer, Gemma; Navarro, Juan Carlos; Porte, Cinta

    2007-09-01

    Recent studies have shown that organotin compounds affect lipid homeostasis in vertebrates, probably through interaction with RXR and/or PPARgamma receptors. Molluscs are sensitive species to the toxic effects of tributyltin (TBT), particularly to masculinization, and TBT has been recently shown to bind to molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes, the synthetic androgen methyl-testosterone (MT) was included in the study due to its masculinization effects, but its lack of binding to the RXR receptor. M. cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed increased percentage of lipids and increased levels of fatty acids in the digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles were altered in both males and females exposed to 125 and 500 ng/L TBT. These effects were not observed in females exposed to MT. Overall, this work suggest that TBT acts as a potent inducer of lipid and fatty acid accumulation in M. cornuarietis as shown in vertebrate studies earlier, and that sex differences in sensitivity do exist.

  17. Control of protozoa contamination and lipid accumulation in Neochloris oleoabundans culture: Effects of pH and dissolved inorganic carbon.

    Science.gov (United States)

    Peng, Licheng; Lan, Christopher Q; Zhang, Zisheng; Sarch, Cody; Laporte, Matt

    2015-12-01

    Combined effects of pH (i.e., 7.5, 8.5, and 9.5) and bicarbonate (i.e., 0, 80 and 160mM NaHCO3) on lipid accumulation and on biological contaminant viability in a protozoa-contaminated culture of the freshwater microalga Neochloris oleoabundans were studied. Cultures grown in the media containing 160mM NaHCO3 at pH 9.5 obtained the highest biomass concentration (DCWmax=1.32g/L), lipid content (LC=327mg/g), which corresponded to a lipid productivity of 56mg/(L·d), and the culture was protozoa free one day after inoculation. Other cultures, 160mM NaHCO3 at pH 8.5 (DCWmax=1.32g/L, LC=223mg/g), and 80mM NaHCO3 at pH 9.5 (DCWmax=1.25g/L, LC=264mg/g) could delay protozoan growth, but not inhibit it completely. These results suggest 160mM NaHCO3 or slightly above at pH levels of 8.5-9.5 may be used in outdoor cultivation processes of freshwater N. oleoabundans to control protozoa contamination while maintain a high lipid content.

  18. Modelling encapsulation of gold and silver nanoparticles inside lipid nanotubes

    Science.gov (United States)

    Baowan, Duangkamon; Thamwattana, Ngamta

    2014-02-01

    Lipid nanotubes are of particular interest for use as a template to create various one-dimensional nanostructures and as a carrier for drug and gene delivery. Understanding the encapsulation process is therefore crucial for such development. This paper models the interactions between lipid nanotubes and spheres of gold and silver nanoparticles and determines the critical dimension of lipid nanotubes that maximises the interaction with the nanoparticles. Our results confirm the acceptance of gold and silver nanoparticles inside lipid nanotubes. Further, we find that the lipid nanotube of radius approximately 10.23 nm is most favourable to encapsulate both types of nanoparticles.

  19. Multiscale molecular modeling of tertiary supported lipid bilayers

    Science.gov (United States)

    Ranz, Holden T.; Faller, Roland

    2015-08-01

    Ternary lipid bilayer systems assembled from mixtures of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol have been studied using coarse-grained molecular dynamics at biologically relevant temperatures (280 K to 310 K), which are between the chain melting temperatures of the pure lipid component. Free lipid bilayers were simulated using the MARTINI model (Stage I) and a variant with water-water interactions reduced to 76% (Stage II). The latter was subsequently used for preparing supported lipid bilayer simulations (Stage III). Clustering of like lipids was observed, but the simulation timescale did not yield larger phaseseparated domains.

  20. Probabilistic Modeling of Fatigue Damage Accumulation for Reliability Prediction

    Directory of Open Access Journals (Sweden)

    Vijay Rathod

    2011-01-01

    Full Text Available A methodology for probabilistic modeling of fatigue damage accumulation for single stress level and multistress level loading is proposed in this paper. The methodology uses linear damage accumulation model of Palmgren-Miner, a probabilistic S-N curve, and an approach for a one-to-one transformation of probability density functions to achieve the objective. The damage accumulation is modeled as a nonstationary process as both the expected damage accumulation and its variability change with time. The proposed methodology is then used for reliability prediction under single stress level and multistress level loading, utilizing dynamic statistical model of cumulative fatigue damage. The reliability prediction under both types of loading is demonstrated with examples.

  1. Lipid accumulation from pinewood pyrolysates by Rhodosporidium diobovatum and Chlorella vulgaris for biodiesel production.

    Science.gov (United States)

    Luque, Luis; Orr, Valerie C A; Chen, Sean; Westerhof, Roel; Oudenhoven, Stijn; Rossum, Guus van; Kersten, Sascha; Berruti, Franco; Rehmann, Lars

    2016-08-01

    This study evaluated the suitability of pinewood pyrolysates as a carbon source for lipid production and cultivation of the oleaginous yeast Rhodosporidium diobovatum and the microalgae Chlorella vulgaris. Thermal decomposition of pinewood and fractional condensation were used to obtain an oil rich in levoglucosan which was upgraded to glucose by acid hydrolysis. Blending of pyrolytic sugars with pure glucose in both nitrogen rich and nitrogen limited conditions was studied for R. diobovatum, and under nitrogen limited conditions for C. vulgaris. Glucose consumption rate decreased with increasing proportions of pyrolytic sugars increasing cultivation time. While R. diobovatum was capable of growth in 100% (v/v) pyrolytic sugars, C. vulgaris growth declined rapidly in blends greater than 20% (v/v) until no growth was detected in blends >40%. Finally, the effects of pyrolysis sugars on lipid composition was evaluated and biodiesel fuel properties were estimated based on the lipid profiles.

  2. Enhanced biomass production and lipid accumulation of Picochlorum atomus using light-emitting diodes (LEDs).

    Science.gov (United States)

    Ra, Chae Hun; Kang, Chang-Han; Jung, Jang-Hyun; Jeong, Gwi-Taek; Kim, Sung-Koo

    2016-10-01

    The effects of light-emitting diode (LED) wavelength, light intensity, nitrate concentration, and time of exposure to different LED wavelength stresses in a two-phase culture on lipid production were evaluated in the microalga, Picochlorum atomus. The biomass produced by red LED light was higher than that produced by purple, blue, green, or yellow LED and fluorescent lights from first phase of two-phase culture. The highest lipid production of P. atomus was 50.3% (w/w) with green LED light at 2days of second phase as light stress. Fatty acid analysis of the microalgae showed that palmitic acid (C16:0) and linolenic acid (C18:3) accounted for 84-88% (w/w) of total fatty acids from P. atomus. The two-phase culture of P. atomus is suitable for biofuel production due to higher lipid productivity and favorable fatty acid composition.

  3. Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway

    DEFF Research Database (Denmark)

    Kase, Eili T; Wensaas, Andreas J; Aas, Vigdis;

    2005-01-01

    . Interestingly, in response to activation of LXRs, myotubes from patients with type 2 diabetes showed an elevated uptake and incorporation of palmitate into complex lipids but an absence of palmitate oxidation to CO(2). These results provide evidence for a functional role of LXRs in both lipid and glucose...... metabolism and energy uncoupling in human myotubes. Furthermore, these data suggest that increased intramyocellular lipid content in type 2 diabetic patients may involve an altered response to activation of components in the LXR pathway........ Consistently, activation of LXRs induced the expression of relevant genes: fatty acid translocase (CD36/FAT), glucose transporters (GLUT1 and -4), sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor-gamma, carnitine palmitoyltransferase-1, and uncoupling protein 2 and 3...

  4. Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish.

    Science.gov (United States)

    Lee, Yeon-Joo; Choi, Hyeon-Son; Seo, Min-Jung; Jeon, Hui-Jeon; Kim, Kui-Jin; Lee, Boo-Yong

    2015-08-01

    Kaempferol is a flavonoid present in Kaempferia galanga and Opuntia ficus indica var. saboten. Recent studies have suggested that it has anti-oxidant, anti-inflammatory, anti-cancer, and anti-obesity effects. In this study, we focused on the anti-adipogenic effects of kaempferol during adipocyte differentiation. The results showed that kaempferol inhibits lipid accumulation in adipocytes and zebrafish. Oil Red O and Nile Red staining showed that the number of intracellular lipid droplets decreased in adipocytes and zebrafish treated with kaempferol. LPAATθ (lysophosphatidic acid acyltransferase), lipin1, and DGAT1 (triglyceride synthetic enzymes) and FASN and SREBP-1C (fatty acid synthetic proteins) showed decreased expression levels in the presence of kaempferol. In addition, treatment of kaempferol showed an inhibitory activity on cell cycle progression. Kaempferol delayed cell cycle progression from the S to G2/M phase through the regulation of cyclins in a dose-dependent manner. Kaempferol blocked the phosphorylation of AKT (protein kinase B) and mammalian target of rapamycin (mTOR) signaling pathway during the early stages of adipogenesis. In addition, kaempferol down-regulated pro-early adipogenic factors such as CCAAT-enhancer binding proteins β (C/EBPβ), and Krüppel-like factors (KLFs) 4 and 5, while anti-early adipogenic factors, such as KLF2 and pref-1(preadipocyte factor-1), were upregulated. These kaempferol-mediated regulations of early adipogenic factors resulted in the attenuation of late adipogenic factors such as C/EBPα and peroxisome proliferator-activated receptor γ (PPARγ). These results were supported in zebrafish based on the decrease in lipid accumulation and expression of adipogenic factors. Our results indicated that kaempferol might have an anti-obesity effect by regulating lipid metabolism.

  5. Combined nitrogen limitation and cadmium stress stimulate total carbohydrates, lipids, protein and amino acid accumulation in Chlorella vulgaris (Trebouxiophyceae)

    Energy Technology Data Exchange (ETDEWEB)

    Chia, Mathias Ahii, E-mail: chia28us@yahoo.com [Department of Botany, Federal University of São Carlos, Rodovia Washington Luis km 235, São Carlos, SP Cep 13565905 (Brazil); Lombardi, Ana Teresa [Department of Botany, Federal University of São Carlos, Rodovia Washington Luis km 235, São Carlos, SP Cep 13565905 (Brazil); Graça Gama Melão, Maria da [Department of Hydrobiology, Federal University of São Carlos, Rodovia Washington Luis km 235, São Carlos, SP Cep 13565905 (Brazil); Parrish, Christopher C. [Department of Ocean Sciences, Memorial University of Newfoundland, St. John’s, Newfoundland A1C 5S7 (Canada)

    2015-03-15

    Highlights: • Chlorella vulgaris was exposed to Cd under varying N concentrations. • Growth rate and cell density decreased with increasing Cd stress and N limitation. • Dry weight, chlorophyll a, total lipid, carbohydrate and protein were accumulated. • Amino acids like proline and glutamine were accumulated under N and Cd stress. • Changes in amino acid composition are sensitive biomarkers for Cd and N stress. - Abstract: Metals have interactive effects on the uptake and metabolism of nutrients in microalgae. However, the effect of trace metal toxicity on amino acid composition of Chlorella vulgaris as a function of varying nitrogen concentrations is not known. In this research, C. vulgaris was used to investigate the influence of cadmium (10{sup −7} and 2.0 × 10{sup −8} mol L{sup −1} Cd) under varying nitrogen (2.9 × 10{sup −6}, 1.1 × 10{sup −5} and 1.1 × 10{sup −3} mol L{sup −1} N) concentrations on its growth rate, biomass and biochemical composition. Total carbohydrates, total proteins, total lipids, as well as individual amino acid proportions were determined. The combination of Cd stress and N limitation significantly inhibited growth rate and cell density of C. vulgaris. However, increasing N limitation and Cd stress stimulated higher dry weight and chlorophyll a production per cell. Furthermore, biomolecules like total proteins, carbohydrates and lipids increased with increasing N limitation and Cd stress. Ketogenic and glucogenic amino acids were accumulated under the stress conditions investigated in the present study. Amino acids involved in metal chelation like proline, histidine and glutamine were significantly increased after exposure to combined Cd stress and N limitation. We conclude that N limitation and Cd stress affects the physiology of C. vulgaris by not only decreasing its growth but also stimulating biomolecule production.

  6. Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity.

    Science.gov (United States)

    Rivas, Donato A; McDonald, Devin J; Rice, Nicholas P; Haran, Prashanth H; Dolnikowski, Gregory G; Fielding, Roger A

    2016-04-01

    The loss of skeletal muscle mass is observed in many pathophysiological conditions, including aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and is characterized by a mismatch between skeletal muscle protein synthesis and breakdown. Characteristic metabolic features of both aging and obesity are increases in intramyocellular lipid (IMCL) content in muscle. IMCL accumulation may play a mechanistic role in the development of anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis, contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obese and aged animals had significantly higher storage of ceramide and diacylglycerol compared with young. Furthermore, there was an attenuated insulin response in components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IκBα with aging and obesity. These data challenge the accepted role of increased inflammation in obesity-induced insulin resistance in skeletal muscle. Furthermore, we have now established IκBα with a novel function in aging-associated muscle loss that may be independent of its previously understood role as an NF-κB inhibitor.

  7. The zinc cluster transcriptional regulator Asg1 transcriptionally coordinates oleate utilization and lipid accumulation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Jansuriyakul, Siripat; Somboon, Pichayada; Rodboon, Napachai; Kurylenko, Olena; Sibirny, Andriy; Soontorngun, Nitnipa

    2016-05-01

    In this study, we characterize a new function for activator of stress response genes (Asg1) in fatty acid utilization. Asg1 is required for full activation of genes in several pathways, including β-oxidation (POX1, FOX2, and POT1), gluconeogenesis (PCK1), glyoxylate cycle (ICL1), triacylglycerol breakdown (TGL3), and peroxisomal transport (PXA1). In addition, the transcriptional activator Asg1 is found to be enriched on promoters of genes in β-oxidation and gluconeogenesis pathways, suggesting that Asg1 is directly involved in the control of fatty acid utilizing genes. In agreement, impaired growth on non-fermentable carbons such as fatty acids and oils and increased sensitivity to some oxidative agents are found for the Δasg1 strain. The lipid class profile of the Δasg1 cells grown in oleate displays approximately 3-fold increase in free fatty acid (FFA) content in comparison to glucose-grown cells, which correlates with decreased expression of β-oxidation genes. The ∆asg1 strain grown in glucose also exhibits higher accumulation of triacylglycerols (TAGs) during log phase, reaching levels typically observed in stationary phase cells. Altered TAG accumulation is partly due to the inability of the Δasg1 cells to efficiently break down TAGs, which is consistent with lowered expression of TGL3 gene, encoding triglycerol lipase. Overall, these results highlight a new role of the transcriptional regulator Asg1 in coordinating expression of genes involved in fatty acid utilization and its role in regulating cellular lipid accumulation, thereby providing an attractive approach to increase FFAs and TAGs content for the production of lipid-derived biofuels and chemicals in Saccharomyces cerevisiae.

  8. Fatty acid transport protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Saini, Nipun; Black, Paul N.; Montefusco, David; DiRusso, Concetta C., E-mail: cdirusso2@unl.edu

    2015-09-25

    The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC{sub 50} 8–11 μM) and prevented palmitate-mediated lipid accumulation and cell death in cell lines that are models for intestines, liver, muscle and pancreas. In adipocytes, uptake inhibition was less effective (IC{sub 50} 58 μM). Inhibition was specific for long chain fatty acids and was ineffective toward medium chain fatty acids, which are transported by diffusion. Kinetic analysis of Grassofermata-dependent FA transport inhibition verified a non-competitive mechanism. By comparison with Grassofermata, several atypical antipsychotic drugs previously implicated as inhibitors of FA uptake were ineffectual. In mice Grassofermata decreased absorption of {sup 13}C-oleate demonstrating its potential as a therapeutic agent. - Highlights: • Grassofermata is a small compound inhibitor of FATP2. • Uptake inhibition is specific for long chain fatty acids. • Uptake kinetics shows low specificity for adipocytes compared to other cell types. • Inhibition is by a non-competitive mechanism. • Atypical antipsychotics do not inhibit FA uptake by comparison with Grassofermata.

  9. N-Terminal Lipid Modification Is Required for the Stable Accumulation of CyanoQ in Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Juneau, Andrea D; Frankel, Laurie K; Bricker, Terry M; Roose, Johnna L

    The CyanoQ protein has been demonstrated to be a component of cyanobacterial Photosystem II (PS II), but there exist a number of outstanding questions concerning its physical association with the complex. CyanoQ is a lipoprotein; upon cleavage of its transit peptide by Signal Peptidase II, which targets delivery of the mature protein to the thylakoid lumenal space, the N-terminal cysteinyl residue is lipid-modified. This modification appears to tether this otherwise soluble component to the thylakoid membrane. To probe the functional significance of the lipid anchor, mutants of the CyanoQ protein have been generated in Synechocystis sp. PCC 6803 to eliminate the N-terminal cysteinyl residue, preventing lipid modification. Substitution of the N-terminal cysteinyl residue with serine (Q-C22S) resulted in a decrease in the amount of detectable CyanoQ protein to 17% that of the wild-type protein. Moreover, the physical properties of the accumulated Q-C22S protein were consistent with altered processing of the CyanoQ precursor. The Q-C22S protein was shifted to a higher apparent molecular mass and partitioned in the hydrophobic phase in TX-114 phase-partitioning experiments. These results suggest that the hydrophobic N-terminal 22 amino acids were not properly cleaved by a signal peptidase. Substitution of the entire CyanoQ transit peptide with the transit peptide of the soluble lumenal protein PsbO yielded the Q-SS mutant and resulted in no detectable accumulation of the modified CyanoQ protein. Finally, the CyanoQ protein was present at normal amounts in the PS II mutant strains ΔpsbB and ΔpsbO, indicating that an association with PS II was not a prerequisite for stable CyanoQ accumulation. Together these results indicate that CyanoQ accumulation in Synechocystis sp. PCC 6803 depends on the presence of the N-terminal lipid anchor, but not on the association of CyanoQ with the PS II complex.

  10. Effects of cannabinoid receptor 1 (brain) on lipid accumulation by transcriptional control of CPT1A and CPT1B.

    Science.gov (United States)

    Zhang, Y-F; Yuan, Z-Q; Song, D-G; Zhou, X-H; Wang, Y-Z

    2014-02-01

    CB1 (also known as CNR1), a main receptor for cannabinoids acting at PPARs, can enhance fat deposition. Carnitine palmitoyltransferase-1 (CPT1), an enzyme responsible for the transport of long-chain fatty acids for β-oxidation, is closely related to fat deposition. Whether CB1 can regulate intramuscular adipocytes lipid accumulation through regulation of CPT1 is unclear. Based on the investigation of tissue- and breed-specific CPT1A and CPT1B mRNA expression levels in Jinhua and Landrace pigs, we studied the effects of CB1 on lipid accumulation and CPT1B expression by treating porcine intramuscular adipocytes with CB1 antagonist Δ9-THC and antagonist SR141716. Results showed that muscle CPT1 mRNA was expressed at higher levels in the longissimus dorsi and subcutaneous fat. Liver CPT1A mRNA expression levels were higher in the pancreas, duodenum and liver. Compared with Landrace pigs, CPT1A and CPT1B in the longissimus dorsi of Jinhua pigs were significantly higher and positively correlated with intramuscular fat content. However, for subcutaneous fat, CPT1 levels were significantly lower and negatively correlated with body fat percentage. Δ9-THC significantly increased CB1 mRNA levels and lipid accumulation but decreased CPT1A and CPT1B mRNA levels. Conversely, SR141716 reduced CB1 mRNA levels but increased CPT1A and CPT1B mRNA levels, resulting in decreased lipid accumulation. The CPT1 antagonist etomoxir did not affect CB1 expression, suggesting that CB1 is likely upstream of CPT1A and CPT1B. Meanwhile, PPARA expression was greatly decreased when CPT1A and CPT1B were inhibited and enhanced when CPT1A and CPT1B were activated. Taken together, these data indicate that CB1 can affect intramuscular fat deposition by regulating both CPT1A and CPT1B mRNA expression, with the PPARA signal pathway likely playing a major role in this process.

  11. Lipid accumulation from pinewood pyrolysates by rhodosporidium diobovatum and chlorella vulgaris for biodiesel production

    NARCIS (Netherlands)

    Luque, L.; Orr, V.C.A.; Chen, S.; Westerhof, R.J.M.; Oudenhoven, S.R.G; Rossum, van G.; Kersten, S.R.A.; Berruti, F.; Rehmann, L.

    2016-01-01

    This study evaluated the suitability of pinewood pyrolysates as a carbon source for lipid production and cultivation of the oleaginous yeast Rhodosporidium diobovatum and the microalgae Chlorella vulgaris. Thermal decomposition of pinewood and fractional condensation were used to obtain an oil rich

  12. Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis

    DEFF Research Database (Denmark)

    Ma, Liqun; Zhong, Jian; Zhao, Zhigang

    2011-01-01

    Activation of transient receptor potential vanilloid type-1 (TRPV1) channels may affect lipid storage and the cellular inflammatory response. Now, we tested the hypothesis that activation of TRPV1 channels attenuates atherosclerosis in apolipoprotein E knockout mice (ApoE(-/-)) but not ApoE...

  13. Lipid accumulation from pinewood pyrolysates by rhodosporidium diobovatum and chlorella vulgaris for biodiesel production

    NARCIS (Netherlands)

    Luque, L.; Orr, V.C.A.; Chen, S.; Westerhof, Roel Johannes Maria; Oudenhoven, Stijn; van Rossum, G.; Kersten, Sascha R.A.; Berruti, F.; Rehmann, L.

    2016-01-01

    This study evaluated the suitability of pinewood pyrolysates as a carbon source for lipid production and cultivation of the oleaginous yeast Rhodosporidium diobovatum and the microalgae Chlorella vulgaris. Thermal decomposition of pinewood and fractional condensation were used to obtain an oil rich

  14. 2-(2-Bromophenyl)-formononetin and 2-heptyl-formononetin are PPARγ partial agonists and reduce lipid accumulation in 3T3-L1 adipocytes

    DEFF Research Database (Denmark)

    Andersen, Charlotte; Kotowska, Dorota Ewa; Tortzen, Christian

    2014-01-01

    peroxisome proliferator-activated receptor (PPAR)-γ binding assay, PPARγ transactivation assay and Western blot for phosphorylated AMP-activated protein kinase (AMPK) were performed. Chronic treatment (day 0-8) with formononetin increased lipid accumulation, whereas the two analogues decreased lipid...... PPARγ whereas both analogues bound to the receptor and behaved as PPARγ partial agonists in the transactivation assay. Neither of the compounds affected phosphorylation of AMPK. In conclusion, the analogues of formononetin decreased lipid accumulation possibly in part by acting as PPARγ partial agonists....

  15. Mango (Mangifera indica L.) peel extract fractions from different cultivars differentially affect lipid accumulation in 3T3-L1 adipocyte cells.

    Science.gov (United States)

    Taing, Meng-Wong; Pierson, Jean-Thomas; Shaw, Paul N; Dietzgen, Ralf G; Roberts-Thomson, Sarah J; Gidley, Michael J; Monteith, Gregory R

    2013-02-26

    Plant phytochemicals are increasingly recognised as sources of bioactive molecules which may have potential benefit in many health conditions. In mangoes, peel extracts from different cultivars exhibit varying effects on adipogenesis in the 3T3-L1 adipocyte cell line. In this study, the effects of preparative HPLC fractions of methanol peel extracts from Irwin, Nam Doc Mai and Kensington Pride mangoes were evaluated. Fraction 1 contained the most hydrophilic components while subsequent fractions contained increasingly more hydrophobic components. High content imaging was used to assess mango peel fraction effects on lipid accumulation, nuclei count and nuclear area in differentiating 3T3-L1 cells. For all three mango cultivars, the more hydrophilic peel fractions 1-3 inhibited lipid accumulation with greater potency than the more hydrophobic peel fractions 4. For all three cultivars, the more lipophilic fraction 4 had concentrations that enhanced lipid accumulation greater than fractions 1-3 as assessed by lipid droplet integrated intensity. The potency of this fraction 4 varied significantly between cultivars. Using mass spectrometry, five long chain free fatty acids were detected in fraction 4; these were not present in any other peel extract fractions. Total levels varied between cultivars, with Irwin fraction 4 containing the highest levels of these free fatty acids. Lipophilic components appear to be responsible for the lipid accumulation promoting effects of some mango extracts and are the likely cause of the diverse effects of peel extracts from different mango cultivars on lipid accumulation.

  16. Dynamic stochastic accumulation model with application to pension savings management

    Directory of Open Access Journals (Sweden)

    Melicherčik Igor

    2010-01-01

    Full Text Available We propose a dynamic stochastic accumulation model for determining optimal decision between stock and bond investments during accumulation of pension savings. Stock prices are assumed to be driven by the geometric Brownian motion. Interest rates are modeled by means of the Cox-Ingersoll-Ross model. The optimal decision as a solution to the corresponding dynamic stochastic program is a function of the duration of saving, the level of savings and the short rate. Qualitative and quantitative properties of the optimal solution are analyzed. The model is tested on the funded pillar of the Slovak pension system. The results are calculated for various risk preferences of a saver.

  17. Application of simulation modeling to lipid peroxidation processes.

    Science.gov (United States)

    Tappel, A L; Tappel, A A; Fraga, C G

    1989-01-01

    A quantitative simulation model was developed that utilized present knowledge of lipid peroxidation in biological systems. The simulation model incorporated the following features: peroxidizability of polyunsaturated lipids, activation of inducers and their initiation of lipid peroxidation, concurrent autoxidation, inhibition of lipid peroxidation by vitamin E, reduction of some of the hydroperoxides by glutathione peroxidase, and formation of thiobarbituric acid-reactive substances. Simulation calculations were done using a computer spreadsheet program. When the simulation program was applied to tissue slice and microsomal peroxidizing systems, the results of the stimulation were in agreement with the experimental data.

  18. Lipid peroxidation-derived 4-hydroxynonenal-modified proteins accumulate in human facial skin fibroblasts during ageing in vitro.

    Science.gov (United States)

    Jørgensen, Peter; Milkovic, Lidija; Zarkovic, Neven; Waeg, Georg; Rattan, Suresh I S

    2014-02-01

    The reactive aldehyde, 4-hydroxynonenal (HNE), is recognized as a product of lipid peroxidation, which binds to macromolecules, in particular proteins. HNE-modified proteins (HNE-MP) have been shown to accumulate during ageing, generally by using polyclonal antibodies, which increase the possibility of detecting false positives. Therefore, we have used a genuine monoclonal antibody specific for HNE-His adducts of proteins/peptides, which were revealed by immunoblotting method for whole-cell HNE-MP measurements in serially passaged human facial skin fibroblasts undergoing ageing in vitro. There was a significant increase in the levels of HNE-MP in serially passaged cells approaching a near senescent state at high passage level (P-61), as compared with low passage level (P-11) young and middle-aged (P-27) cells. However, if the cells were analyzed soon after re-initiation from the frozen samples with little further passaging, the amount of HNE-MP was low even in relatively high passage level (P-37) cells, which is an indication of selective elimination of cells with high molecular damage during the process of thawing and re-initiation in culture. This pilot study on normal human facial skin fibroblasts shows that HNE-MP detection by monoclonal antibody-based dot blot method can be used as a marker for age-related accumulation of lipid peroxidative molecular damage, and could be useful for testing and monitoring the effects of potential skin care products on ageing parameters.

  19. Intramitochondrial accumulation of cationic Atto520-biotin proceeds via voltage-dependent slow permeation through lipid membrane.

    Science.gov (United States)

    Antonenko, Yuri N; Nechaeva, Natalya L; Baksheeva, Victoria E; Rokitskaya, Tatyana I; Plotnikov, Egor Y; Kotova, Elena A; Zorov, Dmitry B

    2015-06-01

    Conjugation to penetrating cations is a general approach for intramitochondrial delivery of physiologically active compounds, supported by a high membrane potential of mitochondria having negative sign on the matrix side. By using fluorescence correlation spectroscopy, we found here that Atto520-biotin, a conjugate of a fluorescent cationic rhodamine-based dye with the membrane-impermeable vitamin biotin, accumulated in energized mitochondria in contrast to biotin-rhodamine 110. The energy-dependent uptake of Atto520-biotin by mitochondria, being slower than that of the conventional mitochondrial dye tetramethyl-rhodamine ethyl ester, was enhanced by the hydrophobic anion tetraphenylborate (TPB). Atto520-biotin also exhibited accumulation in liposomes driven by membrane potential resulting from potassium ion gradient in the presence valinomycin. The induction of electrical current across planar bilayer lipid membrane by Atto520-biotin proved the ability of the compound to permeate through lipid membrane in a cationic form. Atto520-biotin stained mitochondria in a culture of L929 cells, and the staining was enhanced in the presence of TPB. Therefore, the fluorescent Atto520 moiety can serve as a vehicle for intramitochondrial delivery of hydrophilic drugs. Of importance for biotin-streptavidin technology, binding of Atto520-biotin to streptavidin was found to cause quenching of its fluorescence similar to the case of fluorescein-4-biotin.

  20. Eucommia ulmoides Oliver extract, aucubin, and geniposide enhance lysosomal activity to regulate ER stress and hepatic lipid accumulation.

    Directory of Open Access Journals (Sweden)

    Hwa-Young Lee

    Full Text Available Eucommia ulmoides Oliver is a natural product widely used as a dietary supplement and medicinal plant. Here, we examined the potential regulatory effects of Eucommia ulmoides Oliver extracts (EUE on hepatic dyslipidemia and its related mechanisms by in vitro and in vivo studies. EUE and its two active constituents, aucubin and geniposide, inhibited palmitate-induced endoplasmic reticulum (ER stress, reducing hepatic lipid accumulation through secretion of apolipoprotein B and associated triglycerides and cholesterol in human HepG2 hepatocytes. To determine how EUE diminishes the ER stress response, lysosomal and proteasomal protein degradation activities were analyzed. Although proteasomal activity was not affected, lysosomal enzyme activities including V-ATPase were significantly increased by EUE as well as aucubin and geniposide in HepG2 cells. Treatment with the V-ATPase inhibitor, bafilomycin, reversed the inhibition of ER stress, secretion of apolipoprotein B, and hepatic lipid accumulation induced by EUE or its component, aucubin or geniposide. In addition, EUE was determined to regulate hepatic dyslipidemia by enhancing lysosomal activity and to regulate ER stress in rats fed a high-fat diet. Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemia.

  1. Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation in Oleaginous Microorganisms: The State of the Art and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Xiao-Jun Ji

    2017-05-01

    Full Text Available Microbial oils, which are mainly extracted from yeasts, molds, and algae, have been of considerable interest as food additives and biofuel resources due to their high lipid content. While these oleaginous microorganisms generally produce only small amounts of lipids under optimal growth conditions, their lipid accumulation machinery can be induced by environmental stresses, such as nutrient limitation and an inhospitable physical environmental. As common second messengers of many stress factors, reactive oxygen species (ROS may act as a regulator of cellular responses to extracellular environmental signaling. Furthermore, increasing evidence indicates that ROS may act as a mediator of lipid accumulation, which is associated with dramatic changes in the transcriptome, proteome, and metabolome. However, the specific mechanisms of ROS involvement in the crosstalk between extracellular stress signaling and intracellular lipid synthesis require further investigation. Here, we summarize current knowledge on stress-induced lipid biosynthesis and the putative role of ROS in the control of lipid accumulation in oleaginous microorganisms. Understanding such links may provide guidance for the development of stress-based strategies to enhance microbial lipid production.

  2. SIRT1 Disruption in Human Fetal Hepatocytes Leads to Increased Accumulation of Glucose and Lipids.

    Directory of Open Access Journals (Sweden)

    Takamasa Tobita

    Full Text Available There are unprecedented epidemics of obesity, such as type II diabetes and non-alcoholic fatty liver diseases (NAFLD in developed countries. A concerning percentage of American children are being affected by obesity and NAFLD. Studies have suggested that the maternal environment in utero might play a role in the development of these diseases later in life. In this study, we documented that inhibiting SIRT1 signaling in human fetal hepatocytes rapidly led to an increase in intracellular glucose and lipids levels. More importantly, both de novo lipogenesis and gluconeogenesis related genes were upregulated upon SIRT1 inhibition. The AKT/FOXO1 pathway, a major negative regulator of gluconeogenesis, was decreased in the human fetal hepatocytes inhibited for SIRT1, consistent with the higher level of gluconeogenesis. These results indicate that SIRT1 is an important regulator of lipid and carbohydrate metabolisms within human fetal hepatocytes, acting as an adaptive transcriptional response to environmental changes.

  3. Sources and resources: importance of nutrients, resource allocation, and ecology in microalgal cultivation for lipid accumulation

    OpenAIRE

    Fields, Matthew W; Hise, Adam; Lohman, Egan J.; Bell, Tisza; Gardner, Rob D.; Corredor, Luisa; Moll, Karen; Peyton, Brent M.; Characklis, Gregory W.; Gerlach, Robin

    2014-01-01

    Regardless of current market conditions and availability of conventional petroleum sources, alternatives are needed to circumvent future economic and environmental impacts from continued exploration and harvesting of conventional hydrocarbons. Diatoms and green algae (microalgae) are eukaryotic photoautotrophs that can utilize inorganic carbon (e.g., CO2) as a carbon source and sunlight as an energy source, and many microalgae can store carbon and energy in the form of neutral lipids. In addi...

  4. Effects of Exercise Training on Molecular Markers of Lipogenesis and Lipid Partitioning in Fructose-Induced Liver Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Siham Yasari

    2012-01-01

    Full Text Available The present study was designed to investigate the impact of exercise training on lipogenic gene expression in liver and lipid partitioning following the ingestion of a high fructose load. Female rats were exercise-trained for 8 wk or kept sedentary before being submitted to a fasting/refeeding protocol. Rats were further subdivided as follow: rats were fasted for 24 h, refed a standard diet for 24 h, starved for another 24 h, and refed with a standard or a high-fructose diet 24 h before sacrifice. Fructose refeeding was associated with an increase in hepatic lipid content, endocannabinoid receptor 1, sterol regulatory element-binding protein1c, and stearoyl-CoA desaturase1 gene expression in both Sed and TR rats. However, desaturation indexes measured in liver (C16 : 1/C16 : 0 and C18 : 1/C18 : 0 and plasma (C18 : 1/C18 : 0 were higher (P<0.01 in TR than in Sed rats following fructose refeeding. It is concluded that exercise training does not significantly affect fat accumulation and the molecular expression of genes involved in lipogenesis after fasting and fructose refeeding but does modify the partitioning of lipids so as to provide more unsaturated fatty acids in liver without affecting liver fat content.

