Sample records for g-1 lipid median

  1. Birth of Archaeal Cells: Molecular Phylogenetic Analyses of G1P Dehydrogenase, G3P Dehydrogenases, and Glycerol Kinase Suggest Derived Features of Archaeal Membranes Having G1P Polar Lipids

    PubMed Central

    2016-01-01

    Bacteria and Eukarya have cell membranes with sn-glycerol-3-phosphate (G3P), whereas archaeal membranes contain sn-glycerol-1-phosphate (G1P). Determining the time at which cells with either G3P-lipid membranes or G1P-lipid membranes appeared is important for understanding the early evolution of terrestrial life. To clarify this issue, we reconstructed molecular phylogenetic trees of G1PDH (G1P dehydrogenase; EgsA/AraM) which is responsible for G1P synthesis and G3PDHs (G3P dehydrogenase; GpsA and GlpA/GlpD) and glycerol kinase (GlpK) which is responsible for G3P synthesis. Together with the distribution of these protein-encoding genes among archaeal and bacterial groups, our phylogenetic analyses suggested that GlpA/GlpD in the Commonote (the last universal common ancestor of all extant life with a cellular form, Commonote commonote) acquired EgsA (G1PDH) from the archaeal common ancestor (Commonote archaea) and acquired GpsA and GlpK from a bacterial common ancestor (Commonote bacteria). In our scenario based on this study, the Commonote probably possessed a G3P-lipid membrane synthesized enzymatically, after which the archaeal lineage acquired G1PDH followed by the replacement of a G3P-lipid membrane with a G1P-lipid membrane. PMID:27774041

  2. FTO promotes SREBP1c maturation and enhances CIDEC transcription during lipid accumulation in HepG2 cells.

    PubMed

    Chen, Ao; Chen, Xiaodong; Cheng, Shiqiang; Shu, Le; Yan, Meiping; Yao, Lun; Wang, Binyu; Huang, Shuguang; Zhou, Lei; Yang, Zaiqing; Liu, Guoquan

    2018-05-01

    The fat mass and obesity-associated (FTO) gene is tightly related to body weight and fat mass, and plays a pivotal role in regulating lipid accumulation in hepatocytes. However, the mechanisms underlying its function are poorly understood. Sterol regulatory element binding protein-1c (SREBP1c) is a transcription factor that regulates lipogenesis. Cell death-inducing DFFA (DNA fragmentation factor-α)-like effector c (CIDEC) plays a crucial role in lipid droplets (LDs) size controlling and lipid accumulation. In this report, we first observed that FTO overexpression in HepG2 cells resulted in an increase of lipogenesis and up-regulation of SREBP1c and CIDEC, two key regulatory factors in lipogenesis. In contrast, FTO knockdown in HepG2 cells resulted in a decrease of lipogenesis and down-regulation of SREBP1c and CIDEC expression. Moreover, SREBP1c knockdown resulted in a decrease of lipogenesis in HepG2 cells with FTO overexpression. In addition, FTO demethylation defect mutant presented less transcription of the key genes, and less nuclear translocation and maturation of SREBP1c. Further investigation demonstrated that overexpression of SREBP1c in HepG2 cells also promoted high CIDEC expression. Luciferase reporter assays showed that SREBP1c significantly stimulated CIDEC gene promoter activity. Finally, CIDEC knockdown reduced SREBP1c-induced lipogenesis. In conclusion, our studies suggest that FTO increased the lipid accumulation in hepatocytes by increasing nuclear translocation of SREBP1c and SREBP1c maturation, thus improving the transcriptional activity of LD-associated protein CIDEC. Our studies may provide new mechanistic insight into nonalcoholic fatty liver disease (NAFLD) mediated by FTO. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  4. G protein-membrane interactions II: Effect of G protein-linked lipids on membrane structure and G protein-membrane interactions.

    PubMed

    Casas, Jesús; Ibarguren, Maitane; Álvarez, Rafael; Terés, Silvia; Lladó, Victoria; Piotto, Stefano P; Concilio, Simona; Busquets, Xavier; López, David J; Escribá, Pablo V

    2017-09-01

    G proteins often bear myristoyl, palmitoyl and isoprenyl moieties, which favor their association with the membrane and their accumulation in G Protein Coupled Receptor-rich microdomains. These lipids influence the biophysical properties of membranes and thereby modulate G protein binding to bilayers. In this context, we showed here that geranylgeraniol, but neither myristate nor palmitate, increased the inverted hexagonal (H II ) phase propensity of phosphatidylethanolamine-containing membranes. While myristate and palmitate preferentially associated with phosphatidylcholine membranes, geranylgeraniol favored nonlamellar-prone membranes. In addition, Gαi 1 monomers had a higher affinity for lamellar phases, while Gβγ and Gαβγ showed a marked preference for nonlamellar prone membranes. Moreover, geranylgeraniol enhanced the binding of G protein dimers and trimers to phosphatidylethanolamine-containing membranes, yet it decreased that of monomers. By contrast, both myristate and palmitate increased the Gαi 1 preference for lamellar membranes. Palmitoylation reinforced the binding of the monomer to PC membranes and myristoylation decreased its binding to PE-enriched bilayer. Finally, binding of dimers and trimers to lamellar-prone membranes was decreased by palmitate and myristate, but it was increased in nonlamellar-prone bilayers. These results demonstrate that co/post-translational G protein lipid modifications regulate the membrane lipid structure and that they influence the physico-chemical properties of membranes, which in part explains why G protein subunits sort to different plasma membrane domains. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Immunostimulatory Properties of Lipid Modified CpG Oligonucleotides.

    PubMed

    Yu, Chunsong; An, Myunggi; Li, Meng; Liu, Haipeng

    2017-08-07

    Innate immune responses recognizing pathogen associated molecular patterns play important roles in adaptive immunity. As such, ligands which mimic the conserved products of microbial and activate innate immunity are widely used as adjuvants for vaccines. Synthetic single strand oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs which bind Toll-like receptor 9 (TLR9) are powerful molecular adjuvants, potentiating both humoral and cellular responses. However, CpG ODN's in vitro potency has not been translated to in vivo settings primarily due to issues associated with delivery and toxicity. A major challenge in clinical application of CpG ODN is the efficient delivery to lymph nodes, the anatomic sites where all the immune responses are initiated. Targeting CpG to the key antigen presenting cells (APC) is essential for its application as a vaccine adjuvant, as it not only enhances CpG's efficacy, but also greatly reduces the systemic toxicity. We recently discovered an "albumin-hitchhiking" approach by which CpG ODNs were conjugated to a lipophilic lipid tail and follow subcutaneous injection, accumulated in lymph nodes by binding and transporting with endogenous albumin. This molecular approach targets CpG to antigen presenting cells in the draining lymph nodes via an endogenous albumin-mediated mechanism and simultaneously improves both the efficacy and safety of CpG as a vaccine adjuvant. Since CpG ODNs can be divided into structurally distinct classes, and each class of CpG ODN activates different types of immune cells and triggers different types of immunostimulatory activities, it is important to thoroughly evaluate the efficacy of this "albumin-hitchhiking" strategy in each class of CpG. Here we compare the immunostimulatory activities of three classes of lipid conjugated CpG ODNs in vitro and in vivo. Three representative sequences of lipid modified CpG ODNs were synthesized and their stimulatory effects as a vaccine adjuvant

  6. Altered expression of CD1d molecules and lipid accumulation in the human hepatoma cell line HepG2 after iron loading.

    PubMed

    Cabrita, Marisa; Pereira, Carlos F; Rodrigues, Pedro; Cardoso, Elsa M; Arosa, Fernando A

    2005-01-01

    Iron overload in the liver may occur in clinical conditions such as hemochromatosis and nonalcoholic steatohepatitis, and may lead to the deterioration of the normal liver architecture by mechanisms not well understood. Although a relationship between the expression of ICAM-1, and classical major histocompatibility complex (MHC) class I molecules, and iron overload has been reported, no relationship has been identified between iron overload and the expression of unconventional MHC class I molecules. Herein, we report that parameters of iron metabolism were regulated in a coordinated-fashion in a human hepatoma cell line (HepG2 cells) after iron loading, leading to increased cellular oxidative stress and growth retardation. Iron loading of HepG2 cells resulted in increased expression of Nor3.2-reactive CD1d molecules at the plasma membrane. Expression of classical MHC class I and II molecules, ICAM-1 and the epithelial CD8 ligand, gp180 was not significantly affected by iron. Considering that intracellular lipids regulate expression of CD1d at the cell surface, we examined parameters of lipid metabolism in iron-loaded HepG2 cells. Interestingly, increased expression of CD1d molecules by iron-loaded HepG2 cells was associated with increased phosphatidylserine expression in the outer leaflet of the plasma membrane and the presence of many intracellular lipid droplets. These data describe a new relationship between iron loading, lipid accumulation and altered expression of CD1d, an unconventional MHC class I molecule reported to monitor intracellular and plasma membrane lipid metabolism, in the human hepatoma cell line HepG2.

  7. Myosin 1g Contributes to CD44 Adhesion Protein and Lipid Rafts Recycling and Controls CD44 Capping and Cell Migration in B Lymphocytes

    PubMed Central

    López-Ortega, Orestes; Santos-Argumedo, Leopoldo

    2017-01-01

    Cell migration and adhesion are critical for immune system function and involve many proteins, which must be continuously transported and recycled in the cell. Recycling of adhesion molecules requires the participation of several proteins, including actin, tubulin, and GTPases, and of membrane components such as sphingolipids and cholesterol. However, roles of actin motor proteins in adhesion molecule recycling are poorly understood. In this study, we identified myosin 1g as one of the important motor proteins that drives recycling of the adhesion protein CD44 in B lymphocytes. We demonstrate that the lack of Myo1g decreases the cell-surface levels of CD44 and of the lipid raft surrogate GM1. In cells depleted of Myo1g, the recycling of CD44 was delayed, the delay seems to be caused at the level of formation of recycling complex and entry into recycling endosomes. Moreover, a defective lipid raft recycling in Myo1g-deficient cells had an impact both on the capping of CD44 and on cell migration. Both processes required the transportation of lipid rafts to the cell surface to deliver signaling components. Furthermore, the extramembrane was essential for cell expansion and remodeling of the plasma membrane topology. Therefore, Myo1g is important during the recycling of lipid rafts to the membrane and to the accompanied proteins that regulate plasma membrane plasticity. Thus, Myosin 1g contributes to cell adhesion and cell migration through CD44 recycling in B lymphocytes. PMID:29321775

  8. Interaction of lipids with the neurotensin receptor 1.

    PubMed

    Bolivar, Juan H; Muñoz-García, Juan C; Castro-Dopico, Tomas; Dijkman, Patricia M; Stansfeld, Phillip J; Watts, Anthony

    2016-06-01

    Information about lipid-protein interactions for G protein-coupled receptors (GPCRs) is scarce. Here, we use electron spin resonance (ESR) and spin-labelled lipids to study lipid interactions with the rat neurotensin receptor 1 (NTS1). A fusion protein containing rat NTS1 fully able to bind its ligand neurotensin was reconstituted into phosphatidylcholine (PC) bilayers at specific lipid:protein molar ratios. The fraction of motionally restricted lipids in the range of 40:1 to 80:1 lipids per receptor suggested an oligomeric state of the protein, and the result was unaffected by increasing the hydrophobic thickness of the lipid bilayer from C-18 to C-20 or C-22 chain length PC membranes. Comparison of the ESR spectra of different spin-labelled lipids allowed direct measurement of lipid binding constants relative to PC (Kr), with spin-labelled phosphatidylethanolamine (PESL), phosphatidylserine (PSSL), stearic acid (SASL), and a spin labelled cholesterol analogue (CSL) Kr values of 1.05±0.05, 1.92±0.08, 5.20±0.51 and 0.91±0.19, respectively. The results contrast with those from rhodopsin, the only other GPCR studied this way, which has no selectivity for the lipids analysed here. Molecular dynamics simulations of NTS1 in bilayers are in agreement with the ESR data, and point to sites in the receptor where PS could interact with higher affinity. Lipid selectivity could be necessary for regulation of ligand binding, oligomerisation and/or G protein activation processes. Our results provide insight into the potential modulatory mechanisms that lipids can exert on GPCRs. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Zanthoxylum ailanthoides Suppresses Oleic Acid-Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells

    PubMed Central

    Kwon, Eun-Bin; Kang, Myung-Ji; Kim, Soo-Yeon; Lee, Yong-Moon; Lee, Mi-Kyeong; Yuk, Heung Joo; Ryu, Hyung Won; Lee, Su Ui

    2018-01-01

    Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF-α, suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells. PMID:29507591

  10. Zanthoxylum ailanthoides Suppresses Oleic Acid-Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells.

    PubMed

    Kwon, Eun-Bin; Kang, Myung-Ji; Kim, Soo-Yeon; Lee, Yong-Moon; Lee, Mi-Kyeong; Yuk, Heung Joo; Ryu, Hyung Won; Lee, Su Ui; Oh, Sei-Ryang; Moon, Dong-Oh; Lee, Hyun-Sun; Kim, Mun-Ock

    2018-01-01

    Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF- α , suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells.

  11. Association of the TRIB1 tribbles homolog 1 gene rs17321515 A>G polymorphism and serum lipid levels in the Mulao and Han populations

    PubMed Central

    2011-01-01

    Background The association of rs17321515 single nucleotide polymorphism (SNP) near TRIB1 gene and serum lipid profiles has never been studied in the Chinese population. Therefore, the present study was undertaken to detect the association of rs17321515 SNP and several environmental factors on serum lipid levels in the Mulao and Han populations. Methods A total of 639 unrelated subjects of Mulao nationality and 644 participants of Han nationality were randomly selected from our previous stratified randomized cluster samples. Genotypes of the TRIB1 rs17321515 A>G SNP were determined via polymerase chain reaction and restriction fragment length polymorphism, and then confirmed by direct sequencing. Results Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.05). There were no differences in the genotypic and allelic frequencies between the two ethnic groups (P > 0.05). High- and low-density lipoprotein cholesterol (HDL-C and LDL-C) levels in Han were different among the genotypes (P < 0.05 for each), the subjects with AG/GG genotypes had higher HDL-C and LDL-C levels than the subjects with AA genotype. Total cholesterol (TC), HDL-C, LDL-C, ApoA1 and ApoB levels in Han males were different among the genotypes (P < 0.05-0.001), the G carriers had higher TC, HDL-C, LDL-C, ApoA1 and ApoB levels than the G noncarriers. HDL-C levels in Mulao males were different among the genotypes (P < 0.05), the G carriers had lower HDL-C levels than the G noncarriers. Serum HDL-C and LDL-C levels in both ethnic groups and TG levels in Han were correlated with the genotypes or alleles (P < 0.05-0.01). TG and HDL-C levels in Mulao males and TG, HDL-C, LDL-C and ApoA1 levels in Han males were correlated with genotypes or alleles (P < 0.05-0.001). TG and ApoA1 levels in Han females were associated with genotypes (P < 0.05 for each). Serum lipid parameters were also associated with several environmental factors in both ethnic groups. Conclusions The associations of

  12. Demonstration of IgG Subclass (IgG1 and IgG3) in Immuno-Related Hemocytopenia.

    PubMed

    Shao, Yuanyuan; Qi, Xiao; Fu, Rong; Liu, Hui; Wang, Yihao; Ding, Shaoxue; Wang, Huaquan; Li, Lijuan; Shao, Zonghong

    2018-06-01

    Immuno-related hemocytopenia (IRH) is defined as idiopathic cytopenia of undetermined significance (ICUS) patients with autoantibodies. In our previous studies, we found that IgG1 levels were increased in IRH patients and might cause the destruction of hematopoietic cells. In this study, we analyzed IgG subclasses in 30 IRH patients (male:female = 13:17, median age 32 years, range 18 - 56), 15 IRH remission patients (IRH-R) (male:female = 6:9, median age 34, range 20 - 52) and 20 normal controls (male:female = 8:12, median age 27, range 24 - 36) by Cytometric Bead Array, Flow Cytometry and Immunohistochemical staining. Levels of IgG1/IgG3 in the bone marrow supernatant of IRH patents, as well as the proportion of CD5+ B lymphocytes and Th2 cells (CD3+CD8-IL-4+) were higher than those of IRH-R patients and normal controls, and IgG1 levels had a positive correlation with the proportion of Th2 cells. In IRH patients, IgG1 and IgG3 were positive on nucleated erythrocytes and granulocytes, which were negative in IRH-R patients and healthy controls and had inverse correlations with hematopoietic function. Using immunohistochemical staining, IgG1 were also detected on bone marrow biopsies of IRH patients. The results indicated that IgG1 and IgG3 autoantibodies in IRH patients might play a key role in the IRH pathogenesis and in the abnormal immune function of IRH patients.

  13. Lipid rafts are essential for peroxisome biogenesis in HepG2 cells.

    PubMed

    Woudenberg, Jannes; Rembacz, Krzysztof P; Hoekstra, Mark; Pellicoro, Antonella; van den Heuvel, Fiona A J; Heegsma, Janette; van Ijzendoorn, Sven C D; Holzinger, Andreas; Imanaka, Tsuneo; Moshage, Han; Faber, Klaas Nico

    2010-08-01

    Peroxisomes are particularly abundant in the liver and are involved in bile salt synthesis and fatty acid metabolism. Peroxisomal membrane proteins (PMPs) are required for peroxisome biogenesis [e.g., the interacting peroxisomal biogenesis factors Pex13p and Pex14p] and its metabolic function [e.g., the adenosine triphosphate-binding cassette transporters adrenoleukodystrophy protein (ALDP) and PMP70]. Impaired function of PMPs is the underlying cause of Zellweger syndrome and X-linked adrenoleukodystrophy. Here we studied for the first time the putative association of PMPs with cholesterol-enriched lipid rafts and their function in peroxisome biogenesis. Lipid rafts were isolated from Triton X-100-lysed or Lubrol WX-lysed HepG2 cells and analyzed for the presence of various PMPs by western blotting. Lovastatin and methyl-beta-cyclodextrin were used to deplete cholesterol and disrupt lipid rafts in HepG2 cells, and this was followed by immunofluorescence microscopy to determine the subcellular location of catalase and PMPs. Cycloheximide was used to inhibit protein synthesis. Green fluorescent protein-tagged fragments of PMP70 and ALDP were analyzed for their lipid raft association. PMP70 and Pex14p were associated with Triton X-100-resistant rafts, ALDP was associated with Lubrol WX-resistant rafts, and Pex13p was not lipid raft-associated in HepG2 cells. The minimal peroxisomal targeting signals in ALDP and PMP70 were not sufficient for lipid raft association. Cholesterol depletion led to dissociation of PMPs from lipid rafts and impaired sorting of newly synthesized catalase and ALDP but not Pex14p and PMP70. Repletion of cholesterol to these cells efficiently reestablished the peroxisomal sorting of catalase but not ALDP. Human PMPs are differentially associated with lipid rafts independently of the protein homology and/or their functional interaction. Cholesterol is required for peroxisomal lipid raft assembly and peroxisome biogenesis.

  14. Optimised purification and characterisation of lipid transfer protein 1 (LTP1) and its lipid-bound isoform LTP1b from barley malt.

    PubMed

    Nieuwoudt, Melanie; Lombard, Nicolaas; Rautenbach, Marina

    2014-08-15

    In beer brewing, brewers worldwide strive to obtain product consistency in terms of flavour, colour and foam. Important proteins contributing to beer foam are lipid transfer proteins (LTPs), in particular LTP1 and its lipid-bound isoform LTP1b, which are known to transport lipids in vivo and prevent lipids from destabilising the beer foam. LTP1 and LTP1b were successfully purified using only five purification steps with a high purified protein yield (160 mg LTP1 and LTP1b from 200 g barley). Circular dichroism of LTP1 and LTP1b confirmed that both proteins are highly tolerant to high temperatures (>90 °C) and are pH stable, particularly at a neutral to a more basic pH. Only LTP1 exhibited antiyeast and thermo-stable lytic activity, while LTP1b was inactive, indicating that the fatty acid moiety compromised the antimicrobial activity of LTP1. This lack in antiyeast activity and the positive foam properties of LTP1b would benefit beer fermentation and quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A feedback regulatory loop between G3P and lipid transfer proteins DIR1 and AZI1 mediates azelaic-acid-induced systemic immunity.

    PubMed

    Yu, Keshun; Soares, Juliana Moreira; Mandal, Mihir Kumar; Wang, Caixia; Chanda, Bidisha; Gifford, Andrew N; Fowler, Joanna S; Navarre, Duroy; Kachroo, Aardra; Kachroo, Pradeep

    2013-04-25

    Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA) requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P). Pathogen inoculation induced the release of free unsaturated fatty acids (FAs) and thereby triggered AA accumulation, because these FAs serve as precursors for AA. AA accumulation in turn increased the levels of G3P, which is required for AA-conferred SAR. The lipid transfer proteins DIR1 and AZI1, both of which are required for G3P- and AA-induced SAR, were essential for G3P accumulation. Conversely, reduced G3P resulted in decreased AZI1 and DIR1 transcription. Our results demonstrate that an intricate feedback regulatory loop among G3P, DIR1, and AZI1 regulates SAR and that AA functions upstream of G3P in this pathway. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  16. A Lipid Pathway for Ligand Binding Is Necessary for a Cannabinoid G Protein-coupled Receptor*

    PubMed Central

    Hurst, Dow P.; Grossfield, Alan; Lynch, Diane L.; Feller, Scott; Romo, Tod D.; Gawrisch, Klaus; Pitman, Michael C.; Reggio, Patricia H.

    2010-01-01

    Recent isothiocyanate covalent labeling studies have suggested that a classical cannabinoid, (−)-7′-isothiocyanato-11-hydroxy-1′,1′dimethylheptyl-hexahydrocannabinol (AM841), enters the cannabinoid CB2 receptor via the lipid bilayer (Pei, Y., Mercier, R. W., Anday, J. K., Thakur, G. A., Zvonok, A. M., Hurst, D., Reggio, P. H., Janero, D. R., and Makriyannis, A. (2008) Chem. Biol. 15, 1207–1219). However, the sequence of steps involved in such a lipid pathway entry has not yet been elucidated. Here, we test the hypothesis that the endogenous cannabinoid sn-2-arachidonoylglycerol (2-AG) attains access to the CB2 receptor via the lipid bilayer. To this end, we have employed microsecond time scale all-atom molecular dynamics (MD) simulations of the interaction of 2-AG with CB2 via a palmitoyl-oleoyl-phosphatidylcholine lipid bilayer. Results suggest the following: 1) 2-AG first partitions out of bulk lipid at the transmembrane α-helix (TMH) 6/7 interface; 2) 2-AG then enters the CB2 receptor binding pocket by passing between TMH6 and TMH7; 3) the entrance of the 2-AG headgroup into the CB2 binding pocket is sufficient to trigger breaking of the intracellular TMH3/6 ionic lock and the movement of the TMH6 intracellular end away from TMH3; and 4) subsequent to protonation at D3.49/D6.30, further 2-AG entry into the ligand binding pocket results in both a W6.48 toggle switch change and a large influx of water. To our knowledge, this is the first demonstration via unbiased molecular dynamics that a ligand can access the binding pocket of a class A G protein-coupled receptor via the lipid bilayer and the first demonstration via molecular dynamics of G protein-coupled receptor activation triggered by a ligand binding event. PMID:20220143

  17. Elevated Plasma Moxifloxacin Concentrations and SLCO1B1 g.−11187G>A Polymorphism in Adults with Pulmonary Tuberculosis

    PubMed Central

    Gelfond, Jon; Johnson-Pais, Teresa L.; Engle, Melissa; Peloquin, Charles A.; Johnson, John L.; Sizemore, Erin E.; Mac Kenzie, William R.