  5. High lipid accumulation in Yarrowia lipolytica cultivated under double limitation of nitrogen and magnesium.

    Science.gov (United States)

    Bellou, S; Triantaphyllidou, I-E; Mizerakis, P; Aggelis, G

    2016-09-20

    Yarrowia lipolytica cultivated under double nitrogen and magnesium limitation, but not under single nitrogen or single magnesium limitation, produced 12.2g/l biomass containing 47.5% lipids, which corresponds to a lipid production 5.8g/l. These yields are the higher described in the literature for wild strains of Y. lipolytica. Transcription of ACL1 and ACL2, encoding for ATP-citrate lyase (ATP:CL) was observed even under non-oleaginous conditions but high activity of ATP:CL was only detected under oleaginous conditions induced by low or zero activity of NAD(+) dependent isocitrate dehydrogenase. The low activity of malic enzyme (ME), a NADPH donor in typical oleaginous microorganisms, indicated that ME may not be implicated in lipid biosynthesis in this yeast, and NADPH may be provided by the pentose phosphate pathway (PPP). These findings underline the essential role of magnesium in lipogenesis, which is currently quite unexplored. The presence of organic nitrogen in low concentrations during lipogenesis was also required, and this peculiarity was probably related with the PPP functioning, being the NADPH donor of lipogenic machinery in Y. lipolytica.

  6. NaCl as an effective inducer for lipid accumulation in freshwater microalgae Desmodesmus abundans.

    Science.gov (United States)

    Xia, Ling; Rong, Junfeng; Yang, Haijian; He, Qiaoning; Zhang, Delu; Hu, Chunxiang

    2014-06-01

    In order to evaluate the efficiency and potential of salt addition-based two-stage cultivation technology, on the basis of urea as nitrogen source, we compared four types of salts (NaCl, NaHCO3, NaS2O3 and NaAc) as inducers for lipid production in Desmodesmus abundans. The maximum biomass productivity (270.08mgL(-1)d(-1)) was obtained by using 0.25gL(-1) urea. The highest lipid productivity (67.08mgL(-1)d(-1)) and better biodiesel quality were realized by addition of 20gL(-1) NaCl, and the optimal time point for salt addition was determined at 1.79gL(-1) of biomass density. Further cost analysis demonstrated this cultivation process was relatively economical. Above results suggest that NaCl addition is an economical and applicable strategy for lipid enhancement and can be extended for microalgae-based biodiesel production.

  7. Monitoring lipid accumulation in the green microalga Botryococcus braunii with frequency-modulated stimulated Raman scattering

    Science.gov (United States)

    Wang, Chun-Chin; Chandrappa, Dayananda; Smirnoff, Nicholas; Moger, Julian

    2015-03-01

    The potential of microalgae as a source of renewable energy has received considerable interest because they can produce lipids (fatty acids and isoprenoids) that can be readily converted into biofuels. However, significant research in this area is required to increase yields to make this a viable renewable source of energy. An analytical tool that could provide quantitative in situ spectroscopic analysis of lipids synthesis in individual microalgae would significantly enhance our capability to understand the synthesis process at the cellular level and lead to the development of strategies for increasing yield. Stimulated Raman scattering (SRS) microscopy has great potential in this area however, the pump-probe signal from two-color two-photon absorption of pigments (chlorophyll and carotenoids) overwhelm the SRS signal and prevent its application. Clearly, the development of a background suppression technique is of significant value for this important research area. To overcome the limitation of SRS in pigmented specimens, we establish a frequency-modulated stimulated Raman scattering (FM-SRS) microscopy that eliminates the non-Raman background by rapidly toggling on-and-off the targeted Raman resonance. Moreover, we perform the background-free imaging and analysis of intracellular lipid droplets and extracellular hydrocarbons in a green microalga with FM-SRS microscopy. We believe that FM-SRS microscopy demonstrates the potential for many applications in pigmented cells and provides the opportunity for improved selective visualization of the chemical composition of algae and plants

  8. Kinetic model of sucrose accumulation in maturing sugarcane culm tissue.

    Science.gov (United States)

    Uys, Lafras; Botha, Frederik C; Hofmeyr, Jan-Hendrik S; Rohwer, Johann M

    2007-01-01

    Biochemically, it is not completely understood why or how commercial varieties of sugarcane (Saccharum officinarum) are able to accumulate sucrose in high concentrations. Such concentrations are obtained despite the presence of sucrose synthesis/breakdown cycles (futile cycling) in the culm of the storage parenchyma. Given the complexity of the process, kinetic modelling may help to elucidate the factors governing sucrose accumulation or direct the design of experimental optimisation strategies. This paper describes the extension of an existing model of sucrose accumulation (Rohwer, J.M., Botha, F.C., 2001. Analysis of sucrose accumulation in the sugar cane culm on the basis of in vitro kinetic data. Biochem. J. 358, 437-445) to account for isoforms of sucrose synthase and fructokinase, carbon partitioning towards fibre formation, and the glycolytic enzymes phosphofructokinase (PFK), pyrophosphate-dependent PFK and aldolase. Moreover, by including data on the maximal activity of the enzymes as measured in different internodes, a growth model was constructed that describes the metabolic behaviour as sugarcane parenchymal tissue matures from internodes 3-10. While there was some discrepancy between modelled and experimentally determined steady-state sucrose concentrations in the cytoplasm, steady-state fluxes showed a better fit. The model supports a hypothesis of vacuolar sucrose accumulation against a concentration gradient. A detailed metabolic control analysis of sucrose synthase showed that each isoform has a unique control profile. Fructose uptake by the cell and sucrose uptake by the vacuole had a negative control on the futile cycling of sucrose and a positive control on sucrose accumulation, while the control profile for neutral invertase was reversed. When the activities of these three enzymes were changed from their reference values, the effects on futile cycling and sucrose accumulation were amplified. The model can be run online at the JWS Online

  9. Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation*

    Science.gov (United States)

    Kunchithapautham, Kannan; Atkinson, Carl; Rohrer, Bärbel

    2014-01-01

    Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. PMID:24711457

  10. Luxury uptake of phosphorus changes the accumulation of starch and lipid in Chlorella sp. under nitrogen depletion.

    Science.gov (United States)

    Zhu, Shunni; Wang, Yajie; Xu, Jin; Shang, Changhua; Wang, Zhongming; Xu, Jingliang; Yuan, Zhenhong

    2015-12-01

    The aim of this research was to study the effect of phosphorus supply on starch and lipid production under nitrogen starvation using Chlorella sp. as a model. High phosphate level had marginal effect on cell density but increased biomass growth. Massive phosphorus was assimilated quickly and mainly stored in the form of polyphosphate. The algal cells ceased phosphorus uptake when intracellular phosphorus reached a certain level. 5mM phosphate in the culture rendered a 16.7% decrease of starch synthesis and a 22.4% increase of lipid synthesis relative to low phosphate (0.17 mM). It is plausible that phosphate can regulate carbon partitioning between starch and lipid synthesis pathway by influencing ADP-glucose pyrophosphorylase activity. Moreover, high phosphate concentration enhanced the abundance of oleic acid, improving oil quality for biodiesel production. It is a promising cultivation strategy by integration of phosphorus removal from wastewater with biodiesel production for this alga.

  11. The interaction of serum and arterial lipoproteins with elastin of the arterial intima and its role in the lipid accumulation in atherosclerotic plaques.

    Science.gov (United States)

    Kramsch, D M; Hollander, W

    1973-02-01

    Arterial elastin appears to be a proteinlipid complex with the lipid component being bound to elastin peptide groups. In atherosclerotic lesions the lipid content of elastin increases progressively with increasing severity of atherosclerosis. The increases in the lipid content of plaque elastin are mainly due to large increases in cholesterol with about 80% of the cholesterol being cholesterol ester. This deposition of cholesterol in elastin accounts for a substantial part of the total cholesterol accumulation in atherosclerotic lesions of all stages. The present in vitro study suggests that the mechanism involved in the deposition of lipids in arterial elastin may be an interaction of the elastin protein with serum or arterial low density or very low density lipoproteins (LDL and VLDL) resulting in a transfer of lipids, but not of lipoprotein protein to the elastin. No significant lipid transfer occurred from the high density lipoproteins or chylomicrons. The amount of lipid taken up by plaque elastin was strikingly higher than by normal elastin and consisted mainly of cholesterol with over 80% of the cholesterol being cholesterol ester. The precondition for the lipid accumulation in plaque elastin appeared to be an altered amino acid composition of the elastin protein consisting of an increase in polar amino acids and a reduction in cross-linking amino acids. Subsequent treatment of lipoprotein-incubated arterial elastin with hot alkali and apolipoproteins did not reverse the binding of lipoprotein lipid to diseased elastin.

  12. Acute and perinatal programming effects of a fat-rich diet on rat muscle mitochondrial function and hepatic lipid accumulation.

    Science.gov (United States)

    Hellgren, Lars I; Jensen, Runa I; Waterstradt, Michelle S G; Quistorff, Bjørn; Lauritzen, Lotte

    2014-11-01

    Maternal high-fat intake during pregnancy may have long-term consequences in the offspring. Since this might relate to the capacity of mitochondrial metabolic adaptation and hepatic lipid metabolism, we investigated how maternal high-fat intake affected mitochondrial function and hepatic steatosis in the offspring. Sprague-Dawley rats were fed a high-fat (20% w/w) or a control diet (chow, C) from 10 days before pregnancy and throughout lactation. At weaning the litters were split into two groups; one was continued on the maternal diet and the other was fed low-fat chow. Skeletal muscle mitochondria and liver lipids. Mitochondrial respiration and hepatic lipid content were determined during and after weaning, on days 20 and 70 postpartum. Mitochondrial function and hepatic lipids. At 20 days, maternal high-fat diet caused increased Vo2max with pyruvate as substrate (p=0.047), at 70 days, pups born by C-dams, but not those born by high-fat-dams, showed increased oxidation of palmitoylcarnitine in the absence of ADP (p=0.018). Rates of ADP-stimulated oxygen consumption, maximal respiratory capacity and mitochondrial respiratory control ratio with pyruvate, increased post weaning (pdecreased (p=0.013). The increase in respiratory control ratio was most pronounced in pups from C-dams (p=0.05). The high-fat-diet caused pronounced hepatic steatosis in pups at weaning (pfat-feeding after weaning induced triacylglycerol and ceramide accumulation (pfat-rich diet during pregnancy and lactation reduced the age-induced increases in un-coupled fat oxidation. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  13. Nonlinear analysis of lipid tubules by nonlocal beam model.

    Science.gov (United States)

    Shen, Hui-Shen

    2011-05-07

    Postbuckling, nonlinear bending and nonlinear vibration analyses are presented for lipid tubules. The lipid tubule is modeled as a nonlocal micro/nano-beam which contains small scale effect. The material properties are assumed to be size-dependent. The governing equation is solved by a two-step perturbation technique. The numerical results reveal that the small scale parameter e₀a reduces the postbuckling equilibrium paths, the static large deflections and natural frequencies of lipid tubules. In contrast, it increases the nonlinear to linear frequency ratios slightly for the lipid tubule with immovable end conditions.

  14. α-Naphthoflavone Increases Lipid Accumulation in Mature Adipocytes and Enhances Adipocyte-Stimulated Endothelial Tube Formation

    Directory of Open Access Journals (Sweden)

    Mei-Lin Wang

    2015-04-01

    Full Text Available The aryl hydrocarbon receptor (AhR is a ligand-activated factor that regulates biological effects associated with obesity. The AhR agonists, such as environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD and β-naphthoflavone (BNF, inhibit preadipocyte differentiation and interfere with the functions of adipose tissue, whereas the antagonist may have opposite or protective effects in obesity. This study investigated the effects of α-naphthoflavone (α-NF, an AhR antagonist, on adipogenesis- and angiogenesis-associated factors in mature adipocytes and on cross-talk of mature adipocytes with endothelial cells (ECs. Besides, the roles of the AhR on lipid accumulation and on secretion of vascular endothelial growth factor were also determined by introducing siRNA of AhR. Differentiated 3T3-L1 cells were treated with α-naphthoflavone (α-NF (1–5 μM for 16 h. Lipid accumulation and the expressions of AhR-associated factors in the cells were determined. The interaction between adipocytes and ECs was investigated by cultivating ECs with conditioned medium (CM from α-NF-treated mature adipocytes, followed by the determination of endothelial tube formation. The results showed that α-NF significantly increased triglyceride (TG accumulation in mature adipocytes, which was associated with increased expression of hormone-sensitive lipase (HSL, estrogen receptor (ER, as well as decreased expression of AhR, AhR nuclear translocator (ARNT, cytochrome P4501B1 (CYP1B1, and nuclear factor erythroid-2-related factor (NRF-2 proteins. In addition, CM stimulated formation of tube-like structures in ECs, and α-NF further enhanced such stimulation in association with modulated the secretions of various angiogenic mediators by mature adipocytes. Similarly, increased TG accumulation and vascular endothelial growth factor (VEGF secretion were observed in AhR-knockout cells. In conclusion, α-NF increased TG accumulation in mature adipocytes and

  15. Sirt1 and Sirt6 Mediate Beneficial Effects of Rosiglitazone on Hepatic Lipid Accumulation

    OpenAIRE

    Soo Jin Yang; Jung Mook Choi; Eugene Chang; Sung Woo Park; Cheol-Young Park

    2014-01-01

    Background Sirtuin (Sirt), a sensor of the cell metabolic state, regulates glucose and lipid metabolism. The aim of this study was to address whether rosiglitazone (RGZ) alters hepatic Sirt1 and whether Sirt1 and/or Sirt6 have a regulatory role in the protective effects of RGZ on hepatocyte steatosis. Methods To investigate the effect of RGZ on hepatic Sirt1, rats were administered with RGZ for 6 weeks. The involvement of Sirt1/6 in the RGZ-mediated effect against hepatic steatosis was evalua...

  16. Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway

    DEFF Research Database (Denmark)

    Kase, E.T.; Wensaas, A.J.; Aas, V.

    2005-01-01

    Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism and are also involved in glucose metabolism. However, the functional role of LXRs in human skeletal muscle is at present unknown. This study demonstrates that chronic ligand activation of LXRs by a synthetic LXR....... Consistently, activation of LXRs induced the expression of relevant genes: fatty acid translocase (CD36/FAT), glucose transporters (GLUT1 and -4), sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor-gamma, carnitine palmitoyltransferase-1, and uncoupling protein 2 and 3...

  17. Inhibitory effects of green tea catechin on the lipid accumulation in 3T3-L1 adipocytes.

    Science.gov (United States)

    Lee, Mak-Soon; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

    2009-08-01

    The aim of the present study was to evaluate the effects of green tea (-)-epigallocatechin-3-gallate (EGCG) on the depletion of accumulated fat in differentiated 3T3-L1 adipocytes. Intracellular lipid accumulation was decreased significantly after 24 h of incubation with 10 microm EGCG, while the viability of adipocytes was reported to be unaffected. Under the same experimental conditions, the amount of glycerol released from cells into the medium was increased by 10 microm EGCG. The level of mRNA in the 3T3-L1 adipocytes was analysed by quantitative real-time RT-PCR. EGCG notably increased the mRNA level of hormone sensitive lipase (HSL), which catalyses the rate-limiting stage in hydrolysis of stored triacylglycerol to monoacylglycerol and free fatty acids. In conclusion, the experiment produced results which showed that green tea EGCG effectively depleted fat accumulation via the stimulation of lipolysis and increased HSL gene expression in 3T3-L1 adipocytes. These results may relate to the mechanism by which EGCG modulates lipolysis in adipocytes. Copyright 2009 John Wiley & Sons, Ltd.

  18. Lipid-Derived Biofuels: Determination of Factors that Control Triglyceride Accumulation in Microalgae

    Science.gov (United States)

    2012-10-30

    Accumulation in Microalgae Principal Investigator Dr. K.E. Cooksey Department of Microbiology 109 Lewis Hall Montana State University...cultures to find the extent to which previously published results can be considered general for microalgae . Task 2. Quantify growth kinetics and...diatoms cultures to find the extent to which previous results can be found to be general for microalgae . Before this project, detailed

  19. Higher lipid accumulation in broilers fed on saturated fats than in those fed on unsaturated fats.

    Science.gov (United States)

    Sanz, M; Flores, A; De Ayala, P P; Lopez-Bote, C J

    1999-03-01

    1. Two experiments were conducted to assess the effect of fat sources differing in degree of saturation on the performance of and fat deposition in broiler chickens fed on isocaloric and isonitrogenous diets. 2. There were no differences in initial body weight between sexes but female broilers had lower daily gains (Psaturation. Broilers fed on diets containing an animal fat blend or tallow had higher abdominal fat pad weight (Psaturation affects fat accumulation in broiler chickens.

  20. Lipid and protein accumulation in developing seeds of three lupine species: Lupinus luteus L., Lupinus albus L., and Lupinus mutabilis Sweet.

    Science.gov (United States)

    Borek, Slawomir; Pukacka, Stanisława; Michalski, Krzysztof; Ratajczak, Lech

    2009-01-01

    A comparative study was carried out on the dynamics of lipid accumulation in developing seeds of three lupine species. Lupine seeds differ in lipid content; yellow lupine (Lupinus luteus L.) seeds contain about 6%, white lupine (Lupinus albus L.) 7-14%, and Andean lupine (Lupinus mutabilis Sweet) about 20% of lipids by dry mass. Cotyledons from developing seeds were isolated and cultured in vitro for 96 h on Heller medium with 60 mM sucrose (+S) or without sucrose (-S). Each medium was additionally enriched with 35 mM asparagine or 35 mM NaNO3. Asparagine caused an increase in protein accumulation and simultaneously decreased the lipid content, but nitrate increased accumulation of both protein and lipid. Experiments with [1-14C]acetate and [2-14C]acetate showed that the decrease in lipid accumulation in developing lupine seeds resulted from exhaustion of lipid precursors rather than from degradation or modification of the enzymatic apparatus. The carbon atom from the C-1 position of acetate was liberated mainly as CO2, whereas the carbon atom from the C-2 position was preferentially used in anabolic pathways. The dominant phospholipid in the investigated lupine seed storage organs was phosphatidylcholine. The main fatty acid in yellow lupine cotyledons was linoleic acid, in white lupine it was oleic acid, and in Andean lupine it was both linoleic and oleic acids. The relationship between stimulation of lipid and protein accumulation by nitrate in developing lupine cotyledons and enhanced carbon flux through glycolysis caused by the inorganic nitrogen form is discussed.

  1. Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

    Science.gov (United States)

    Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R; Kukic, Ira; Kiselyov, Kirill; Halfter, Willi; Finegold, David; do Monte, Semiramis Jamil Hadad; Weisz, Ora A

    2014-02-01

    Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by α-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of α-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI)-anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of α-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed.

  2. Catechins and Caffeine Inhibit Fat Accumulation in Mice through the Improvement of Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Chikako Sugiura

    2012-01-01

    Full Text Available To elucidate the inhibiting mechanisms of fat accumulation by catechins, caffeine, and epigallocatechin gallate (EGCG, ICR mice were fed diets containing either 0.3% catechins or 0.1% EGCG and/or 0.05% caffeine for 4 weeks. After the feeding, intraperitoneal adipose tissues weights were significantly lower in the caffeine, catechins + caffeine, and EGCG + caffeine groups compared to controls. Hepatic fatty acid synthase (FAS activity in the catechins + caffeine group was significantly lower, and the activities of acyl-CoA oxidase (ACO and carnitine palmitoyltransferase-II (CPT-II were significantly higher, compared to the control group. However, these activities were not observed in the other groups. FAS mRNA expression levels in the catechins + caffeine group were significantly lower than in the control group. ACO and CPT-II mRNA levels were not different among all of the treatment groups. These findings indicate that the inhibitory effects of fat accumulation via a combination of catechins, EGCG, or caffeine were stronger collectively than by either catechins, EGCG, or caffeine alone. Moreover, it was demonstrated that the combination of catechins and caffeine induced inhibition of fat accumulation by suppression of fatty acid synthesis and upregulation of the enzymatic activities involved in β-oxidation of fatty acid in the liver, but this result was not observed by combination of EGCG and caffeine.

  3. Catechins and Caffeine Inhibit Fat Accumulation in Mice through the Improvement of Hepatic Lipid Metabolism.

    Science.gov (United States)

    Sugiura, Chikako; Nishimatsu, Shiho; Moriyama, Tatsuya; Ozasa, Sayaka; Kawada, Teruo; Sayama, Kazutoshi

    2012-01-01

    To elucidate the inhibiting mechanisms of fat accumulation by catechins, caffeine, and epigallocatechin gallate (EGCG), ICR mice were fed diets containing either 0.3% catechins or 0.1% EGCG and/or 0.05% caffeine for 4 weeks. After the feeding, intraperitoneal adipose tissues weights were significantly lower in the caffeine, catechins + caffeine, and EGCG + caffeine groups compared to controls. Hepatic fatty acid synthase (FAS) activity in the catechins + caffeine group was significantly lower, and the activities of acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-II (CPT-II) were significantly higher, compared to the control group. However, these activities were not observed in the other groups. FAS mRNA expression levels in the catechins + caffeine group were significantly lower than in the control group. ACO and CPT-II mRNA levels were not different among all of the treatment groups. These findings indicate that the inhibitory effects of fat accumulation via a combination of catechins, EGCG, or caffeine were stronger collectively than by either catechins, EGCG, or caffeine alone. Moreover, it was demonstrated that the combination of catechins and caffeine induced inhibition of fat accumulation by suppression of fatty acid synthesis and upregulation of the enzymatic activities involved in β-oxidation of fatty acid in the liver, but this result was not observed by combination of EGCG and caffeine.

  4. Genetic improvement of the microalga Phaeodactylum tricornutum for boosting neutral lipid accumulation.

    Science.gov (United States)

    Xue, Jiao; Niu, Ying-Fang; Huang, Tan; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2015-01-01

    To obtain fast growing oil-rich microalgal strains has been urgently demanded for microalgal biofuel. Malic enzyme (ME), which is involved in pyruvate metabolism and carbon fixation, was first characterized in microalgae here. Overexpression of Phaeodactylum tricornutum ME (PtME) significantly enhanced the expression of PtME and its enzymatic activity in transgenic P. tricornutum. The total lipid content in transgenic cells markedly increased by 2.5-fold and reached a record 57.8% of dry cell weight with a similar growth rate to wild type, thus keeping a high biomass. The neutral lipid content was further increased by 31% under nitrogen-deprivation treatment, still 66% higher than that of wild type. Transgenic microalgae cells exhibited obvious morphological changes, as the cells were shorter and thicker and contained larger oil bodies. Immuno-electron microscopy targeted PtME to the mitochondrion. This study markedly increased the oil content in microalgae, suggesting a new route for developing ideal microalgal strains for industrial biodiesel production.

  5. Artificial Neural Network Model of Hydrocarbon Migration and Accumulation

    Institute of Scientific and Technical Information of China (English)

    刘海滨; 吴冲龙

    2002-01-01

    Based on the dynamic simulation of the 3-D structure the sedimentary modeling, the unit entity model has been adopted to transfer the heterogeneous complex pas sage system into limited simple homogeneous entity, and then the traditional dyn amic simulation has been used to calculate the phase and the drive forces of the hyd rocarbon , and the artificial neural network(ANN) technology has been applied to resolve such problems as the direction, velocity and quantity of the hydrocarbo n migration among the unit entities. Through simulating of petroleum migration a nd accumulation in Zhu Ⅲ depression, the complex mechanism of hydrocarbon migra tion and accumulation has been opened out.

  6. D-stat culture for studying the metabolic shifts from oxidative metabolism to lipid accumulation and citric acid production in Yarrowia lipolytica.

    Science.gov (United States)

    Ochoa-Estopier, Abril; Guillouet, Stéphane E

    2014-01-20

    Lipid accumulation in oleaginous yeasts is triggered by nutrient imbalance in the culture medium between the carbon source in excess and the nitrogen source in limiting concentration. However Yarrowia lipolytica when cultivated on glucose as the sole carbon source, mainly produces citric acid upon nitrogen limitation over lipid accumulation (only 5-10% triacylglycerol). Therefore for developing bioprocess for the production of triacylglycerol from renewable carbon source as glucose it is of first importance to control this imbalance in order to avoid citric acid production during TAG accumulation. Using D-stat cultivation system, where the N/C was linearly decreased using a constant change rate we were able to identify the N/C ratio inducing TAG accumulation (0.085NmolCmol(-1)) and citric acid (0.021NmolCmol(-1)). We therefore demonstrated that it was possible to accumulate lipids without excretion citric acid as long as the N/C was within this indicated range. Moreover enzyme specific activities measurement during the D-stat indicated that ATP-citrate lyase, malic enzyme and acetyl-coA carboxylase were strongly induced at the onset of lipid accumulation and showed different patterns when citric acid was excreted. Our results give relevant information for future industrial bioprocess development concerning the production of lipids using renewable carbohydrate substrates as an alternative way to produce synthons for fuel or chemical industry. By controlling the N/C over the fermentation process on glucose Y. lipolytica can accumulate lipids without excreting citric acid.

  7. MODELING OF TEMPERATURE FIELDS IN A SOLID HEAT ACCUMULLATORS

    Directory of Open Access Journals (Sweden)

    S. S. Belimenko

    2016-10-01

    Full Text Available Purpose. Currently, one of the priorities of energy conservation is a cost savings for heating in commercial and residential buildings by the stored thermal energy during the night and its return in the daytime. Economic effect is achieved due to the difference in tariffs for the cost of electricity in the daytime and at night. One of the most common types of devices that allow accumulating and giving the resulting heat are solid heat accumulators. The main purpose of the work: 1 software development for the calculation of the temperature field of a flat solid heat accumulator, working due to the heat energy accumulation in the volume of thermal storage material without phase transition; 2 determination the temperature distribution in its volumes at convective heat transfer. Methodology. To achieve the study objectives a heat transfer theory and Laplace integral transform were used. On its base the problems of determining the temperature fields in the channels of heat accumulators, having different cross-sectional shapes were solved. Findings. Authors have developed the method of calculation and obtained solutions for the determination of temperature fields in channels of the solid heat accumulator in conditions of convective heat transfer. Temperature fields over length and thickness of channels were investigated. Experimental studies on physical models and industrial equipment were conducted. Originality. For the first time the technique of calculating the temperature field in the channels of different cross-section for the solid heat accumulator in the charging and discharging modes was proposed. The calculation results are confirmed by experimental research. Practical value. The proposed technique is used in the design of solid heat accumulators of different power as well as full-scale production of them was organized.

  8. A generic model for lipid monolayers, bilayers, and membranes

    CERN Document Server

    Schmid, F; Lenz, O; West, B

    2007-01-01

    We describe a simple coarse-grained model which is suited to study lipid layers and their phase transitions. Lipids are modeled by short semiflexible chains of beads with a solvophilic head and a solvophobic tail component. They are forced to self-assemble into bilayers by a computationally cheap `phantom solvent' environment. The model reproduces the most important phases and phase transitions of monolayers and bilayers. Technical issues such as Monte Carlo parallelization schemes are briefly discussed.

  9. Evidence accumulation as a model for lexical selection.

    Science.gov (United States)

    Anders, R; Riès, S; van Maanen, L; Alario, F X

    2015-11-01

    We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Incorporating microbial ecology into the metabolic modelling of polyphosphate accumulating organisms and glycogen accumulating organisms.

    Science.gov (United States)

    Oehmen, A; Carvalho, G; Lopez-Vazquez, C M; van Loosdrecht, M C M; Reis, M A M

    2010-09-01

    In the enhanced biological phosphorus removal (EBPR) process, the competition between polyphosphate accumulating organisms (PAO) and glycogen accumulating organisms (GAO) has been studied intensively in recent years by both microbiologists and engineers, due to its important effects on phosphorus removal performance and efficiency. This study addresses the impact of microbial ecology on assessing the PAO-GAO competition through metabolic modelling, focussing on reviewing recent developments, discussion of how the results from molecular studies can impact the way we model the process, and offering perspectives for future research opportunities based on unanswered questions concerning PAO and GAO metabolism. Indeed, numerous findings that are seemingly contradictory could in fact be explained by the metabolic behaviour of different sub-groups of PAOs and/or GAOs exposed to different environmental and operational conditions. Some examples include the glycolysis pathway (i.e. Embden-Meyerhof-Parnas (EMP) vs. Entner-Doudoroff (ED)), denitrification capacity, anaerobic tricarboxylic acid (TCA) cycle activity and PAOs' ability to adjust their metabolism to e.g. a GAO-like metabolism. Metabolic modelling may further yield far-reaching influences on practical applications as well, and serves as a bridge between molecular/biochemical research studies and the optimisation of wastewater treatment plant operation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Exogenous glutamine increases lipid accumulation in developing seeds of castor bean (Ricinus communis L. cultured in vitro

    Directory of Open Access Journals (Sweden)

    Zhang Yang

    2015-01-01

    Full Text Available This report describes biomass production and compositional changes of developing castor seeds in response to change in the nitrogen resource (glutamine of the medium. During the early developmental period (24-36 days after pollination, oil was found to initially accumulate in the developing seeds. Carbohydrates and oil were inversely related after glutamine provision (35 mM, in the culture medium. [U-14C] sucrose labeling was used to investigate the effect of metabolic fluxes among different storage materials. Addition of glutamine led to a 7% increase of labeling in lipids and an inverse decrease of labeling in carbohydrates. It was postulated that changes in the glutamine concentration in the medium are likely to influence the partitioning of resources between the various storage products, especially carbohydrates and oil. These observations will contribute to a better understanding of assimilate partitioning in developing castor seeds and the development of molecular strategies to improve castor bean seed quality and plant breeding studies.

  12. Building a multilevel modeling network for lipid processing systems

    DEFF Research Database (Denmark)

    Mustaffa, Azizul Azri; Díaz Tovar, Carlos Axel; Hukkerikar, Amol

    2011-01-01

    data collected from existing process plants, and application of validated models in design and analysis of unit operations; iv) the information and models developed are used as building blocks in the development of methods and tools for computer-aided synthesis and design of process flowsheets (CAFD......The aim of this work is to present the development of a computer aided multilevel modeling network for the systematic design and analysis of processes employing lipid technologies. This is achieved by decomposing the problem into four levels of modeling: i) pure component property modeling...... and a lipid-database of collected experimental data from industry and generated data from validated predictive property models, as well as modeling tools for fast adoption-analysis of property prediction models; ii) modeling of phase behavior of relevant lipid mixtures using the UNIFAC-CI model, development...

  13. Lipid Processing Technology: Building a Multilevel Modeling Network

    DEFF Research Database (Denmark)

    Díaz Tovar, Carlos Axel; Mustaffa, Azizul Azri; Mukkerikar, Amol

    2011-01-01

    in design and analysis of unit operations; iv) the information and models developed are used as building blocks in the development of methods and tools for computer-aided synthesis and design of process flowsheets (CAFD). The applicability of this methodology is highlighted in each level of modeling through......The aim of this work is to present the development of a computer aided multilevel modeling network for the systematic design and analysis of processes employing lipid technologies. This is achieved by decomposing the problem into four levels of modeling: i) pure component property modeling...... and a lipid-database of collected experimental data from industry and generated data from validated predictive property models, as well as modeling tools for fast adoption-analysis of property prediction models; ii) modeling of phase behavior of relevant lipid mixtures using the UNIFACCI model, development...

  14. Evidence accumulation as a model for lexical selection

    NARCIS (Netherlands)

    Anders, R.; Riès, S.; van Maanen, L.; Alario, F.-X.

    2015-01-01

    We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of

  15. Combined nitrogen limitation and cadmium stress stimulate total carbohydrates, lipids, protein and amino acid accumulation in Chlorella vulgaris (Trebouxiophyceae).

    Science.gov (United States)

    Chia, Mathias Ahii; Lombardi, Ana Teresa; da Graça Gama Melão, Maria; Parrish, Christopher C

    2015-03-01

    Metals have interactive effects on the uptake and metabolism of nutrients in microalgae. However, the effect of trace metal toxicity on amino acid composition of Chlorella vulgaris as a function of varying nitrogen concentrations is not known. In this research, C. vulgaris was used to investigate the influence of cadmium (10(-7) and 2.0×10(-8)molL(-1) Cd) under varying nitrogen (2.9×10(-6), 1.1×10(-5) and 1.1×10(-3)molL(-1)N) concentrations on its growth rate, biomass and biochemical composition. Total carbohydrates, total proteins, total lipids, as well as individual amino acid proportions were determined. The combination of Cd stress and N limitation significantly inhibited growth rate and cell density of C. vulgaris. However, increasing N limitation and Cd stress stimulated higher dry weight and chlorophyll a production per cell. Furthermore, biomolecules like total proteins, carbohydrates and lipids increased with increasing N limitation and Cd stress. Ketogenic and glucogenic amino acids were accumulated under the stress conditions investigated in the present study. Amino acids involved in metal chelation like proline, histidine and glutamine were significantly increased after exposure to combined Cd stress and N limitation. We conclude that N limitation and Cd stress affects the physiology of C. vulgaris by not only decreasing its growth but also stimulating biomolecule production.

  16. Defective lipid metabolism in neurodegeneration with brain iron accumulation (NBIA) syndromes: not only a matter of iron.

    Science.gov (United States)

    Colombelli, Cristina; Aoun, Manar; Tiranti, Valeria

    2015-01-01

    Neurodegeneration with brain iron accumulation (NBIA) is a group of devastating and life threatening rare diseases. Adult and early-onset NBIA syndromes are inherited as X-chromosomal, autosomal dominant or recessive traits and several genes have been identified as responsible for these disorders. Among the identified disease genes, only two code for proteins directly involved in iron metabolism while the remaining NBIA genes encode proteins with a wide variety of functions ranging from fatty acid metabolism and autophagy to still unknown activities. It is becoming increasingly evident that many neurodegenerative diseases are associated with metabolic dysfunction that often involves altered lipid metabolism. This is not surprising since neurons have a peculiar and heterogeneous lipid composition critical for the development and correct functioning of the nervous system. This review will focus on specific NBIA forms, namely PKAN, CoPAN, PLAN, FAHN and MPAN, which display an interesting link between neurodegeneration and alteration of phospholipids and sphingolipids metabolism, mitochondrial morphology and membrane remodelling.

  17. Effect of Tween 80 on the growth, lipid accumulation and fatty acid composition of Thraustochytrium aureum ATCC 34304.

    Science.gov (United States)

    Taoka, Yousuke; Nagano, Naoki; Okita, Yuji; Izumida, Hitoshi; Sugimoto, Shinichi; Hayashi, Masahiro

    2011-04-01

    Thraustochytrium aureum ATCC 34304 was grown in the presence and absence of polyoxyethylene sorbitan monooleate (Tween 80). The aim of this work was to obtain basic knowledge about the effect of Tween 80 on growth, lipid accumulation and fatty acid composition in T. aureum. The addition of Tween 80 to a culture medium significantly enhanced the growth of T. aureum, and the biomass increased with an increase of Tween 80 content. Total lipid content and total fatty acid content were significantly higher in 1.0% Tween 80 in comparison with the control (absence of Tween 80). The fatty acid profile showed that the content of C18:1n-9 (oleic acid) significantly increased as a result of the addition of Tween 80. These results indicated that part of the Tween 80 added to the medium was utilized as a carbon source or that the oleate included in Tween 80 was directly incorporated into T. aureum cells as a fatty acid. Neither the DHA content nor the percentage of DHA did not change in spite of the addition of Tween 80. However, the DHA yield significantly increased because the biomass increased due to the addition of Tween 80.

  18. Selection of microalgae for high CO2 fixation efficiency and lipid accumulation from ten Chlorella strains using municipal wastewater.

    Science.gov (United States)

    Hu, Xia; Zhou, Jiti; Liu, Guangfei; Gui, Bing

    2016-08-01

    As significant differences in cellular physiology, metabolic potential and genetics occur among strains with morphological similarity, the screening of appropriate microalgae species for effective CO2 fixation and biodiesel production is extremely critical. In this study, ten strains of Chlorella were cultivated in municipal wastewater influent (MWI) and their tolerance for MWI, CO2 fixation efficiency and lipid productivity were assessed. The results showed that the biomass concentrations of four strains (Chlorella vulgaris, Chlorella 64.01, Chlorella regularis var. minima and Chlorella sp.) were significantly higher than other strains. When the cultivation systems were aerated with 10% CO2, Chlorella sp. showed the highest CO2 fixation efficiency (35.51%), while the highest lipid accumulation (58.48%) was observed with C. vulgaris. Scanning electron microscopy images revealed that the cells of both Chlorella sp. and C. vulgaris kept their normal morphologies after 15day batch culture. These findings indicated that Chlorella sp. and C. vulgaris have fairly good tolerance for MWI, and moreover, Chlorella sp. was appropriate for CO2 fixation while C. vulgaris represented the highest potential for producing biodiesel.

  19. Ginger Essential Oil Ameliorates Hepatic Injury and Lipid Accumulation in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Lai, Yi-Syuan; Lee, Wan-Ching; Lin, Yu-En; Ho, Chi-Tang; Lu, Kuan-Hung; Lin, Shih-Hang; Panyod, Suraphan; Chu, Yung-Lin; Sheen, Lee-Yan

    2016-03-16

    The objective of this study was to investigate the hepatoprotective efficacy and mechanism of action of ginger essential oil (GEO) against the development of nonalcoholic fatty liver disease (NAFLD). Mice were maintained on either a control diet or high-fat diet (HFD) supplemented with GEO (12.5, 62.5, and 125 mg/kg) or citral (2.5 and 25 mg/kg) for 12 weeks. We demonstrated that GEO and its major component (citral) lowered HFD-induced obesity in a dose-dependent manner, accompanied by anti-hyperlipidemic effects by reducing serum free fatty acid, triglyceride, and total cholesterol levels. Moreover, liver histological results showed that administration of 62.5 and 125 mg/kg GEO and 25 mg/kg citral significantly reduced hepatic lipid accumulation. Further assessment by Western blotting and investigation of the lipid metabolism revealed that hepatic protein expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and cytochrome P450 2E1 (CYP2E1) were down-regulated by GEO and citral, indicating that GEO and citral suppressed HFD-stimulated lipid biosynthesis and oxidative stress. Furthermore, GEO and citral effectively enhanced the antioxidant capacities and reduced inflammatory response in mouse liver, which exerted protective effects against steatohepatitis. Collectively, GEO and citral exhibited potent hepatoprotective effects against NAFLD induced by HFD in obese mice. Thus, GEO might be an effective dietary supplement to ameliorate NAFLD-related metabolic diseases, and citral could play a vital role in its management.

  20. Effects of recombinant human growth hormone on hepatic lipid and carbohydrate metabolism in HIV-infected patients with fat accumulation.

    Science.gov (United States)

    Schwarz, Jean-Marc; Mulligan, Kathleen; Lee, Jeongae; Lo, Joan C; Wen, Michael; Noor, Mustafa A; Grunfeld, Carl; Schambelan, Morris

    2002-02-01

    We recently reported that treatment with a pharmacologic dose of recombinant human growth hormone (GH) resulted in a significant loss of body fat and gain in lean tissue in HIV-infected patients with syndromes of fat accumulation. However, insulin-mediated glucose disposal decreased transiently after one month of GH therapy. The present paper focuses on the changes of hepatic carbohydrate and fat metabolism associated with GH treatment in the same subjects. We assessed hepatic insulin sensitivity under both fasting and hyperinsulinemic-euglycemic clamp conditions prior to and after one and six months of GH treatment (3 mg/day) in five patients using stable isotope tracer techniques. Indirect calorimetry, and measurements of lipid concentrations. Fasting endogenous glucose production (EGP) increased significantly at one month (12.0 +/- 0.7 to 14.9 +/- 0.9 micromol/kg/min, P glucogenesis (GNG) (3.5 +/- 0.9 to 5.2 +/- 0.9 and 5.8 +/-1.2 micromol/kg/min, n = 4, P < 0.01 and P < 0.01 at one and six months, respectively); small changes in hepatic glycogenolysis also contributed. Sustained increases in lipolysis and progressive decreases in hepatic fractional de novo lipogenesis (DNL) and triglyceride concentrations occurred with GH treatment. These changes were accompanied by an improved lipid profile with a significant increase in HDL cholesterol and significant decreases in total and LDL cholesterol and triglyceride levels, the latter consistent with the decrease in hepatic DNL. During a hyperinsulinemic-euglycemic glucose clamp, EGP and GNG were markedly suppressed compared to the corresponding time points under fasting conditions, albeit less so when measured after one month of GH treatment. Thus, in HIV-infected patients with abnormal fat distribution, pharmacologic doses of GH improved the overall lipid profile, but worsened glucose homeostasis under both fasting and hyperinsulinemic conditions. The combined implications of these positive and negative metabolic

  1. Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats.

    Science.gov (United States)

    Bonen, Arend; Jain, Swati S; Snook, Laelie A; Han, Xiao-Xia; Yoshida, Yuko; Buddo, Kathryn H; Lally, James S; Pask, Elizabeth D; Paglialunga, Sabina; Beaudoin, Marie-Soleil; Glatz, Jan F C; Luiken, Joost J F P; Harasim, Ewa; Wright, David C; Chabowski, Adrian; Holloway, Graham P

    2015-10-01

    The mechanisms for diet-induced intramyocellular lipid accumulation and its association with insulin resistance remain contentious. In a detailed time-course study in rats, we examined whether a high-fat diet increased intramyocellular lipid accumulation via alterations in fatty acid translocase (FAT/CD36)-mediated fatty acid transport, selected enzymes and/or fatty acid oxidation, and whether intramyocellular lipid accretion coincided with the onset of insulin resistance. We measured, daily (on days 1-7) and/or weekly (for 6 weeks), the diet-induced changes in circulating substrates, insulin, sarcolemmal substrate transporters and transport, selected enzymes, intramyocellular lipids, mitochondrial fatty acid oxidation and basal and insulin-stimulated sarcolemmal GLUT4 and glucose transport. We also examined whether upregulating fatty acid oxidation improved glucose transport in insulin-resistant muscles. Finally, in Cd36-knockout mice, we examined the role of FAT/CD36 in intramyocellular lipid accumulation, insulin sensitivity and diet-induced glucose intolerance. Within 2-3 days, diet-induced increases occurred in insulin, sarcolemmal FAT/CD36 (but not fatty acid binding protein [FABPpm] or fatty acid transporter [FATP]1 or 4), fatty acid transport and intramyocellular triacylglycerol, diacylglycerol and ceramide, independent of enzymatic changes or muscle fatty acid oxidation. Diet-induced increases in mitochondria and mitochondrial fatty acid oxidation and impairments in insulin-stimulated glucose transport and GLUT4 translocation occurred much later (≥21 days). FAT/CD36 ablation impaired insulin-stimulated fatty acid transport and lipid accumulation, improved insulin sensitivity and prevented diet-induced glucose intolerance. Increasing fatty acid oxidation in insulin-resistant muscles improved glucose transport. High-fat feeding rapidly increases intramyocellular lipids (in 2-3 days) via insulin-mediated upregulation of sarcolemmal FAT/CD36 and fatty acid

  2. Lipid domains control myelin basic protein adsorption and membrane interactions between model myelin lipid bilayers.

    Science.gov (United States)

    Lee, Dong Woog; Banquy, Xavier; Kristiansen, Kai; Kaufman, Yair; Boggs, Joan M; Israelachvili, Jacob N

    2014-02-25

    The surface forces apparatus and atomic force microscope were used to study the effects of lipid composition and concentrations of myelin basic protein (MBP) on the structure of model lipid bilayers, as well as the interaction forces and adhesion between them. The lipid bilayers had a lipid composition characteristic of the cytoplasmic leaflets of myelin from "normal" (healthy) and "disease-like" [experimental allergic encephalomyelitis (EAE)] animals. They showed significant differences in the adsorption mechanism of MBP. MBP adsorbs on normal bilayers to form a compact film (3-4 nm) with strong intermembrane adhesion (∼0.36 mJ/m(2)), in contrast to its formation of thicker (7-8 nm) swelled films with weaker intermembrane adhesion (∼0.13 mJ/m(2)) on EAE bilayers. MBP preferentially adsorbs to liquid-disordered submicron domains within the lipid membranes, attributed to hydrophobic attractions. These results show a direct connection between the lipid composition of membranes and membrane-protein adsorption mechanisms that affects intermembrane spacing and adhesion and has direct implications for demyelinating diseases.

  3. Perfluorooctanoic acid rigidifies a model lipid membrane

    NARCIS (Netherlands)

    Brüning, B.A.; Farago, B.

    2014-01-01

    We report a combined dynamic light scattering and neutron spin-echo (NSE) study on vesicles composed of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine under the influence of varying amounts of perfluorooctanoic acid. We study local lipid bilayer undulations using NSE on time

  4. Perfluorooctanoic acid rigidifies a model lipid membrane

    NARCIS (Netherlands)

    Brüning, B.A.; Farago, B.

    2014-01-01

    We report a combined dynamic light scattering and neutron spin-echo (NSE) study on vesicles composed of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine under the influence of varying amounts of perfluorooctanoic acid. We study local lipid bilayer undulations using NSE on time scale

  5. High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation.

    Science.gov (United States)

    Mock, Kaitlin; Lateef, Sundus; Benedito, Vagner A; Tou, Janet C

    2017-01-01

    High-fructose corn syrup-55 (HFCS-55) has been suggested to be more lipogenic than sucrose, which increases the risk for nonalcoholic fatty liver disease (NAFLD) and dyslipidemia. The study objectives were to determine the effects of drinking different sugar-sweetened solutions on hepatic gene expression in relation to liver fatty acid composition and risk of NAFLD. Female rats were randomly assigned (n=7 rats/group) to drink water or water sweetened with 13% (w/v) HFCS-55, sucrose or fructose for 8 weeks. Rats drinking HFCS-55 solution had the highest (P=.03) hepatic total lipid and triglyceride content and histological evidence of fat infiltration. Rats drinking HFCS-55 solution had the highest hepatic de novo lipogenesis indicated by the up-regulation of stearoyl-CoA desaturase-1 and the highest (P55 solution. The observed lipogenic effects were attributed to the slightly higher fructose content of HFCS-55 solution in the absence of differences in macronutrient and total caloric intake between rats drinking HFCS-55 and sucrose solution. Results from gene expression and fatty acid composition analysis showed that, in a hypercaloric state, some types of sugars are more detrimental to the liver. Based on these preclinical study results, excess consumption of caloric sweetened beverage, particularly HFCS-sweetened beverages, should be limited. Published by Elsevier Inc.

  6. Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation.

    Science.gov (United States)

    Malandrino, Maria Ida; Fucho, Raquel; Weber, Minéia; Calderon-Dominguez, María; Mir, Joan Francesc; Valcarcel, Lorea; Escoté, Xavier; Gómez-Serrano, María; Peral, Belén; Salvadó, Laia; Fernández-Veledo, Sonia; Casals, Núria; Vázquez-Carrera, Manuel; Villarroya, Francesc; Vendrell, Joan J; Serra, Dolors; Herrero, Laura

    2015-05-01

    Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.

  7. Lipid accumulation by pelletized culture of Mucor circinelloides on corn stover hydrolysate.

    Science.gov (United States)

    Reis, Cristiano E R; Zhang, Jianguo; Hu, Bo

    2014-09-01

    Microbial oil accumulated by fungal cells is a potential feedstock for biodiesel production, and lignocellulosic materials can serve as the carbon source to support the fungal growth. The dilute acid pretreatment of corn stover can effectively break down its lignin structure, and this process generates a hydrolysate containing mostly xylose at very dilute concentration and numerous by-products that may significantly inhibit the cell growth. This study utilized corn stover hydrolysate as the culture media for the growth of Mucor circinelloides. The results showed that Mucor cells formed pellets during the cell growth, which facilitates the cell harvest from dilute solution. The results also showed that the inhibitory effect of furfural, 5-hydroxymethylfurfural (HMF), and acetic acid could be avoided if their concentration was low. In fact, all these by-products may be assimilated as carbon sources for the fungal growth. The results proved the feasibility to reuse the cultural broth water for acid pretreatment and then use for subsequent cell cultivation. The results will have a direct impact on the overall water usage of the process.

  8. Nickel-induced changes in lipid peroxidation, antioxidative enzymes, and metal accumulation in Lemna gibba.

    Science.gov (United States)

    Yilmaz, Dilek Demirezen; Parlak, Kadiriye Uruç

    2011-09-01

    In this study, an experiment was carried out to study the process of stress adaptation in Lemna gibba grown under nickel stress (0-20 mg Ni L(-1)). The results showed that Ni concentrations in plants increased with increasing Ni supply levels and reached a maximum of 142.82 mg.kg1 DW at 0.5 mg x L(-1) Ni treatments. The level of photosynthetic pigments (Chl a, Chi b, and total Chl) and soluble proteins increased upon exposure to high Ni concentrations. At the same time, the level of malondialdehyde (MDA) increased with increasing Ni concentration. These results suggested an alleviation of stress that was presumably the results of antioxidants such as superoxide dismutase (SOD), catalase (CAT) which generally increased linearly with increasing Ni levels. In addition, the proline content in L. gibba increased with increasing nickel levels. Our present work concluded that Lemna gibba has a high level of nickel tolerance and accumulation. We also found that moderate nickel treatment (0.05-5 mg x L(-1)) alleviated oxidative stress in plants, while the addition of higher amounts of nickel (10-20 mg x L(-1)) could cause an increasing generation of ROS, which was effectively scavenged by the antioxidative system. Therefore, L. gibba may be used as a phytoremediator in moderately polluted aquatic ecosystems.

  9. Modelling phagosomal lipid networks that regulate actin assembly

    Directory of Open Access Journals (Sweden)

    Schwarz Roland

    2008-12-01

    Full Text Available Abstract Background When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel. Results We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds. In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator. However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP. Conclusion By establishing an active 'dialogue' between an

  10. 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

    Science.gov (United States)

    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.

  11. 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.

    Science.gov (United States)

    Yang, Zhenhua; Zhao, Yue; Liu, Zhiyong; Liu, Chenfeng; Hu, Zhipeng; Hou, Yuyong

    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.

  12. 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

    Directory of Open Access Journals (Sweden)

    Zhenhua Yang

    2017-01-01

    Full Text Available 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.

  13. Pycnogenol® inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses.

    Science.gov (United States)

    Lee, Ok-Hwan; Seo, Min-Jung; Choi, Hyeon-Son; Lee, Boo-Yong

    2012-03-01

    Pycnogenol® is a group of flavonoids with antioxidant effects. Adipogenesis is the process of adipocyte differentiation. It causes the increase of lipids as well as ROS (reactive oxygen species). Lipid accumulation and ROS production were determined in 3 T3-L1 adipocyte, and the effect of Pycnogenol® was evaluated. Lipid accumulation was elevated in adipocyte treated with hydrogen peroxide, one of the ROS. Pycnogenol® showed an inhibitory effect on the lipid accumulation and ROS production during the adipogenesis. We also investigated the molecular events associated with ROS production and lipid accumulation. Our results showed that Pycnogenol® inhibited the mRNA expression of pro-oxidant enzymes, such as NOX4 (NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase 4), and the NADPH-producing G6PDH (glucose-6-phosphate dehydrogenase) enzyme. In addition, Pycnogenol® suppressed the mRNA abundance of adipogenic transcription factors, PPAR-γ (peroxisome proliferator-activated receptor γ) and C/EBP-α (CCAAT/enhancer binding protein α), and their target gene, aP2 (adipocyte protein 2) responsible for fatty acid transportation. On the other hand, Pycnogenol® increased the abundance of antioxidant proteins such as Cu/Zn-SOD (copper-zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and GR (glutathione reductase). Our results suggest that Pycnogenol® inhibits lipid accumulation and ROS production by regulating adipogenic gene expression and pro-/antioxidant enzyme responses in adipocytes.

  14. Identification of multiple lipid genes with modifications in expression and sequence associated with the evolution of hydroxy fatty acid accumulation in Physaria fendleri.

    Science.gov (United States)

    Horn, Patrick J; Liu, Jinjie; Cocuron, Jean-Christophe; McGlew, Kathleen; Thrower, Nicholas A; Larson, Matt; Lu, Chaofu; Alonso, Ana P; Ohlrogge, John

    2016-05-01

    Two Brassicaceae species, Physaria fendleri and Camelina sativa, are genetically very closely related to each other and to Arabidopsis thaliana. Physaria fendleri seeds contain over 50% hydroxy fatty acids (HFAs), while Camelina sativa and Arabidopsis do not accumulate HFAs. To better understand how plants evolved new biochemical pathways with the capacity to accumulate high levels of unusual fatty acids, transcript expression and protein sequences of developing seeds of Physaria fendleri, wild-type Camelina sativa, and Camelina sativa expressing a castor bean (Ricinus communis) hydroxylase were analyzed. A number of potential evolutionary adaptations within lipid metabolism that probably enhance HFA production and accumulation in Physaria fendleri, and, in their absence, limit accumulation in transgenic tissues were revealed. These adaptations occurred in at least 20 genes within several lipid pathways from the onset of fatty acid synthesis and its regulation to the assembly of triacylglycerols. Lipid genes of Physaria fendleri appear to have co-evolved through modulation of transcriptional abundances and alterations within protein sequences. Only a handful of genes showed evidence for sequence adaptation through gene duplication. Collectively, these evolutionary changes probably occurred to minimize deleterious effects of high HFA amounts and/or to enhance accumulation for physiological advantage. These results shed light on the evolution of pathways for novel fatty acid production in seeds, help explain some of the current limitations to accumulation of HFAs in transgenic plants, and may provide improved strategies for future engineering of their production.

  15. Selective Interaction of a Cationic Polyfluorene with Model Lipid Membranes: Anionic versus Zwitterionic Lipids

    Directory of Open Access Journals (Sweden)

    Zehra Kahveci

    2014-03-01

    Full Text Available This paper explores the interaction mechanism between the conjugated polyelectrolyte {[9,9-bis(6'-N,N,N-trimethylammoniumhexyl]fluorene-phenylene}bromide (HTMA-PFP and model lipid membranes. The study was carried out using different biophysical techniques, mainly fluorescence spectroscopy and microscopy. Results show that despite the preferential interaction of HTMA-PFP with anionic lipids, HTMA-PFP shows affinity for zwitterionic lipids; although the interaction mechanism is different as well as HTMA-PFP’s final membrane location. Whilst the polyelectrolyte is embedded within the lipid bilayer in the anionic membrane, it remains close to the surface, forming aggregates that are sensitive to the physical state of the lipid bilayer in the zwitterionic system. The different interaction mechanism is reflected in the polyelectrolyte fluorescence spectrum, since the maximum shifts to longer wavelengths in the zwitterionic system. The intrinsic fluorescence of HTMA-PFP was used to visualize the interaction between polymer and vesicles via fluorescence microscopy, thanks to its high quantum yield and photostability. This technique allows the selectivity of the polyelectrolyte and higher affinity for anionic membranes to be observed. The results confirmed the appropriateness of using HTMA-PFP as a membrane fluorescent marker and suggest that, given its different behaviour towards anionic and zwitterionic membranes, HTMA-PFP could be used for selective recognition and imaging of bacteria over mammalian cells.

  16. Modelling komatiitic melt accumulation and segregation in the transition zone

    Science.gov (United States)

    Schmeling, H.; Arndt, N.

    2017-08-01

    Komatiites are probably produced in very hot mantle upwellings or plumes. Under such conditions, melting will take place deep within the upper mantle or even within the mantle transition zone. Due to its compressibility at such pressures, melt might be denser than olivine, but would remain buoyant with respect to a peridotitic mantle both above and below the olivine-wadsleyite phase boundary because of the presence of its higher temperature and denser garnet. We studied the physics of melting and melt segregation within hot upwelling mantle passing through the transition zone, with particular emphasis on the effect of depth-dependent density contrasts between melt and ambient mantle. Assuming a 1D plume, we solved the two-phase flow equations of the melt-matrix system accounting for matrix compaction and porosity-dependent shear and bulk viscosity. We assumed a constant ascent velocity and melt generation rate. In a first model series, the level of neutral buoyancy zneutr is assumed to lie above the depth of onset of melting, i.e. there exists a region where dense melt may lag behind the solid phases within the rising plume. Depending on two non-dimensional numbers (accumulation number Ac, compaction resistance number Cr) we find four regimes: 1) time-dependent melt accumulation in standing porosity waves that scale with the compaction length. The lowermost of these waves broadens with time until a high melt accumulation zone is formed in steady state. During this transient solitary porosity waves may cross the depth of neutral density and escape. 2) steady-state weak melt accumulation near zneutr, 3) no melt accumulation due to small density contrast or, 4) high matrix viscosity. In regime 4 the high mantle viscosity prevents the opening of pore space necessary to accumulate melt. In a second series, the rising mantle crosses the olivine-wadsleyite phase boundary, which imposes a jump in density contrast between melt and ambient mantle. A sharp melt porosity

  17. Models to estimate phytomass accumulation of hydroponic lettuce

    OpenAIRE

    Lopes,Sidinei José; Dourado Neto,Durval; MANFRON, Paulo Augusto; Jasniewicz,Luís Renato

    2004-01-01

    The protected and hydroponics cultivation are increasing in Brazil, demanding a better knowledge of crop performance in this environment. Plant dry matter accumulation as a function of solar radiation, temperature, relative humidity and other weather parameters in greenhouse is different when compared with field cultivation. With the purpose of proposing models to characterize the temporal variation of leaf and total dry matter production of hydroponics-grown lettuce (Lactuca sativa L.) and t...

  18. Growth versus environment in dynamic models of capital accumulation

    Directory of Open Access Journals (Sweden)

    Toichiro Asada

    2002-01-01

    Full Text Available In this paper, we study the economic implications of the trade off between growth and environment in the context of dynamic models of capital accumulation. The collective solution is formulated in terms of dynamic optimization of the central planner, and the decentralized solution is formulated in terms of differential game between workers and capitalists. We compare the economic properties of two solutions.

  19. Changes in mechanical properties of the cuticle and lipid accumulation in relation to adult diapause in the bean bug, Riptortus clavatus.

    Science.gov (United States)

    Morita, A; Soga, K; Hoson, T; Kamisaka, S; Numata, H

    1999-03-01

    Photoperiodically controlled adult diapause in the bean bug, Riptortus clavatus (Thunberg) (Heteroptera: Alydidae) was due to suppression of corpus allatum activity under short-day conditions. The mechanical extensibility of the cuticle of the pronotum was significantly higher in nondiapause adults reared under long-day conditions than in diapause adults reared under short-day conditions. Furthermore, diapause adults accumulated significantly larger amount of lipids than nondiapause ones. It was then examined whether these two characteristics of adult diapause also depend on activity of the corpus allatum, by removal of the corpus allatum and transection of the nervi corporis allati. Even after these two kinds of surgery, adults responded to photoperiod and showed similar differences both in mechanical properties of the cuticle and in lipid content between long-day and short-day conditions. Therefore, inactivity of the corpus allatum is not responsible for the stiffer cuticle or higher lipid accumulation in diapause adults.

  20. An exactly solvable, spatial model of mutation accumulation in cancer

    Science.gov (United States)

    Paterson, Chay; Nowak, Martin A.; Waclaw, Bartlomiej

    2016-12-01

    One of the hallmarks of cancer is the accumulation of driver mutations which increase the net reproductive rate of cancer cells and allow them to spread. This process has been studied in mathematical models of well mixed populations, and in computer simulations of three-dimensional spatial models. But the computational complexity of these more realistic, spatial models makes it difficult to simulate realistically large and clinically detectable solid tumours. Here we describe an exactly solvable mathematical model of a tumour featuring replication, mutation and local migration of cancer cells. The model predicts a quasi-exponential growth of large tumours, even if different fragments of the tumour grow sub-exponentially due to nutrient and space limitations. The model reproduces clinically observed tumour growth times using biologically plausible rates for cell birth, death, and migration rates. We also show that the expected number of accumulated driver mutations increases exponentially in time if the average fitness gain per driver is constant, and that it reaches a plateau if the gains decrease over time. We discuss the realism of the underlying assumptions and possible extensions of the model.

  1. Chalcones suppress fatty acid-induced lipid accumulation through a LKB1/AMPK signaling pathway in HepG2 cells.

    Science.gov (United States)

    Zhang, Tianshun; Yamamoto, Norio; Ashida, Hitoshi

    2014-06-01

    Excessive lipid accumulation in the liver has been proposed to cause hyperlipidemia, diabetes and fatty liver disease. 4-Hydroxyderricin (4HD), xanthoangelol (XAG), cardamonin (CAR) and flavokawain B (FKB) are chalcones that have exhibited various biological effects against obesity, inflammation, and diabetes; however, little is known about the inhibitory effects of these chalcones on fatty liver disease. In the present study, we investigated the ability of 4HD, XAG, CAR, and FKB to reduce lipid accumulation in hepatocytes. When HepG2 cells were treated with a mixture of fatty acids (FAs; palmitic acid : oleic acid = 1 : 2 ratio), significant lipid accumulation was observed. Under the same experimental conditions, addition of chalcones at 5 μM significantly suppressed the FA-induced lipid accumulation. We found that the expression of sterol regulatory element-binding protein-1 (SREBP-1), a key molecule involved in lipogenesis, was decreased in these chalcone-treated cells. We also found that these chalcones increased the expression of peroxisome proliferator-activated receptor α (PPARα), which is involved in FA oxidation. Moreover, these chalcones increased phosphorylation of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1), upstream regulators of SREBP-1 and PPARα. We confirmed that an AMPK inhibitor, compound C, reversed chalcone-induced changes in SREBP-1 and PPARα expression in the HepG2 cells. Collectively, we found that 4HD, XAG, CAR, and XAG attenuated lipid accumulation through activation of the LKB1/AMPK signaling pathway in HepG2 cells.

  2. Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity.

    Science.gov (United States)

    Vogel, Alexander; Nikolaus, Jörg; Weise, Katrin; Triola, Gemma; Waldmann, Herbert; Winter, Roland; Herrmann, Andreas; Huster, Daniel

    2014-07-01

    Ternary lipid mixtures composed of cholesterol, saturated (frequently with sphingosine backbone), and unsaturated phospholipids show stable phase separation and are often used as model systems of lipid rafts. Yet, their ability to reproduce raft properties and function is still debated. We investigated the properties and functional aspects of three lipid raft model systems of varying degrees of biological relevance--PSM/POPC/Chol, DPPC/POPC/Chol, and DPPC/DOPC/Chol--using 2H solid-state nuclear magnetic resonance (NMR) spectroscopy, fluorescence microscopy, and atomic force microscopy. While some minor differences were observed, the general behavior and properties of all three model mixtures were similar to previously investigated influenza envelope lipid membranes, which closely mimic the lipid composition of biological membranes. For the investigation of the functional aspects, we employed the human N-Ras protein, which is posttranslationally modified by two lipid modifications that anchor the protein to the membrane. It was previously shown that N-Ras preferentially resides in liquid-disordered domains and exhibits a time-dependent accumulation in the domain boundaries of influenza envelope lipid membranes. For all three model mixtures, we observed the same membrane partitioning behavior for N-Ras. Therefore, we conclude that even relatively simple models of raft membranes are able to reproduce many of their specific properties and functions.

  3. Fish oil feeding is associated with an increased accumulation of dietary lipids in enterocytes: Results from an in vivo study in rats

    DEFF Research Database (Denmark)

    Larsen, L.F.; Marckmann, P.; Hansen, A.K.

    2003-01-01

    Background: Chronic fish oil consumption is associated with reduced postprandial lipaemia, but the mechanism behind this effect is not fully understood. We studied whether lipid absorption might be altered in rats fed fish oil. Methods: Male Wistar rats were fed fish oil enriched chow (n = 6...... contents of enterocytes were determined by liquid scintillation counting. Two other groups of rats (2 x 6) fed the experimental diets were given an oral fat load and fasting and postprandial blood samples were taken. Results: The accumulation of H-3-lipids in enterocytes was higher in rats fed fish oil...... than in controls (area under the H-3-lipid time curve: 1041.3 versus 670.3 nmol oleic acid x min/mug DNA, P acids occurred in rats fed fish oil. The amount of non-absorbed H-3-lipid tended to be higher in the fish...

  4. Numerical Results of 3-D Modeling of Moon Accumulation

    Science.gov (United States)

    Khachay, Yurie; Anfilogov, Vsevolod; Antipin, Alexandr

    2014-05-01

    For the last time for the model of the Moon usually had been used the model of mega impact in which the forming of the Earth and its sputnik had been the consequence of the Earth's collision with the body of Mercurial mass. But all dynamical models of the Earth's accumulation and the estimations after the Pb-Pb system, lead to the conclusion that the duration of the planet accumulation was about 1 milliard years. But isotopic results after the W-Hf system testify about a very early (5-10) million years, dividing of the geochemical reservoirs of the core and mantle. In [1,2] it is shown, that the account of energy dissipating by the decay of short living radioactive elements and first of all Al26,it is sufficient for heating even small bodies with dimensions about (50-100) km up to the iron melting temperature and can be realized a principal new differentiation mechanism. The inner parts of the melted preplanets can join and they are mainly of iron content, but the cold silicate fragments return to the supply zone and additionally change the content of Moon forming to silicates. Only after the increasing of the gravitational radius of the Earth, the growing area of the future Earth's core can save also the silicate envelope fragments [3]. For understanding the further system Earth-Moon evolution it is significant to trace the origin and evolution of heterogeneities, which occur on its accumulation stage.In that paper we are modeling the changing of temperature,pressure,velocity of matter flowing in a block of 3d spherical body with a growing radius. The boundary problem is solved by the finite-difference method for the system of equations, which include equations which describe the process of accumulation, the Safronov equation, the equation of impulse balance, equation Navier-Stocks, equation for above litho static pressure and heat conductivity in velocity-pressure variables using the Businesque approach.The numerical algorithm of the problem solution in velocity

  5. Insights into thermophilic archaebacterial membrane stability from simplified models of lipid membranes

    Science.gov (United States)

    Davis, Charles H.; Nie, Huifen; Dokholyan, Nikolay V.

    2007-05-01

    Lipid aggregation into fluid bilayers is an essential process for sustaining life. Simplified models of lipid structure, which allow for long time scales or large length scales not obtainable with all-atom simulations, have recently been developed and show promise for describing lipid dynamics in biological systems. Here, we describe two simplified models, a reduced-lipid model and a bola-lipid model for thermophilic bacterial membranes, developed for use with the rapid discrete molecular dynamics simulation method. In the reduced-lipid model, we represent the lipid chain by a series of three beads interacting through pairwise discrete potentials that model hydrophobic attractions between hydrocarbon tails in implicit solvent. Our phase diagram recapitulates those produced by continuous potential models with similar coarse-grained lipid representations. We also find that phase transition temperatures for our reduced-lipid model are dependent upon the flexibility of the lipid chain, giving an insight into archaebacterial membrane stability and prompting development of a bola-lipid model specific for archaebacteria lipids. With both the reduced-lipid and bola-lipid model, we find that the reduced flexibility inherent in archaebacteria lipids yields more stable bilayers as manifested by increased phase transition temperatures. The results of these studies provide a simulation methodology for lipid molecules in biological systems and show that discrete molecular dynamics is applicable to lipid aggregation and dynamics.

  6. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

    Directory of Open Access Journals (Sweden)

    Sabiha S. Chowdhury

    2016-08-01

    Full Text Available Along with diabetes and obesity, chronic kidney disease (CKD is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD for 13–14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.