    2018-01-01

    ABSTRACT Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity against Mycobacterium tuberculosis. However, moxifloxacin plasma concentrations are variable between patients. We evaluated whether human gene polymorphisms affect moxifloxacin plasma concentrations in tuberculosis patients from two geographic regions. We enrolled a convenience sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and the United States enrolled in two treatment trials of moxifloxacin as part of multidrug therapy. Pharmacokinetic parameters were evaluated by noncompartmental techniques. Human single-nucleotide polymorphisms of transporter genes were evaluated by analysis of covariance (ANCOVA) on moxifloxacin exposure and the peak (maximum) concentration (Cmax). The moxifloxacin area under the concentration-time curve from 0 to 24 h (AUC0–24) and Cmax were significantly increased by the drug milligram-per-kilogram dosage and the genotype of variant g.−11187G>A in the SLCO1B1 gene (rs4149015) but not by geographic region. The median moxifloxacin AUC0–24 was 46% higher and the median Cmax was 30% higher in 4 (8%) participants who had the SLCO1B1 g.−11187 AG genotype than in 45 participants who had the wild-type GG genotype (median AUC0–24 from the model, 34.4 versus 23.6 μg · h/ml [P = 0.005, ANCOVA]; median Cmax from the model, 3.5 versus 2.7 μg/ml [P = 0.009, ANCOVA]). Because moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and prolonged QTc intervals are associated with cardiac arrhythmia, further study is needed to evaluate the risk associated with the SLCO1B1 g.−11187G>A variant. (This study has been registered at ClinicalTrials.gov under identifier NCT00164463.) PMID:29463526

  18. The impact of production type and region on polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) concentrations in Canadian chicken egg yolks.

    PubMed

    Rawn, Dorothea F K; Sadler, Amy R; Quade, Sue C; Sun, Wing-Fung; Kosarac, Ivana; Hayward, Stephen; Ryan, J Jake

    2012-11-01

    Chicken eggs from five different production types (conventional, omega-3 enriched, free range, organic and free run) were collected, when available, from three regions (west, central and east) of Canada to determine persistent organic pollutant (POP) concentrations. Total polychlorinated biphenyl (PCB) concentrations (∑37 congeners) in yolks from the eggs ranged from 0.162 ng g(-1) lipid to 24.8 ng g(-1) lipid (median 1.25 ng g(-1) lipid) while the concentration of the sum of the 6 indicator PCBs ranged from 0.100 ng g(-1) lipid to 9.33 ng g(-1) lipid (median 0.495 ng g(-1) lipid). Total polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F) concentrations ranged from 2.37 pg g(-1) lipid to 382 pg g(-1) lipid (median 9.53 pg g(-1) lipid). The 2005 WHO toxic equivalency (TEQ) ranged from 0.089 pg TEQ(PCDD/F+dioxin-like[DL]-PCB) g(-1) lipid to 12.8 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid (median 0.342 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid). PCB and PCDD/F concentrations were significantly different (p<0.001) in egg yolks from different regions of collection. In contrast to observations in Europe, PCB and PCDD/F concentrations in Canadian egg yolks were not impacted solely by the production type (e.g., conventional, free range, organic, etc.) used to maintain the laying chickens. Additionally, only one Canadian free range yolk from western Canada (12.8 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid) exceeded the European toxic equivalent concentration limits for eggs (5 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid). This differs from observations in Europe where free range/home produced eggs frequently have higher POP concentrations than eggs from other production types. Median PCB dietary intake estimates based on consumption of eggs were less than 10 ng d(-1) while median PCDD/F intakes were less than 45 pg d(-1). Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  19. Muscle MRI in neutral lipid storage disease with myopathy carrying mutation c.187+1G>A.

    PubMed

    Xu, Chunxiao; Zhao, Yawen; Liu, Jing; Zhang, Wei; Wang, Zhaoxia; Yuan, Yun

    2015-06-01

    We describe the clinical and muscle MRI changes in 2 siblings with neutral lipid storage disease with myopathy (NLSDM) carrying the mutation c.187+1G>A. Peripheral blood smears, genetic tests, and muscle biopsies were performed. Thigh MRI was performed to observe fatty replacement, muscle edema, and muscle bulk from axial sections. Both siblings had similar fatty infiltration and edema. T1-weighted images of the gluteus maximus, adductor magnus, semitendinosus, and semimembranosus revealed marked and diffuse fatty infiltration. There was asymmetric involvement in biceps femoris and quadriceps. There was extensive fatty infiltration in the quadriceps, except for the rectus femoris. Gracilis and sartorius were relatively spared. Thigh muscle volume was decreased, while the gracilis and sartorius appeared to show compensatory hypertrophy. Compared with previous reports in NLSDM, MRI changes in this myopathy tended to be more severe. Asymmetry and relatively selective fatty infiltration were characteristics. © 2014 Wiley Periodicals, Inc.

  20. Adsorption of lipids on silicalite-1

    NASA Astrophysics Data System (ADS)

    Atyaksheva, L. F.; Ivanova, I. I.; Ivanova, M. V.; Tarasevich, B. N.; Fedosov, D. A.

    2017-05-01

    The adsorption of egg lecithin and cholesterol from chloroform solutions onto silicalite-1 (hydrophobic silica with MFI zeolite structure) is investigated. Adsorption isotherms of the L-type for lecithin and the S-type for cholesterol are obtained in the 0.05-4.5 mg/mL range of equilibrium lipid concentrations. The maximum adsorption for lecithin is 30 mg/g; for cholesterol it is 70 mg/g. Chloroform treatment results in the desorption of no more than 10% of the lecithin and up to 50% of the cholesterol from the silicalite-1 surface. The lecithin molecules in the monolayer on the silicalite-1 are oriented such that their hydrophobic tails are oriented toward the surface and are partially inside the pores of the adsorbent.

  1. Lipid Production of Heterotrophic Chlorella sp. from Hydrolysate Mixtures of Lipid-Extracted Microalgal Biomass Residues and Molasses.

    PubMed

    Zheng, Hongli; Ma, Xiaochen; Gao, Zhen; Wan, Yiqin; Min, Min; Zhou, Wenguang; Li, Yun; Liu, Yuhuan; Huang, He; Chen, Paul; Ruan, Roger

    2015-10-01

    This study investigated the feasibility of lipid production of Chlorella sp. from waste materials. Lipid-extracted microalgal biomass residues (LMBRs) and molasses were hydrolyzed, and their hydrolysates were analyzed. Five different hydrolysate mixture ratios (w/w) of LMBRs/molasses (1/0, 1/1, 1/4, 1/9, and 0/1) were used to cultivate Chlorella sp. The results showed that carbohydrate and protein were the two main compounds in the LMBRs, and carbohydrate was the main compound in the molasses. The highest biomass concentration of 5.58 g/L, Y biomass/sugars of 0.59 g/g, lipid productivity of 335 mg/L/day, and Y lipids/sugars of 0.25 g/g were obtained at the hydrolysate mixture ratio of LMBRs/molasses of 1/4. High C/N ratio promoted the conversion of sugars into lipids. The lipids extracted from Chlorella sp. shared similar lipid profile of soybean oil and is therefore a potential viable biodiesel feedstock. These results showed that Chlorella sp. can utilize mixed sugars and amino acids from LMBRs and molasses to accumulate lipids efficiently, thus reducing the cost of microalgal biodiesel production and improving its economic viability.

  2. Effect of nitrogen sources on biomass, lipid and docosahexanoic acid production by Aurantiochytrium sp. SW1

    NASA Astrophysics Data System (ADS)

    Auma, Khairunnisa; Hamid, Aidil Abdul; Yusoff, Wan Mohtar Wan

    2018-04-01

    A local isolate, Aurantiochytrium sp. SW1 has been verified to have high content of docosahexanoic acid (DHA). However, the effect of different nitrogen sources on biomass, lipid concentration and DHA content in Aurantiochytrium sp. SW1 is still unknown. Hence, this study is focused in using six different organic and inorganic nitrogen sources to grow Aurantiochytrium sp. SW1 in optimized Burja medium. Monosodium glutamate (MSG) gave the highest biomass concentration of 15.97 g/L followed by ammonium nitrate (NH4NO3) with 13.37 g/L at 96 hr. These two nitrogen sources had significant effect on the biomass concentration (p<0.05). The highest lipid accumulated was obtained using MSG that reached 79.6% in biomass concentration. DHA content in lipid showed cultivation using MSG reached 47.9% (4.95 g/L). Statistical analysis using least significant difference (LSD) showed significant lipid production (p<0.05) when cultivated in MSG compared to other five nitrogen sources. The highest DHA productivity (0.052 g/L hr-1) was obtained in medium containing MSG. This study proves that nitrogen component in the medium significantly affects the biomass concentration, lipid and DHA content.

  3. Integral lipids of mammalian hair.

    PubMed

    Wertz, P W; Downing, D T

    1989-01-01

    1. It has been demonstrated that hair contains lipids which cannot be removed by extensive extraction with chloroform-methanol mixtures. These integral lipids can be extracted only after the hair has been subjected to alkaline hydrolysis. 2. Integral hair lipids include cholesterol sulfate (0.7-2.9 mg/g hair), ceramides (0.6-1.4 mg/g), cholesterol (0.3-1.4 mg/g), fatty alcohols (trace-0.2 mg/g) and fatty acids (2.3-4.0 mg/g). 3. One of the major integral hair lipids, representing 38.4-47.6% of the total fatty acids, is the anteisobranched 18-methyleicosanoic acid. 4. The species examined included human (Homo sapiens), pig (Sus scrofa), dog (Canis familiaris), sheep (Ovis ammon aries) and cow (Bos taurus).

  4. Recommendations for placement of cable median barriers on 6:1 and 4:1 sloped medians with horizontal curvatures.

    DOT National Transportation Integrated Search

    2012-09-01

    This report summarizes the research efforts of using finite element modeling and simulations to evaluate the performance of generic lowtension : cable median barriers (CMBs) on four-lane and six-lane freeways with a 46-foot median, horizontal curvatu...

  5. Solid lipid nanodispersions containing mixed lipid core and a polar heterolipid: characterization.

    PubMed

    Attama, A A; Schicke, B C; Paepenmüller, T; Müller-Goymann, C C

    2007-08-01

    This paper describes the characterization of solid lipid nanodispersions (SLN) prepared with a 1:1 mixture of theobroma oil and goat fat as the main lipid matrix and Phospholipon 90G (P90G) as a stabilizer heterolipid, using polysorbate 80 as the mobile surfactant, with a view to applying the SLN in drug delivery. The 1:1 lipid mixture and P90G constituting the lipid matrix was first homogeneously prepared by fusion. Thereafter, the SLN were formulated with a gradient of polysorbate 80 and constant lipid matrix concentration by melt-high pressure homogenisation. The SLN were characterized by time-resolved particle size analysis, zeta potential and osmotic pressure measurements, differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Transmission electron microscopy (TEM) and isothermal heat conduction microcalorimetry (IMC) which monitors the in situ crystallization were also carried out on the SLN containing P90G and 1.0 % w/w of polysorbate 80. The results obtained in these studies were compared with SLN prepared with theobroma oil with and without phospholipid. Particle size analysis of SLN indicated reduction in size with increase in concentration of mobile surfactant and was in the lower nanometer range after 3 months except SLN prepared without P90G or polysorbate 80. The lipid nanoparticles had negative potentials after 3 months. WAXD and DSC studies revealed low crystalline SLN after 3 months of storage except in WAXD of SLN formulated with 1.0 % w/w polysorbate 80. TEM micrograph of the SLN containing 1.0 % w/w polysorbate 80 revealed discrete particles whose sizes were in consonance with the static light scattering measurement. In situ crystallization studies in IMC revealed delayed crystallization of the SLN with 1.0 % w/w polysorbate 80. Results indicate lipid mixtures produced SLN with lower crystallinity and higher particle sizes compared with SLN prepared with theobroma oil alone with or without P90G, and would lead to higher

  6. Statin-induced myopathy SLCO1B1 521T > C is associated with prediabetes, high body mass index and normal lipid profile in Emirati population.

    PubMed

    Saber-Ayad, Maha; Manzoor, Shaista; El-Serafi, Ahmed; Mahmoud, Ibrahim; Abusnana, Salah; Sulaiman, Nabil

    2018-05-01

    Statin-induced myopathy has been linked to the C allele of a single nucleotide polymorphism (SNP) (rs4149056) of SLCO1B1 gene. This effect is more significant, but not restricted to simvastatin. Many studies have included European, American, African and Southeast Asian ancestries, but few were carried out on Middle Eastern population. To detect the prevalence of SLCO1B1 rs4149056 (521T > C) in Emirati population. We recruited 282 Emiratis through the UAE National Diabetes and Lifestyle Project. Ethical approval was obtained before the study starts. Besides basic data collection, venous blood samples were collected. Fasting blood glucose, Lipid profile, and insulin levels were measured. Genotyping for rs4149056 (521T > C) was tested in triplicates through Real Time-PCR using TaqMan® Drug Metabolism Genotyping Assay. rs2306283 (388A > G) was analyzed for comparison. In addition, presence of minor alleles of both SNPs define stronger association with statin-induced myopathy. The study included 282 individuals, 52.8% were males with median age of 39.5 years. 10% had Diabetes Mellitus and 23% were hypertensive. Median of body mass index (BMI) was 27.68 kg/m 2 in males and 28.38 kg/m 2 in females. One-hundred ninety-seven (69.9%) showed abnormal lipid profile (either increased LDL-cholesterol or triglycerides or both). For rs4149056, C allele was present in 21.3% (2.8% homozygous C and 18.4% heterozygous CT). Although homozygous C genotype prevalence was low, compared with Caucasians (4%) and Africans (0%), C allele was associated with a trend of having higher BMI and abnormal lipid profile. C allele subjects were all pre-diabetics with mean glycated hemoglobin above 6%. Mean BMI in CC, CT, and TT genotypes was 30.91 ± 4.4, 29.48 ± 4.2, 27.96 ± 5.5 kg/m 2 respectively, with lack of such a trend observed with the different genotypes of the rs2306283 (used for comparison). Abnormal lipid profile was observed in 7/8(87.5%), 38/52(73.1

  7. Houttuynia cordata attenuates lipid accumulation via activation of AMP-activated protein kinase signaling pathway in HepG2 cells.

    PubMed

    Kang, Hyun; Koppula, Sushruta

    2014-01-01

    Houttuynia cordata (H. cordata) from the family Saururaceae is a perennial herb native to Southeast Asia. It possesses a range of medicinal properties to treat several disease symptoms including allergic inflammation and anaphylaxis. In the present investigation, we provided the molecular mechanisms underlying the role of H. cordata extract (HCE) in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes. HepG2 cells were pre-treated with various concentrations of HCE (0, 10, 20, 40, and 80 μg/mL) and treated with serum-free medium with normal glucose (5 mM) for 1 h, followed by exposure to high glucose (25 mM D-glucose) for 24 h. HCE significantly and dose-dependently attenuated lipid accumulation in human HepG2 hepatocytes when exposed to high glucose (25 mM D-glucose) (p < 0.05, p < 0.01 and p < 0.001 at 20, 40, and 80 μg/mL concentrations, respectively). Further, HCE attenuated the expression of fatty acid synthase (FAS), sterol regulatory element-binding protein-1 and glycerol 3-phosphate acyltransferases (GPATs). The adenosine monophosphate-activated protein kinase (AMPK) was also activated by HCE treatment when exposed to high glucose (25 mM D-glucose) in human HepG2 hepatocytes. This study suggests the hypolipidemic effects of HCE by the inhibition of lipid biosynthesis mediated through AMPK signaling, which may play an active role and can be developed as an anti-obesity agent.

  8. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol[S

    PubMed Central

    Zhu, Xuewei; Owen, John S.; Wilson, Martha D.; Li, Haitao; Griffiths, Gary L.; Thomas, Michael J.; Hiltbold, Elizabeth M.; Fessler, Michael B.; Parks, John S.

    2010-01-01

    We previously showed that macrophages from macrophage-specific ATP-binding cassette transporter A1 (ABCA1) knockout (Abca1-M/-M) mice had an enhanced proinflammatory response to the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), compared with wild-type (WT) mice. In the present study, we demonstrate a direct association between free cholesterol (FC), lipid raft content, and hyper-responsiveness of macrophages to LPS in WT mice. Abca1-M/-M macrophages were also hyper-responsive to specific agonists to TLR2, TLR7, and TLR9, but not TLR3, compared with WT macrophages. We hypothesized that ABCA1 regulates macrophage responsiveness to TLR agonists by modulation of lipid raft cholesterol and TLR mobilization to lipid rafts. We demonstrated that Abca1-M/-M vs. WT macrophages contained 23% more FC in isolated lipid rafts. Further, mass spectrometric analysis suggested raft phospholipid composition was unchanged. Although cell surface expression of TLR4 was similar between Abca1-M/-M and WT macrophages, significantly more TLR4 was distributed in membrane lipid rafts in Abca1-M/-M macrophages. Abca1-M/-M macrophages also exhibited increased trafficking of the predominantly intracellular TLR9 into lipid rafts in response to TLR9-specific agonist (CpG). Collectively, our data suggest that macrophage ABCA1 dampens inflammation by reducing MyD88-dependent TLRs trafficking to lipid rafts by selective reduction of FC content in lipid rafts. PMID:20650929

  9. The cellular source for APOBEC3G's incorporation into HIV-1

    PubMed Central

    2011-01-01

    Background Human APOBEC3G (hA3G) has been identified as a cellular inhibitor of HIV-1 infectivity. Viral incorporation of hA3G is an essential step for its antiviral activity. Although the mechanism underlying hA3G virion encapsidation has been investigated extensively, the cellular source of viral hA3G remains unclear. Results Previous studies have shown that hA3G forms low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. Our work herein provides evidence that the majority of newly-synthesized hA3G interacts with membrane lipid raft domains to form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of the mature HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM form, the RA LMM form and the mature forms of HMM is regulated by a mechanism involving the N-terminal part of the linker region and the C-terminus of hA3G. Mutagenesis studies reveal a direct correlation between the ability of hA3G to form the RA LMM complex and its viral incorporation. Conclusions Together these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G. PMID:21211018

  10. Median statistics estimates of Hubble and Newton's constants

    NASA Astrophysics Data System (ADS)

    Bethapudi, Suryarao; Desai, Shantanu

    2017-02-01

    Robustness of any statistics depends upon the number of assumptions it makes about the measured data. We point out the advantages of median statistics using toy numerical experiments and demonstrate its robustness, when the number of assumptions we can make about the data are limited. We then apply the median statistics technique to obtain estimates of two constants of nature, Hubble constant (H0) and Newton's gravitational constant ( G , both of which show significant differences between different measurements. For H0, we update the analyses done by Chen and Ratra (2011) and Gott et al. (2001) using 576 measurements. We find after grouping the different results according to their primary type of measurement, the median estimates are given by H0 = 72.5^{+2.5}_{-8} km/sec/Mpc with errors corresponding to 95% c.l. (2 σ) and G=6.674702^{+0.0014}_{-0.0009} × 10^{-11} Nm2kg-2 corresponding to 68% c.l. (1σ).

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

    PubMed

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

    2012-07-01

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

  12. HNF1α defect influences post-prandial lipid regulation

    PubMed Central

    St-Jean, Matthieu; Boudreau, François; Carpentier, André C.

    2017-01-01

    Purpose Hepatocyte nuclear factor 1 alpha (HNF1α) defects cause Mature Onset Diabetes of the Young type 3 (MODY3), characterized by defects in beta-cell insulin secretion. However, HNF1α is involved in many other metabolic pathways with relevance for monogenic or polygenic type 2 diabetes. We aimed to investigate gut hormones, lipids, and insulin regulation in response to a meal test in HNF1α defect carriers (MODY3) compared to non-diabetic subjects (controls) and type 2 diabetes (T2D). Methods We administered a standardized liquid meal to each participant. Over 6 hours, we measured post-meal responses of insulin regulation (blood glucose, c-peptide, insulin), gut hormones (ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1) and lipids (non-esterified fatty acids [NEFA] and triglycerides). Results We found that MODY3 participants had lower insulin secretion indices than controls and T2D participants, showing the expected β-cell defect. MODY3 had similar glycated hemoglobin levels (HbA1c median [IQR]: 6.5 [5.6–7.6]%) compared to T2D (median: 6.6 [6.2–6.9]%; P<0.05). MODY3 had greater insulin sensitivity (Matsuda index: 71.9 [29.6; 125.5]) than T2D (3.2 [4.0; 6.0]; P<0.05). MODY3 experienced a larger decrease in the ratio of NEFA to insulin (NEFA 30–0 / insulin 30–0: -39 [-78; -30] x104) in the early post-prandial period (0–30 minutes) compared to controls and to T2D (-2.0 [-0.6; -6.4] x104; P<0.05). MODY3 had lower fasting (0.66 [0.46; 1.2] mM) and post-meal triglycerides levels compared to T2D (fasting: 2.3 [1.7; 2.7] mM; P<0.05). We did not detect significant post-meal differences in ghrelin and incretins between MODY3 and other groups. Conclusion In response to a standard meal test, MODY3 showed greater early post-prandial NEFA diminution in response to relatively low early insulin secretion, and they maintained very low post-prandial triglycerides levels. PMID:28493909

  13. Novel structure of cockroach allergen Bla g 1 has implications for allergenicity and exposure assessment

    PubMed Central

    Mueller, Geoffrey A.; Pedersen, Lars C.; Lih, Fred B.; Glesner, Jill; Moon, Andrea F.; Chapman, Martin D.; Tomer, Kenneth B.; London, Robert E.; Pomés, Anna

    2013-01-01

    Background Sensitization to cockroach allergens is a major risk factor for asthma. The cockroach allergen Bla g 1 has multiple repeats of ~100 amino acids, but the fold of the protein and the biological function are unknown. Objective To determine the structure of Bla g 1, investigate the implications for allergic disease, and standardize cockroach exposure assays. Methods Natural Bla g 1 and recombinant constructs were compared by ELISA using specific murine IgG and human IgE. The structure of Bla g 1 was determined by X-ray crystallography. Mass spectrometry and NMR were utilized to examine ligand-binding properties of the allergen. Results The structure of a recombinant Bla g 1 construct with comparable IgE and IgG reactivity to the natural allergen was solved by X-ray crystallography. The Bla g 1 repeat forms a novel fold with 6 helices. Two repeats encapsulate a large and nearly spherical hydrophobic cavity, defining the basic structural unit. Lipids in the cavity varied depending on the allergen origin. Palmitic, oleic and stearic acids were associated with nBla g 1 from cockroach frass. One Unit of Bla g 1 was equivalent to 104 ng of allergen. Conclusions Bla g 1 has a novel fold with a capacity to bind various lipids, which suggests a digestive function associated with non-specific transport of lipid molecules in cockroaches. Defining the basic structural unit of Bla g 1 facilitates the standardization of assays in absolute units for the assessment of environmental allergen exposure. PMID:23915714

  14. Regulation of endothelial nitric oxide synthase: involvement of protein kinase G 1 beta, serine 116 phosphorylation and lipid structures.