  7. Inhibition of preadipocyte differentiation and lipid accumulation by Orengedokuto treatment of 3T3-L1 cultures.

    Science.gov (United States)

    Ikarashi, Nobutomo; Tajima, Masataka; Suzuki, Kunihiro; Toda, Takahiro; Ito, Kiyomi; Ochiai, Wataru; Sugiyama, Kiyoshi

    2012-01-01

    Obesity is a major cause of metabolic syndrome and is due to an increase in the number and hypertrophy of adipocytes. Accordingly, inhibition of the differentiation and proliferation of adipocytes may be used in the treatment and prevention of metabolic syndrome. This study investigated the effects of 50 commonly used Kampo medicines on the differentiation of 3T3-L1 preadipocytes to search for a drug with an antiobesity effect. Kampo medicines were screened, and the strongest differentiation-inhibitory effect was noted with Orengedokuto. To explore the active ingredients in Orengedokuto, the effects of four crude drug components of Orengedokuto were investigated. It was found that the differentiation-inhibitory effect of Orengedokuto was accounted for by Coptidis rhizome and Phellodendri cortex. Furthermore, berberine, a principal ingredient common to Coptidis rhizome and Phellodendri cortex, showed a differentiation-inhibitory effect. The effect of berberine involves an inhibition of the mRNA and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). Moreover, berberine inhibited lipid accumulation in adipocytes. These findings suggest that an antiobesity effect could be a new indication for Orengedokuto and that its active ingredient is berberine, with a mechanism involving the inhibition of PPARγ and C/EBPα expression.

  8. Replacing Fish Oil with Vegetable Oils in Salmon Feed Increases Hepatic Lipid Accumulation and Reduces Insulin Sensitivity in Mice

    DEFF Research Database (Denmark)

    Midtbø, Lisa Kolden

    %) of FO with different vegetable oils (VOs); rape seed oil (WDRO), olive oil (WD-OO) or soybean oil (WD-SO). These diets were given to C57BL/6J mice, and mice had higher hepatic lipid accumulation and lower insulin sensitivity when given WD-SO compared with WD-FO. Mice given WD-SO had higher hepatic......Background: Due to a growing global aquaculture production, fish oil (FO) and fish meal (FM) are partly replaced with vegetable ingredients in aqua feed for Atlantic salmon. These replacements in the feed lead to an altered fatty acid composition in the salmon fillet. We aimed to investigate how...... levels of diacylglycerol (DAG), ceramides and arachidonic acid (AA)-derived oxylipins compared with mice fed WD-FO. In addition, C57BL/6J mice were fed fish oil-enriched diets with different carbohydrate sources, and we observed that sucrose dose-dependently abrogate the antiobesity effect of fish oil...

  9. Betel-quid and alcohol use were associated with lipid accumulation product among male factory workers in Taiwan.

    Science.gov (United States)

    Huang, Chih-Fang; Chen, Chao-Tung; Wang, Pei-Ming; Koo, Malcolm

    2015-05-01

    In this study, cardiometabolic risk associated with betel-quid, alcohol and cigarette use, based on a simple index-lipid accumulation product (LAP), was investigated in Taiwanese male factory workers. Male factory workers were recruited during their annual routine health examination at a hospital in south Taiwan. The risk of cardiometabolic disorders was estimated by the use of LAP, calculated as (waist circumference [cm]-65)×(triglyceride concentration [mmol/l]). Multiple linear regression analyses were conducted to assess the risk factors of natural logarithm-transformed LAP. Of the 815 participants, 40% (325/815) were current alcohol users, 30% (248/815) were current smokers and 7% (53/815) were current betel-quid users. Current betel-quid use, alcohol use, older age, lack of exercise and higher body mass index were found to be significant and independent factors associated with natural logarithm-transformed LAP. Betel-quid and alcohol, but not cigarette use, were independent risk factors of logarithm-transformed LAP, adjusting for age, exercise and body mass index in male Taiwanese factory workers. LAP can be considered as a simple and useful method for screening of cardiometabolic risk. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Min Suk; Kim, Jung Hwan; Kim, Hye Jung; Chang, Ki Churl; Park, Sang Won, E-mail: parksw@gnu.ac.kr

    2015-04-15

    Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated protein kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free fatty

  11. Simultaneous effect of nitrate (NO3- concentration, carbon dioxide (CO2 supply and nitrogen limitation on biomass, lipids, carbohydrates and proteins accumulation in Nannochloropsis oculata

    Directory of Open Access Journals (Sweden)

    Aarón Millán-Oropeza

    2015-03-01

    Full Text Available Biodiesel from microalgae is a promising technology. Nutrient limitation and the addition of CO2 are two strategies to increase lipid content in microalgae. There are two different types of nitrogen limitation, progressive and abrupt limitation. In this work, the simultaneous effect of initial nitrate concentration, addition of CO2, and nitrogen limitation on biomass, lipid, protein and carbohydrates accumulation were analyzed. An experimental design was established in which initial nitrogen concentration, culture time and CO2 aeration as independent numerical variables with three levels were considered. Nitrogen limitation was taken into account as a categorical independent variable. For the experimental design, all the experiments were performed with progressive nitrogen limitation. The dependent response variables were biomass, lipid production, carbohydrates and proteins. Subsequently, comparison of both types of limitation i.e. progressive and abrupt limitation, was performed. Nitrogen limitation in a progressive mode exerted a greater effect on lipid accumulation. Culture time, nitrogen limitation and the interaction of initial nitrate concentration with nitrogen limitation had higher influences on lipids and biomass production. The highest lipid production and productivity were at 582 mgL-1 (49.7 % lipid, dry weight basis and 41.5 mgL-1d-1, respectively; under the following conditions: 250 mgL-1 of initial nitrate concentration, CO2 supply of 4% (v/v, 12 d of culturing and 2 d in state of nitrogen starvation induced by progressive limitation. This work presents a novel way to perform simultaneous analysis of the effect of the initial concentration of nitrate, nitrogen limitation, and CO2 supply on growth and lipid production of Nannochloropsis oculata, with the aim to produce potential biofuels feedstock.

  12. Microporous device for local electric recordings on model lipid bilayers

    Science.gov (United States)

    Kaufeld, Theresa; Steinem, Claudia; Schmidt, Christoph F.

    2015-01-01

    A powerful approach for characterizing lipid membranes and embedded proteins is the reconstitution of model lipid bilayers. The extreme fragility of 5 nm thick bilayers is a challenge for device design and requires a trade off of stability against accessibility. We here present a microporous lab-on-chip device that allows us to form stable, solvent-free lipid bilayers from giant unilamellar vesicles (GUVs) in a geometry that provides a unique set of access possibilities. The device is constructed around a micro-fabricated silicon chip with clusters of 1 µm-diameter pores and provides optical access to the lipid bilayers for high-NA epifluorescence imaging. At the same time, solvent exchange is possible on both sides of the lipid bilayer. Complete coverage can be achieved with GUVs, so that voltages can be applied across the lipid bilayer and single-channel currents can be measured using external or integrated silver/silver chloride electrodes. We describe the micro-fabrication by standard cleanroom techniques and the characterization of the device by atomic force microscopy, scanning electron microscopy and impedance spectroscopy. In proof-of-concept experiments we demonstrate that the device is capable of low-noise, single-ion-channel recordings. Electronic Supplementary Information (ESI) available: See DOI: 10.1039/b000000x/

  13. Helical crystallization on lipid nanotubes: streptavidin as a model protein.

    Science.gov (United States)

    Dang, Thanh X; Farah, Sammy J; Gast, Alice; Robertson, Channing; Carragher, Bridget; Egelman, Edward; Wilson-Kubalek, Elizabeth M

    2005-04-01

    In this study, we use streptavidin (SA) as a model system to study helical protein array formation on lipid nanotubes, an alternative to 2D studies on lipid monolayers. We demonstrate that wild-type and a mutant form of SA form helical arrays on biotinylated lipid nanotubes. 3D maps from helical arrays of wild-type and mutant SA were reconstructed using two different approaches: Fourier-Bessel methods and an iterative single particle algorithm. The maps show that wild-type and mutant streptavidin molecules order differently. The molecular packing arrangements of SA on the surface of the lipid nanotubes differ from previously reported lattice packing of SA on biotinylated monolayers. Helical crystallization on lipid nanotubes presents an alternative platform to explore fundamentals of protein ordering, intermolecular protein interaction and phase behavior. We demonstrate that lipid nanotubes offer a robust and reproducible substrate for forming helical protein arrays which present a means for studying protein structure and structure-function relationships.

  14. Asparagine decarboxylation by lipid oxidation products in model systems.

    Science.gov (United States)

    Hidalgo, Francisco J; Delgado, Rosa M; Navarro, José L; Zamora, Rosario

    2010-10-13

    The decarboxylation of asparagine in the presence of alkanals, alkenals, and alkadienals, among other lipid derivatives, was studied in an attempt to understand the reaction pathways by which some lipid oxidation products are able to convert asparagine into acrylamide. Asparagine was converted into 3-aminopropionamide in the presence of lipid derivatives as a function of reaction conditions (pH, water content, time, and temperature), as well as the type and amount of lipid compound involved. Alkadienals (and analogous ketodienes) were the most reactive lipids followed by hydroperoxides and alkenals. Saturated carbonyls and polyunsaturated fatty acids, or other polyunsaturated derivatives, also exhibited some reactivity. On the other hand, saturated lipids or monounsaturated alcohols did not degrade asparagine. A mechanism for the decarboxylation of asparagine in the presence of alkadienals based on the deuteration results obtained when asparagine/2,4-decadienal model systems were heated in the presence of deuterated water was proposed. The activation energy (E(a)) of asparagine decarboxylation by 2,4-decadienal was 81.0 kJ/mol, which is higher than that found for the conversion of 3-aminopropionamide into acrylamide in the presence of 2,4-decadienal. This result points to the decarboxylation step as the key step in the conversion of asparagine into acrylamide in the presence of alkadienals. Therefore, any inhibiting strategy for suppressing the formation of acrylamide by alkadienals should be mainly directed to the inhibition of this step.

  15. Simulation modeling of supported lipid membranes - a review.

    Science.gov (United States)

    Hirtz, Michael; Kumar, Naresh; Chi, Lifeng

    2014-03-01

    Lipid membranes are of great importance for many biological systems and biotechnological applications. One method to gain a profound understanding of the dynamics in lipid membranes and their interaction with other system components is by modeling these systems by computer simulations. Many different approaches have been undertaken in this endeavor that have led to molecular level insights into the underlying mechanisms of several experimental observations and biological processes with an extremely high temporal resolution. As compared to the free-standing lipid bilayers, there are fewer simulation studies addressing the systems of supported lipid membranes. Nevertheless, these have significantly enhanced our understanding of the behavior of lipid layers employed in applications spanning from biosensors to drug delivery and for biological processes such as the breathing cycle of lung surfactants. In this review, we give an account of the state of the art of methods and applications of the simulations of supported lipid bilayers, interfacial membranes at the air/water interface and on solid surfaces.

  16. Protein-lipid interactions in bilayer membranes: a lattice model.

    Science.gov (United States)

    Pink, D A; Chapman, D

    1979-04-01

    A lattice model has been developed to study the effects of intrinsic membrane proteins upon the thermodynamic properties of a lipid bilayer membrane. We assume that only nearest-neighbor van der Waals and steric interactions are important and that the polar group interactions can be represented by effective pressure-area terms. Phase diagrams, the temperature T(0), which locates the gel-fluid melting, the transition enthalpy, and correlations were calculated by mean field and cluster approximations. Average lipid chain areas and chain areas when the lipid is in a given protein environment were obtained. Proteins that have a "smooth" homogeneous surface ("cholesterol-like") and those that have inhomogeneous surfaces or that bind lipids specifically were considered. We find that T(0) can vary depending upon the interactions and that another peak can appear upon the shoulder of the main peak which reflects the melting of a eutectic mixture. The transition enthalpy decreases generally, as was found before, but when a second peak appears departures from this behavior reflect aspects of the eutectic mixture. We find that proteins have significant nonzero probabilities for being adjacent to one another so that no unbroken "annulus" of lipid necessarily exists around a protein. If T(0) does not increase much, or decreases, with increasing c, then lipids adjacent to a protein cannot all be all-trans on the time scale (10(-7) sec) of our system. Around a protein the lipid correlation depth is about one lipid layer, and this increases with c. Possible consequences of ignoring changes in polar group interactions due to clustering of proteins are discussed.

  17. A Combination of Flaxseed Oil and Astaxanthin Improves Hepatic Lipid Accumulation and Reduces Oxidative Stress in High Fat-Diet Fed Rats

    Directory of Open Access Journals (Sweden)

    Jiqu Xu

    2017-03-01

    Full Text Available Hepatic lipid accumulation and oxidative stress are crucial pathophysiological mechanisms for non-alcoholic fatty liver disease (NAFLD. Thus, we examined the effect of a combination of flaxseed oil (FO and astaxanthin (ASX on hepatic lipid accumulation and oxidative stress in rats fed a high-fat diet. ASX was dissolved in flaxseed oil (1 g/kg; FO + ASX. Animals were fed diets containing 20% fat, where the source was lard, or 75% lard and 25% FO + ASX, or 50% lard and 50% FO + ASX, or FO + ASX, for 10 weeks. Substitution of lard with FO + ASX reduced steatosis and reduced hepatic triacylglycerol and cholesterol. The combination of FO and ASX significantly decreased hepatic sterol regulatory element-binding transcription factor 1 and 3-hydroxy-3-methylglutaryl-CoA reductase but increased peroxisome proliferator activated receptor expression. FO + ASX significantly suppressed fatty acid synthase and acetyl CoA carboxylase but induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. FO + ASX also significantly elevated hepatic SOD, CAT and GPx activity and GSH, and markedly reduced hepatic lipid peroxidation. Thus, FO and ASX may reduce NAFLD by reversing hepatic steatosis and reducing lipid accumulation and oxidative stress.

  18. A Combination of Flaxseed Oil and Astaxanthin Improves Hepatic Lipid Accumulation and Reduces Oxidative Stress in High Fat-Diet Fed Rats

    Science.gov (United States)

    Xu, Jiqu; Rong, Shuang; Gao, Hui; Chen, Chang; Yang, Wei; Deng, Qianchun; Huang, Qingde; Xiao, Lingyun; Huang, Fenghong

    2017-01-01

    Hepatic lipid accumulation and oxidative stress are crucial pathophysiological mechanisms for non-alcoholic fatty liver disease (NAFLD). Thus, we examined the effect of a combination of flaxseed oil (FO) and astaxanthin (ASX) on hepatic lipid accumulation and oxidative stress in rats fed a high-fat diet. ASX was dissolved in flaxseed oil (1 g/kg; FO + ASX). Animals were fed diets containing 20% fat, where the source was lard, or 75% lard and 25% FO + ASX, or 50% lard and 50% FO + ASX, or FO + ASX, for 10 weeks. Substitution of lard with FO + ASX reduced steatosis and reduced hepatic triacylglycerol and cholesterol. The combination of FO and ASX significantly decreased hepatic sterol regulatory element-binding transcription factor 1 and 3-hydroxy-3-methylglutaryl-CoA reductase but increased peroxisome proliferator activated receptor expression. FO + ASX significantly suppressed fatty acid synthase and acetyl CoA carboxylase but induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. FO + ASX also significantly elevated hepatic SOD, CAT and GPx activity and GSH, and markedly reduced hepatic lipid peroxidation. Thus, FO and ASX may reduce NAFLD by reversing hepatic steatosis and reducing lipid accumulation and oxidative stress. PMID:28335388

  19. Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle.

    Science.gov (United States)

    Vendelbo, M H; Clasen, B F F; Treebak, J T; Møller, L; Krusenstjerna-Hafstrøm, T; Madsen, M; Nielsen, T S; Stødkilde-Jørgensen, H; Pedersen, S B; Jørgensen, J O L; Goodyear, L J; Wojtaszewski, J F P; Møller, N; Jessen, N

    2012-01-15

    During fasting, human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction of insulin-stimulated glucose uptake. The underlying mechanisms controlling insulin action on skeletal muscle under these conditions are unresolved. In a randomized design, we investigated eight healthy subjects after a 72-h fast compared with a 10-h overnight fast. Insulin action on skeletal muscle was assessed by a hyperinsulinemic euglycemic clamp and by determining insulin signaling to glucose transport. In addition, substrate oxidation, skeletal muscle lipid content, regulation of glycogen synthesis, and AMPK signaling were assessed. Skeletal muscle insulin sensitivity was reduced profoundly in response to a 72-h fast and substrate oxidation shifted to predominantly lipid oxidation. This was associated with accumulation of both lipid and glycogen in skeletal muscle. Intracellular insulin signaling to glucose transport was impaired by regulation of phosphorylation at specific sites on AS160 but not TBC1D1, both key regulators of glucose uptake. In contrast, fasting did not impact phosphorylation of AMPK or insulin regulation of Akt, both of which are established upstream kinases of AS160. These findings show that insulin resistance in muscles from healthy individuals is associated with suppression of site-specific phosphorylation of AS160, without Akt or AMPK being affected. This impairment of AS160 phosphorylation, in combination with glycogen accumulation and increased intramuscular lipid content, may provide the underlying mechanisms for resistance to insulin in skeletal muscle after a prolonged fast.

  20. Rapid Accumulation of Total Lipid in Rhizoclonium africanum Kutzing as Biodiesel Feedstock under Nutrient Limitations and the Associated Changes at Cellular Level

    Directory of Open Access Journals (Sweden)

    Gour Gopal Satpati

    2015-01-01

    Full Text Available Increase of total lipid and the proportion of the favorable fatty acids in marine green filamentous macroalga Rhizoclonium africanum (Chlorophyceae was studied under nitrate and phosphate limitations. These stresses were given by both eliminating and doubling the required amounts of nitrate and phosphate salts in the growth media. A significant twofold increase in total lipid (193.03 mg/g was achieved in cells in absence of nitrate in the culture medium, followed by phosphate limitation (142.65 mg/g. The intracellular accumulation of neutral lipids was observed by fluorescence microscopy. The scanning electron microscopic study showed the major structural changes under nutrient starvation. Fourier transform infrared spectroscopy (FTIR revealed the presence of ester (C-O-C stretching, ketone (C-C stretching, carboxylic acid (O-H bending, phosphine (P-H stretching, aromatic (C-H stretching and bending, and alcohol (O-H stretching and bending groups in the treated cells indicating the high accumulation of lipid hydrocarbons in the treated cells. Elevated levels of fatty acids favorable for biodiesel production, that is, C16:0, C16:1, C18:1, and C20:1, were identified under nitrate- and phosphate-deficient conditions. This study shows that the manipulation of cultural conditions could affect the biosynthetic pathways leading to increased lipid production while increasing the proportion of fatty acids suitable for biodiesel production.

  1. CHARMM36 united atom chain model for lipids and surfactants.

    Science.gov (United States)

    Lee, Sarah; Tran, Alan; Allsopp, Matthew; Lim, Joseph B; Hénin, Jérôme; Klauda, Jeffery B

    2014-01-16

    Molecular simulations of lipids and surfactants require accurate parameters to reproduce and predict experimental properties. Previously, a united atom (UA) chain model was developed for the CHARMM27/27r lipids (Hénin, J., et al. J. Phys. Chem. B. 2008, 112, 7008-7015) but suffers from the flaw that bilayer simulations using the model require an imposed surface area ensemble, which limits its use to pure bilayer systems. A UA-chain model has been developed based on the CHARMM36 (C36) all-atom lipid parameters, termed C36-UA, and agreed well with bulk, lipid membrane, and micelle formation of a surfactant. Molecular dynamics (MD) simulations of alkanes (heptane and pentadecane) were used to test the validity of C36-UA on density, heat of vaporization, and liquid self-diffusion constants. Then, simulations using C36-UA resulted in accurate properties (surface area per lipid, X-ray and neutron form factors, and chain order parameters) of various saturated- and unsaturated-chain bilayers. When mixed with the all-atom cholesterol model and tested with a series of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/cholesterol mixtures, the C36-UA model performed well. Simulations of self-assembly of a surfactant (dodecylphosphocholine, DPC) using C36-UA suggest an aggregation number of 53 ± 11 DPC molecules at 0.45 M of DPC, which agrees well with experimental estimates. Therefore, the C36-UA force field offers a useful alternative to the all-atom C36 lipid force field by requiring less computational cost while still maintaining the same level of accuracy, which may prove useful for large systems with proteins.

  2. Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood

    NARCIS (Netherlands)

    Baars, Annemarie; Oosting, Annemarie; Engels, Eefje; Kegler, Diane; Kodde, Andrea; Schipper, Lidewij; Verkade, Henkjan J.; van der Beek, Eline M.

    2016-01-01

    Epidemiological studies have demonstrated protective effects of breast-feeding on childhood obesity. Differences between human milk and infant milk formula (IMF) in dietary lipid structure may contribute to this effect. In our mouse model, feeding a diet containing large lipid droplets coated with

  3. Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood

    NARCIS (Netherlands)

    Baars, Annemarie; Oosting, Annemarie; Engels, Eefje; Kegler, Diane; Kodde, Andrea; Schipper, Lidewij; Verkade, Henkjan J; van der Beek, Eline M

    2016-01-01

    Epidemiological studies have demonstrated protective effects of breast-feeding on childhood obesity. Differences between human milk and infant milk formula (IMF) in dietary lipid structure may contribute to this effect. In our mouse model, feeding a diet containing large lipid droplets coated with p

  4. Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Hiroe Go

    2015-01-01

    Full Text Available The present study was conducted to investigate the effect of Sagunja-tang on the lipid related disease in a rat model of menopausal hyperlipidemia and lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells. In in vivo study using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media thickness, and nonalcoholic steatohepatitis score, when compared to menopausal hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased the lipid accumulation, total cholesterol levels, and low-density/very-low-density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-β-cyclodextrin-induced decrease in the protein levels of critical molecule involved in cholesterol synthesis, sterol regulatory element binding protein-2, and low-density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of AMP-activated protein kinase was stimulated by Sagunja-tang. These results suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation through regulation of cholesterol synthesis and AMPK activity in vitro. These observations support the idea that Sagunja-tang is bioavailable both in vivo and in vitro and could be developed as a preventive and therapeutic agent of hyperlipidemia in postmenopausal females.

  5. Statistical 3D damage accumulation model for ion implant simulators

    CERN Document Server

    Hernandez-Mangas, J M; Enriquez, L E; Bailon, L; Barbolla, J; Jaraiz, M

    2003-01-01

    A statistical 3D damage accumulation model, based on the modified Kinchin-Pease formula, for ion implant simulation has been included in our physically based ion implantation code. It has only one fitting parameter for electronic stopping and uses 3D electron density distributions for different types of targets including compound semiconductors. Also, a statistical noise reduction mechanism based on the dose division is used. The model has been adapted to be run under parallel execution in order to speed up the calculation in 3D structures. Sequential ion implantation has been modelled including previous damage profiles. It can also simulate the implantation of molecular and cluster projectiles. Comparisons of simulated doping profiles with experimental SIMS profiles are presented. Also comparisons between simulated amorphization and experimental RBS profiles are shown. An analysis of sequential versus parallel processing is provided.

  6. Statistical 3D damage accumulation model for ion implant simulators

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez-Mangas, J.M. E-mail: jesman@ele.uva.es; Lazaro, J.; Enriquez, L.; Bailon, L.; Barbolla, J.; Jaraiz, M

    2003-04-01

    A statistical 3D damage accumulation model, based on the modified Kinchin-Pease formula, for ion implant simulation has been included in our physically based ion implantation code. It has only one fitting parameter for electronic stopping and uses 3D electron density distributions for different types of targets including compound semiconductors. Also, a statistical noise reduction mechanism based on the dose division is used. The model has been adapted to be run under parallel execution in order to speed up the calculation in 3D structures. Sequential ion implantation has been modelled including previous damage profiles. It can also simulate the implantation of molecular and cluster projectiles. Comparisons of simulated doping profiles with experimental SIMS profiles are presented. Also comparisons between simulated amorphization and experimental RBS profiles are shown. An analysis of sequential versus parallel processing is provided.

  7. Comparative analyses of three Chlorella species in response to light and sugar reveal distinctive lipid accumulation patterns in the Microalga C. sorokiniana.

    Science.gov (United States)

    Rosenberg, Julian N; Kobayashi, Naoko; Barnes, Austin; Noel, Eric A; Betenbaugh, Michael J; Oyler, George A

    2014-01-01

    While photosynthetic microalgae, such as Chlorella, serve as feedstocks for nutritional oils and biofuels, heterotrophic cultivation can augment growth rates, support high cell densities, and increase triacylglycerol (TAG) lipid content. However, these species differ significantly in their photoautotrophic and heterotrophic characteristics. In this study, the phylogeny of thirty Chlorella strains was determined in order to inform bioprospecting efforts and detailed physiological assessment of three species. The growth kinetics and lipid biochemistry of C. protothecoides UTEX 411, C. vulgaris UTEX 265, and C. sorokiniana UTEX 1230 were quantified during photoautotrophy in Bold's basal medium (BBM) and heterotrophy in BBM supplemented with glucose (10 g L-1). Heterotrophic growth rates of UTEX 411, 265, and 1230 were found to be 1.5-, 3.7-, and 5-fold higher than their respective autotrophic rates. With a rapid nine-hour heterotrophic doubling time, Chlorella sorokiniana UTEX 1230 maximally accumulated 39% total lipids by dry weight during heterotrophy compared to 18% autotrophically. Furthermore, the discrete fatty acid composition of each strain was examined in order to elucidate lipid accumulation patterns under the two trophic conditions. In both modes of growth, UTEX 411 and 265 produced 18:1 as the principal fatty acid while UTEX 1230 exhibited a 2.5-fold enrichment in 18:2 relative to 18:1. Although the total lipid content was highest in UTEX 411 during heterotrophy, UTEX 1230 demonstrated a two-fold increase in its heterotrophic TAG fraction at a rate of 28.9 mg L(-1) d(-1) to reach 22% of the biomass, corresponding to as much as 90% of its total lipids. Interestingly, UTEX 1230 growth was restricted during mixotrophy and its TAG production rate was suppressed to 18.2 mg L-1 d-1. This constraint on carbon flow raises intriguing questions about the impact of sugar and light on the metabolic regulation of microalgal lipid biosynthesis.

  8. Comparative analyses of three Chlorella species in response to light and sugar reveal distinctive lipid accumulation patterns in the Microalga C. sorokiniana.

    Directory of Open Access Journals (Sweden)

    Julian N Rosenberg

    Full Text Available While photosynthetic microalgae, such as Chlorella, serve as feedstocks for nutritional oils and biofuels, heterotrophic cultivation can augment growth rates, support high cell densities, and increase triacylglycerol (TAG lipid content. However, these species differ significantly in their photoautotrophic and heterotrophic characteristics. In this study, the phylogeny of thirty Chlorella strains was determined in order to inform bioprospecting efforts and detailed physiological assessment of three species. The growth kinetics and lipid biochemistry of C. protothecoides UTEX 411, C. vulgaris UTEX 265, and C. sorokiniana UTEX 1230 were quantified during photoautotrophy in Bold's basal medium (BBM and heterotrophy in BBM supplemented with glucose (10 g L-1. Heterotrophic growth rates of UTEX 411, 265, and 1230 were found to be 1.5-, 3.7-, and 5-fold higher than their respective autotrophic rates. With a rapid nine-hour heterotrophic doubling time, Chlorella sorokiniana UTEX 1230 maximally accumulated 39% total lipids by dry weight during heterotrophy compared to 18% autotrophically. Furthermore, the discrete fatty acid composition of each strain was examined in order to elucidate lipid accumulation patterns under the two trophic conditions. In both modes of growth, UTEX 411 and 265 produced 18:1 as the principal fatty acid while UTEX 1230 exhibited a 2.5-fold enrichment in 18:2 relative to 18:1. Although the total lipid content was highest in UTEX 411 during heterotrophy, UTEX 1230 demonstrated a two-fold increase in its heterotrophic TAG fraction at a rate of 28.9 mg L(-1 d(-1 to reach 22% of the biomass, corresponding to as much as 90% of its total lipids. Interestingly, UTEX 1230 growth was restricted during mixotrophy and its TAG production rate was suppressed to 18.2 mg L-1 d-1. This constraint on carbon flow raises intriguing questions about the impact of sugar and light on the metabolic regulation of microalgal lipid biosynthesis.

  9. Assessment of persistent organic pollutants accumulation and lipid peroxidation in two reproductive stages of wild silverside (Odontesthes bonariensis).

    Science.gov (United States)

    Barni, María Florencia Silva; Gonzalez, Mariana; Miglioranza, Karina S B

    2014-01-01

    Persistent organic pollutants (POPs) in streamwater can sometimes exceed the guidelines values reported for biota and human protection in watersheds with intensive agriculture. Oxidative stress and cytotoxicity are some of the markers of exposure to POPs in fish. Accumulation of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) as well as lipid peroxidation (LPO) was assessed in wild silverside (Odontesthes bonariensis) from maturation and pre-spawning stages sampled in a typical soybean growing area. Pollutants were quantified by gas chromatography with electron capture detection and LPO by the method of thiobarbituric acid reactive substances. Concentrations of POPs were in the following order: OCPs>PCBs>PBDEs in all organs and stages. Liver, gills and gonads had the highest OCP concentrations in both sexes and stages with a predominance of endosulfan in all samples. Matured individuals, sampled after endosulfan application period, showed higher endosulfan concentrations than pre-spawning individuals. The predominance of endosulfan sulfate could be due to direct uptake from diet and water column, as well as to the metabolism of the parent compounds in fish. The prevalence of p,p'-DDE in liver would also reflect both the direct uptake and the metabolic transformation of p,p'-DDT to p,p'-DDE by fish. The highest levels of PBDEs and PCBs were found in gills and brain of both stages of growth. The pattern BDE-47>BDE-100 in all samples corresponds to pentaBDE exposure. In the case of PCBs, penta (#101 and 110) and hexa-CB congeners (#153 and 138) dominated in the maturation stages and tri (#18) and tetra-CB (#44 and 52) in pre-spawning stages, suggesting biotransformation or preferential accumulation of heavier congeners during gonadal development. Differences in LPO levels in ovaries were associated with growth dilution and reproductive stage. Differences in LPO levels in gills were related with pesticide

  10. Lamellar cationic lipid-DNA complexes from lipids with a strong preference for planar geometry: A Minimal Electrostatic Model.

    Science.gov (United States)

    Perico, Angelo; Manning, Gerald S

    2014-11-01

    We formulate and analyze a minimal model, based on condensation theory, of the lamellar cationic lipid (CL)-DNA complex of alternately charged lipid bilayers and DNA monolayers in a salt solution. Each lipid bilayer, composed by a random mixture of cationic and neutral lipids, is assumed to be a rigid uniformly charged plane. Each DNA monolayer, located between two lipid bilayers, is formed by the same number of parallel DNAs with a uniform separation distance. For the electrostatic calculation, the model lipoplex is collapsed to a single plane with charge density equal to the net lipid and DNA charge. The free energy difference between the lamellar lipoplex and a reference state of the same number of free lipid bilayers and free DNAs, is calculated as a function of the fraction of CLs, of the ratio of the number of CL charges to the number of negative charges of the DNA phosphates, and of the total number of planes. At the isoelectric point the free energy difference is minimal. The complex formation, already favoured by the decrease of the electrostatic charging free energy, is driven further by the free energy gain due to the release of counterions from the DNAs and from the lipid bilayers, if strongly charged. This minimal model compares well with experiment for lipids having a strong preference for planar geometry and with major features of more detailed models of the lipoplex.

  11. The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

    Science.gov (United States)

    Malavazos, Alexis Elias; Cereda, Emanuele; Ermetici, Federica; Caccialanza, Riccardo; Briganti, Silvia; Rondanelli, Mariangela; Morricone, Lelio

    2015-01-01

    Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P = 0.006 and P = 0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose. PMID:25792981

  12. The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

    Directory of Open Access Journals (Sweden)

    Alexis Elias Malavazos

    2015-01-01

    Full Text Available “Lipid accumulation product” (LAP is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23% adult (age: 18–70 years overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2 having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT and type-2 diabetes mellitus (T2-DM. According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM and composite (IGT + T2-DM abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006 and P=0.007, resp.. LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Manal Mused Almatrafi

    2017-06-01

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

  15. Lipid accumulation product (LAP) as a criterion for the identification of the healthy obesity phenotype in postmenopausal women.

    Science.gov (United States)

    Lwow, Felicja; Jedrzejuk, Diana; Milewicz, Andrzej; Szmigiero, Leszek

    2016-09-01

    Obesity and its complications constitute a major health problem in postmenopausal women. The identification of the obesity phenotype, especially that of metabolically healthy obese (MHO) patients, is a necessary part of obesity treatment protocols. There are several methods to define MHO, but unfortunately, all of them are arbitrary and inconsistent. The aim of this work was to determine whether lipid accumulation product (LAP) could be used as a marker of the MHO phenotype in postmenopausal women. A sample of 345 Polish postmenopausal women aged 50-60years old participated in the study. Participants were classified as obese when their BMI was >27. Receiver operating characteristic curve analysis was performed to estimate the best cutoff for the LAP index value to identify postmenopausal women without metabolic syndrome components. We found that the best cutoff value was LAP ≤29.9, and this value was used to define MHO individuals. With this definition, the identification of MHO individuals could be made when both of the following criteria were met: LAP index ≤29.9 and no arterial hypertension (SBP<130mmHg, DBP<85mmHg). The anthropometric and body fat distribution measurements, as well as the metabolic characteristics of MHO women identified according to the above definition, were compared with those of MHO women identified by two other methods in the literature. These methods and our definition identified similar proportions of MHO women ranging from 11.6% to 16.9%. We found that MHO women identified by all of the definitions used in this study possessed a similar metabolic status, and they did not differ in anthropometric indices or body fat distribution measurements. We concluded that the combination of LAP estimation and arterial blood pressure measurement appear to constitute a useful method for identifying the MHO phenotype in postmenopausal women.