    PubMed

    John, Theresa A; Ibe, Basil O; Raj, J Usha

    2008-02-01

    1. Endothelial nitric oxide synthase (NOS3) is important for vascular homeostasis. The role of protein kinase G (PKG) in regulation of NOS3 activity was studied in primary cultures of newborn lamb lung microvascular endothelial cells (LMVEC). 2. We determined the presence of PKG in fetal and neonatal LMVEC as well as subcellular localization of PKG isoforms in the neonatal cells by fluorescence immunohistochemistry. We used diaminofluorescein (DAF) fluorophore to measure nitric oxide (NO) production from neonatal LMVEC. We confirmed that NO measured was from constitutive NOS3 by inhibiting it with NOS inhibitors. 3. To identify a role for PKG in basal NO production, we measured NO release from LMVEC cells using 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM; 0.5-0.8 micromol/L) with and without prior stimulation with the PKG activator 8-bromo-cGMP (8-Br-cGMP; 0.3 and 3 micromol/L) or prior PKG inhibition with beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothionate (BPC; 0.3 and 3 micromol/L). With the same drugs, we determined the role of PKG on cellular expression of NOS3 and serine 116 phosphorylated NOS (pSer116-NOS) by qualitative and quantitative immunofluorescence assays, as well as western blotting. 4. Because PKG 1 beta was distributed throughout the cytosol in a punctate expression, we used 2 mmol/L cyclodextrin, a cholesterol extractor, to determine a role for lipid vesicles in PKG regulation of NO production. 5. Protein kinase G 1 beta gave a punctate appearance, indicating its presence in intracellular vesicles. Nitric oxide production decreased by approximately 20% with 300 nmol/L and 3 micromol/L 8-Br cGMP (P < 0.05) and increased by 20.8 +/- 3.7% with 3 micromol/L BPC (P < 0.001), indicating that both stimulated and basal PKG activity has inhibitory effects on basal NOS3 function. Nitric oxide synthase immunofluorescence and immunoblot expression were decreased and pSer116-NOS immunofluorescence was increased by 800 nmol

  15. Global fibrinolytic activity, PAI-1 level, and 4G/5G polymorphism in Thai children with arterial ischemic stroke.

    PubMed

    Natesirinilkul, Rungrote; Sasanakul, Werasak; Chuansumrit, Ampaiwan; Kadegasem, Praguywan; Visudtibhan, Anannit; Wongwerawattanakoon, Pakawan; Sirachainan, Nongnuch

    2014-01-01

    Prolonged euglobulin clot lysis time (ECLT) and increased level of plasminogen activator inhibitor-1 (PAI-1) were reported to be risk factors of arterial ischemic stroke (AIS) by some studies; however, these findings were not supported by other studies. The objective of this study was to determine the association of ECLT, PAI-1 level, and polymorphisms of 4G and 5G of PAI-1 gene to the development of AIS in Thai children. This study included patients aged 1-18 years old. Diagnosis of AIS was confirmed by imaging study. The control group was age- and sex-matched healthy subjects. Demographic data were recorded, and blood was tested for ECLT, PAI-1 level, lipid profiles, fasting blood sugar (FBS), and 4G and 5G polymorphisms of PAI-1 gene. There were 70 subjects participating in this study, consisting of 30 patients and 40 controls. Demographic data, lipid profiles, and FBS were similar between the 2 groups. Furthermore, ECLT and PAI-1 level did not differ between patient and control groups; however, both showed significant correlation (r = .352, P = .006). The 4G/5G polymorphism was the most common genotype in both patient and control groups (69.0% vs. 80.0%). However, 4G and 5G polymorphisms of PAI-1 gene did not correlate with PAI-1 level in this study (P = .797). The PAI-1 level and 4G/5G polymorphism may not be a risk factor of AIS in this population. It was also found that the 4G/5G polymorphism was the most common PAI-1 genotype in this study. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type I glycoprotein gH occurs through a cholesterol-dependent mechanism.

    PubMed

    Vitiello, Giuseppe; Falanga, Annarita; Petruk, Ariel Alcides; Merlino, Antonello; Fragneto, Giovanna; Paduano, Luigi; Galdiero, Stefania; D'Errico, Gerardino

    2015-04-21

    A wealth of evidence indicates that lipid rafts are involved in the fusion of the viral lipid envelope with the target cell membrane. However, the interplay between these sterol- and sphingolipid-enriched ordered domains and viral fusion glycoproteins has not yet been clarified. In this work we investigate the molecular mechanism by which a membranotropic fragment of the glycoprotein gH of the Herpes Simplex Virus (HSV) type I (gH625) drives fusion of lipid bilayers formed by palmitoyl oleoyl phosphatidylcholine (POPC)-sphingomyelin (SM)-cholesterol (CHOL) (1 : 1 : 1 wt/wt/wt), focusing on the role played by each component. The comparative analysis of the liposome fusion assays, Dynamic Light Scattering (DLS), spectrofluorimetry, Neutron Reflectivity (NR) and Electron Spin Resonance (ESR) experiments, and Molecular Dynamics (MD) simulations shows that CHOL is fundamental for liposome fusion to occur. In detail, CHOL stabilizes the gH625-bilayer association by specific interactions with the peptide Trp residue. The interaction with gH625 causes an increased order of the lipid acyl chains, whose local rotational motion is significantly hampered. SM plays only a minor role in the process, favoring the propagation of lipid perturbation to the bilayer inner core. The stiffening of the peptide-interacting bilayer leaflet results in an asymmetric perturbation of the membrane, which is locally destabilized thus favoring fusion events. Our results show that viral fusion glycoproteins are optimally suited to exert a high fusogenic activity on lipid rafts and support the relevance of cholesterol as a key player of membrane-related processes.

  17. Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.

    PubMed

    Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

    2017-05-06

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. Copyright © 2017. Published by Elsevier Inc.

  18. Clinical experience with a lipid-free, ready-made parenteral nutrition solution in dogs: 70 cases (2006-2012).

    PubMed

    Gajanayake, Isuru; Wylie, Claire E; Chan, Daniel L

    2013-01-01

    To review the clinical use of a lipid-free, ready-made amino acid and glucose parenteral nutrition (PN) solution in dogs. Retrospective study of dogs from 2006 to 2012 that received this form of PN. University veterinary teaching hospital. Seventy dogs presented to the hospital for treatment of various diseases in which PN was used as part of patient management. Dogs were administered PN at the discretion of the primary clinician. A lipid-free, ready-made solution containing amino acid (59 g/L) and dextrose (100 g/L) was administered intravenously as a constant rate infusion to provide nutritional support. PN was provided for a median of 2.2 days (range 0.5-9.5 days) in the 70 dogs, totaling 168 days of PN. The PN provided a median of 5.5 g/100 kcal of protein (range 1-9.5 g/100 kcal) and a median of 2.2 mg/kg of bodyweight per minute (range 0.8-5.2 mg/kg/min) of glucose, which reflected a median of 57% of the resting energy requirement (range 9-100%). Metabolic complications developed in 43 of 67 dogs where these data were recorded, but the development of hyperkalemia was the only complication associated with a poor outcome (eg, death or euthanasia). Mechanical complications were seen in 28 dogs, and all but one of these occurred when PN was delivered through peripheral catheters. Septic complications were confirmed in 5 dogs. This form of PN is suitable for clinical use and can provide both protein and calories to ill dogs. It was, however, associated with a high rate of complications and requires careful patient monitoring. © Veterinary Emergency and Critical Care Society 2013.

  19. The Roles of APOBEC3G Complexes in the Incorporation of APOBEC3G into HIV-1

    PubMed Central

    Zhang, Quan; Liu, Zhenlong; Jia, Pingping; Zhou, Jinming; Guo, Fei; You, Xuefu; Yu, Liyan; Zhao, Lixun; Jiang, Jiandong; Cen, Shan

    2013-01-01

    Background The incorporation of human APOBEC3G (hA3G) into HIV is required for exerting its antiviral activity, therefore the mechanism underlying hA3G virion encapsidation has been investigated extensively. hA3G was shown to form low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. The function of different forms of hA3G in its viral incorporation remains unclear. Methodology/Principal Findings In this study, we investigated the subcellular distribution and lipid raft association of hA3G using subcellular fractionation, membrane floatation assay and pulse-chase radiolabeling experiments respectively, and studied the correlation between the ability of hA3G to form the different complex and its viral incorporation. Our work herein provides evidence that the majority of newly-synthesized hA3G interacts with membrane lipid raft domains to form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of mature HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM form, the RA LMM form and the mature forms of HMM is regulated by a mechanism involving the N-terminal part of the linker region and the C-terminus of hA3G. Mutagenesis studies reveal a direct correlation between the ability of hA3G to form the RA LMM complex and its viral incorporation. Conclusions/Significance Together these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G. PMID:24098356

  20. The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers

    PubMed Central

    Touhara, Kouki K; Wang, Weiwei; MacKinnon, Roderick

    2016-01-01

    G protein gated inward rectifier potassium (GIRK) channels are gated by direct binding of G protein beta-gamma subunits (Gβγ), signaling lipids, and intracellular Na+. In cardiac pacemaker cells, hetero-tetramer GIRK1/4 channels and homo-tetramer GIRK4 channels play a central role in parasympathetic slowing of heart rate. It is known that the Na+ binding site of the GIRK1 subunit is defective, but the functional difference between GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers remains unclear. Here, using purified proteins and the lipid bilayer system, we characterize Gβγ and Na+ regulation of GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers. We find in GIRK4 homo-tetramers that Na+ binding increases Gβγ affinity and thereby increases the GIRK4 responsiveness to G protein stimulation. GIRK1/4 hetero-tetramers are not activated by Na+, but rather are in a permanent state of high responsiveness to Gβγ, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with Na+ permanently bound. DOI: http://dx.doi.org/10.7554/eLife.15750.001 PMID:27074664

  1. Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

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

    Yang, Guang; Wang, Yuan; Feng, Jinyan

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. Inmore » addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. - Highlights: • Aspirin inhibits the levels of liquid droplets, triglyceride and cholesterol in HCC cells. • Aspirin is able to down-regulate ACSL1 in HCC cells. • NF-κB inhibitor PDTC can down-regulate ACSL1 and reduces lipogenesis in HCC cells. • Aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling.« less

  2. Milk Polar Lipids Affect In Vitro Digestive Lipolysis and Postprandial Lipid Metabolism in Mice.

    PubMed

    Lecomte, Manon; Bourlieu, Claire; Meugnier, Emmanuelle; Penhoat, Armelle; Cheillan, David; Pineau, Gaëlle; Loizon, Emmanuelle; Trauchessec, Michèle; Claude, Mathilde; Ménard, Olivia; Géloën, Alain; Laugerette, Fabienne; Michalski, Marie-Caroline

    2015-08-01

    Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism, but focused studies on postprandial lipemia are lacking. We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro. Female Swiss mice were gavaged with 150 μL of an oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 μg/mL vs. 90 μg/mL; P = 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 μg/mL vs. 44 μg/mL; P < 0.05). The opposite was observed after 4 h with lower TGs (21 μg/mL vs. 35 μg/mL; P < 0.01) and NEFAs (20 μg/mL vs. 32 μg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B (Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B (Sar1b), in the duodenum of MPL mice compared with SPL mice (P < 0.05). In vitro, during the intestinal phase, TGs were hydrolyzed more in the MPL emulsion than in the SPL emulsion (decremental AUCs were 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipid absorption and sharper kinetics of lipemia. Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partly through differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism. © 2015 American Society for Nutrition.

  3. Engineering Rhodosporidium toruloides for increased lipid production.

    PubMed

    Zhang, Shuyan; Skerker, Jeffrey M; Rutter, Charles D; Maurer, Matthew J; Arkin, Adam P; Rao, Christopher V

    2016-05-01

    Oleaginous yeast are promising organisms for the production of lipid-based chemicals and fuels from simple sugars. In this work, we explored Rhodosporidium toruloides for the production of lipid-based products. This oleaginous yeast natively produces lipids at high titers and can grow on glucose and xylose. As a first step, we sequenced the genomes of two strains, IFO0880, and IFO0559, and generated draft assemblies and annotations. We then used this information to engineer two R. toruloides strains for increased lipid production by over-expressing the native acetyl-CoA carboxylase and diacylglycerol acyltransferase genes using Agrobacterium tumefaciens mediated transformation. Our best strain, derived from IFO0880, was able to produce 16.4 ± 1.1 g/L lipid from 70 g/L glucose and 9.5 ± 1.3 g/L lipid from 70 g/L xylose in shake-flask experiments. This work represents one of the first examples of metabolic engineering in R. toruloides and establishes this yeast as a new platform for production of fatty-acid derived products. © 2015 Wiley Periodicals, Inc.

  4. Overweight children with type 1 diabetes have a more favourable lipid profile than overweight non-diabetic children.

    PubMed

    van Vliet, Mariska; van der Heyden, Josine C; Diamant, Michaela; von Rosenstiel, Inès A; Schindhelm, Roger K; Heymans, Martijn W; Brandjes, Desiderius P M; Beijnen, Jos H; Aanstoot, Henk J; Veeze, Henk J

    2012-03-01

    In the present article, we aimed to compare the cardiometabolic risk between overweight children with and without type 1 diabetes (T1DM). Therefore, data with regard to cardiometabolic risk parameters of 44 overweight Caucasian children (3-18 years) with T1DM were matched with 44 overweight peers without T1DM for sex, ethnicity, age and standard deviation score of BMI (Z-BMI). Detailed history was taken, information regarding anthropometrics and family history were collected and blood pressure was measured. Blood samples were collected for evaluation of lipid profiles (fasting in controls, non-fasting in T1DM children), alanine aminotransferase and HbA1c (in children with T1DM). It was found that overweight children with T1DM had lower median standard deviation score of waist circumference (Z-WC) as compared to the overweight control group [median, 2.0 (interquartile range, IQR, 1.5-2.3) vs. 2.6 (IQR, 2.0-2.9), P < 0.001]. After adjustment for Z-WC, in children with T1DM, median high-density lipoprotein cholesterol levels were significantly higher and median low-density lipoprotein cholesterol lower in T1DM children, as compared to their peers without T1DM [1.40 (IQR, 1.2-1.5) vs. 1.2 (IQR, 1.0-1.3) and 2.7 (IQR, 2.5-3.2) vs. 3.0 (IQR, 2.5-3.4), respectively, all P < 0.01]. When dividing children according to glycaemic status, children with suboptimal glycaemic control had higher values of triglycerides as compared to well-controlled children [1.3 (IQR, 1.0-1.8) vs. 0.96 (IQR, 0.80-1.2), P = 0.036]. In conclusion, overweight children with T1DM have a more favourable lipid profile, as compared to non-diabetic overweight controls, in spite of a higher frequency of a positive family history of CVD, T2DM and hypertension. Still, paediatricians should give extra attention to cardiometabolic risk factors within this vulnerable group, taking into account the already high cardiometabolic risk.

  5. The Compound of Mangiferin-Berberine Salt Has Potent Activities in Modulating Lipid and Glucose Metabolisms in HepG2 Cells

    PubMed Central

    Wang, Can; Jiang, Jian-Dong; Wu, Wei; Kong, Wei-Jia

    2016-01-01

    The mangiferin-berberine (MB) salt was synthesized by ionic bonding of mangiferin (M) and berberine (B) at an equal molecular ratio. This study aimed to investigate the activities of MB salt in modulating lipid and glucose metabolisms in HepG2 cells. After 24 h treatment of the studying compounds, cellular AMP-activated protein kinase α (AMPKα)/acetyl-CoA carboxylase (ACC) protein levels and carnitine palmitoyltransferase (CPT) 1 activities, intracellular lipid contents, mRNA expression levels of target genes, glucose consumption, and glucose production amounts were determined. Compound C (CC) was used in the blocking experiments. Our results showed that MB salt increased p-AMPKα (Thr172)/p-ACC (Ser79) levels and CPT1 activity and suppressed oleic acid- (OA-) induced lipid accumulation and upregulation of lipogenic genes potently in HepG2 cells. The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration. MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone. The inhibiting activity of MB salt on cellular gluconeogenesis was AMPK dependent. Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future. PMID:27123455

  6. Probing the binding of cationic lipids with dendrimers.

    PubMed

    Mandeville, J S; Bourassa, P; Tajmir-Riahi, H A

    2013-01-14

    Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell. We report the bindings of several lipids cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane(DOTAP), dioctadecyldimethylammoniumbromide (DDAB), and dioleoylphosphatidylethanolamine (DOPE) to dendrimers of different compositions such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) under physiological conditions. FTIR, UV-visible spectroscopic, methods and molecular modeling were used to analyze the lipid binding mode, the binding constant, and the effects of lipid complexation on the dendrimer structure. The structural analysis showed that lipids bind dendrimers through both hydrophilic and hydrophobic contacts with overall binding constants of K(chol-mPEG-G3) = 1.7 × 10(3) M(-1), K(chol-mPEG-PAMAM-G4) = 2.7 × 10(3) M(-1), K(chol-PAMAM-G4) = 1.0 × 10(3) M(-1), K(DOPE-mPEG-G3) = 1.5 × 10(3) M(-1), K(DOPE-mPEG-PAMAM-G4) = 1.6 × 10(3) M(-1), K(DOPE-PAMAM-G4) = 5.3 × 10(2) M(-1), K(DDAB-mPEG-G3) = 1.5 × 10(3) M(-1), K(DDAB-mPEG-PAMAM-G4) = 1.9 × 10(2) M(-1), K(DDAB-PAMAM-G4) = 7.0 × 10(2) M(-1), K(DOTAP-mPEG-G3) = 1.9 × 10(3) M(-1), K(DOTAP-mPEG-PAMAM-G4) = 1.5 × 10(3) M(-1), and K(DOTAP-PAMAM-G4) = 5.7 × 10(2) M(-1). Weaker interaction was observed as dendrimer cationic charges increased. The free binding energies from docking were -5.15 (cholesterol), -5.79 (DDAB), and -5.36 kcal/mol (DOTAP) with the order of stability DDAB-PAMAM-G-4 > DOTAP-PAMAM-G4 > cholesterol-PAMAM-G4, consistent with the spectroscopic results. Dendrimers might act as carriers to transport lipids in vitro.

  7. Iatroscan-measured particulate and dissolved lipids in the Almeria-Oran frontal system (Almofront-1, May 1991)

    NASA Astrophysics Data System (ADS)

    Gérin, C.; Goutx, M.

    1994-08-01

    The Chromarod-Iatroscan system was used to measure dissolved and particulate lipids at six sites representative of the main hydrological zones of the Almeria-Oran frontal system in May 1991. Concentrations ranged from 9 to 113 μg 1 -1 and from 3 to 84 μg 1 -1 respectively. Particulate carbon was estimated on a CHN Leco analyzer. Dissolved lipid concentrations were highly variable with depth and exhibited clear signatures of phytoplankton degradation throughout the profiles. In the 300-400 m layer, particulate wax esters denoted the presence of deep zooplankton which may be benefit from the downward fluxes of organic matter from the frontal zone. In surface water, high concentrations of dissolved lipids and particulate carbon marked the presence of the jet front. Particulate lipid classes in samples were related to the presence of zooplankton and to the physiological state of cells rather than to phytoplankton biomass. Particulate triglyceride concentrations (storage lipids in phytoplankton) increased from the left to the right border of the jet core and further southwards, culminating in the Atlantic anticyclonic gyre. The distribution of particulate lipids to carbon and chlorophyllatios and the increasing level of triglycerides from the jet and southwards suggested a rapid removal of the frontal production by physical transports. The ability of anticyclonic structures to enhance accumulations of energetically rich compounds and thus to play a role as fertilizers of the oligotrophic waters of the Mediterranean Sea is discussed.

  8. Retinal lipid and glucose metabolism dictates angiogenesis through lipid sensor Ffar1

    PubMed Central

    Joyal, Jean-Sébastien; Sun, Ye; Gantner, Marin L.; Shao, Zhuo; Evans, Lucy P.; Saba, Nicholas; Fredrick, Thomas; Burnim, Samuel; Kim, Jin Sung; Patel, Gauri; Juan, Aimee M.; Hurst, Christian G.; Hatton, Colman J.; Cui, Zhenghao; Pierce, Kerry A.; Bherer, Patrick; Aguilar, Edith; Powner, Michael B.; Vevis, Kristis; Boisvert, Michel; Fu, Zhongjie; Levy, Emile; Fruttiger, Marcus; Packard, Alan; Rezende, Flavio A.; Maranda, Bruno; Sapieha, Przemyslaw; Chen, Jing; Friedlander, Martin; Clish, Clary B.; Smith, Lois E.H.

    2016-01-01

    Tissues with high metabolic rates often use lipid as well as glucose for energy, conferring a survival advantage during feast and famine.1 Current dogma suggests that high-energy consuming photoreceptors depend on glucose.2,3 Here we show that retina also uses fatty acids (FA) β-oxidation for energy. Moreover, we identify a lipid sensor Ffar1 that curbs glucose uptake when FA are available. Very low-density lipoprotein receptor (VLDLR), expressed in tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived FA.4,5 Vldlr is present in photoreceptors.6 In Vldlr−/− retinas, Ffar1, sensing high circulating lipid levels despite decreased FA uptake5, suppresses glucose transporter Glut1. This impaired glucose entry into photoreceptors results in a dual lipid/glucose fuel shortage and reduction in the Krebs cycle intermediate α-ketoglutarate (KG). Low α-KG levels promote hypoxia-induced factor-1α (Hif1a) stabilization and vascular endothelial growth factor (Vegfa) secretion by starved Vldlr−/− photoreceptors, attracting neovessels to supply fuel. These aberrant vessels invading normally avascular photoreceptors in Vldlr−/− retinas are reminiscent of retinal angiomatous proliferation (RAP), a subset of neovascular age-related macular degeneration (AMD)7, associated with high vitreous VEGF levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in neovascular AMD and other retinal diseases. PMID:26974308

  9. 1. WEST AND SOUTH SIDES, FROM MEDIAN IN B STREET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. WEST AND SOUTH SIDES, FROM MEDIAN IN B STREET WEST OF 4TH STREET, LOOKING NORTHEAST. - Oakland Naval Supply Center, Firehouse, East of Fourth Street, between A & B Streets, Oakland, Alameda County, CA

  10. Regulation of Lipid Synthesis in Soybeans by Two Benzoic Acid Herbicides 1

    PubMed Central

    Muslih, Raad K.; Linscott, Dean L.

    1977-01-01

    The effects of 3-nitro-2,5-dichlorobenzoic acid (dinoben) and 3-amino-2,4-dichlorobenzoic acid (chloramben) on lipid formation and on the incorporation of various substrates into lipids by intact seeds and subcellular fractions of germinating soybean (Glycine max [L.] Merr. `Amsoy') were studied. Dinoben (20 μg/ml) inhibited synthesis of total lipids 67%, neutral lipids 73%, glycolipids 51%, and phospholipids 39% in germinating seeds. When polar lipids were analyzed further, inhibition of individual lipid classes was also observed. Chloramben (20 μg/ml) stimulated total lipid synthesis 25%. With the exception of the mitochondrial fraction where malonate thiokinase was absent, dinoben inhibited up to 99% the incorporation of acetate and malonate into lipids, but did not inhibit acetyl-CoA and malonyl-CoA incorporation. Chloramben stimulated the incorporation of all substrates tested into lipids by all fractions except the mitochondrial fraction when malonate was the substrate. When dinoben and chloramben were used in combinations, chloramben did not reverse the inhibitory effect of dinoben. It is concluded that the dinoben inhibitory effect is specific and is associated with the acetate and malonate thiokinase systems. The chloramben effect is stimulatory to either acetyl-CoA carboxylase or fatty acid synthetase or both. PMID:16660173

  11. Scenedesmus sp. NJ-1 isolated from Antarctica: a suitable renewable lipid source for biodiesel production.

    PubMed

    Chen, Zhuo; Gong, Yangmin; Fang, Xiantao; Hu, Hanhua

    2012-11-01

    Microalgal lipids are promising alternative feedstocks for biodiesel production. Scenedesmus sp. NJ-1, an oil-rich freshwater microalga isolated from Antarctica, was identified to be a suitable candidate to produce biodiesel in this study. This strain could grow at temperatures ranging from 4 to 35 °C. With regular decrease in nitrate concentration in the medium, large quantities of triacylglycerols accumulated under batch culture conditions detected by thin layer chromatography and BODIPY 505/515 fluorescent staining. Scenedesmus sp. NJ-1 achieved the average biomass productivity of 0.105 g l⁻¹ d⁻¹ (dry weight) and nearly the highest lipid content (35 % of dry cell weight) was reached at day 28 in the batch culture. Neutral lipids accounted for 78 % of total lipids, and C18:1 (n-9), C16:0 were the major fatty acids in total lipids, composing 37 and 20 % of total fatty acids of Scenedesmus sp. NJ-1 grown for 36 days, respectively. These results suggested that Scenedesmus sp. NJ-1 was a good source of microalgal oils for biodiesel production.