  16. VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Hsiang-Chun Lee

    2016-01-01

    Full Text Available Metabolic syndrome (MetS represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF. We hypothesized that very low density lipoproteins (VLDL in MetS (MetS-VLDL may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL, and MetS-VLDL (msVLDL groups. VLDL (15 µg/g and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 ± 0.23 mm; nVLDL, n = 7, 1.84 ± 0.13 mm; msVLDL, n = 10, 2.18 ± 0.24 mm; p < 0.0001 at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% ± 7.7%, vs. msVLDL, n = 10, 52.9% ± 9.6%; p < 0.05. Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals.

  17. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice.

    Science.gov (United States)

    Goedeke, Leigh; Salerno, Alessandro; Ramírez, Cristina M; Guo, Liang; Allen, Ryan M; Yin, Xiaoke; Langley, Sarah R; Esau, Christine; Wanschel, Amarylis; Fisher, Edward A; Suárez, Yajaira; Baldán, Angel; Mayr, Manuel; Fernández-Hernando, Carlos

    2014-09-01

    Plasma high-density lipoprotein (HDL) levels show a strong inverse correlation with atherosclerotic vascular disease. Previous studies have demonstrated that antagonism of miR-33 in vivo increases circulating HDL and reverse cholesterol transport (RCT), thereby reducing the progression and enhancing the regression of atherosclerosis. While the efficacy of short-term anti-miR-33 treatment has been previously studied, the long-term effect of miR-33 antagonism in vivo remains to be elucidated. Here, we show that long-term therapeutic silencing of miR-33 increases circulating triglyceride (TG) levels and lipid accumulation in the liver. These adverse effects were only found when mice were fed a high-fat diet (HFD). Mechanistically, we demonstrate that chronic inhibition of miR-33 increases the expression of genes involved in fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the livers of mice treated with miR-33 antisense oligonucleotides. We also report that anti-miR-33 therapy enhances the expression of nuclear transcription Y subunit gamma (NFYC), a transcriptional regulator required for DNA binding and full transcriptional activation of SREBP-responsive genes, including ACC and FAS. Taken together, these results suggest that persistent inhibition of miR-33 when mice are fed a high-fat diet (HFD) might cause deleterious effects such as moderate hepatic steatosis and hypertriglyceridemia. These unexpected findings highlight the importance of assessing the effect of chronic inhibition of miR-33 in non-human primates before we can translate this therapy to humans. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  18. Autotrophic growth and lipid production of Chlorella sorokiniana in lab batch and BIOCOIL photobioreactors: Experiments and modeling.

    Science.gov (United States)

    Concas, Alessandro; Malavasi, Veronica; Costelli, Cristina; Fadda, Paolo; Pisu, Massimo; Cao, Giacomo

    2016-07-01

    A novel mathematical model for the quantitative assessment of the effect of dissolved nitrogen on the autotrophic batch-growth and lipid accumulation of Chlorella sorokiniana, is proposed in this work. Model results have been validated through comparison with suitable experimental data performed in lab photobioreactors. Further experiments have been then performed using the BIOCOIL photobioreactor operated in fed-batch mode. The experimental results, which show that a maximum growth rate of 0.52day(-1) and a lipid content equal to 25%wt can be achieved with the BIOICOIL, have been successfully predicted through the proposed model. Therefore, the model might represent a first step toward the development of a tool for the scale-up and optimization of the operating conditions of BIOCOIL photobioreactors. Finally, the fatty acid methyl esters obtained by trans-esterification of lipids extracted from C. sorokiniana, have been analyzed in view of the assessment of their usability for producing biodiesel.

  19. Modeling the Elastic Properties of Lipid Bilayer Membranes

    Science.gov (United States)

    Barry, Edward; Gibaud, Thomas; Zakhary, Mark; Dogic, Zvonimir

    2011-03-01

    Model membranes such as lipid bilayers have been indispensable tools for our understanding of the elastic properties of biological membranes. In this talk, I will introduce a colloidal model for membranes and demonstrate that the physical properties of these colloidal membranes are identical to lipid bilayers. The model system is unique in that the constituent molecules are homogenous and non-amphiphilic, yet their self-assembly into membranes and other hierarchical assemblages, such as a lamellar type phases and chiral ribbons, proceeds spontaneously in solution. Owing to the large size of the constituent molecules, individual molecules can be directly visualized and simultaneous observations at the continuum and molecular lengthscales are used to characterize the behavior of model membranes with unprecedented detail. Moreover, once assembled in solution, molecular interactions can be controlled in situ. In particular, the strength of chiral interactions can be varied, leading to fascinating transitions in behavior that resembles the formation of starfish vesicles. These observations point towards the important role of line tension, and have potential implications for phase separated lipid mixtures or lipid rafts.

  20. Enhancing Alkane Production in Cyanobacterial Lipid Droplets: A Model Platform for Industrially Relevant Compound Production

    Directory of Open Access Journals (Sweden)

    Anantha Peramuna

    2015-03-01

    Full Text Available Cyanobacterial lipid droplets (LDs are packed with hydrophobic energy-dense compounds and have great potential for biotechnological expression and the compartmentalization of high value compounds. Nostoc punctiforme normally accumulates LDs containing neutral lipids, and small amounts of heptadecane, during the stationary phase of growth. In this study, we further enhanced heptadecane production in N. punctiforme by introducing extrachromosomal copies of aar/adc genes, and report the discovery of a putative novel lipase encoded by Npun_F5141, which further enhanced alkane production. Extra copies of all three genes in high light conditions resulted in a 16-fold higher accumulation of heptadecane compared to the wild type strain in the exponential phase. LD accumulation during exponential phase also increased massively to accommodate the heptadecane production. A large number of small, less fluorescent LDs were observed at the cell periphery in exponential growth phase, whereas fewer number of highly fluorescent, much larger LDs were localized towards the center of the cell in the stationary phase. These advances demonstrate that cyanobacterial LDs are an ideal model platform to make industrially relevant compounds, such as alkanes, during exponential growth, and provide insight into LD formation in cyanobacteria.

  1. Fourier transform infrared spectroscopy studies of lipid domain formation in normal and ceramide deficient stratum corneum lipid models.

    Science.gov (United States)

    Gorcea, Mihaela; Hadgraft, Jonathan; Moore, David J; Lane, Majella E

    2012-10-01

    The current work describes thermotropic and kinetic Fourier transform infrared (FTIR) spectroscopy studies of lipid dynamics and domain formation in normal and ceramide (CER) deficient lipid samples designed as simple models of the stratum corneum (SC). For the first time, this work focuses on the time dependence of lipid reorganization and domain formation in CER deficient models. By utilizing deuterated fatty acid (FA) and simultaneously monitoring the methylene vibrational modes of both CER and FA chains these experiments follow the time evolution of lipid organization in these SC lipid models following an external stress. Kinetic and thermotropic experiments demonstrate differences in both CER and FA chain fluidity and ordered domain formation with decreased levels of CER. In the CER deficient model, the formation of CER orthorhombic domains is retarded compared to the normal model. Furthermore, there is little evidence of hexongally packed (or mixed) FA domains in the CER deficient model compared to the models of normal SC. These data demonstrate that barrier lipid organization, in terms of ceramide domain formation, is altered in the ceramide deficient model. This work highlights the successful development of an experimental methodology to study time dependent changes in lipid biophysics in simple SC model membranes and suggests this approach will prove useful for understanding some of the biophysical changes that underlie impaired physiological barrier function in diseased skin. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Isolation of thermo-tolerant and high lipid content green microalgae: oil accumulation is predominantly controlled by photosystem efficiency during stress treatments in Desmodesmus.

    Science.gov (United States)

    Pan, Yi-Ying; Wang, Suz-Ting; Chuang, Lu-Te; Chang, Yen-Wei; Chen, Ching-Nen Nathan

    2011-11-01

    Discoveries of new microalgae with thermo-tolerance, high growth rate, and high lipid content are crucial to algal biodiesel production in tropical and subtropical zones. Four new green microalgae were isolated in southern Taiwan. All four species are members of the genus Desmodesmus under the family Scenedesmaceae based on molecular and morphological analyses. Two of the four species survived at 45 °C for 24 h, with 5-13% of mortality rates caused by the heat. Total lipid contents of the two species reached over 50% in dry biomass under nitrogen starvation, and their triacylglycerols constituted around 75% of the total lipids. Thus the two species are good potential feedstocks for biodiesel production. Oil accumulation in the four species positively correlates with their photosystem II efficiencies during stress treatments (R2=0.90). This finding further supports that photosynthesis is essential for oil body formation under nitrogen starvation in green microalgae. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. The synergistic effects for the co-cultivation of oleaginous yeast-Rhodotorula glutinis and microalgae-Scenedesmus obliquus on the biomass and total lipids accumulation.

    Science.gov (United States)

    Yen, Hong-Wei; Chen, Pin-Wen; Chen, Li-Juan

    2015-05-01

    In this co-culture of oleaginous yeast-Rhodotorula glutinis and microalgae-Scenedesmus obliquus, microalgae potentially acts as an oxygen generator for the growth of aerobic yeast while the yeast mutually provides CO2 to the microalgae as both carry out the production of lipids. To explore the synergistic effects of co-cultivation on the cells growth and total lipids accumulation, several co-culture process parameters including the carbon source concentration, temperature and dissolved oxygen level would be firstly investigated in the flask trials. The results of co-culture in a 5L photobioreactor revealed that about 40-50% of biomass increased and 60-70% of total lipid increased was observed as compared to the single culture batches. Besides the synergistic effects of gas utilization, the providing of trace elements to each other after the natural cells lysis was believed to be another benefit to the growth of the overall co-culture system.

  4. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation

    Science.gov (United States)

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  5. Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

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    Li Hong

    2011-07-01

    Full Text Available Abstract Background The role of renal lipoprotein lipase (LPL per se in kidney diseases is still controversial and obscure. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD. Methods Male Chinese Bama minipigs were fed a control diet or HSFD with or without 0.1 g/kg/day Ibrolipim for 5 months. Body weight, plasma glucose, insulin, lipids, LPL activity, and urinary microalbumin were measured. Renal tissue was obtained for detecting LPL activity and contents of triglyceride and cholesterol, observing the renal lipid accumulation by Oil Red O staining, and examining the mRNA and protein expression of LPL by real time PCR, Western Blot and immunohistochemistry. Results Feeding HSFD to minipigs caused weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia and microalbuminuria. HSFD increased plasma LPL activity while it decreased the mRNA and protein expression and activity of LPL in the kidney. The increases in renal triglyceride and cholesterol contents were associated with the decrease in renal LPL activity of HSFD-fed minipigs. In contrast, supplementing Ibrolipim into HSFD lowered body weight, plasma glucose, insulin, triglyceride and urinary albumin concentrations while it increased plasma total cholesterol and HDL-C. Ibrolipim suppressed the renal accumulation of triglyceride and cholesterol, and stimulated the diet-induced down-regulation of LPL expression and activity in the kidney. Conclusions Ibrolipim exerts renoprotective and hypolipidemic effects via the increase in renal LPL activity and expression, and thus the increased expression and activity of renal LPL play a vital role in suppressing renal lipid accumulation and ameliorating proteinuria in diet-induced diabetic minipigs.

  6. ACCUMULATED DEFORMATION MODELING OF PERMANENT WAY BASED ON ENTROPY SYSTEM

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    D. M. Kurhan

    2015-07-01

    Full Text Available Purpose. The work provides a theoretical research about the possibility of using methods that determine the lifetime of a railway track not only in terms of total stresses, and accounting its structure and dynamic characteristics. The aim of these studies is creation the model of deformations accumulation for assessment of service life of a railway track taking into account these features. Methodology. To simulate a gradual change state during the operation (accumulation of deformations the railway track is presented as a system that consists of many particles of different materials collected in a coherent design. It is appropriate to speak not about the appearance of deformations of a certain size in a certain section of the track, and the probability of such event on the site. If to operate the probability of occurrence of deviations, comfortable state of the system is characterized by the number of breaks of the conditional internal connections. The same state of the system may correspond to different combinations of breaks. The more breaks, the more the number of options changes in the structure of the system appropriate to its current state. Such a process can be represented as a gradual transition from an ordered state to a chaotic one. To describe the characteristics of the system used the numerical value of the entropy. Findings. Its entropy is constantly increasing at system aging. The growth of entropy is expressed by changes in the internal energy of the system, which can be determined using mechanical work forces, which leads to deformation. This gives the opportunity to show quantitative indication of breaking the bonds in the system as a consequence of performing mechanical work. According to the results of theoretical research methods for estimation of the timing of life cycles of railway operation considering such factors as the structure of the flow of trains, construction of the permanent way, the movement of trains at high

  7. Comparison of existing models to simulate anaerobic digestion of lipid-rich waste.

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    Béline, F; Rodriguez-Mendez, R; Girault, R; Bihan, Y Le; Lessard, P

    2017-02-01

    Models for anaerobic digestion of lipid-rich waste taking inhibition into account were reviewed and, if necessary, adjusted to the ADM1 model framework in order to compare them. Experimental data from anaerobic digestion of slaughterhouse waste at an organic loading rate (OLR) ranging from 0.3 to 1.9kgVSm(-3)d(-1) were used to compare and evaluate models. Experimental data obtained at low OLRs were accurately modeled whatever the model thereby validating the stoichiometric parameters used and influent fractionation. However, at higher OLRs, although inhibition parameters were optimized to reduce differences between experimental and simulated data, no model was able to accurately simulate accumulation of substrates and intermediates, mainly due to the wrong simulation of pH. A simulation using pH based on experimental data showed that acetogenesis and methanogenesis were the most sensitive steps to LCFA inhibition and enabled identification of the inhibition parameters of both steps.

  8. Etude de stratégies de culture de Dunaliella tertiolecta combinant haute densité cellulaire et accumulation de lipides en vue de produire du biodiesel

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    Massart, A.

    2010-01-01

    Full Text Available Study of culture strategies of Dunaliella tertiolecta combining high cell density and accumulation of lipids to produce biodiesel. Microalgae are photosynthetic organisms using light to capture CO2. Some species can accumulate, under specific growth conditions, carbon as lipids (triglycerides. This characteristic led the scientists to think about cultivating this microorganism to produce biodiesel. The following study is based on the cultivation of a 5 to 10 µm length green biflagellate microalgae, Dunaliella tertiolecta. Two objectives will be presented in parallel: first, the growth rate and then the oil content. An optimal design of experiment has been used to determine the influence of the concentration of different components in the medium as sodium chloride, nitrate and phosphate on the two responses. The fluorescence technique allows measurements of oil level within the microalgae. The experimental results show that increasing the growth leads to an oil level reduction. The sudden depletion (stress of an essential nutrient stops the growth but increase the lipids' storage. A nitrate stress allows lipid dry mass percentage of around 19%.

  9. Effect of pH on growth and lipid accumulation kinetics of the microalga Chlorella vulgaris grown heterotrophically under sulfur limitation.

    Science.gov (United States)

    Sakarika, Myrsini; Kornaros, Michael

    2016-11-01

    The goal of the present study was to investigate the pH range that can support the growth of C. vulgaris, and, more specifically, to identify the optimal pH for the microalga's growth, under heterotrophic conditions. Furthermore, the effect of pH on the accumulation of intracellular lipids was studied. A wide range of pH values was tested using the respective buffer solutions. The optimal pH for biomass growth and lipid accumulation under sulfur limitation was found to be 7.5, resulting in maximum specific growth rate of 0.541days(-1) and maximum total lipid content of 53.43%ggDW(-1). The fatty acid composition of C. vulgaris was found to be unrelated to pH, as the lipid content did not present significant variations in the pH values tested. The fatty acid profile was mainly composed of monounsaturated fatty acids (MUFAs) with the dominant one being oleic acid (C18:1). Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Enhancing effect of lipids and emulsifiers on the accumulation of quercetin metabolites in blood plasma after the short-term ingestion of onion by rats.

    Science.gov (United States)

    Azuma, Keiko; Ippoushi, Katsunari; Ito, Hidekazu; Horie, Hideki; Terao, Junji

    2003-12-01

    The effects of co-ingested lipids and emulsifiers on the accumulation of quercetin metabolites in blood plasma after the short-term ingestion of onion by rats were investigated. Plasma extracts of rats that had been fed onion-containing diets for one and two weeks were analyzed by HPLC with electrochemical detection after a treatment with sulfatase/beta-glucuronidase. Almost all of the quercetin metabolites in the plasma were sulfate/glucuronide conjugates of quercetin and isorhamnetin. More than 4.6% (w/w) of soybean oil in the diets significantly enhanced the accumulation of quercetin metabolites in the plasma. Fish oil and beef tallow increased this to an extent similar to that with soybean oil, and lecithin was more effective than the other three lipids. Two emulsifiers, sodium caseinate and sucrose fatty acid ester, also showed an enhancing effect on the accumulation of quercetin metabolites. These results indicate that co-ingested lipids and emulsifiers could enhance the bioavailability of quercetin glucosides in onion.

  11. The roles of protein and lipid in the accumulation and distribution of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in plants grown in biosolids-amended soils.

    Science.gov (United States)

    Wen, Bei; Wu, Yali; Zhang, Hongna; Liu, Yu; Hu, Xiaoyu; Huang, Honglin; Zhang, Shuzhen

    2016-09-01

    The roles of protein and lipid in the accumulation and distribution of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in seven species of plants from biosolids-amended soils were investigated. The PFOS and PFOA root concentration factors (Croot/Csoil) ranged from 1.37 to 4.68 and 1.69 to 10.3 (ng/groot)/(ng/gsoil), respectively, while the translocation factors (Cshoot/Croot) ranged from 0.055 to 0.16 and 0.093 to 1.8 (ng/gshoot)/(ng/groot), respectively. The PFOS and PFOA accumulations in roots correlated positively with root protein contents (P protein and inhibition effects of lipid on root uptake. The translocation factors correlated positively with the ratios between protein contents in shoots to those in roots (P protein on PFOS and PFOA translocation. This study is the first to reveal the different roles of protein and lipid in the accumulation and distribution of PFOS and PFOA in plants.

  12. Efficacy of EDTA and Phosphorous on Biomass Yield and Total Lipid Accumulation in Two Green Microalgae with Special Emphasis on Neutral Lipid Detection by Flow Cytometry

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    Gour Gopal Satpati

    2016-01-01

    Full Text Available Chlorella ellipsoidea and Chlorococcum infusionum, promising microalgae for biodiesel feedstock production, were treated with ethylenediaminetetraacetate (EDTA and phosphorous to induce stress which was then followed by flow cytometry to study the enhanced intracellular neutral lipid content. Treatment resulted in up to a threefold increase in total lipid content of Chlorella (41.8±1.9% at 16 days of incubation period and more than twofold increases in Chlorococcum (31.3±1.0% at 18 days of incubation period under phosphorous starvation in the culture. It was observed that maximum biomass yields in Chlorella and Chlorococcum were 1.56±0.06 and 2.17±0.12 g/L at 1.5 g/L of phosphorous after 20 and 18 days of incubation periods, respectively. The qualitative analyses of neutral lipid bodies under stress conditions were performed by confocal microscopy and revealed bright golden-yellow lipid droplets in stress exposed cells. Significant increase of monounsaturated fatty acids under the nutrient limited conditions was suitable to produce biodiesel. The maximum biomass (g/L and lipid content (% dry cell weight at different stresses showed significant results (p<0.05 by single-factor Analysis of Variance (ANOVA followed by Duncan’s Multiple Range Test (DMRT.

  13. Dietary constituents reduce lipid accumulation in murine C3H10 T1/2 adipocytes: A novel fluorescent method to quantify fat droplets.

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    Warnke, Ines; Goralczyk, Regina; Fuhrer, Erna; Schwager, Joseph

    2011-05-12

    Adipocyte volume (fat accumulation) and cell number (adipogenesis) is increased in obese individuals. Our objective was the identification of dietary constituents with inhibitory effects on triglyceride formation during adipogenesis. Therefore an in vitro adipose cell assay in murine C3H10 T1/2 cells was developed, which enabled rapid quantification of intracellular fat droplet accumulation during adipocyte differentiation. Results were corroborated by expression levels of several specific adipogenic and lipogenic genes which are known to regulate triglyceride accumulation. C3H10 T1/2 adipocyte differentiation was conducted with rosiglitazone in the presence of test compounds for 7 days. Accumulation of intracellular lipid droplets was measured using the Cellomics® ArrayScan® VTI HCS reader and SpotDetector® BioApplication from ThermoFisher. Fluorescent images were automatically acquired and analysed employing the fluorescent dyes BODIPY® 493/503 and Hoechst 33342, for staining neutral lipids and localisation of nuclei, respectively. The expression levels of adipogenic and lipogenic genes, such as PPARα and PPARγ, C/EBPα, aP2, adiponectin, LPL and HSL, CPT-1β, ACC1, Glut4 and FAS, were determined by quantitative RT-PCR. Dietary ingredients including PUFAs, carotenoids, polyphenols and catechins were tested for their effect on lipid accumulation. The ω-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the carotenoid β-carotene and hydroxytyrosol exhibited the strongest inhibitory effects on the rosiglitazone-stimulated lipid formation. (all-E)-lycopene and epigallocatechin gallate (EGCG) showed a moderate inhibition, whereas resveratrol did not reduce fat droplet formation. Additionally, it was demonstrated that adipogenic and lipogenic gene expression was attenuated. DHA, β-carotene and hydroxytyrosol inhibited the gene expression of PPARγ, C/EBPα, aP2 and CPT-1β. This in vitro assay in differentiating adipocytes enables automated

  14. Dietary constituents reduce lipid accumulation in murine C3H10 T1/2 adipocytes: A novel fluorescent method to quantify fat droplets

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    Fuhrer Erna

    2011-05-01

    Full Text Available Abstract Background Adipocyte volume (fat accumulation and cell number (adipogenesis is increased in obese individuals. Our objective was the identification of dietary constituents with inhibitory effects on triglyceride formation during adipogenesis. Therefore an in vitro adipose cell assay in murine C3H10 T1/2 cells was developed, which enabled rapid quantification of intracellular fat droplet accumulation during adipocyte differentiation. Results were corroborated by expression levels of several specific adipogenic and lipogenic genes which are known to regulate triglyceride accumulation. Methods C3H10 T1/2 adipocyte differentiation was conducted with rosiglitazone in the presence of test compounds for 7 days. Accumulation of intracellular lipid droplets was measured using the Cellomics® ArrayScan® VTI HCS reader and SpotDetector® BioApplication from ThermoFisher. Fluorescent images were automatically acquired and analysed employing the fluorescent dyes BODIPY® 493/503 and Hoechst 33342, for staining neutral lipids and localisation of nuclei, respectively. The expression levels of adipogenic and lipogenic genes, such as PPARα and PPARγ, C/EBPα, aP2, adiponectin, LPL and HSL, CPT-1β, ACC1, Glut4 and FAS, were determined by quantitative RT-PCR. Dietary ingredients including PUFAs, carotenoids, polyphenols and catechins were tested for their effect on lipid accumulation. Results The ω-3 PUFAs docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, the carotenoid β-carotene and hydroxytyrosol exhibited the strongest inhibitory effects on the rosiglitazone-stimulated lipid formation. (all-E-lycopene and epigallocatechin gallate (EGCG showed a moderate inhibition, whereas resveratrol did not reduce fat droplet formation. Additionally, it was demonstrated that adipogenic and lipogenic gene expression was attenuated. DHA, β-carotene and hydroxytyrosol inhibited the gene expression of PPARγ, C/EBPα, aP2 and CPT-1β. Conclusion This in

  15. Effect of ursolic acid and Rosiglitazone combination on hepatic lipid accumulation in high fat diet-fed C57BL/6J mice.

    Science.gov (United States)

    Sundaresan, Arjunan; Radhiga, Thangaiyan; Pugalendi, Kodukkur Viswanathan

    2014-10-15

    This study investigated the combined effect of ursolic acid (UA) and Rosiglitazone (RSG) on lipid regulatory genes in high fat diet (HFD)-fed mice. Male C57BL/6J mice were fed either normal diet or HFD for 10 weeks, after which animals in each dietary group were divided into following six groups, (normal diet, normal diet plus UA and RSG, HFD alone, HFD plus UA, HFD plus RSG, and HFD plus UA and RSG), for the next 5 weeks. UA (5mg/kg BW) and RSG (4mg/kg BW) were administered as suspensions directly into the stomach using a gastric tube. At the end of the study (106th day), their liver was analyzed for lipid content. RT-PCR and western blotting methods were used to analyze lipid regulatory genes. HFD-fed mice showed increased activities of hepatic marker enzymes (aspartate aminotransferase and alanine aminotransferase) in plasma and an increased concentration of total cholesterol, triglyceride and free fatty acid in liver. These results were confirmed by upregulated mRNA expression of lipogenic genes such as sterol-regulatory-element-binding protein-1c, fatty acid synthase and acetyl-CoA carboxylase and downregulated mRNA expression of fatty acid oxidative genes such as carnitine palmitoyltransferase-1, acetyl-CoA carboxylase and peroxisome proliferator activated receptor-α in HFD-fed mice. Combined treatment (UA/RSG) significantly reduced the hepatic marker enzyme activities and decreased the lipid accumulation in liver. Furthermore, combination treatment (UA/RSG) down-regulated lipogenic genes and upregulated fatty acid oxidative genes in HFD-fed mice. This study suggests that UA in combination with RSG reduced lipid accumulation in liver.

  16. Effects of dietary plant meal and soya-saponin supplementation on intestinal and hepatic lipid droplet accumulation and lipoprotein and sterol metabolism in Atlantic salmon (Salmo salar L.).

    Science.gov (United States)

    Gu, Min; Kortner, Trond M; Penn, Michael; Hansen, Anne Kristine; Krogdahl, Åshild

    2014-02-01

    Altered lipid metabolism has been shown in fish fed plant protein sources. The present study aimed to gain further insights into how intestinal and hepatic lipid absorption and metabolism are modulated by plant meal (PM) and soya-saponin (SA) inclusion in salmon feed. Post-smolt Atlantic salmon were fed for 10 weeks one of four diets based on fishmeal or PM, with or without 10 g/kg SA. PM inclusion resulted in decreased growth performance, excessive lipid droplet accumulation in the pyloric caeca and liver, and reduced plasma cholesterol levels. Intestinal and hepatic gene expression profiling revealed an up-regulation of the expression of genes involved in lipid absorption and lipoprotein (LP) synthesis (apo, fatty acid transporters, microsomal TAG transfer protein, acyl-CoA cholesterol acyltransferase, choline kinase and choline-phosphate cytidylyltransferase A), cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA reductase) and associated transcription factors (sterol regulatory element-binding protein 2 and PPARγ). SA inclusion resulted in reduced body pools of cholesterol and bile salts. The hepatic gene expression of the rate-limiting enzyme in bile acid biosynthesis (cytochrome P450 7A1 (cyp7a1)) as well as the transcription factor liver X receptor and the bile acid transporter abcb11 (ATP-binding cassette B11) was down-regulated by SA inclusion. A significant interaction was observed between PM inclusion and SA inclusion for plasma cholesterol levels. In conclusion, gene expression profiling suggested that the capacity for LP assembly and cholesterol synthesis was up-regulated by PM exposure, probably as a compensatory mechanism for excessive lipid droplet accumulation and reduced plasma cholesterol levels. SA inclusion had hypocholesterolaemic effects on Atlantic salmon, accompanied by decreased bile salt metabolism.

  17. Acetylshikonin from Zicao Prevents Obesity in Rats on a High-Fat Diet by Inhibiting Lipid Accumulation and Inducing Lipolysis.

    Directory of Open Access Journals (Sweden)

    Meiling Su

    Full Text Available Various drugs have been developed to treat obesity, but these have undesirable secondary effects, and an efficient but non-toxic anti-obesity drug from natural sources is desired. This study investigated the anti-obesity effects and mechanisms of action of acetylshikonin (AS-which is used in traditional Chinese medicine-in rats on a high-fat diet (HFD. Rats were fed a normal diet or an HFD; the latter group was received no treatment or were treated with 100, 300, or 900 mg/kg AS extract by intragastric administration for 6 weeks. In addition, 3T3-L1 adipocytes were treated with AS and the effects on adipogenesis and lipolysis were evaluated by western blot analysis of adipogenic transcription factors and lipid-metabolizing enzyme levels and the phosphorylation status of protein kinase (PK A and hormone-sensitive lipase (HSL. AS prevented HFD-induced obesity including reduction in body weight, white adipose tissue content, liver mass, and serum triglyceride and free fatty acid levels in rats. It also suppressed the expression of adipogenic differentiation transcription factors and decreased the expression of the adipocyte-specific proteins HSL and adipose triglyceride lipase (ATGL. Furthermore, AS treatment induced lipolysis, leading to the release of glycerol and increased in PKA and HSL phosphorylation. These findings demonstrate that AS has anti-obesity effects in a rat model and may be a safe treatment for obesity in humans.

  18. Acetylshikonin from Zicao Prevents Obesity in Rats on a High-Fat Diet by Inhibiting Lipid Accumulation and Inducing Lipolysis.

    Science.gov (United States)

    Su, Meiling; Huang, Wendong; Zhu, Banghao

    2016-01-01

    Various drugs have been developed to treat obesity, but these have undesirable secondary effects, and an efficient but non-toxic anti-obesity drug from natural sources is desired. This study investigated the anti-obesity effects and mechanisms of action of acetylshikonin (AS)-which is used in traditional Chinese medicine-in rats on a high-fat diet (HFD). Rats were fed a normal diet or an HFD; the latter group was received no treatment or were treated with 100, 300, or 900 mg/kg AS extract by intragastric administration for 6 weeks. In addition, 3T3-L1 adipocytes were treated with AS and the effects on adipogenesis and lipolysis were evaluated by western blot analysis of adipogenic transcription factors and lipid-metabolizing enzyme levels and the phosphorylation status of protein kinase (PK) A and hormone-sensitive lipase (HSL). AS prevented HFD-induced obesity including reduction in body weight, white adipose tissue content, liver mass, and serum triglyceride and free fatty acid levels in rats. It also suppressed the expression of adipogenic differentiation transcription factors and decreased the expression of the adipocyte-specific proteins HSL and adipose triglyceride lipase (ATGL). Furthermore, AS treatment induced lipolysis, leading to the release of glycerol and increased in PKA and HSL phosphorylation. These findings demonstrate that AS has anti-obesity effects in a rat model and may be a safe treatment for obesity in humans.

  19. Relationship between starch and lipid accumulation induced by nutrient depletion and replenishment in the microalga Parachlorella kessleri.

    Science.gov (United States)

    Fernandes, Bruno; Teixeira, José; Dragone, Giuliano; Vicente, António A; Kawano, Shigeyuki; Bišová, Kateřina; Přibyl, Pavel; Zachleder, Vilém; Vítová, Milada

    2013-09-01

    Photosynthetic carbon partitioning into starch and neutral lipids, as well as the influence of nutrient depletion and replenishment on growth, pigments and storage compounds, were studied in the microalga, Parachlorella kessleri. Starch was utilized as a primary carbon and energy storage compound, but nutrient depletion drove the microalgae to channel fixed carbon into lipids as secondary storage compounds. Nutrient depletion inhibited both cellular division and growth and caused degradation of chlorophyll. Starch content decreased from an initial value of 25, to around 10% of dry weight (DW), while storage lipids increased from almost 0 to about 29% of DW. After transfer of cells into replenished mineral medium, growth, reproductive processes and chlorophyll content recovered within 2 days, while the content of both starch and lipids decreased markedly to 3 or less % of DW; this suggested that they were being used as a source of energy and carbon.

  20. Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood

    NARCIS (Netherlands)

    Oosting, Annemarie; Kegler, Diane; Wopereis, Harm J.; Teller, Inga C.; van de Heijning, Bert J. M.; Verkade, Henkjan J.; van der Beek, Eline M.

    2012-01-01

    BACKGROUND: In addition to contemporary lifestyle factors that contribute to the increased obesity prevalence worldwide, early nutrition is associated with sustained effects on later life obesity. We hypothesized that physical properties of dietary lipids contribute to this nutritional programming.

  1. Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood

    NARCIS (Netherlands)

    Oosting, Annemarie; Kegler, Diane; Wopereis, Harm J.; Teller, Inga C.; van de Heijning, Bert J. M.; Verkade, Henkjan J.; van der Beek, Eline M.

    2012-01-01

    BACKGROUND: In addition to contemporary lifestyle factors that contribute to the increased obesity prevalence worldwide, early nutrition is associated with sustained effects on later life obesity. We hypothesized that physical properties of dietary lipids contribute to this nutritional programming.

  2. Profiling of lipid and glycogen accumulations under different growth conditions in the sulfothermophilic red alga Galdieria sulphuraria.

    Science.gov (United States)

    Sakurai, Toshihiro; Aoki, Motohide; Ju, Xiaohui; Ueda, Tatsuya; Nakamura, Yasunori; Fujiwara, Shoko; Umemura, Tomonari; Tsuzuki, Mikio; Minoda, Ayumi

    2016-01-01

    The unicellular red alga Galdieria sulphuraria grows efficiently and produces a large amount of biomass in acidic conditions at high temperatures. It has great potential to produce biofuels and other beneficial compounds without becoming contaminated with other organisms. In G. sulphuraria, biomass measurements and glycogen and lipid analyses demonstrated that the amounts and compositions of glycogen and lipids differed when cells were grown under autotrophic, mixotrophic, and heterotrophic conditions. Maximum biomass production was obtained in the mixotrophic culture. High amounts of glycogen were obtained in the mixotrophic cultures, while the amounts of neutral lipids were similar between mixotrophic and heterotrophic cultures. The amounts of neutral lipids were highest in red algae, including thermophiles. Glycogen structure and fatty acids compositions largely depended on the growth conditions. Copyright © 2015. Published by Elsevier Ltd.

  3. Jinlida granule inhibits palmitic acid induced-intracellular lipid accumulation and enhances autophagy in NIT-1 pancreatic β cells through AMPK activation.

    Science.gov (United States)

    Wang, Dingkun; Tian, Min; Qi, Yuan; Chen, Guang; Xu, Lijun; Zou, Xin; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2015-02-23

    Jinlida granule (JLDG), composed of seventeen Chinese medical herbs, is a widely used Chinese herbal prescription for treating diabetes mellitus. However, the mechanism underlying this effect remains unclear. To determine the main components in JLDG and to explore the effect of JLDG on autophagy and lipid accumulation in NIT-1 pancreatic β cells exposed to politic acid (PA) through AMP activated protein kinase (AMPK) signaling pathway. JLDG was prepared and the main components contained in the granules were identified by ultra performance liquid chromatography (UPLC) fingerprint. Intracellular lipid accumulation in NIT-1 cells was induced by culturing with medium containing PA. Intracellular lipid droplets were observed by Oil Red O staining and triglyceride (TG) content was measured by colorimetric assay. The formation of autophagosomes was observed under transmission electron microscope. The expression of AMPK and phospho-AMPK (pAMPK) proteins as well as its downstream fatty acid metabolism-related proteins (fatty acid synthase, FAS; acetyl-coA carboxylase, ACC; carnitine acyltransferase 1, CPT-1) and autophagy-related genes (mammal target of rapamycin, mTOR; tuberous sclerosis complex 1, TSC1; microtubule-associated protein 1 light chain 3, LC3-II) were determined by Western blot. The expression of sterol regulating element binding protein 1c (SREBP-1c) mRNA was examined by real time PCR (RT-PCR). Our data showed that JLDG could significantly reduce PA-induced intracellular lipid accumulation in NIT-1 pancreatic β cells. This effect was associated with increased protein expression of pAMPK and AMPK in NIT-1 cells. Treatment with JLDG also decreased the expression of AMPK downstream lipogenic genes (SREBP-1c mRNA, FAS and ACC proteins) whereas increased the expression of fatty acid oxidation gene (CPT-1 protein). Additionally, JLDG-treated cells displayed a markedly increase in the number of autophagosomes which was accompanied by the down-regulation of m

  4. Boosting accumulation of neutral lipids in Rhodosporidium kratochvilovae HIMPA1 grown on hemp (Cannabis sativa Linn) seed aqueous extract as feedstock for biodiesel production.

    Science.gov (United States)

    Patel, Alok; Pravez, Mohammad; Deeba, Farha; Pruthi, Vikas; Singh, Rajesh P; Pruthi, Parul A

    2014-08-01

    Hemp seeds aqueous extract (HSAE) was used as cheap renewable feedstocks to grow novel oleaginous yeast Rhodosporidium kratochvilovae HIMPA1 isolated from Himalayan permafrost soil. The yeast showed boosted triglyceride (TAG) accumulation in the lipid droplets (LDs) which were transesterified to biodiesel. The sonicated HSAE prepared lacked toxic inhibitors and showed enhanced total lipid content and lipid yield 55.56%, 8.39±0.57g/l in comparison to 41.92%, 6.2±0.8g/l from industrially used glucose synthetic medium, respectively. Supersized LDs (5.95±1.02μm) accumulated maximum TAG in sonicated HSAE grown cells were visualized by fluorescent BODIPY (505/515nm) stain. GC-MS analysis revealed unique longer carbon chain FAME profile containing Arachidic acid (C20:0) 5%, Behenic acid (C22:0) 9.7%, Heptacosanoic acid (C27:0) 14.98%, for the first time in this yeast when grown on industrially competent sonicated HSAE, showing more similarity to algal oils.

  5. Malfunction in Mitochondrial β-Oxidation Contributes to Lipid Accumulation in Hepatocyte-Like Cells Derived from Citrin Deficiency-Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kim, Yeji; Choi, Jung-Yun; Lee, Sang-Hee; Lee, Beom-Hee; Yoo, Han-Wook; Han, Yong-Mahn

    2016-04-15

    Citrin deficiency (CD) is a recessive genetic disorder caused by mutations in the citrin gene SLC25A13. CD causes various symptoms related to nutrient metabolism such as urea cycle failure, abnormal amino acid levels, and fatty liver. To understand the pathophysiology of CD, the molecular phenotypes were investigated using induced pluripotent stem cells derived from fibroblasts of CD patient (CD-iPSCs). In this study, we demonstrate that aberrant mitochondrial β-oxidation may lead to fatty liver in CD patients. CD-iPSCs normally differentiated into hepatocytes, similar to wild-type iPSCs (WT-iPSCs). However, hepatocytes derived from CD-iPSCs (CD-HLCs) did not exhibit ureogenesis. Cellular triglyceride and lipid granule levels were significantly increased in CD-HLCs compared with WT-HLCs. Peroxisome proliferator-activated receptor-α (PPAR-α) and its target genes which are involved in mitochondrial β-oxidation were downregulated in CD-HLCs, and treatment with a PPAR-α agonist partially reduced the lipid accumulation in CD-HLCs. In addition, the mitochondria in CD-HLCs exhibited abnormal morphologies. Based on these observations, we conclude that the lipid accumulation in CD-HLCs results from dysfunctional mitochondrial β-oxidation and abnormal mitochondrial structure.

  6. Mechanism of the Inhibitory Effects of Eucommia ulmoides Oliv. Cortex Extracts (EUCE in the CCl4-Induced Acute Liver Lipid Accumulation in Rats

    Directory of Open Access Journals (Sweden)

    Chang-Feng Jin

    2013-01-01

    Full Text Available Eucommia ulmoides Oliv. (EU has been used for treatment of liver diseases. The protective effects of Eucommia Ulmoides Oliv. cortex extracts (EUCE on the carbon tetrachloride- (CCl4- induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4 decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4 treatment decreased glutathione (GSH and increased malondialdehyde (MDA accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4 treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4 reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.

  7. High light exposure on seed coat increases lipid accumulation in seeds of castor bean (Ricinus communis L.), a nongreen oilseed crop.

    Science.gov (United States)

    Zhang, Yang; Mulpuri, Sujatha; Liu, Aizhong

    2016-05-01

    Little was known on how sunlight affects the seed metabolism in nongreen seeds. Castor bean (Ricinus communis L.) is a typical nongreen oilseed crop and its seed oil is an important feedstock in industry. In this study, photosynthetic activity of seed coat tissues of castor bean in natural conditions was evaluated in comparison to shaded conditions. Our results indicate that exposure to high light enhances photosynthetic activity in seed coats and consequently increases oil accumulation. Consistent results were also reached using cultured seeds. High-throughput RNA-Seq analyses further revealed that genes involved in photosynthesis and carbon conversion in both the Calvin-Benson cycle and malate transport were differentially expressed between seeds cultured under light and dark conditions, implying several venues potentially contributing to light-enhanced lipid accumulation such as increased reducing power and CO2 refixation which underlie the overall lipid biosynthesis. This study demonstrated the effects of light exposure on oil accumulation in nongreen oilseeds and greatly expands our understanding of the physiological roles that light may play during seed development in nongreen oilseeds. Essentially, our studies suggest that potential exists to enhance castor oil yield through increasing exposure of the inflorescences to sunlight either by genetically changing the plant architecture (smart canopy) or its growing environment.

  8. Transient scrotal hyperthermia induces lipid droplet accumulation and reveals a different ADFP expression pattern between the testes and liver in mice.

    Directory of Open Access Journals (Sweden)

    Mingxi Liu

    Full Text Available BACKGROUND: In most mammals, the testes provide a stable environment for spermatogenesis, which depends on a lower temperature than the core body temperature. It has been reported that mild testicular heating safely and reversibly suppresses spermatogenesis, and is under consideration for its potential application as a male contraceptive. Previously, we focused on the molecular mechanism of germ cell apoptosis and anti-apoptotic factors induced by heat treatment in humans and mice. However, the recovery process remains under investigation. RESULTS: In this study, we found that lipid droplets in mouse testes are dramatically increased after a brief period of scrotal hyperthermia, and gradually dissipate following temperature normalization. Analysis of the human testis proteome revealed nine proteins associated with lipid droplets. Two of them, ADFP (also known as ADRP and PLIN2 and TIP47 (also known as PLIN3 may participate in acute lipid droplet formation in mammalian testes. We show that Adfp expression is upregulated after scrotal heat treatment in mice. Surprisingly, we find Adfp lacking its 5'-UTR is observed in Adfp(Δ1/Δ1 mouse testes, but is not detectable in liver. CONCLUSIONS: These results reveal testis Adfp transcriptional regulation is tissue-specific, and is associated with lipid droplet accumulation induced by heat. The results also indicate that the testes could retain functional proteins through testes-specific transcriptional regulation.

  9. Development and application of coarse-grained models for lipids

    Science.gov (United States)

    Cui, Qiang

    2013-03-01

    I'll discuss a number of topics that represent our efforts in developing reliable molecular models for describing chemical and physical processes involving biomembranes. This is an exciting yet challenging research area because of the multiple length and time scales that are present in the relevant problems. Accordingly, we attempt to (1) understand the value and limitation of popular coarse-grained (CG) models for lipid membranes with either a particle or continuum representation; (2) develop new CG models that are appropriate for the particular problem of interest. As specific examples, I'll discuss (1) a comparison of atomistic, MARTINI (a particle based CG model) and continuum descriptions of a membrane fusion pore; (2) the development of a modified MARTINI model (BMW-MARTINI) that features a reliable description of membrane/water interfacial electrostatics and its application to cell-penetration peptides and membrane-bending proteins. Motivated specifically by the recent studies of Wong and co-workers, we compare the self-assembly behaviors of lipids with cationic peptides that include either Arg residues or a combination of Lys and hydrophobic residues; in particular, we attempt to reveal factors that stabilize the cubic ``double diamond'' Pn3m phase over the inverted hexagonal HII phase. For example, to explicitly test the importance of the bidentate hydrogen-bonding capability of Arg to the stabilization of negative Gaussian curvature, we also compare results using variants of the BMW-MARTINI model that treat the side chain of Arg with different levels of details. Collectively, the results suggest that both the bidentate feature of Arg and the overall electrostatic properties of cationic peptides are important to the self-assembly behavior of these peptides with lipids. The results are expected to have general implications to the mechanism of peptides and proteins that stimulate pore formation in biomembranes. Work in collaboration with Zhe Wu, Leili Zhang

  10. Reduction of adipogenesis and lipid accumulation by Taraxacum officinale (Dandelion) extracts in 3T3L1 adipocytes: an in vitro study.

    Science.gov (United States)

    González-Castejón, Marta; García-Carrasco, Belén; Fernández-Dacosta, Raquel; Dávalos, Alberto; Rodriguez-Casado, Arantxa

    2014-05-01

    In this in vitro study, we have investigated the ability of Taraxacum officinale (dandelion) to inhibit adipocyte differentiation and lipogenesis in 3T3-L1 preadipocytes. HPLC analysis of the three plant extracts used in this study-leaf and root extracts and a commercial root powder-identified caffeic and chlorogenic acids as the main phenolic constituents. Oil Red O staining and triglyceride levels analysis showed decreased lipid and triglyceride accumulation, respectively. Cytotoxicity was assessed with the MTT assay showing non-toxic effect among the concentrations tested. DNA microarray analysis showed that the extracts regulated the expression of a number of genes and long non-coding RNAs that play a major role in the control of adipogenesis. Taken together, our results indicate that the dandelion extracts used in this study may play a significant role during adipogenesis and lipid metabolism, and thus, supporting their therapeutic interest as potential candidates for the treatment of obesity.

  11. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Shu-Hui [Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan (China); Wen, Chih-Jen; Yen, Tzu-Chen [Animal Molecular Imaging Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan (China); Al-Suwayeh, S A; Fang, Jia-You [Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Chang, Hui-Wen, E-mail: fajy@mail.cgu.edu.tw [Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan 333, Taiwan (China)

    2010-10-08

    Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

  12. Effects of EPA and DHA on lipid droplet accumulation and mRNA abundance of PAT proteins in caprine monocytes.

    Science.gov (United States)

    Lecchi, Cristina; Invernizzi, Guido; Agazzi, Alessandro; Modina, Silvia; Sartorelli, Paola; Savoini, Giovanni; Ceciliani, Fabrizio

    2013-04-01

    The present study investigated the in vitro effects on caprine monocytes of two ω-3 PUFAs, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on lipid droplet formation, an emerging process of fundamental importance in innate immunity regulation. The mRNA abundance of PAT protein family (PLIN1, PLIN2 and PLIN3), involved in the formation and trafficking of the droplets, was also assessed. The effects of EPA and DHA on monocyte apoptosis were studied as well. The number of lipid droplets per cell was found to be dependent on both type and concentration of fatty acid. ω-3 PUFAs upregulated PLIN3 and PLIN2 gene expression, as well as apoptosis rate. The present findings suggest that PUFA might modify innate immune functions of goat monocytes by interfering with the formation of lipid droplets and by upregulating proteins belonging to PAT protein family.

  13. Lipid accumulation, oxidative stress and immune-related molecules affected by tributyltin exposure in muscle tissues of rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Zhang, Jiliang; Zhang, Chunnuan; Ma, Dongdong; Liu, Min; Huang, Shuntao

    2017-09-26

    Tributyltin (TBT) is reported to induce adipogenesis in fish, which might affect nutritional qualities and health status. Muscle tissues account for the majority of body mass, and have been described as a major site of fat deposition and an immunologically active organ. Therefore, the present study aims to evaluate whether chronic exposures of TBT, at environmental concentrations of 1, 10 and 100 ng/L, affects lipid accumulation, oxidative stress and immune status in muscle tissues of rare minnow (Gobiocypris rarus). After 60 d of exposure, TBT increased contents of total lipid, total cholesterol, triglyceride and fatty acids in muscle tissues. Interestingly, TBT exposure disrupted fatty acid composition and increased contents of unsaturated fatty acids (such as eicosapentaenoic acid and docosahexaenoic acid) in muscle tissues, which might be a response to preserve membrane functions from TBT exposure. Meanwhile, the concentrations of hepatic fatty acid desaturase 2 (Δ6-desaturase) and stearoyl-CoA desaturase (Δ9-desaturase) were increased after TBT exposure, which might contribute the increase of unsaturated fatty acids. Furthermore, TBT increased muscle lipid peroxidation products, antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), and the expression of immune-related molecules (tumor necrosis factor alpha, interleukin 1 beta and nuclear factor kappa B) in muscle tissues. The disruption of TBT on the lipid accumulation, oxidative stress and immune-toxic effects in muscle tissues of fish might reduce nutritional qualities, and affect growth and health status, which might pose a constant and serious threat to fish and result in economic loss in aquaculture. Copyright © 2017. Published by Elsevier Ltd.

  14. Lipid and moisture content modeling of amphidromous Dolly Varden using bioelectrical impedance analysis

    Science.gov (United States)

    Stolarski, J.T.; Margraf, F.J.; Carlson, J.G.; Sutton, T.M.

    2014-01-01

    The physiological well-being or condition of fish is most commonly estimated from aspects of individual morphology. However, these metrics may be only weakly correlated with nutritional reserves stored as lipid, the primary form of accumulated energy in fish. We constructed and evaluated bioelectrical impedance analysis (BIA) models as an alternative method of assessing condition in amphidromous Dolly Varden Salvelinus malma collected from nearshore estuarine and lotic habitats of the Alaskan Arctic. Data on electrical resistance and reactance were collected from the lateral and ventral surfaces of 192 fish, and whole-body percent lipid and moisture content were determined using standard laboratory methods. Significant inverse relationships between temperature and resistance and reactance prompted the standardization of these data to a constant temperature using corrective equations developed herein. No significant differences in resistance or reactance were detected among spawning and nonspawning females after accounting for covariates, suggesting that electrical pathways do not intersect the gonads. Best-fit BIA models incorporating electrical variables calculated from the lateral and ventral surfaces produced the strongest associations between observed and model-predicted estimates of proximate content. These models explained between 6% and 20% more of the variability in laboratory-derived estimates of proximate content than models developed from single-surface BIA data and 32% more than models containing only length and weight data. While additional research is required to address the potential effects of methodological variation, bioelectrical impedance analysis shows promise as a way to provide high-quality, minimally invasive estimates of Dolly Varden lipid or moisture content in the field with only small increases in handling time.

  15. Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle

    DEFF Research Database (Denmark)

    Chursa, Urszula; Nuñez-Durán, Esther; Cansby, Emmelie

    2017-01-01

    AIMS/HYPOTHESIS: Understanding the molecular networks controlling ectopic lipid deposition and insulin responsiveness in skeletal muscle is essential for developing new strategies to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator...... of liver steatosis, hepatic lipid metabolism and whole body glucose and insulin homeostasis. Here, we assessed the role of STK25 in control of ectopic fat storage and insulin responsiveness in skeletal muscle. METHODS: Skeletal muscle morphology was studied by histological examination, exercise performance...

  16. Abdominal Fat Accumulation with Hyperuricemia and Hypercholesterolemia Quail Model Induced by High Fat Diet

    Institute of Scientific and Technical Information of China (English)

    Zhi-jian Lin; Bing Zhang; Xiao-qing Liu; Hong-lian Yang

    2009-01-01

    Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet.And then to investigate the pathological characteristics of this quail model.Methods Thirty Longcheng quails were randomly divided into two groups:control group and model group(n=15).The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days.After a 12-hour overnight fast,liver and abdominal fat at euthanasia as well as serum were collected.The levels of serum uric acid,total cholesterol,high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol(LDL-C),triglyceride,free fatty acid(FFA),and blood glucose were assayed.The activity changes of adenosine deaminase(ADA),xanthine oxidase(XOD),lipoprotein lipase(LPL),hepatic lipase(HL),and fatty acid synthetase(FAS)were analyzed.Results Comparcd with control group,the abdominal fat content(0.74±0.63 vs.1.36±0.65 g,P<0.05)and abdominal fat index(0.44% ±0.30% vs.0.85% ±0.30% ,P<0.01)as well as live lipid index (3.61% ±0.65% vs.11.33% ±2.14% ,P<0.01)in model group significantly increased;the levels of serum uric acid(210.61±94.76 vs.304.25±141.94 μmol/L,P<0.05),total cholesterol(4.20±0.51 vs.20.10±11.25 mmol/L,P<0.01),LDL-C(1.16±0.29 vs.10.78±6.48 mmol/L,P<0.01),and FFA(0.39±0.14 vs.0.55±0.15 mmol/L,P<0.01)in model group significantly increased;HDL-C(5.85±0.95 vs.4.14±2.03mmol/L,P<0.05)significantly decreased;the levels of triglyceride and blood glucose had no significant changes(P>0.05);the activities of ADA(9.71±3.05 vs.17.19±5.10 U/ml,P<0.01)and XOD(10.58±6.88vs.19.22±9.44 U/L,P<0.01)in model group significantly increased;and FAS,LPL,HL had no significant changes(P>0.05).Conclusions High fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model.The changes of uric acid and lipid metabolic enzyme activities may be the pathological

  17. Modelling Holocene carbon accumulation and methane emissions of boreal wetlands – an Earth system model approach

    Directory of Open Access Journals (Sweden)

    R. J. Schuldt

    2013-03-01

    Full Text Available Since the Last Glacial Maximum, boreal wetlands have accumulated substantial amounts of peat, estimated at 180–621 Pg of carbon. Wetlands have significantly affected the atmospheric greenhouse gas composition in the past and will play a significant role in future changes of atmospheric CO2 and CH4 concentrations. In order to investigate those changes with an Earth system model, biogeochemical processes in boreal wetlands need to be accounted for. Thus, a model of peat accumulation and decay was developed and included in the land surface model JSBACH of the Max Planck Institute Earth System Model (MPI-ESM. Here we present the evaluation of model results from 6000 yr BP to the pre-industrial period. Over this period of time, 240 Pg of peat carbon accumulated in the model in the areas north of 40° N. Simulated peat accumulation rates agree well with those reported for boreal wetlands. The model simulates CH4 emissions of 49.3 Tg CH4 yr−1 for 6000 yr BP and 51.5 Tg CH4 yr−1 for pre-industrial times. This is within the range of estimates in the literature, which range from 32 to 112 Tg CH4 yr−1 for boreal wetlands. The modelled methane emission for the West Siberian Lowlands and Hudson Bay Lowlands agree well with observations. The rising trend of methane emissions over the last 6000 yr is in agreement with measurements of Antarctic and Greenland ice cores.

  18. Modeling Signal Transduction and Lipid Rafts in Immune Cells

    Science.gov (United States)

    Prasad, Ashok

    2011-03-01

    Experimental evidence increasingly suggests that lipid rafts are nanometer sized cholesterol dependent dynamic assemblies enriched in sphingolipids and associated proteins. Lipid rafts are dynamic structures that break-up and reform on a relatively short time-scale, and are believed to facilitate the interactions of raft-associated proteins. The role of these rafts in signaling has been controversial, partly due to controversies regarding the existence and nature of the rafts themselves. Experimental evidence has indicated that in several cell types, especially T cells, rafts do influence signal transduction and T cell activation. Given the emerging consensus on the biophysical character of lipid rafts, the question can be asked as to what roles they possibly play in signal transduction. Here we carry out simulations of minimal models of the signal transduction network that regulates Src-family kinase dynamics in T cells and other cell types. By separately treating raft-based biochemical interactions, we find that rafts can indeed putatively play an important role in signal transduction, and in particular may affect the sensitivity of signal transduction. This illuminates possible functional consequences of membrane heterogeneities on signal transduction and points towards mechanisms for spatial control of signaling by cells.

  19. Lipid composition of membrane rafts, isolated with and without detergent, from the spleen of a mouse model of Gaucher disease.

    Science.gov (United States)

    Hattersley, Kathryn J; Hein, Leanne K; Fuller, Maria

    2013-12-01

    Biological membranes are composed of functionally relevant liquid-ordered and liquid-disordered domains that coexist. Within the liquid-ordered domains are low-density microdomains known as rafts with a unique lipid composition that is crucial for their structure and function. Lipid raft composition is altered in sphingolipid storage disorders, and here we determined the lipid composition using a detergent and detergent-free method in spleen tissue, the primary site of pathology, in a mouse model of the sphingolipid storage disorder, Gaucher disease. The accumulating lipid, glucosylceramide, was 30- and 50-fold elevated in the rafts with the detergent and detergent-free method, respectively. Secondary accumulation of di- and trihexosylceramide resided primarily in the rafts with both methods. The phospholipids distributed differently with more than half residing in the rafts with the detergent-free method and less than 10% with the detergent method, with the exception of the fully saturated species that were primarily in the rafts. Individual isoforms of sphingomyelin correlated with detergent-free extraction and more than half resided in the raft fractions. However, this correlation was not seen with the detergent extraction method as sphingomyelin species were spread across both the raft and non-raft domains. Therefore caution must be exercised when interpreting phospholipid distribution in raft domains as it differs considerably depending on the method of isolation. Importantly, both methods revealed the same lipid alterations in the raft domains in the spleen of the Gaucher disease mouse model highlighting that either method is appropriate to determine membrane lipid changes in the diseased state.

  20. Lipid Processing Technology: Building a Multilevel Modeling Network

    DEFF Research Database (Denmark)

    Diaz Tovar, Carlos Axel; Mustaffa, Azizul Azri; Hukkerikar, Amol

    of these unit operations with respect to performance parameters such as minimum total cost, product yield improvement, operability etc., and process intensification for the retrofit of existing biofuel plants. In the fourth level the information and models developed are used as building blocks...... in the upcoming years major challenges in terms of design and development of better products and more sustainable processes. Although the oleo chemical industry is mature and based on well established processes, the complex systems that lipid compounds form, the lack of accurate predictive models...... for their physical properties and unit operation models for their processing have limited computeraided methods and tools for process synthesis, modeling and simulation to be widely used for design, analysis, and optimization of these processes. In consequence, the aim of this work is to present the development...

  1. Building a Multilevel Modeling Network for Lipid Processing Systems

    DEFF Research Database (Denmark)

    Diaz Tovar, Carlos Axel; Mustaffa, Azizul Azri; Hukkerikar, Amol

    for their physical properties and unit operation models for their processing have limited computer-aided methods and tools for process synthesis, modeling and simulation to be widely used for design, analysis, and optimization of these processes. The world’s fats and oils production has been growing rapidly over...... limited computer-aided methods and tools for process synthesis, modeling and simulation to be widely used for design, analysis, and optimization of these processes....... in the upcoming years major challenges in terms of design and development of better products and more sustainable processes. Although the oleo chemical industry is mature and based on well established processes, the complex systems that lipid compounds form, the lack of accurate predictive models...

  2. Improvement and modeling of culture parameters to enhance biomass and lipid production by the oleaginous yeast Cryptococcus curvatus grown on acetate.

    Science.gov (United States)

    Béligon, Vanessa; Poughon, Laurent; Christophe, Gwendoline; Lebert, André; Larroche, Christian; Fontanille, Pierre

    2015-09-01

    The improvement of culture parameters for lipid production from acetate as carbon source was investigated using the oleaginous yeast Cryptococcus curvatus. A new pH regulation system dispensing acetate was developed for fed-batch culture and allowed obtaining nearly 80 g/L biomass within 60 h with a maximal growth rate of 0.28 h(-1). A biological model was developed from experimental data. The influence of three C/N ratios of 300, 500 and 900 were tested during a multi-phases process on lipid accumulation. The C/N ratio of 300 was reported to be the most suitable for lipid storage. No significant increase of lipids content was obtained with higher value. A maximal content of 60% DCW of lipid was obtained. The determination of fatty acids profiles of the microbial oils has confirmed that the valorization of acetate by microbial oils production was a promising perspective.

  3. Tethered bimolecular lipid membranes - A novel model membrane platform

    Energy Technology Data Exchange (ETDEWEB)

    Knoll, Wolfgang; Koeper, Ingo; Naumann, Renate; Sinner, Eva-Kathrin [Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz (Germany)

    2008-10-01

    stabilization of lipid bilayers, i.e., the protein-tethered membrane. Our efforts in experimentally characterizing the resulting membrane functions and correlating the data with the structural details of the bilayer architectures are complemented by theoretical studies modeling the electrical and electrochemical response of functional tethered lipid bilayer membranes by extended SPICE simulations. (author)

  4. Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

    Science.gov (United States)

    Katsumura, Masanori; Takagi, Shoko; Oya, Hana; Tamura, Shohei; Saneyasu, Takaoki; Honda, Kazuhisa; Kamisoyama, Hiroshi

    2016-12-02

    Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet.

  5. Soy Leaf Extract Containing Kaempferol Glycosides and Pheophorbides Improves Glucose Homeostasis by Enhancing Pancreatic β-Cell Function and Suppressing Hepatic Lipid Accumulation in db/db Mice.

    Science.gov (United States)

    Li, Hua; Ji, Hyeon-Seon; Kang, Ji-Hyun; Shin, Dong-Ha; Park, Ho-Yong; Choi, Myung-Sook; Lee, Chul-Ho; Lee, In-Kyung; Yun, Bong-Sik; Jeong, Tae-Sook

    2015-08-19

    This study investigated the molecular mechanisms underlying the antidiabetic effect of an ethanol extract of soy leaves (ESL) in db/db mice. Control groups (db/+ and db/db) were fed a normal diet (ND), whereas the db/db-ESL group was fed ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The pancreatic insulin content of the db/db-ESL group was significantly greater than that of the db/db group. ESL supplementation altered pancreatic IRS1, IRS2, Pdx1, Ngn3, Pax4, Ins1, Ins2, and FoxO1 expression. Furthermore, ESL suppressed lipid accumulation and increased glucokinase activity in the liver. ESL primarily contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of kaempferol glycosides, improved β-cell proliferation through IRS2-related FoxO1 signaling, whereas pheophorbide a, a product of chlorophyll breakdown, improved insulin secretion and β-cell proliferation through IRS1-related signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose homeostasis by enhancing IRS-mediated β-cell insulin signaling and suppressing SREBP-1-mediated hepatic lipid accumulation in db/db mice.

  6. BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2014-01-01

    Full Text Available The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat and the age-matched control mice were fed with control diet (10% kcal as fat for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.

  7. Rosiglitazone, a PPAR-γ agonist, fails to attenuate CLA-induced milk fat depression and hepatic lipid accumulation in lactating mice.

    Science.gov (United States)

    Vyas, Diwakar; Teter, Beverly B; Delmonte, Pierluigi; Erdman, Richard A

    2014-07-01

    Our objective was to investigate the combination of rosiglitazone (ROSI) and conjugated linoleic acid (CLA) on mammary and hepatic lipogenesis in lactating C57Bl/6 J mice. Twenty-four lactating mice were randomly assigned to one of four treatments applied from postpartum day 6 to day 10. Treatments included: (1) control diet, (2) control plus 1.5 % dietary CLA (CLA) substituted for soybean oil, (3) control plus daily intra-peritoneal (IP) rosiglitazone injections (10 mg/kg body weight) (ROSI), and (4) CLA plus ROSI (CLA-ROSI). Dam food intake and milk fat concentration were depressed with CLA. However, no effects were observed with ROSI. The CLA-induced milk fat depression was due to reduced expression for mammary lipogenic genes involved in de-novo fatty acid (FA) synthesis, FA uptake and desaturation, and triacyglycerol synthesis. Liver weight (g/100 g body weight) was increased by CLA due to an increase in lipid accumulation triggering a compensatory reduction in mRNA abundance of hepatic lipogenic enzymes, including acetyl-CoA carboxylase I and stearoyl-CoA desaturase I. On the contrary, no effects were observed with ROSI on hepatic and mammary lipogenic gene and enzyme expression. Overall, feeding CLA to lactating mice induced milk fat depression and increased hepatic lipid accumulation, probably due to the presence of trans-10, cis-12 CLA isomer, while ROSI failed to significantly attenuate both hepatic steatosis and reduction in milk fat content.

  8. Chronic endocannabinoid system stimulation induces muscle macrophage and lipid accumulation in type 2 diabetic mice independently of metabolic endotoxaemia.

    Directory of Open Access Journals (Sweden)

    Lucie Geurts

    Full Text Available AIMS: Obesity and type 2 diabetes are characterised by low-grade inflammation, metabolic endotoxaemia (i.e., increased plasma lipopolysaccharides [LPS] levels and altered endocannabinoid (eCB-system tone. The aim of this study was to decipher the specific role of eCB-system stimulation or metabolic endotoxaemia in the onset of glucose intolerance, metabolic inflammation and altered lipid metabolism. METHODS: Mice were treated with either a cannabinoid (CB receptor agonist (HU210 or low-dose LPS using subcutaneous mini-pumps for 6 weeks. After 3 weeks of the treatment under control (CT diet, one-half of each group of mice were challenged with a high fat (HF diet for the following 3-week period. RESULTS: Under basal conditions (control diet, chronic CB receptor agonist treatment (i.e., 6 weeks induced glucose intolerance, stimulated metabolic endotoxaemia, and increased macrophage infiltration (CD11c and F4/80 expression in the muscles; this phenomenon was associated with an altered lipid metabolism (increased PGC-1α expression and decreased CPT-1b expression in this tissue. Chronic LPS treatment tended to increase the body weight and fat mass, with minor effects on the other metabolic parameters. Challenging mice with an HF diet following pre-treatment with the CB agonist exacerbated the HF diet-induced glucose intolerance, the muscle macrophage infiltration and the muscle's lipid content without affecting the body weight or the fat mass. CONCLUSION: Chronic CB receptor stimulation under basal conditions induces glucose intolerance, stimulates metabolic inflammation and alters lipid metabolism in the muscles. These effects worsen following the concomitant ingestion of an HF diet. Here, we highlight the central roles played by the eCB system and LPS in the pathophysiology of several hallmarks of obesity and type 2 diabetes.

  9. Deep Sequencing of the Fruit Transcriptome and Lipid Accumulation in a Non-Seed Tissue of Chinese Tallow, a Potential Biofuel Crop.

    Science.gov (United States)

    Divi, Uday K; Zhou, Xue-Rong; Wang, Penghao; Butlin, Jamie; Zhang, Dong-Mei; Liu, Qing; Vanhercke, Thomas; Petrie, James R; Talbot, Mark; White, Rosemary G; Taylor, Jennifer M; Larkin, Philip; Singh, Surinder P

    2016-01-01

    Chinese tallow (Triadica sebifera) is a valuable oilseed-producing tree that can grow in a variety of conditions without competing for food production, and is a promising biofuel feedstock candidate. The fruits are unique in that they contain both saturated and unsaturated fat present in the tallow and seed layer, respectively. The tallow layer is poorly studied and is considered only as an external fatty deposition secreted from the seed. In this study we show that tallow is in fact a non-seed cellular tissue capable of triglyceride synthesis. Knowledge of lipid synthesis and storage mechanisms in tissues other than seed is limited but essential to generate oil-rich biomass crops. Here, we describe the annotated transcriptome assembly generated from the fruit coat, tallow and seed tissues of Chinese tallow. The final assembly was functionally annotated, allowing for the identification of candidate genes and reconstruction of lipid pathways. A tallow tissue-specific paralog for the transcription factor gene WRINKLED1 (WRI1) and lipid droplet-associated protein genes, distinct from those expressed in seed tissue, were found to be active in tallow, underpinning the mode of oil synthesis and packaging in this tissue. Our data have established an excellent knowledge base that can provide genetic and biochemical insights for engineering non-seed tissues to accumulate large amounts of oil. In addition to the large data set of annotated transcripts, the study also provides gene-based simple sequence repeat and single nucleotide polymorphism markers.

  10. Age-Related Inducibility of Carboxylesterases by the Antiepileptic Agent Phenobarbital and Implications in Drug Metabolism and Lipid Accumulation 1, 2

    Science.gov (United States)

    Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang

    2014-01-01

    Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142

  11. Effects of organic carbon source and light-dark period on growth and lipid accumulation of Scenedesmus sp. AARL G022

    Directory of Open Access Journals (Sweden)

    Doungpen Dittamart

    2014-08-01

    Full Text Available The levels of different organic carbon supplements in a mixotrophic culture were optimised to enhance biomass and lipid accumulation in Scenedesmus sp. AARL G022. The supplement nutrients, viz. glucose, glycerol and sodium acetate, were compared with non-organic carbon supplement (photoautotrophic culture. The most suitable carbon source was found to be 0.05M glucose, giving a yield of 2.78 ± 0.86 g.L -1 of biomass and 233.68 ± 35.34 mg.L -1 of crude lipid. The highest yield of biomass (4.04 ± 0.36 g.L -1 was obtained from a light-dark cycle of 24:0 hr. The highest crude lipid yield of 396.35 ± 11.60 mg.L -1 was obtained from a light-dark cycle of 16:8 hr. The optimised condition for culturing Scenedesmus sp. AARL G022 is to cultivate it under a mixotrophic condition using 0.05M of glucose supplement with a light-dark cycle of 16:8 hr.