  12. Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism.

    PubMed

    Delgado-Lista, Javier; Garcia-Rios, Antonio; Perez-Martinez, Pablo; Solivera, Juan; Yubero-Serrano, Elena M; Fuentes, Francisco; Parnell, Laurence D; Shen, Jian; Gomez, Purificacion; Jimenez-Gomez, Yolanda; Gomez-Luna, Maria J; Marin, Carmen; Belisle, Sarah E; Rodriguez-Cantalejo, Fernando; Meydani, Simin N; Ordovas, Jose M; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

    2011-05-01

    IL1b (IL1B or IL1β), a key modulator of the immune response, exerts its functions mainly via IL6 regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susceptibility. We evaluated the influence of a genetic variant located in the promoter region of IL1B (-1473G/C) on fasting and postprandial lipids and IL6. A total of 477 people over age 65 yr were genotyped for IL1B -1473G/C, and we evaluated fasting lipids depending on genotype. Then, 88 healthy young men were also genotyped and were fed a saturated fatty acid-rich meal. Serial blood samples were drawn for 11 h after the meal, and lipid fractions and IL6 were assayed. MAIN OUTCOME AND INTERVENTIONS: Fasting lipids were studied in the aged persons. Fasting and postprandial measurements of lipids and IL6 were performed in the healthy young men. In the aged persons, CC subjects (minor allele homozygotes) showed higher triglyceride (P = 0.002) and cholesterol (P = 0.011) levels. Healthy young male carriers of the minor C allele showed higher postprandial triglycerides (P = 0.037), and those carried into large triglyceride-rich lipoproteins (P = 0.004). In addition, they showed higher postprandial IL6 concentrations (P = 0.008). Our work shows that inflammatory genes may regulate fasting and postprandial lipids because the carriers of the minor allele of an IL gene variant have altered lipid metabolism. To reinforce these gene-phenotype findings, IL6 (the natural effector of IL1B) was increased in these persons.

  13. The significance of nitrogen limited condition in the initiation of lipid biosynthesis in Aurantiochytrium sp. SW1

    NASA Astrophysics Data System (ADS)

    Haladu, Zangoma Maryam; Ibrahim, Izyanti; Hamid, Aidil Abdul

    2018-04-01

    The manner of the onset of lipid synthesis in Aurantiochytrium sp. SW1 as well as the possible role of NAD+ dependent isocitrate dehydrogenase (NAD+: ICDH) in the initiation of lipid biosynthesis were studied. The initiation of lipid synthesis in the microalgae was not associated with the cessation of growth, but commence at the early phase of growth. Substantial amount of lipid (30 %, g/g biomass) was accumulated during the active growth phase at 48 h with growth rate decreasing from 0.11 g/L/h during active growth to 0.02 g/L/h in the limited growth phase. At that period the activity of NAD+: ICDH was still detectable although it slightly decreased to 20 nmol/min/mg in 48 h from 25 nmol/min/mg at 24 h. Analysis of ammonium sulfate fractionated of NAD+: ICDH activity showed that NAD+: ICDH was not completely dependent on adenosine monophosphate (AMP) for its activity, although the presence of AMP increased the enzyme's affinity towards its substrate (isocitrate) indicated by the low Km value of the enzyme for isocitrate. While citrate acts as inhibitor of the enzyme only at high concentration. The probable implications of these properties to the regulation of lipid are discussed.

  14. Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway

    PubMed Central

    Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M.

    2016-01-01

    Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122

  15. Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway.

    PubMed

    Wei, Shengnan; Zhang, Ming; Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M

    2016-01-01

    Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122

  16. Determining median urinary iodine concentration that indicates adequate iodine intake at population level.

    PubMed Central

    Delange, François; de Benoist, Bruno; Burgi, Hans

    2002-01-01

    OBJECTIVE: Urinary iodine concentration is the prime indicator of nutritional iodine status and is used to evaluate population-based iodine supplementation. In 1994, WHO, UNICEF and ICCIDD recommended median urinary iodine concentrations for populations of 100- 200 micro g/l, assuming the 100 micro g/l threshold would limit concentrations <50 micro g/l to g/l. The study was carried out to determine the frequency distribution of urinary iodine in iodine-replete populations (schoolchildren and adults) and the proportion of concentrations <50 micro g/l. METHOD: A questionnaire on frequency distribution of urinary iodine in iodine-replete populations was circulated to 29 scientific groups. FINDINGS: Nineteen groups reported data from 48 populations with median urinary iodine concentrations >100 micro g/l. The total population was 55 892, including 35 661 (64%) schoolchildren. Median urinary iodine concentrations were 111-540 (median 201) micro g/l for all populations, 100-199 micro g/l in 23 (48%) populations and >/=200 micro g/l in 25 (52%). The frequencies of values <50 micro g/l were 0-20.8 (mean 4.8%) overall and 7.2% and 2.5% in populations with medians of 100-199 micro g/l and >200 micro g/l, respectively. The frequency reached 20% only in two places where iodine had been supplemented for <2 years. CONCLUSION: The frequency of urinary iodine concentrations <50 micro g/l in populations with median urinary iodine concentrations >/=100 micro g/l has been overestimated. The threshold of 100 micro g/l does not need to be increased. In populations, median urinary iodine concentrations of 100-200 micro g/l indicate adequate iodine intake and optimal iodine nutrition. PMID:12219154

  17. Alteration of lipid status and lipid metabolism, induction of oxidative stress and lipid peroxidation by 2,4-dichlorophenoxyacetic herbicide in rat liver.

    PubMed

    Tayeb, Wafa; Nakbi, Amel; Cheraief, Imed; Miled, Abdelhedi; Hammami, Mohamed

    2013-07-01

    This study aims to investigate the effects of the 2,4-dichlorophenoxyacetic herbicide (2,4-D) on plasma lipids, lipoproteins concentrations, hepatic lipid peroxidation, fatty acid composition and antioxidant enzyme activities in rats. Animals were randomly divided into four groups of 10 each: control group and three 2,4-D-treated groups G1, G2 and G3 were administered 15, 75 and 150 mg/kg/BW/d 2,4-D by gavage for 28 d, respectively. Results showed that 2,4-D caused significant negative changes in the biochemical parameters investigated. The malondialdehyde level was significantly increased in 2,4-D-treated groups. Fatty acid composition of the liver was also significantly changed with 2,4-D exposure. Furthermore, the hepatic antioxidant enzyme activities were significantly affected. Finally, 2,4-D at the studied doses modifies lipidic status, disrupt lipid metabolism and induce hepatic oxidative stress. In conclusion, at higher doses, 2,4-D may play an important role in the development of vascular disease via metabolic disorder of lipoproteins, lipid peroxidation and oxidative stress.

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

    PubMed

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

    2018-01-01

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

  19. Lipids and buoyancy in Southern ocean pteropods.

    PubMed

    Phleger, C F; Nichols, P D; Virtue, P

    1997-10-01

    The lipids of Clione limacina, a Southern Ocean pteropod (order Gymnosomata), contain 28% diacylglyceryl ether (DAGE) (as percentage of total lipid) whereas the pteropod Limacina helicina (order Thecosomata) lacks DAGE. The alkyl glyceryl ether diols (1-O-alkyl glycerols, GE) of Clione DAGE are dominated by 16:0 (60%) and 15:0 (21%), in contrast with deep-sea shark liver DAGE, which is dominated by 18:1 GE. The fatty acid profiles of Clione and Limacina are similar (28-32% polyunsaturated, 26-34% monounsaturated) as are the sterols, which include 24-methylenecholesterol, transdehydrocholesterol, cholesterol, and desmosterol. This finding probably reflects the fact that Limacina is the major food source for Clione. Spongiobranchaea australis, another Southern Ocean pteropod (order Gymnosomata), has 0.9-1.7% DAGE, but has less lipid (3.3-4.8 mg/g lipid, wet weight) than Clione (50.8 mg/g lipid, wet weight). We propose a buoyancy role for DAGE in Clione since Limacina has bubbles for flotation which Clione lack; DAGE provides 23% more uplift than triacylglycerol at a concentration of 1.025 g/mL seawater.

  20. Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level.

    PubMed

    Liu, Yu; Yang, Huarong; Song, Zhi; Gu, Shaojuan

    2014-12-01

    Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood. Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis. The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10 μM, 200 μM and 500 μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70 kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited. These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.

  1. Nociceptive and Histomorphometric Evaluation of Neural Mobilization in Experimental Injury of the Median Nerve

    PubMed Central

    Marcioli, Marieli Araujo Rossoni; Coradini, Josinéia Gresele; Kunz, Regina Inês; Ribeiro, Lucinéia de Fátima Chasko; Brancalhão, Rose Meire Costa; Bertolini, Gladson Ricardo Flor

    2013-01-01

    The carpal tunnel syndrome is the most common peripheral neuropathy in the upper limb, but its treatment with conservative therapies such as neural mobilization (NM) is still controversial. The aim of this study was to investigate the efficacy of the NM as treatment in a model of median nerve compression. 18 Wistar rats were subjected to compression of the median nerve in the right elbow proximal region. Were randomly divided into G1 (untreated), G2 (NM for 1 minute), and G3 (NM for 3 minutes). For treatment, the animals were anesthetized and the right forelimb received mobilization adapted to humans, on alternated days, from the 3rd to the 13th day postoperatively (PO), totaling six days of therapy. Nociception was assessed by withdrawal threshold, and after euthanasia histomorphometric analysis of the median nerve was performed. The nociceptive evaluation showed in G2 and G3 delay in return to baseline. Histomorphometric analysis showed no significant differences in the variables analyzed. It is concluded that the NM was not effective in reducing nociceptive sensation and did not alter the course of nerve regeneration. PMID:23935419

  2. Interleukin 1B Variant -1473G/C (rs1143623) Influences Triglyceride and Interleukin 6 Metabolism

    PubMed Central

    Delgado-Lista, Javier; Garcia-Rios, Antonio; Perez-Martinez, Pablo; Solivera, Juan; Yubero-Serrano, Elena M.; Fuentes, Francisco; Parnell, Laurence D.; Shen, Jian; Gomez, Purificacion; Jimenez-Gomez, Yolanda; Gomez-Luna, Maria J.; Marin, Carmen; Belisle, Sarah E.; Rodriguez-Cantalejo, Fernando; Meydani, Simin N.; Ordovas, Jose M.; Perez-Jimenez, Francisco

    2011-01-01

    Context: IL1b (IL1B or IL1β), a key modulator of the immune response, exerts its functions mainly via IL6 regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susceptibility. Objective: We evaluated the influence of a genetic variant located in the promoter region of IL1B (-1473G/C) on fasting and postprandial lipids and IL6. Design, Setting, and Participants: A total of 477 people over age 65 yr were genotyped for IL1B -1473G/C, and we evaluated fasting lipids depending on genotype. Then, 88 healthy young men were also genotyped and were fed a saturated fatty acid-rich meal. Serial blood samples were drawn for 11 h after the meal, and lipid fractions and IL6 were assayed. Main Outcome and Interventions: Fasting lipids were studied in the aged persons. Fasting and postprandial measurements of lipids and IL6 were performed in the healthy young men. Results: In the aged persons, CC subjects (minor allele homozygotes) showed higher triglyceride (P = 0.002) and cholesterol (P = 0.011) levels. Healthy young male carriers of the minor C allele showed higher postprandial triglycerides (P = 0.037), and those carried into large triglyceride-rich lipoproteins (P = 0.004). In addition, they showed higher postprandial IL6 concentrations (P = 0.008). Conclusions: Our work shows that inflammatory genes may regulate fasting and postprandial lipids because the carriers of the minor allele of an IL gene variant have altered lipid metabolism. To reinforce these gene-phenotype findings, IL6 (the natural effector of IL1B) was increased in these persons. PMID:21307135