  12. Nitrogen deprivation induces lipid droplet accumulation and alters fatty acid metabolism in symbiotic dinoflagellates isolated from Aiptasia pulchella.

    Science.gov (United States)

    Weng, Li-Chi; Pasaribu, Buntora; Lin, I-Ping; Tsai, Ching-Hsiu; Chen, Chii-Shiarng; Jiang, Pei-Luen

    2014-07-22

    The stability of cnidarian-dinoflagellate (genus Symbiodinium spp.) endosymbioses depends on the regulation of nutrient transport between Symbiodinium populations and their hosts. Previously, we successfully induced the production of lipid droplets in the free-living cultured Symbiodinium (clade B) under the nitrogen-deprivation condition for 5 days. Therefore, the present study aimed at understanding the disruption of the endosymbiotic relationship between the cnidarians and dinoflagellates by nitrogen deprivation using Aiptasia pulchella as an example. Transmission electron micrographs revealed the formation of lipid droplets induced by nitrogen deprivation, and the lipid analyses further showed that polyunsaturated fatty acids were drastically enriched in Symbiodinium after 30 days of nitrogen deprivation, although these were unaffected after 5 days of nitrogen starvation. The present study also suggested that the host provided nitrogen to the symbiotic cells during short-term environmental stress. However, the relationship started to deteriorate after 30 days. These findings provide a more detailed understanding of the mechanisms of the symbiotic relationship between the symbiotic dinoflagellates in terms of the nitrogen source, which might provide more information for the explanation of the regulatory mechanism underlying endosymbiotic associations.

  13. Investigation of heat induced reactions between lipid oxidation products and amino acids in lipid rich model systems and hazelnuts.

    Science.gov (United States)

    Karademir, Yeşim; Göncüoğlu, Neslihan; Gökmen, Vural

    2013-07-01

    This study aimed to investigate the contribution of lipid oxidation to non-enzymatic browning reactions in lipid rich model and actual food systems. Hazelnut oil and model reaction mixtures consisting of different amino acids were heated under certain conditions to determine possible lipid oxidation and non-enzymatic browning reaction products. In model systems, the Schiff base of 2,4-decadienal, its decarboxylated form, and reaction products formed after hydrolytic cleavage of the Schiff base or decarboxylated form were identified by high resolution mass spectrometry. No furosine was detected in hazelnuts after roasting at 160 °C while the concentration of free amino acids significantly decreased. 2,4-Decadienal reacted effectively with all amino acids studied through a Maillard type carbonyl-amine condensation pathway. (2E,4E)-Deca-2,4-dien-1-amine was identified as a typical reaction product in model systems and roasted hazelnuts. In lipid-rich foods like hazelnuts, lipid-derived carbonyls might be responsible for potential modifications of free and protein bound amino acids during heating.

  14. The molecular face of lipid rafts in model membranes

    NARCIS (Netherlands)

    Risselada, H. Jelger; Marrink, Siewert J.

    2008-01-01

    Cell membranes contain a large number of different lipid species. Such a multicomponent mixture exhibits a complex phase behavior with regions of structural and compositional heterogeneity. Especially domains formed in ternary mixtures, composed of saturated and unsaturated lipids together with

  15. N(ϵ) -Carboxymethyllysine Increases the Expression of miR-103/143 and Enhances Lipid Accumulation in 3T3-L1 Cells.

    Science.gov (United States)

    Holik, Ann-Katrin; Lieder, Barbara; Kretschy, Nicole; Somoza, Mark M; Held, Sandra; Somoza, Veronika

    2016-10-01

    Advanced glycation endproducts, formed in vivo, but also by the Maillard reaction upon thermal treatment of foods, have been associated with the progression of pathological conditions such as diabetes mellitus. In addition to the accumulation with age, exogenous AGEs are introduced into the circulation from dietary sources. In this study, we investigated the effects of addition of free N(ϵ) -carboxymethyllysine (CML), a well-characterized product of the Maillard reaction, on adipogenesis in 3T3-L1 preadipocytes. Treatment with 5, 50, or 500 μM CML resulted in increased lipid accumulation to similar extents, by 11.5 ± 12.6%, 12.9 ± 8.6%, and 12.8 ± 8.5%, respectively. Long-term treatment with 500 μM CML during adipogenesis resulted in increases in miR-103 and miR-143 levels, two miRNAs described to be involved in impaired glucose homeostasis and increased lipid accumulation. Furthermore, the expression of genes associated with these miRNAs, consisting of Akt1, PI3k, and Cav1 was regulated by CML. Short-term treatment of mature 3T3-L1 adipocytes with CML resulted in decreased basal glucose uptake. These results, indicate that the addition of protein-free CML to 3T3-L1 cells influence parameters associated with adipogenesis and glucose homeostasis at transcriptional, and functional level; this indicates that free CML derived from exogenous sources, in addition to protein-bound CML may be relevant in this context. J. Cell. Biochem. 117: 2413-2422, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

  16. 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.

    Science.gov (United States)

    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.

  17. Effects of pomegranate peel polyphenols on lipid accumulation and cholesterol metabolic transformation in L-02 human hepatic cells via the PPARγ-ABCA1/CYP7A1 pathway.

    Science.gov (United States)

    Lv, Ou; Wang, Lifang; Li, Jianke; Ma, Qianqian; Zhao, Wei

    2016-12-07

    To study the effect of pomegranate peel polyphenols on lipid accumulation and cholesterol metabolic transformation in human hepatic cells, purified pomegranate peel polyphenols (PPPs), their main component, punicalagin (PC), and the metabolite of PC, pomegranate ellagic acid (PEA), were chosen as the polyphenols to be tested. At the same time the human hepatocyte cell line L-02 was selected as the experimental cell and a model of steatotic L-02 hepatocytes in vitro was constructed in this paper. The results showed that PPPs, PC and PEA in different concentrations could decrease the total cholesterol (TC) content and increase the total bile acid (TBA) content, and so possess a lipid-lowering effect. The order of the lipid-lowering effect from strong to weak is PEA > PPPs > PC. The relative mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), ATP-binding cassette transporter A1 (ABCA1) and cholesterol 7α hydroxylase (CYP7A1) was up-regulated by PPPs, PC and PEA in a dose-dependent manner. The effect on the relative mRNA expression can be listed in descending order as: PEA > PPPs > PC. Similar results were found in a western blot analysis. The PPARγ protein, ABCA1 protein and CYP7A1 protein were up-regulated in L-02 cells treated with the three tested polyphenols. All the results indicated that PPPs, PC and PEA could regulate upstream the expression of PPARγ, ABCA1 and CYP7A1, both at transcript and protein levels, to activate the PPARγ-ABCA1/CYP7A1 cell signaling pathway and enhance cholesterol metabolism in L-02 cells. Therefore, PPPs, as a kind of natural material, may be paid more attention in the prevention and treatment of diseases related to excessive cholesterol accumulation.

  18. Computer-Aided Modeling of Lipid Processing Technology

    DEFF Research Database (Denmark)

    Diaz Tovar, Carlos Axel

    2011-01-01

    are widely used for design, analysis, and optimization of processes in the chemical and petrochemical industries. These computer-aided tools have helped the chemical industry to evolve beyond commodities toward specialty chemicals and ‘consumer oriented chemicals based products’. Unfortunately...... this is not the case for the edible oil and biodiesel industries. The oleochemical industry lags behind the chemical industry in terms of thermophysical property modeling and development of computational tools suitable for the design/analysis, and optimization of lipid-related processes. The aim of this work has been...... increase along with growing interest in biofuels, the oleochemical industry faces in the upcoming years major challenges in terms of design and development of better products and more sustainable processes to make them. Computer-aided methods and tools for process synthesis, modeling and simulation...

  19. Enhancement of lipid productivity in oleaginous Colletotrichum fungus through genetic transformation using the yeast CtDGAT2b gene under model-optimized growth condition.

    Directory of Open Access Journals (Sweden)

    Prabuddha Dey

    Full Text Available Oleaginous fungi are of special interest among microorganisms for the production of lipid feedstocks as they can be cultured on a variety of substrates, particularly waste lingocellulosic materials, and few fungal strains are reported to accumulate inherently higher neutral lipid than bacteria or microalgae. Previously, we have characterized an endophytic filamentous fungus Colletotrichum sp. DM06 that can produce total lipid ranging from 34% to 49% of its dry cell weight (DCW upon growing with various carbon sources and nutrient-stress conditions. In the present study, we report on the genetic transformation of this fungal strain with the CtDGAT2b gene, which encodes for a catalytically efficient isozyme of type-2 diacylglycerol acyltransferase (DGAT from oleaginous yeast Candida troplicalis SY005. Besides the increase in size of lipid bodies, total lipid titer by the transformed Colletotrichum (lipid content ∼73% DCW was found to be ∼1.7-fold more than the wild type (lipid content ∼38% DCW due to functional activity of the CtDGAT2b transgene when grown under standard condition of growth without imposition of any nutrient-stress. Analysis of lipid fractionation revealed that the neutral lipid titer in transformants increased up to 1.8-, 1.6- and 1.5-fold compared to the wild type when grown under standard, nitrogen stress and phosphorus stress conditions, respectively. Lipid titer of transformed cells was further increased to 1.7-fold following model-based optimization of culture conditions. Taken together, ∼2.9-fold higher lipid titer was achieved in Colletotrichum fungus due to overexpression of a rate-limiting crucial enzyme of lipid biosynthesis coupled with prediction-based bioprocess optimization.

  20. Enhancement of lipid productivity in oleaginous Colletotrichum fungus through genetic transformation using the yeast CtDGAT2b gene under model-optimized growth condition.

    Science.gov (United States)

    Dey, Prabuddha; Mall, Nikunj; Chattopadhyay, Atrayee; Chakraborty, Monami; Maiti, Mrinal K

    2014-01-01

    Oleaginous fungi are of special interest among microorganisms for the production of lipid feedstocks as they can be cultured on a variety of substrates, particularly waste lingocellulosic materials, and few fungal strains are reported to accumulate inherently higher neutral lipid than bacteria or microalgae. Previously, we have characterized an endophytic filamentous fungus Colletotrichum sp. DM06 that can produce total lipid ranging from 34% to 49% of its dry cell weight (DCW) upon growing with various carbon sources and nutrient-stress conditions. In the present study, we report on the genetic transformation of this fungal strain with the CtDGAT2b gene, which encodes for a catalytically efficient isozyme of type-2 diacylglycerol acyltransferase (DGAT) from oleaginous yeast Candida troplicalis SY005. Besides the increase in size of lipid bodies, total lipid titer by the transformed Colletotrichum (lipid content ∼73% DCW) was found to be ∼1.7-fold more than the wild type (lipid content ∼38% DCW) due to functional activity of the CtDGAT2b transgene when grown under standard condition of growth without imposition of any nutrient-stress. Analysis of lipid fractionation revealed that the neutral lipid titer in transformants increased up to 1.8-, 1.6- and 1.5-fold compared to the wild type when grown under standard, nitrogen stress and phosphorus stress conditions, respectively. Lipid titer of transformed cells was further increased to 1.7-fold following model-based optimization of culture conditions. Taken together, ∼2.9-fold higher lipid titer was achieved in Colletotrichum fungus due to overexpression of a rate-limiting crucial enzyme of lipid biosynthesis coupled with prediction-based bioprocess optimization.

  1. Oil accumulation in the model green alga Chlamydomonas reinhardtii: characterization, variability between common laboratory strains and relationship with starch reserves

    National Research Council Canada - National Science Library

    Siaut, Magali; Cuiné, Stéphan; Cagnon, Caroline; Fessler, Boris; Nguyen, Mai; Carrier, Patrick; Beyly, Audrey; Beisson, Fred; Triantaphylidès, Christian; Li-Beisson, Yonghua; Peltier, Gilles

    2011-01-01

    ...). The model green microalga Chlamydomonas reinhardtii has recently emerged as a model to test genetic engineering or cultivation strategies aiming at increasing lipid yields for biodiesel production...

  2. Computer-Aided Modeling of Lipid Processing Technology

    DEFF Research Database (Denmark)

    Diaz Tovar, Carlos Axel

    2011-01-01

    the analysis, in terms of their design variables and their impact in the process behavior, of three lipid-related processes has been performed: the solvent recovery section of the extraction of crude soybean oil, the deodorization of palm oil, and the deacidification of soybean oil.......Vegetable oils and fats have an important role in human nutrition and in the chemical industry since they are a source of energy, fat-soluble vitamins, and now also in the production of renewable sources of energy. Nowadays as the consumer preferences for natural products and healthier foods...... increase along with growing interest in biofuels, the oleochemical industry faces in the upcoming years major challenges in terms of design and development of better products and more sustainable processes to make them. Computer-aided methods and tools for process synthesis, modeling and simulation...

  3. Isoflavonoids from Crotalaria albida Inhibit Adipocyte Differentiation and Lipid Accumulation in 3T3-L1 Cells via Suppression of PPAR-γ Pathway.

    Directory of Open Access Journals (Sweden)

    Qinhu Sun

    Full Text Available Two 2″-isopropenyl dihydrofuran isoflavonoids (1 and 3, one 2″-isopropenyl dihydrofuran chromone (2, as well as 13 known compounds were isolated from the herbs of Crotalaria albida. Their structures and relative configurations were elucidated via NMR and HRESIMS analyses. The 2″ S absolute configuration of 1 and 2 were deduced by comparing their NOESY spectra with that of 3, which was determined via single crystal X-ray diffraction (CuKα. The 3R absolute configuration of 1 was determined by CD. Compounds 1, 2, and 3 inhibit the adipocyte differentiation and lipid accumulation of 3T3-L1 through down-regulation of PPAR-γ activity.

  4. The edible red alga, Gracilaria verrucosa, inhibits lipid accumulation and ROS production, but improves glucose uptake in 3T3-L1 cells.

    Science.gov (United States)

    Woo, Mi-Seon; Choi, Hyeon-Son; Lee, Ok-Hwan; Lee, Boo-Yong

    2013-07-01

    Gracilaria verrucosa is a red alga that is widely distributed in seaside areas of many countries. We examined the effect of G. verrucosa extract on adipogenesis, reactive oxygen species (ROS) production, and glucose uptake in 3T3-L1 cells. Oil red O staining and a nitroblue tetrazolium assay showed that G. verrucosa extract inhibited lipid accumulation and ROS production, respectively. mRNA levels of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha, as well as of their target gene, adipocyte protein 2, were reduced upon treatment with G. verrucosa extract. However, G. verrucosa extract increased glucose uptake, glucose transporter-4 expression, and AMP-activated protein kinaseα (AMPKα) phosphorylation compared to the control. Our results suggest that the anti-adipogenic and insulin-sensitive effects of G. verrucosa extract can be recapitulated to activation of AMPKα.

  5. Oil accumulation in the model green alga Chlamydomonas reinhardtii: characterization, variability between common laboratory strains and relationship with starch reserves

    Directory of Open Access Journals (Sweden)

    Carrier Patrick

    2011-01-01

    Full Text Available Abstract Background When cultivated under stress conditions, many microalgae species accumulate both starch and oil (triacylglycerols. The model green microalga Chlamydomonas reinhardtii has recently emerged as a model to test genetic engineering or cultivation strategies aiming at increasing lipid yields for biodiesel production. Blocking starch synthesis has been suggested as a way to boost oil accumulation. Here, we characterize the triacylglycerol (TAG accumulation process in Chlamydomonas and quantify TAGs in various wild-type and starchless strains. Results In response to nitrogen deficiency, Chlamydomonas reinhardtii produced TAGs enriched in palmitic, oleic and linoleic acids that accumulated in oil-bodies. Oil synthesis was maximal between 2 and 3 days following nitrogen depletion and reached a plateau around day 5. In the first 48 hours of oil deposition, a ~80% reduction in the major plastidial membrane lipids occurred. Upon nitrogen re-supply, mobilization of TAGs started after starch degradation but was completed within 24 hours. Comparison of oil content in five common laboratory strains (CC124, CC125, cw15, CC1690 and 11-32A revealed a high variability, from 2 μg TAG per million cell in CC124 to 11 μg in 11-32A. Quantification of TAGs on a cell basis in three mutants affected in starch synthesis (cw15sta1-2, cw15sta6 and cw15sta7-1 showed that blocking starch synthesis did not result in TAG over-accumulation compared to their direct progenitor, the arginine auxotroph strain 330. Moreover, no significant correlation was found between cellular oil and starch levels among the twenty wild-type, mutants and complemented strains tested. By contrast, cellular oil content was found to increase steeply with salt concentration in the growth medium. At 100 mM NaCl, oil level similar to nitrogen depletion conditions could be reached in CC124 strain. Conclusion A reference basis for future genetic studies of oil metabolism in Chlamydomonas

  6. Hydrocarbon accumulation model of the Cretaceous in southern China

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The Cretaceous in southern China is mainly a set of red and mauve clastic rock,with evaporation layers. For lack of source rock,it has been paid little attention to in the exploration process. With the development of research on hydrocarbon exploration,the masses of Cretaceous reservoirs and shows have been found in recent years. This means that the Cretaceous has great exploration potential. According to the research,authors find that the high-quality reservoir and efficient cap rocks develop in the Cretaceous. At the same time,the Cretaceous and underlying Paleozoic-Early Mesozoic marine strata and overlying Cenozoic nonmarine strata constitute a superimposed basin. Moreover,high-quality source rocks developed in the above-mentioned two sets of strata. In the south,especially in the middle and lower Yangtze region since the Himalayan strong rift was associated with a large number of faults,These faults connect the Cretaceous reservoir and its overlying and underlying source rocks,forming the fault-based and unconformity-based discontinuous source-reservoir-cap accumulation assemblages. Because the Cretaceous has the abundant oil and gas from Paleogene source rocks or Mesozoic–Paleozoic source rocks with secondary hydrocarbon generation ability,three types of reservoirs develop in the Cretaceous:"new-generating and old-reservoiring" reservoirs,"old-generating andnew-reservoiring" reservoirs,and few "self-generating andself-reservoiring" reservoirs. The hydrocarbon enrichment depends on two key factors. Firstly,Cretaceous reservoirs are near to the source kitchens,so its oil and gas source is ample. Secondly,the fault system is well developed,which provides the necessary conducting systems for hydrocarbon accumulation.

  7. Measurement of lipid accumulation in Chlorella vulgaris via flow cytometry and liquid-state ¹H NMR spectroscopy for development of an NMR-traceable flow cytometry protocol.

    Science.gov (United States)

    Bono, Michael S; Garcia, Ravi D; Sri-Jayantha, Dylan V; Ahner, Beth A; Kirby, Brian J

    2015-01-01

    In this study, we cultured Chlorella vulgaris cells with a range of lipid contents, induced via nitrogen starvation, and characterized them via flow cytometry, with BODIPY 505/515 as a fluorescent lipid label, and liquid-state 1H NMR spectroscopy. In doing so, we demonstrate the utility of calibrating flow cytometric measurements of algal lipid content using triacylglyceride (TAG, also known as triacylglycerol or triglyceride) content per cell as measured via quantitative 1H NMR. Ensemble-averaged fluorescence of BODIPY-labeled cells was highly correlated with average TAG content per cell measured by bulk NMR, with a linear regression yielding a linear fit with r2 = 0.9974. This correlation compares favorably to previous calibrations of flow cytometry protocols to lipid content measured via extraction, and calibration by NMR avoids the time and complexity that is generally required for lipid quantitation via extraction. Flow cytometry calibrated to a direct measurement of TAG content can be used to investigate the distribution of lipid contents for cells within a culture. Our flow cytometry measurements showed that Chlorella vulgaris cells subjected to nitrogen limitation exhibited higher mean lipid content but a wider distribution of lipid content that overlapped the relatively narrow distribution of lipid content for replete cells, suggesting that nitrogen limitation induces lipid accumulation in only a subset of cells. Calibration of flow cytometry protocols using direct in situ measurement of TAG content via NMR will facilitate rapid development of more precise flow cytometry protocols, enabling investigation of algal lipid accumulation for development of more productive algal biofuel feedstocks and cultivation protocols.

  8. Measurement of lipid accumulation in Chlorella vulgaris via flow cytometry and liquid-state ¹H NMR spectroscopy for development of an NMR-traceable flow cytometry protocol.

    Directory of Open Access Journals (Sweden)

    Michael S Bono

    Full Text Available In this study, we cultured Chlorella vulgaris cells with a range of lipid contents, induced via nitrogen starvation, and characterized them via flow cytometry, with BODIPY 505/515 as a fluorescent lipid label, and liquid-state 1H NMR spectroscopy. In doing so, we demonstrate the utility of calibrating flow cytometric measurements of algal lipid content using triacylglyceride (TAG, also known as triacylglycerol or triglyceride content per cell as measured via quantitative 1H NMR. Ensemble-averaged fluorescence of BODIPY-labeled cells was highly correlated with average TAG content per cell measured by bulk NMR, with a linear regression yielding a linear fit with r2 = 0.9974. This correlation compares favorably to previous calibrations of flow cytometry protocols to lipid content measured via extraction, and calibration by NMR avoids the time and complexity that is generally required for lipid quantitation via extraction. Flow cytometry calibrated to a direct measurement of TAG content can be used to investigate the distribution of lipid contents for cells within a culture. Our flow cytometry measurements showed that Chlorella vulgaris cells subjected to nitrogen limitation exhibited higher mean lipid content but a wider distribution of lipid content that overlapped the relatively narrow distribution of lipid content for replete cells, suggesting that nitrogen limitation induces lipid accumulation in only a subset of cells. Calibration of flow cytometry protocols using direct in situ measurement of TAG content via NMR will facilitate rapid development of more precise flow cytometry protocols, enabling investigation of algal lipid accumulation for development of more productive algal biofuel feedstocks and cultivation protocols.

  9. RKIP phosphorylation-dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3.

    Science.gov (United States)

    Hahm, Jong Ryeal; Ahmed, Mahmoud; Kim, Deok Ryong

    2016-09-01

    3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-l-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or β, PPARγ, SREBP2). In particular, SREBP2 was highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-l-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity.

  10. Acidophilic green alga Pseudochlorella sp. YKT1 accumulates high amount of lipid droplets under a nitrogen-depleted condition at a low-pH.

    Directory of Open Access Journals (Sweden)

    Shunsuke Hirooka

    Full Text Available Microalgal storage lipids are considered to be a promising source for next-generation biofuel feedstock. However, microalgal biodiesel is not yet economically feasible due to the high cost of production. One of the reasons for this is that the use of a low-cost open pond system is currently limited because of the unavoidable contamination with undesirable organisms. Extremophiles have an advantage in culturing in an open pond system because they grow in extreme environments toxic to other organisms. In this study, we isolated the acidophilic green alga Pseudochlorella sp. YKT1 from sulfuric acid mine drainage in Nagano Prefecture, Japan. The vegetative cells of YKT1 display the morphological characteristics of Trebouxiophyceae and molecular phylogenetic analyses indicated it to be most closely related to Pseudochlorella pringsheimii. The optimal pH and temperature for the growth of YKT1 are pH 3.0-5.0 and a temperature 20-25°C, respectively. Further, YKT1 is able to grow at pH 2.0 and at 32°C, which corresponds to the usual water temperature in the outdoors in summer in many countries. YKT1 accumulates a large amount of storage lipids (∼30% of dry weigh under a nitrogen-depleted condition at low-pH (pH 3.0. These results show that acidophilic green algae will be useful for industrial applications by acidic open culture systems.

  11. RKIP phosphorylation–dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3

    Energy Technology Data Exchange (ETDEWEB)

    Hahm, Jong Ryeal [Department of Internal Medicine, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Ahmed, Mahmoud [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Kim, Deok Ryong, E-mail: drkim@gnu.ac.kr [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of)

    2016-09-09

    3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-L-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or β, PPARγ, SREBP2). In particular, SREBP2 was highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-L-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity. - Highlights: • Overexpression of GFP-LC3 in 3T3-L1 cells produces intracellular lipid droplets. • SREBP2 is highly activated in preadipocytes transfected with adenoviral GFP-LC3. • RKIP phosphorylation at serine 153 is significantly increased during adipogenesis. • RKIP knockdown promotes ERK1 and PPARγ activation during adipogenesis. • RKIP-dependent ERK1 activation increases triacylglycerides in

  12. Interaction of lipid nanoparticles with human epidermis and an organotypic cell culture model

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Bunjes, Heike; Fahr, Alfred

    2008-01-01

    Various lipid nanoparticle formulations were investigated with respect to (trans)dermal drug delivery with special regard to the mechanism of their effects on human and an organotypic cell culture epidermis. Potential alterations of stratum corneum lipid domains were studied using fluorescence...... was visualized by fluorescence microscopy of cross sections of human epidermis after incubation with cubic and solid lipid nanoparticles. Corticosterone permeation was limited when applied in matrix-type lipid nanoparticles (fat emulsion, smectic and solid lipid nanoparticles). An adhesion of solid lipid...... studies and thermal analysis of human and cell culture epidermis indicate that surface lipids, which are not present to the same extent in the cell culture model than in human epidermis, seem to play an important role....

  13. Light intensity and N/P nutrient affect the accumulation of lipid and unsaturated fatty acids by Chlorella sp.

    Science.gov (United States)

    Guo, Xiaoyi; Su, Gaomin; Li, Zheng; Chang, Jingyu; Zeng, Xianhai; Sun, Yong; Lu, Yinghua; Lin, Lu

    2015-09-01

    In this study, different light intensities (80, 160, 240 and 320 μmol/m(2) s) and various mediums including control medium (CM), N/P rich medium (NPM), N rich medium (NM), and P rich medium (PM) were applied for cultivation of Chlorella sp. It was revealed that cultivation of Chlorella sp. in CM under the light intensity of 320 μmol/m(2) s led to a lipid content up to 30% enhancement, which was higher than the results of other cases. A rather high unsaturated fatty acid (UFA) content of 7.5% and unsaturated fatty acid/total fatty acid (UFA/TFA) ratio of 0.73 were obtained under 320 μmol/m(2) s in CM, indicating that the CM-320 system was applicable for the generation of UFA. Moreover, Chlorella sp. cultivated in PM under 320 μmol/m(2) s provided higher TFA content (7.3%), which was appropriate for biofuel production.

  14. Study on the lipid organization of stratum corneum lipid models by (cryo-) electron diffraction

    NARCIS (Netherlands)

    Pilgram, GSK; Pelt, AMEV; Oostergetel, GT; Koerten, HK; Bouwstra, JA

    The barrier function of the skin resides in the stratum corneum (SC), This outermost layer consists of protein-rich corneocytes and lipid-rich intercellular domains. These domains form the rate-limiting step for transepidermal water loss and the penetration of substances from the environment. To

  15. Modelling Accumulator Stripper Foil Heating for ESSNUSB Facility

    CERN Document Server

    Martini, Michel

    2015-01-01

    It is proposed to use the 2.0 GeV, 5 MW proton linac, 2.86 ms long pulses at 14 Hz of the European Spallation Source [1], [2] being built in Lund, Sweden to deliver, alternately with the spallation neutron production a very intense neutrino beam to enable the discovery of leptonic CP violation. To this end the linac would be upgraded to supply, in addition to the 2.86 ms long proton pulses at 14 Hz, four 0.72 ms H short pulses at 70 Hz for neutrino production. Because of the high current required in the pulsed neutrino horn, the length of the pulses used for neutrino production will need to be compressed to a few s with the aid of an accumulator ring. Charge exchange injection of an H- beam from the linac will be used, the linac delivering 1.1E15 H- per pulse. This paper is about stripping foil heating considerations, emphasizing the detailed evaluation of the foil temperature over the multiple ring re-fills

  16. Predictive performances of lipid accumulation product vs. adiposity measures for cardiovascular diseases and all-cause mortality, 8.6-year follow-up: Tehran lipid and glucose study

    Directory of Open Access Journals (Sweden)

    Azizi Fereidoun

    2010-09-01

    Full Text Available Abstract Background The body mass index (BMI is the most commonly used marker for evaluating obesity related risks, however, central obesity measures have been proposed to be more informative. Lipid accumulation product (LAP is an alternative continuous index of lipid accumulation. We sought in this study to assess if LAP can outperform BMI, waist-to-height-ratio (WHtR, or waist-to-hip-ratio (WHpR in predicting incident cardiovascular disease (CVD or all-cause mortality. Results Among participants of Tehran Lipid and Glucose Study, 6,751 participants (2,964 men, aged ≥ 30 years, were followed for a median of 8.6 years. We observed 274 deaths (men: 168 and 447 CVD events (men: 257. Levels of common CVD risk factors significantly increased across LAP quartiles. Mortality rates did not differ by LAP quartiles. Among participants free of CVD at baseline [6331 (2,741 men], CVD incident rates per 1000 person increased in a stepwise fashion with increasing LAP quartile values in both men (from 6.9 to 17.0 and women (from 1.3 to 13.0, (Ps Among women, a 1-SD increment in log-LAP conferred a 41% increased risk for CVD (HR 1.41, 95% CIs 1.02-1.96. Among men, however, LAP was not observed to be independently associated with increased risk of CVD; except in a sub-group of men assigned to the lifestyle modification interventions, where, LAP predicted CVD risk. After adjustment with CVD risk factors LAP turned to be inversely associated with risk of all-cause mortality (HR, men 0.74, 95% CIs 0.61-0.90; women, 0.94 95% CIs 0.74-1.20. Among women, magnitude of increased risk of CVD due to LAP was not different from those of anthropometric measures. Among men, however, WHpR was observed to be more strongly associated with increased risk of CVD than was LAP. Among neither men nor women were the predictive performances (discrimination, calibration, goodness-of-fit of the LAP better than those of different anthropometric measures were. Conclusions If LAP is to be

  17. Differential tissue accumulation of 2,3,7,8-Tetrachlorinated dibenzo-p-dioxin in Arabidopsis thaliana affects plant chronology, lipid metabolism and seed yield.

    Science.gov (United States)

    Hanano, Abdulsamie; Almousally, Ibrahem; Shaban, Mouhnad; Moursel, Nour; Shahadeh, AbdAlbaset; Alhajji, Eskander

    2015-08-11

    Dioxins are one of the most toxic groups of persistent organic pollutants. Their biotransmission through the food chain constitutes a potential risk for human health. Plants as principal actors in the food chain can play a determinant role in removing dioxins from the environment. Due to the lack of data on dioxin/plant research, this study sets out to determine few responsive reactions adopted by Arabidopsis plant towards 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins. Using a high resolution gas chromatography/mass spectrometry, we demonstrated that Arabidopsis plant uptakes TCDD by the roots and accumulates it in the vegetative parts in a tissue-specific manner. TCDD mainly accumulated in rosette leaves and mature seeds and less in stem, flowers and immature siliques. Moreover, we observed that plants exposed to high doses of TCDD exhibited a delay in flowering and yielded fewer seeds of a reduced oil content with a low vitality. A particular focus on the plant fatty acid metabolism showed that TCDD caused a significant reduction in C18-unsaturated fatty acid level in plant tissues. Simultaneously, TCDD induced the expression of 9-LOX and 13-LOX genes and the formation of their corresponding hydroperoxides, 9- and 13-HPOD as well as 9- or 13-HPOT, derived from linoleic and linolenic acids, respectively. The current work highlights a side of toxicological effects resulting in the administration of 2,3,7,8-TCDD on the Arabidopsis plant. Similarly to animals, it seems that plants may accumulate TCDD in their lipids by involving few of the FA-metabolizing enzymes for sculpting a specific oxylipins "signature" typified to plant TCDD-tolerance. Together, our results uncover novel responses of Arabidopsis to dioxin, possibly emerging to overcome its toxicity.

  18. IMPLEMENTATION AND VALIDATION OF A FULLY IMPLICIT ACCUMULATOR MODEL IN RELAP-7

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Haihua [Idaho National Laboratory; Zou, Ling [Idaho National Laboratory; Zhang, Hongbin [Idaho National Laboratory; Martineau, Richard Charles [Idaho National Laboratory

    2016-01-01

    This paper presents the implementation and validation of an accumulator model in RELAP-7 under the framework of preconditioned Jacobian free Newton Krylov (JFNK) method, based on the similar model used in RELAP5. RELAP-7 is a new nuclear reactor system safety analysis code being developed at the Idaho National Laboratory (INL). RELAP-7 is a fully implicit system code. The JFNK and preconditioning methods used in RELAP-7 is briefly discussed. The slightly modified accumulator model is summarized for completeness. The implemented model was validated with LOFT L3-1 test and benchmarked with RELAP5 results. RELAP-7 and RELAP5 had almost identical results for the accumulator gas pressure and water level, although there were some minor difference in other parameters such as accumulator gas temperature and tank wall temperature. One advantage of the JFNK method is its easiness to maintain and modify models due to fully separation of numerical methods from physical models. It would be straightforward to extend the current RELAP-7 accumulator model to simulate the advanced accumulator design.

  19. Off-lattice model for the phase behavior of lipid-cholesterol bilayers

    DEFF Research Database (Denmark)

    Nielsen, Morten; Miao, Ling; Ipsen, John Hjorth

    1999-01-01

    Lipid bilayers exhibit a phase behavior that involves two distinct, but coupled, order-disorder processes, one in terms of lipid-chain crystalline packing (translational degrees of freedom) and the other in terms of lipid-chain conformational ordering (internal degrees of freedom). Experiments...... and previous approximate theories have suggested that cholesterol incorporated into lipid bilayers has different microscopic effects on lipid-chain packing and conformations and that cholesterol thereby leads to decoupling of the two ordering processes, manifested by a special equilibrium phase, "liquid......-lattice model based on a two-dimensional random triangulation algorithm and represents lipid and cholesterol molecules by hard-core particles with internal (spin-type) degrees of freedom that have nearest-neighbor interactions. The phase equilibria described by the model, specifically in terms of phase diagrams...

  20. Modeling, Optimization, and Detailed Design of a Hydraulic Flywheel-Accumulator

    Science.gov (United States)

    Strohmaier, Kyle Glenn

    Improving mobile energy storage technology is an important means of addressing concerns over fossil fuel scarcity and energy independence. Traditional hydraulic accumulator energy storage, though favorable in power density, durability, cost, and environmental impact, suffers from relatively low energy density and a pressure-dependent state of charge. The hydraulic flywheel-accumulator concept utilizes both the hydro-pneumatic and rotating kinetic energy domains by employing a rotating pressure vessel. This thesis provides an in-depth analysis of the hydraulic flywheel-accumulator concept and an assessment of the advantages it offers over traditional static accumulator energy storage. After specifying a practical architecture for the hydraulic flywheel-accumulator, this thesis addresses the complex fluid phenomena and control implications associated with multi-domain energy storage. To facilitate rapid selection of the hydraulic flywheel-accumulator dimensions, computationally inexpensive material stress models are developed for each component. A drive cycle simulation strategy is also developed to assess the dynamic performance of the device. The stress models and performance simulation are combined to form a toolset that facilitates computationally-efficient model-based design. The aforementioned toolset has been embedded into a multi-objective optimization algorithm that aims to minimize the mass of the hydraulic flywheel-accumulator system and to minimize the losses it incurs over the course of a drive cycle. Two optimizations have been performed - one with constraints that reflect a vehicle-scale application, and one with constraints that reflect a laboratory application. At both scales, the optimization results suggest that the hydraulic flywheel-accumulator offers at least an order of magnitude improvement over traditional static accumulator energy storage, while operating at efficiencies between 75% and 93%. A particular hydraulic flywheel-accumulator design

  1. Intake of farmed Atlantic salmon fed soybean oil increases insulin resistance and hepatic lipid accumulation in mice.

    Directory of Open Access Journals (Sweden)

    Lisa Kolden Midtbø

    Full Text Available BACKGROUND: To ensure sustainable aquaculture, fish derived raw materials are replaced by vegetable ingredients. Fatty acid composition and contaminant status of farmed Atlantic salmon (Salmo salar L. are affected by the use of plant ingredients and a spillover effect on consumers is thus expected. Here we aimed to compare the effects of intake of Atlantic salmon fed fish oil (FO with intake of Atlantic salmon fed a high proportion of vegetable oils (VOs on development of insulin resistance and obesity in mice. METHODOLOGY/PRINCIPAL FINDINGS: Atlantic salmon were fed diets where FO was partly (80% replaced with three different VOs; rapeseed oil (RO, olive oil (OO or soy bean oil (SO. Fillets from Atlantic salmon were subsequently used to prepare Western diets (WD for a mouse feeding trial. Partial replacement of FO with VOs reduced the levels of polychlorinated biphenyls (PCB and dichloro-diphenyl-tricloroethanes (DDT with more than 50% in salmon fillets, in WDs containing the fillets, and in white adipose tissue from mice consuming the WDs. Replacement with VOs, SO in particular, lowered the n-3 polyunsaturated fatty acid (PUFA content and increased n-6 PUFA levels in the salmon fillets, in the prepared WDs, and in red blood cells collected from mice consuming the WDs. Replacing FO with VO did not influence obesity development in the mice, but replacement of FO with RO improved glucose tolerance. Compared with WD-FO fed mice, feeding mice WD-SO containing lower PCB and DDT levels but high levels of linoleic acid (LA, exaggerated insulin resistance and increased accumulation of fat in the liver. CONCLUSION/SIGNIFICANCE: Replacement of FO with VOs in aqua feed for farmed salmon had markedly different spillover effects on metabolism in mice. Our results suggest that the content of LA in VOs may be a matter of concern that warrants further investigation.

  2. Investigating the barrier function of skin lipid models with varying compositions.

    Science.gov (United States)

    Groen, Daniël; Poole, Dana S; Gooris, Gert S; Bouwstra, Joke A

    2011-10-01

    The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the barrier function. The main lipid classes in stratum corneum are ceramides, cholesterol, and free fatty acids. In previous publications, a lipid model was presented, referred to as the stratum corneum substitute (SCS), that closely mimics the SC lipid organization and SC barrier function. In the present study, we use the SCS to study the effect of changes in lipid organization on the lipid barrier function using benzoic acid as permeation compound. First, in the SCS, we increased the level of one of the three major lipid classes keeping the ratio between the other lipid classes constant. An increased cholesterol level resulted in an increase in phase-separated cholesterol and a reduction in the permeability. An increase in ceramide or free fatty acid level resulted in the formation of additional phases, but had no significant influence on the permeability. We also examined models that mimic selected changes in lipid composition reported for dry or diseased skin. The SCS that mimics the composition in recessive X-linked ichthyosis skin displayed a twofold increase in permeability. This increase is possibly related to the formation of an additional, less ordered phase in this model. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Computational and analytical modeling of cationic lipid-DNA complexes.

    Science.gov (United States)

    Farago, Oded; Grønbech-Jensen, Niels

    2007-05-01

    We present a theoretical study of the physical properties of cationic lipid-DNA (CL-DNA) complexes--a promising synthetically based nonviral carrier of DNA for gene therapy. The study is based on a coarse-grained molecular model, which is used in Monte Carlo simulations of mesoscopically large systems over timescales long enough to address experimental reality. In the present work, we focus on the statistical-mechanical behavior of lamellar complexes, which in Monte Carlo simulations self-assemble spontaneously from a disordered random initial state. We measure the DNA-interaxial spacing, d(DNA), and the local cationic area charge density, sigma(M), for a wide range of values of the parameter (c) representing the fraction of cationic lipids. For weakly charged complexes (low values of (c)), we find that d(DNA) has a linear dependence on (c)(-1), which is in excellent agreement with x-ray diffraction experimental data. We also observe, in qualitative agreement with previous Poisson-Boltzmann calculations of the system, large fluctuations in the local area charge density with a pronounced minimum of sigma(M) halfway between adjacent DNA molecules. For highly-charged complexes (large (c)), we find moderate charge density fluctuations and observe deviations from linear dependence of d(DNA) on (c)(-1). This last result, together with other findings such as the decrease in the effective stretching modulus of the complex and the increased rate at which pores are formed in the complex membranes, are indicative of the gradual loss of mechanical stability of the complex, which occurs when (c) becomes large. We suggest that this may be the origin of the recently observed enhanced transfection efficiency of lamellar CL-DNA complexes at high charge densities, because the completion of the transfection process requires the disassembly of the complex and the release of the DNA into the cytoplasm. Some of the structural properties of the system are also predicted by a continuum

  4. Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

    Science.gov (United States)

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

    2016-09-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc.

  5. 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.

    Science.gov (United States)

    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.

  6. Gelidium elegans, an edible red seaweed, and hesperidin inhibit lipid accumulation and production of reactive oxygen species and reactive nitrogen species in 3T3-L1 and RAW264.7 cells.

    Science.gov (United States)

    Jeon, Hui-Jeon; Seo, Min-Jung; Choi, Hyeon-Son; Lee, Ok-Hwan; Lee, Boo-Yong

    2014-11-01

    Gelidium elegans is an edible red alga native to the intertidal area of northeastern Asia. We investigated the effect of G. elegans extract and its main flavonoids, rutin and hesperidin, on lipid accumulation and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3-L1 and RAW264.7 cells. Our data show that G. elegans extract decreased lipid accumulation and ROS/RNS production in a dose-dependent manner. The extract also inhibited the mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha, while enhancing the protein expression of the antioxidant enzymes superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase compared with controls. In addition, lipopolysaccharide-induced nitric oxide production was significantly reduced in G. elegans extract-treated RAW264.7 cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid accumulation and ROS production; rutin did not affect adipogenesis and ROS status. The antiadipogenic effect of hesperidin was evidenced by the downregulation of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and fatty acid binding protein 4 gene expression. Collectively, our data suggest that G. elegans is a potential food source containing antiobesity and antioxidant constituents.

  7. Effects of microalgal polyunsaturated fatty acid oil on body weight and lipid accumulation in the liver of C57BL/6 mice fed a high fat diet.

    Science.gov (United States)

    Go, Ryeo-Eun; Hwang, Kyung-A; Park, Geon-Tae; Lee, Hae-Miru; Lee, Geum-A; Kim, Cho-Won; Jeon, So-Ye; Seo, Jeong-Woo; Hong, Won-Kyung; Choi, Kyung-Chul

    2016-05-01

    Dietary polyunsaturated fatty acids (PUFAs), which are abundant in marine fish oils, have recently received global attention for their prominent anti-obesogenic effects. Among PUFAs, eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), which are n-3 long-chain PUFAs widely referred to as omega-3 oils, were reported to prevent the development of obesity in rodents and humans. In the present study, we evaluated the anti-obesity effects of microalgal oil on high-fat induced obese C57BL/6 mice, compared with commercial omega-3 fish oil and vegetable corn oil. Microalgal oil is an inherent mixture of several PUFAs, including EPA, DHA and other fatty acids produced from a marine microalgal strain of Thraustochytriidae sp. derived mutant. It was found to contain more PUFAs (>80%) and more omega-3 oils than commercial omega-3 fish oil (PUFAs >31%) and corn oil (PUFAs 59%). All three types of oils induced weight loss in high-fat-induced obese mice, with the loss induced by microalgal oil being most significant at 9 weeks (10% reduction). However, the oils tested did not improve blood lipid levels, although microalgal oil showed an apparent inhibitory effect on lipid accumulation in the liver. These findings may be attributed to the higher PUFA content, including omega-3 oils of microalgal oil than other oils. Collectively, these findings suggest that microalgal oil, derived from Thraustochytriidae sp. derived mutant, is a prominent candidate for replacement of omega-3 fish oils based on its apparent anti-obesity effect in vivo.

  8. An implicit solvent coarse-grained lipid model with correct stress profile

    Science.gov (United States)

    Sodt, Alex J.; Head-Gordon, Teresa

    2010-05-01

    We develop a coarse-grained parametrization strategy for lipid membranes that we illustrate for a dipalmitoylphosphatidylcholine bilayer. Our coarse-graining approach eliminates the high cost of explicit solvent but maintains more lipid interaction sites. We use a broad attractive tail-tail potential and extract realistic bonded potentials of mean force from all-atom simulations, resulting in a model with a sharp gel to fluid transition, a correct bending modulus, and overall very reasonable dynamics when compared with experiment. We also determine a quantitative stress profile and correct breakdown of contributions from lipid components when compared with detailed all-atom simulation benchmarks, which has been difficult to achieve for implicit membrane models. Such a coarse-grained lipid model will be necessary for efficiently simulating complex constructs of the membrane, such as protein assembly and lipid raft formation, within these nonaqueous chemical environments.

  9. Partitioning, diffusion, and ligand binding of raft lipid analogs in model and cellular plasma membranes.

    Science.gov (United States)

    Sezgin, Erdinc; Levental, Ilya; Grzybek, Michal; Schwarzmann, Günter; Mueller, Veronika; Honigmann, Alf; Belov, Vladimir N; Eggeling, Christian; Coskun, Unal; Simons, Kai; Schwille, Petra

    2012-07-01

    Several simplified membrane models featuring coexisting liquid disordered (Ld) and ordered (Lo) lipid phases have been developed to mimic the heterogeneous organization of cellular membranes, and thus, aid our understanding of the nature and functional role of ordered lipid-protein nanodomains, termed "rafts". In spite of their greatly reduced complexity, quantitative characterization of local lipid environments using model membranes is not trivial, and the parallels that can be drawn to cellular membranes are not always evident. Similarly, various fluorescently labeled lipid analogs have been used to study membrane organization and function in vitro, although the biological activity of these probes in relation to their native counterparts often remains uncharacterized. This is particularly true for raft-preferring lipids ("raft lipids", e.g. sphingolipids and sterols), whose domain preference is a strict function of their molecular architecture, and is thus susceptible to disruption by fluorescence labeling. Here, we analyze the phase partitioning of a multitude of fluorescent raft lipid analogs in synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). We observe complex partitioning behavior dependent on label size, polarity, charge and position, lipid headgroup, and membrane composition. Several of the raft lipid analogs partitioned into the ordered phase in GPMVs, in contrast to fully synthetic GUVs, in which most raft lipid analogs mis-partitioned to the disordered phase. This behavior correlates with the greatly enhanced order difference between coexisting phases in the synthetic system. In addition, not only partitioning, but also ligand binding of the lipids is perturbed upon labeling: while cholera toxin B binds unlabeled GM1 in the Lo phase, it binds fluorescently labeled GMI exclusively in the Ld phase. Fluorescence correlation spectroscopy (FCS) by stimulated emission depletion (STED) nanoscopy on intact

  10. Dynamical clustering and a mechanism for raft-like structures in a model lipid membrane.

    Science.gov (United States)

    Starr, Francis W; Hartmann, Benedikt; Douglas, Jack F

    2014-05-01

    We use molecular dynamics simulations to examine the dynamical heterogeneity of a model single-component lipid membrane using a coarse-grained representation of lipid molecules. This model qualitatively reproduces the known phase transitions between disordered, ordered, and gel membrane phases, and the phase transitions are accompanied by significant changes in the nature of the lipid dynamics. In particular, lipid diffusion in the liquid-ordered phase is hindered by the transient trapping of molecules by their neighbors, similar to the dynamics of a liquid approaching its glass transition. This transient molecular caging gives rise to two distinct mobility groups within a single-component membrane: lipids that are transiently trapped, and lipids with displacements on the scale of the intermolecular spacing. Most significantly, lipids within these distinct mobility states spatially segregate, creating transient "islands" of enhanced mobility having a size and time scale compatible with lipid "rafts," dynamical structures thought to be important for cell membrane function. Although the dynamic lipid clusters that we observe do not themselves correspond to rafts (which are more complex, multicomponent structures), we hypothesize that such rafts may develop from the same universal mechanism, explaining why raft-like regions should arise, regardless of lipid structural or compositional details. These clusters are strikingly similar to the dynamical clusters found in glass-forming fluids, and distinct from phase-separation clusters. We also show that mobile lipid clusters can be dissected into smaller clusters of cooperatively rearranging molecules. The geometry of these clusters can be understood in the context of branched equilibrium polymers, related to percolation theory. We discuss how these dynamical structures relate to a range observations on the dynamics of lipid membranes.

  11. 2D lattice model of a lipid bilayer: Microscopic derivation and thermodynamic exploration

    Science.gov (United States)

    Hakobyan, Davit; Heuer, Andreas

    2017-02-01

    Based on all-atom Molecular Dynamics (MD) simulations of a lipid bilayer we present a systematic mapping on a 2D lattice model. Keeping the lipid type and the chain order parameter as key variables we derive a free energy functional, containing the enthalpic interaction of adjacent lipids as well as the tail entropy. The functional form of both functions is explicitly determined for saturated and polyunsaturated lipids. By studying the lattice model via Monte Carlo simulations it is possible to reproduce the temperature dependence of the distribution of order parameters of the pure lipids, including the prediction of the gel transition. Furthermore, application to a mixture of saturated and polyunsaturated lipids yields the correct phase separation behavior at lower temperatures with a simulation time reduced by approximately 7 orders of magnitude as compared to the corresponding MD simulations. Even the time-dependence of the de-mixing is reproduced on a semi-quantitative level. Due to the generality of the approach we envisage a large number of further applications, ranging from modeling larger sets of lipids, sterols, and solvent proteins to predicting nucleation barriers for the melting of lipids. Particularly, from the properties of the 2D lattice model one can directly read off the enthalpy and entropy change of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine gel-to-liquid transition in excellent agreement with experimental and MD results.

  12. Comparison of Two Models for Damage Accumulation in Simulations of System Performance

    Energy Technology Data Exchange (ETDEWEB)

    Youngblood, R. [Idaho National Laboratory, Idaho Falls, ID (United States); Mandelli, D. [Idaho National Laboratory, Idaho Falls, ID (United States)

    2015-11-01

    A comprehensive simulation study of system performance needs to address variations in component behavior, variations in phenomenology, and the coupling between phenomenology and component failure. This paper discusses two models of this: 1. damage accumulation is modeled as a random walk process in each time history, with component failure occurring when damage accumulation reaches a specified threshold; or 2. damage accumulation is modeled mechanistically within each time history, but failure occurs when damage reaches a time-history-specific threshold, sampled at time zero from each component’s distribution of damage tolerance. A limiting case of the latter is classical discrete-event simulation, with component failure times sampled a priori from failure time distributions; but in such models, the failure times are not typically adjusted for operating conditions varying within a time history. Nowadays, as discussed below, it is practical to account for this. The paper compares the interpretations and computational aspects of the two models mentioned above.

  13. Parallel flow accumulation algorithms for graphical processing units with application to RUSLE model

    Science.gov (United States)

    Sten, Johan; Lilja, Harri; Hyväluoma, Jari; Westerholm, Jan; Aspnäs, Mats

    2016-04-01

    Digital elevation models (DEMs) are widely used in the modeling of surface hydrology, which typically includes the determination of flow directions and flow accumulation. The use of high-resolution DEMs increases the accuracy of flow accumulation computation, but as a drawback, the computational time may become excessively long if large areas are analyzed. In this paper we investigate the use of graphical processing units (GPUs) for efficient flow accumulation calculations. We present two new parallel flow accumulation algorithms based on dependency transfer and topological sorting and compare them to previously published flow transfer and indegree-based algorithms. We benchmark the GPU implementations against industry standards, ArcGIS and SAGA. With the flow-transfer D8 flow routing model and binary input data, a speed up of 19 is achieved compared to ArcGIS and 15 compared to SAGA. We show that on GPUs the topological sort-based flow accumulation algorithm leads on average to a speedup by a factor of 7 over the flow-transfer algorithm. Thus a total speed up of the order of 100 is achieved. We test the algorithms by applying them to the Revised Universal Soil Loss Equation (RUSLE) erosion model. For this purpose we present parallel versions of the slope, LS factor and RUSLE algorithms and show that the RUSLE erosion results for an area of 12 km x 24 km containing 72 million cells can be calculated in less than a second. Since flow accumulation is needed in many hydrological models, the developed algorithms may find use in many other applications than RUSLE modeling. The algorithm based on topological sorting is particularly promising for dynamic hydrological models where flow accumulations are repeatedly computed over an unchanged DEM.

  14. Control of facies/potential on hydrocarbon accumulation:a geological model for Iacustrine rift basins

    Institute of Scientific and Technical Information of China (English)

    Chen Dongxia; Pang Xiongqi; Zhang Shanwen; Wang Yongshi; Zhang Jun

    2008-01-01

    The formation and distribution of hydrocarbon accumulations are jointly controlled by"stratigraphic facies"and"fluid potential",which can be abbreviated in"control of facies/potential on hydrocarbon accumulation".Facies and potential control the time-space distribution of hydrocarbon accumulation macroscopically and the petroliferous characteristics of hydrocarbon accumulation microscopically.Tectonic facies and sedimentary facies control the time-space distribution.Lithofacies and petrophysical facies control the petroliferous characteristics.Favorable facies and high porosity and permeability control hydrocarbon accumulation in the lacustrine rift basins in China.Fluid potential is represented by the work required,which comprises the work against gravity,pressure,interfacial energy and kinetic energy.Hydrocarbon migration and accumulation are controlled by the joint action of multiple driving forces,and are characterized by accumulation in the area of low potential.At the structural high,low geopotential energy caused by buoyancy control anticlinal reservoir.The formation of lithological oil pool is controlled by low interfacial energy caused by capillary force.Low compressive energy caused by overpressure and faulting activity control the formation of the faulted block reservoir.Low geopotential energy of the basin margin caused by buoyancy control stratigraphic reservoir.The statistics of a large number of oil reservoirs show that favorable facies and low potential control hydrocarbon accumulation in the rift basin.where over 85% of the discovered hydrocarbon accumulations are distributed in the trap with favorable facies and lOW potentials.The case study showed that the prediction of favorable areas by application of the near source-favorable facies-low potential accumulation model correlated well with over 90% of the discovered oil pools' distribution of the middle section of the third member of the Shahejie Formation in the Dongying Depression,Bohai Bay

  15. Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Mirko Lanuti

    Full Text Available The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.

  16. Buddleja officinalis Maximowicz Extract Inhibits Lipid Accumulation on Adipocyte Differentiation in 3T3-L1 Cells and High-Fat Mice

    Directory of Open Access Journals (Sweden)

    Jin-Kyu Kim

    2012-07-01

    Full Text Available Obesity is a global health problem. It is also known to be a risk factor for the development of metabolic disorders, type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we elucidated that Buddleja officinalis Maximowicz extract significantly inhibited lipid accumulation during 3T3-L1 adipocyte differentiation. Furthermore, Buddleja officinalis Maximowicz extract reduced the body weight gain induced through feeding a high-fat diet to C57BL/6 mice. The treatment of Buddleja officinalis Maximowicz extract significantly reduced the adipose tissue weight to 2.7/100 g of body weight in high-fat mice. When their adipose tissue morphology was investigated for histochemical staining, the distribution of cell size in the high-fat diet groups was hypertrophied compared with those from Buddleja officinalis Maximowicz extract-treated mice. In addition, in Buddleja officinalis Maximowicz extract-treated mice, a significant reduction of serum triglyceride and T-cholesterol was observed at to 21% and 17%, respectively. The discovery of bioactive compounds from diet or dietary supplementation is one of possible ways to control obesity and to prevent or reduce the risks of various obesity-related diseases. These results support that Buddleja officinalis Maximowicz extract is expected to create the therapeutic interest with respect to the treatment of obesity.

  17. Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    Young-Sil Lee; Bong-Keun Choi; Hae Jin Lee; Dong-Ryung Lee; Jinhua Cheng; Won-Keun Lee; Seung Hwan Yang; Joo-Won Suh

    2015-01-01

    Objective: To explore the anti-obesity effects and the mechanism of action of Monascus pilosus (M. pilosus)-fermented black soybean (MFBS) extracts (MFBSE) and MFBS powders (MFBSP) in adipocytes and high-fat diet (HFD)-induced obese mice, respectively. Methods:Black soybean was fermented with M. pilosus, and the main constituents in MFBS were analyzed by HPLC analysis. In vitro, MFBSE were examined for anti-adipogenic effects using Oil-Red O staining. In vivo, mice were fed a normal-fat diet (NFD) control, HFD control or HFD containing 1 g/kg MFBSP for 12 weeks, and then body weight gain and tissues weight measured. Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects. Results: MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity. MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice. MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes, such as peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS), in adipocytes and in white adipose tissue (WAT) of HFD-induced obese mice. Conclusions: These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFD-induced obese mice.

  18. Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

    Science.gov (United States)

    Lanuti, Mirko; Talamonti, Emanuela; Maccarrone, Mauro; Chiurchiù, Valerio

    2015-01-01

    The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9)-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.

  19. Effects of Waterborne Cu and Cd on Anti-oxidative Response, Lipid Peroxidation and Heavy Metals Accumulation in AbaloneHaliotis discus hannai Ino

    Institute of Scientific and Technical Information of China (English)

    LEI Yanju; ZHANG Wenbing; XU Wei; ZHANG Yanjiao; ZHOU Huihui; MAI Kangsen

    2015-01-01

    The aim of this study was to compare the effects of waterborne copper (Cu) and cadmium (Cd) on survival, anti-oxida- tive response, lipid peroxidation and metal accumulation in abaloneHaliotis discus hannai. Experimental animals (initial weight: 7.49g±0.01g) were exposed to graded concentrations of waterborne Cu (0.02, 0.04, 0.06, 0.08mgL-1) or Cd (0.025, 0.05, 0.25, 0.5 mgL-1) for 28 days, respectively. Activities of the anti-oxidative enzymes (catalase, CAT; superoxide dismutase, SOD; glutathione peroxidases, GPx; glutathione S-transferase, GST), contents of the reduced glutathione (GSH) and malondiadehyde (MDA) in the hepatopancreas, and metal accumulation in hepatopancreas and muscles were analyzed after 0, 1, 3, 6, 10, 15, 21, 28 days of metal exposure, respectively. Results showed that 0.04mgL-1, 0.06mgL-1 and 0.08mgL-1 Cu caused 100% death of abalone on the 21st, 10th and 6th day, respectively. However, no dead abalone was found during the 28-day waterborne Cd exposure at all experimental concentrations. Generally, activities of SOD and GST in hepatopancreas under all Cu concentrations followed a decrease trend as the exposure time prolonged. However, these activities were firstly increased and then decreased to the control level and increased again during Cd exposure. Activities of CAT in all Cu exposure treatments were higher than those in the control. These activities were firstly increased and then decreased to the control level and increased again during Cd exposure. Contents of MDA in hepatopancreas in all Cu treatments significantly increased first and then decreased to the control level. However, the MDA contents in hepatopan-creas were not significantly changed during the 28-day Cd exposure. The metals accumulation in both hepatopancreas and muscles of abalone significantly increased with the increase of waterborne metals concentration and exposure time. These results indicated that H. discus hannai has a positive anti-oxidative defense against Cu

  20. Mathematical model for drug molecules encapsulated in lipid nanotube

    Science.gov (United States)

    Putthikorn, Sasipim; Baowan, Duangkamon

    2016-11-01

    Lipid nanotube is considered as a nanocontainer for drug and gene delivery. It is important to understand a basic idea of the encapsulation process. In this paper, we use the Lennard-Jones potential function and the continuous approximation to explain the energy behaviour of three hollow shapes of Doxorubicin (DOX) clusters that are a sphere, a cylinder, and an ellipsoid interacting with the lipid nanotube. On assuming that the surface areas of the three structures are equal, we can find the minimum size of the lipid nanotube that encapsulates DOX inside by determining the suction energy. Moreover, we find that a long cylindrical drug provides the largest suction energy among other structures studied here due to the perfect fit between the cylindrical drug and the cylindrical tube. This investigation is the first step to develop the design of nanocapsule for medical application.

  1. Buffers affect the bending rigidity of model lipid membranes.

    Science.gov (United States)

    Bouvrais, Hélène; Duelund, Lars; Ipsen, John H

    2014-01-14

    In biophysical and biochemical studies of lipid bilayers the influence of the used buffer is often ignored or assumed to be negligible on membrane structure, elasticity, or physical properties. However, we here present experimental evidence, through bending rigidity measurements performed on giant vesicles, of a more complex behavior, where the buffering molecules may considerably affect the bending rigidity of phosphatidylcholine bilayers. Furthermore, a synergistic effect on the bending modulus is observed in the presence of both salt and buffer molecules, which serves as a warning to experimentalists in the data interpretation of their studies, since typical lipid bilayer studies contain buffer and ion molecules.

  2. Novel preparation of intercellular lipid models of the stratum corneum containing stereoactive ceramide.

    Science.gov (United States)

    Watanabe, Hiroshi; Obata, Yasuko; Onuki, Yoshinori; Ishida, Kenya; Takayama, Kozo

    2010-03-01

    The microstructure formed by intercellular lipids in the stratum corneum is important for the barrier function of the skin. However, the correlation between lipid composition and microstructure has not yet been clarified. To elucidate the microstructure of intercellular lipids in the stratum corneum, an intercellular lipid model was prepared from ceramide 5 (CER5), cholesterol (CHOL), and palmitic acid (PA), considering the nonuniformity of the lipid components of the stratum corneum. A response surface method incorporating thin-plate spline interpolation (RSM-S) was employed to prepare the CER5/CHOL/PA lipid bilayers. Fluorescence anisotropy of the CER5/CHOL/PA bilayers showed four distinct clusters based on Kohonen's self-organizing maps (SOM). At the centroid formulation of those clusters, the microstructures of CER5/CHOL/PA bilayers were determined using synchrotron X-ray scattering. Three kinds of lamellar structures and two kinds of lateral packing-namely, hexagonal and orthorhombic-were formed. The microstructure of the CER5/CHOL/PA bilayers was likely to be intrinsic to the intercellular lipids in the stratum corneum. In conclusion, the CER5/CHOL/PA bilayers prepared based on RSM-S and SOM were useful as models of the intercellular lipids in the stratum corneum.

  3. Modelling metal accumulation using humic acid as a surrogate for plant roots.

    Science.gov (United States)

    Le, T T Yen; Swartjes, Frank; Römkens, Paul; Groenenberg, Jan E; Wang, Peng; Lofts, Stephen; Hendriks, A Jan

    2015-04-01

    Metal accumulation in roots was modelled with WHAM VII using humic acid (HA) as a surrogate for root surface. Metal accumulation was simulated as a function of computed metal binding to HA, with a correction term (E(HA)) to account for the differences in binding site density between HA and root surface. The approach was able to model metal accumulation in roots to within one order of magnitude for 95% of the data points. Total concentrations of Mn in roots of Vigna unguiculata, total concentrations of Ni, Zn, Cu and Cd in roots of Pisum sativum, as well as internalized concentrations of Cd, Ni, Pb and Zn in roots of Lolium perenne, were significantly correlated to the computed metal binding to HA. The method was less successful at modelling metal accumulation at low concentrations and in soil experiments. Measured concentrations of Cu internalized in L. perenne roots were not related to Cu binding to HA modelled and deviated from the predictions by over one order of magnitude. The results indicate that metal uptake by roots may under certain conditions be influenced by conditional physiological processes that cannot simulated by geochemical equilibrium. Processes occurring in chronic exposure of plants grown in soil to metals at low concentrations complicate the relationship between computed metal binding to HA and measured metal accumulation in roots.

  4. Lipid Models for United-Atom Molecular Dynamics Simulations of Proteins.

    Science.gov (United States)

    Kukol, Andreas

    2009-03-10

    United-atom force fields for molecular dynamics (MD) simulations provide a higher computational efficiency, especially in lipid membrane simulations, with little sacrifice in accuracy, when compared to all-atom force fields. Excellent united-atom lipid models are available, but in combination with depreciated protein force fields. In this work, a united-atom model of the lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine has been built with standard parameters of the force field GROMOS96 53a6 that reproduces the experimental area per lipid of a lipid bilayer within 3% accuracy to a value of 0.623 ± 0.011 nm(2) without the assumption of a constant surface area or the inclusion of surface pressure. In addition, the lateral self-diffusion constant and deuterium order parameters of the acyl chains are in agreement with experimental data. Furthermore, models for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) result in areas per lipid of 0.625 nm(2) (DMPC), 0.693 nm(2) (POPC), and 0.700 nm(2) (POPG) from 40 ns MD simulations. Experimental lateral self-diffusion coefficients are reproduced satisfactorily by the simulation. The lipid models can form the basis for molecular dynamics simulations of membrane proteins with current and future versions of united-atom protein force fields.

  5. Annual Greenland accumulation derived from airborne radar and comparisons to modeled and in situ data

    Science.gov (United States)

    Koenig, L.; Ivanoff, A.; Alexander, P. M.; MacGregor, J. A.; Cullather, R. I.; Nowicki, S.

    2015-12-01

    Mass loss across the Greenland Ice Sheet (GrIS) has accelerated in recent decades and recently a fundamental change in the nature of this mass loss has begun. The dominant GrIS mass-loss process has switched from ice dynamics to surface mass balance (SMB) processes, including melt generation and runoff. This recent shift further emphasizes the need to monitor and constrain SMB, which, across most of the GrIS, is dominated by accumulation. High resolution, near-surface radar data have shown good fidelity at mapping spatial patterns of accumulation to validate model outputs. To better constrain accumulation over the GrIS, we derive annual accumulation rates using NASA Operation IceBridge (OIB) Snow Radar data collected from 2009 through 2012. Accumulation is calculated using the radar-determined depth to an annual layer and the local snow/firn density profile. Up to 30 years of annual stratigraphy is observed in the interior of the ice sheet, near Summit Station, while only the past year is detectable in the ablation zone around the perimeter of the ice sheet. Annual layering is traced using a semi-automatic algorithm and mapped across large areas (tens of thousands of line kilometers). A combined measured and modeled density profile is used to convert the annual stratigraphy into accumulation. Modeled density profiles from the Modèle Atmosphérique Régional (MAR) model are shown to be less than half of in situ observations in the top 1 m of snow/firn and are, therefore, replaced with in situ measurements. Using a compilation of in situ measurements, the mean GrIS snow/firn density is found to be ~340 +/- 40 kg/m3 in the top 1 m. Error in the snow density profile represents the largest error in the radar-derived accumulation. The pattern of radar-derived accumulation rate compares well with MAR estimates, although the latter has a mean bias of 4.6 cm water equivalent, a root mean square error of 16.8 cm water equivalent and a correlation coefficient of 0.6 across

  6. Partitioning of Lipids at Domain Boundaries in Model Membranes

    NARCIS (Netherlands)

    Schafer, Lars V.; Marrink, Siewert J.

    2010-01-01

    Line-active molecules ("linactants") that bind to the boundary interface between different fluid lipid domains in membranes have a strong potential as regulators of the lateral heterogeneity that is important for many biological processes. Here, we use molecular dynamics simulations in combination w

  7. Self-Segregation of Myelin Membrane Lipids in Model Membranes

    NARCIS (Netherlands)

    Yurlova, Larisa; Kahya, Nicoletta; Aggarwal, Shweta; Kaiser, Hermann-Josef; Chiantia, Salvatore; Bakhti, Mostafa; Pewzner-Jung, Yael; Ben-David, Oshrit; Futerman, Anthony H.; Bruegger, Britta; Simons, Mikael

    2011-01-01

    Rapid conduction of nerve impulses requires coating of axons by myelin sheaths, which are multilamellar, lipid-rich membranes produced by oligodendrocytes in the central nervous system. To act as an insulator, myelin has to form a stable and firm membrane structure. In this study, we have analyzed t

  8. Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation

    DEFF Research Database (Denmark)

    Axelsen, Lene N; Lademann, Jacob B; Petersen, Jørgen S

    2010-01-01

    Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model...... of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure...... AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications....

  9. The Effect of Lidocaine · HCl on the Fluidity of Native and Model Membrane Lipid Bilayers.

    Science.gov (United States)

    Park, Jun-Seop; Jung, Tae-Sang; Noh, Yang-Ho; Kim, Woo-Sung; Park, Won-Ick; Kim, Young-Soo; Chung, In-Kyo; Sohn, Uy Dong; Bae, Soo-Kyung; Bae, Moon-Kyoung; Jang, Hye-Ock; Yun, Il

    2012-12-01

    The purpose of this study is to investigated the mechanism of pharmacological action of local anesthetic and provide the basic information about the development of new effective local anesthetics. Fluorescent probe techniques were used to evaluate the effect of lidocaine·HCl on the physical properties (transbilayer asymmetric lateral and rotational mobility, annular lipid fluidity and protein distribu