  3. Brominated flame retardants and organochlorine pollutants in eggs of little owls (Athene noctua) from Belgium.

    PubMed

    Jaspers, Veerle; Covaci, Adrian; Maervoet, Johan; Dauwe, Tom; Voorspoels, Stefan; Schepens, Paul; Eens, Marcel

    2005-07-01

    Residues of brominated diphenylethers (PBDEs), organochlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 40 eggs of little owls (Athene noctua), a terrestrial top predator from Belgium. The major organohalogens detected were PCBs (median 2,600 ng/g lipid, range 790-23 000 ng/g lipid). PCB 153,138/163, 170, 180 and 187 were the predominant congeners and constituted 71% of total sum PCBs. PBDEs were measurable in all samples, but their concentrations were much lower than for PCBs, with a range from 29-572 ng/g lipid (median 108 ng/g lipid). The most prevalent PBDE congeners in little owl egg samples were BDE 47, 99 and 153. This profile differs from the profile in marine bird species, for which BDE 47 was the dominant congener, indicating that terrestrial birds may be more exposed to higher brominated BDE congeners than marine birds. The fully brominated BDE 209 could be detected in one egg sample (17 ng/g lipid), suggesting that higher brominated BDEs may accumulate in terrestrial food chains. Brominated biphenyl (BB) 153 was determined in all egg samples, with levels ranging from 0.6 to 5.6 ng/g lipid (median 1.3 ng/g lipid). Additionally, hexabromocyclododecane (HBCD) could be identified and quantified in only two eggs at levels of 20 and 50 ng/g lipid. OCPs were present at low concentrations, suggesting a rather low contamination of the sampled environment with OCPs (median concentrations of sum DDTs: 826 ng/g lipid, sum chlordanes: 1,016 ng/g lipid, sum HCHs: 273 ng/g lipid). Hexachlorobenzene (HCB) and octachlorostyrene (OCS) were also found at low median levels of 134 and 3.4 ng/g lipid, respectively. Concentrations of most analytes were significantly higher in eggs collected from deserted nests in comparison to addled (unhatched) eggs, while eggshell thickness did not differ between deserted and addled eggs. No significant correlations were found between eggshell thickness and the analysed organohalogens.

  4. Lipid composition of some commonly consumed traditional Nigerian dishes.

    PubMed

    Onabanjo, O O; Sanni, S A; Afolabi, W A O; Oyawoye, O O; Obanla, O O

    2014-08-01

    Lipids in the diet have been associated with the rising prevalence of many chronic diseases. The present study aimed to provide information on total lipid, free fatty acids, triacylglycerol and cholesterol contents of some dishes consumed in northern, southern, western parts of Nigeria, as well as dishes generally consumed in all parts of Nigeria. This would result in a resource that would be used by nutritionists and dietitians in meal planning. The present study is analytical in nature. The composite dishes included a blend of cereals, roots and tubers, legumes, fat and oil and vegetables and were analysed for total lipid, free fatty acids, triacylglycerol and cholesterol contents spectrophotometrically. Burabisko (a millet based dish) had the lowest free fatty acid (0.1 mg per 100 g) and cholesterol (1. 9 mg per 100 g) contents, yam with eggs (7.1 mg per 100 g) and miyan-kuka with semovita (415.9 mg per 100 g) contained the highest amounts of free fatty acid and cholesterol, respectively. The total lipid and triacylglycerol content were lowest in gbegiri with eko (2.6 g per 100 g) and 3.1 mg per 100 g respectively. Stewed beans with fried plantain, however, had the highest total lipid (86.5 g per 100 g) content and yam with eggs had the highest triacylglycerol (122.5 mg per 100 g) contents. The moisture content of the dishes ranged between 59.68 and 81.73% in melon seed with vegetable soup and burabisko, respectively. For the first time, we have provided the lipid profile of standardised traditional dishes consumed in Nigeria. These dishes contribute a significant proportion of lipids to the diet of Nigerians, which are essential for assessing the nutrient intake of Nigerians. © 2013 The British Dietetic Association Ltd.

  5. Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity

    PubMed Central

    Maples, Jill M.; Brault, Jeffrey J.; Witczak, Carol A.; Park, Sanghee; Hubal, Monica J.; Weber, Todd M.; Houmard, Joseph A.

    2015-01-01

    The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity. PMID:26058865

  6. Energy conversion analysis of microalgal lipid production under different culture modes.

    PubMed

    Ren, Hong-Yu; Liu, Bing-Feng; Kong, Fanying; Zhao, Lei; Xie, Guo-Jun; Ren, Nan-Qi

    2014-08-01

    Growth and lipid production performance of Scenedesmus sp. under different culture modes were investigated. Under heterotrophic aerobic mode, algal biomass concentration and total lipid content reached 3.42 g L(-1) and 43.0 wt.%, which were much higher than those in autotrophic aerobic mode (0.55 g L(-1)/20.2 wt.%). The applied light exposure of 7.0 Wm(-2) was beneficial to biomass and lipid accumulation. Mixotrophic aerobic mode produced the highest biomass concentration of 3.84 g L(-1). The biomass was rich in lipids (51.3 wt.%) and low in proteins (17.9 wt.%) and carbohydrates (10.3 wt.%). However, lower algal biomass concentration (2.93 g L(-1)) and total lipid content (36.1 wt.%) were obtained in mixotrophic anaerobic mode. Mixotrophic aerobic mode gave the maximum heat value conversion efficiency of 45.7%. These results indicate that mixotrophic aerobic cultivation was a promising culture mode for lipid production by Scenedesmus sp. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Prevalence of Abnormal Lipid Profiles and the Relationship With the Development of Microalbuminuria in Adolescents With Type 1 Diabetes

    PubMed Central

    Marcovecchio, M. Loredana; Dalton, R. Neil; Prevost, A. Toby; Acerini, Carlo L.; Barrett, Timothy G.; Cooper, Jason D.; Edge, Julie; Neil, Andrew; Shield, Julian; Widmer, Barry; Todd, John A.; Dunger, David B.

    2009-01-01

    OBJECTIVE To explore the prevalence of lipid abnormalities and their relationship with albumin excretion and microalbuminuria in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS The study population comprised 895 young subjects with type 1 diabetes (490 males); median age at the baseline assessment was 14.5 years (range 10–21.1), and median diabetes duration was 4.8 years (0.2–17). A total of 2,194 nonfasting blood samples were collected longitudinally for determination of total cholesterol, LDL cholesterol, HDL cholesterol, TG, and non-HDL cholesterol. Additional annually collected data on anthropometric parameters, A1C, and albumin-to-creatinine ratio (ACR) were available. RESULTS Total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol were higher in females than in males (all P < 0.001). A significant proportion of subjects presented sustained lipid abnormalities during follow-up: total cholesterol >5.2 mmol/l (18.6%), non-HDL cholesterol >3.4 mmol/l (25.9%), TG >1.7 mmol/l (20.1%), and LDL cholesterol >3.4 mmol/l (9.6%). Age and duration were significantly related to all lipid parameters (P < 0.001); A1C was independently related to all parameters (P < 0.001) except HDL cholesterol, whereas BMI SD scores were related to all parameters (P < 0.05) except total cholesterol. Total cholesterol and non-HDL cholesterol were independently related to longitudinal changes in ACR (B coefficient ± SE): 0.03 ± 0.01/1 mmol/l, P = 0.009, and 0.32 ± 0.014/1 mmol/l, P = 0.02, respectively. Overall mean total cholesterol and non-HDL cholesterol were higher in microalbuminuria positive (n = 115) than in normoalbuminuric subjects (n = 780): total cholesterol 4.7 ± 1.2 vs. 4.5 ± 0.8 mmol/l (P = 0.04) and non-HDL cholesterol 3.2 ± 1.2 vs. 2.9 ± 0.8 mmol/l (P = 0.03). CONCLUSIONS In this longitudinal study of adolescents with type 1 diabetes, sustained lipid abnormalities were related to age, duration, BMI, and A1C. Furthermore, ACR was

  8. Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and coagulation factor VII Arg353-->Gln polymorphism in Korean patients with coronary artery disease.

    PubMed Central

    Song, J.; Yoon, Y. M.; Jung, H. J.; Hong, S. H.; Park, H.; Kim, J. Q.

    2000-01-01

    An increased risk for arterial thrombosis is associated with high plasma levels of coagulation and fibrinolytic factors such as PAI-1 and FVII. In this study, the 4G/5G polymorphism in the promoter of PAI-1 gene and Arg353-->Gln polymorphism in the FVII gene were analysed in 139 normal adults and 158 patients with coronary artery disease (CAD), and their association with plasma lipid traits was investigated. There were no significant differences in the allele frequencies of PAI-1 and FVII polymorphisms between control and patient groups. The allelic distributions of both polymorphisms in Koreans were similar to those in Japanese but significantly different from those in Caucasians. In the CAD group, the 4G homozygotes of PAI-1 polymorphism showed significantly higher levels of total (p=0.0250) and LDL cholesterol (p=0.0335) with individuals having other genotypes. However, FVII polymorphism showed no association with lipid levels. In conclusion, the 4G/5G PAI-1 promoter polymorphism and Arg353-->Gln FVII polymorphism are not major genetic risk factors for CAD in Koreans. However, 4G allele of PAI-1 polymorphism revealed to be associated with the levels of cholesterol, especially LDL cholesterol levels in CAD patients. PMID:10803689

  9. A comparison of freeway median crash frequency, severity, and barrier strike outcomes by median barrier type.

    PubMed

    Russo, Brendan J; Savolainen, Peter T

    2018-08-01

    Median-crossover crashes are among the most hazardous events that can occur on freeways, often resulting in severe or fatal injuries. The primary countermeasure to reduce the occurrence of such crashes is the installation of a median barrier. When installation of a median barrier is warranted, transportation agencies are faced with the decision among various alternatives including concrete barriers, beam guardrail, or high-tension cable barriers. Each barrier type differs in terms of its deflection characteristics upon impact, the required installation and maintenance costs, and the roadway characteristics (e.g., median width) where installation would be feasible. This study involved an investigation of barrier performance through an in-depth analysis of crash frequency and severity data from freeway segments where high-tension cable, thrie-beam, and concrete median barriers were installed. A comprehensive manual review of crash reports was conducted to identify crashes in which a vehicle left the roadway and encroached into the median. This review also involved an examination of crash outcomes when a barrier strike occurred, which included vehicle containment, penetration, or re-direction onto the travel lanes. The manual review of crash reports provided critical supplementary information through narratives and diagrams not normally available through standard fields on police crash report forms. Statistical models were estimated to identify factors that affect the frequency, severity, and outcomes of median-related crashes, with particular emphases on differences between segments with varying median barrier types. Several roadway-, traffic-, and environmental-related characteristics were found to affect these metrics, with results varying across the different barrier types. The results of this study provide transportation agencies with important guidance as to the in-service performance of various types of median barrier. Copyright © 2018 Elsevier Ltd. All rights

  10. Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles.

    PubMed

    Mui, B; Raney, S G; Semple, S C; Hope, M J

    2001-09-01

    The therapeutic benefit from phosphorothioate oligodeoxynucleotides (PS ODN) containing immune stimulatory sequences (ISS) has been demonstrated in animal models of cancer and infection. In particular, when CpG-containing PS ODN are administered to mice, activation of macrophages and dendritic, NK, T, and B cells occurs, resulting in the release of an array of cytokines, including interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We have previously described stabilized antisense-lipid particles (SALP) for the i.v. administration of antisense ODN [Biochim Biophys Acta (2001) 1510:152--166]. Given the propensity for SALP to target macrophages in vivo it was of interest to determine whether they could enhance the potency of CpG ODN to induce an immune response. In this report we show that when CpG-containing SALP are administered intravenously to ICR mice the plasma concentrations of IL-12, IFN-gamma, IL-6, monocyte chemoattractant protein-1, and TNF-alpha are greatly increased compared with the same dose of free ODN. The pattern of cytokine induction indicates that the immune response is T helper cell type 1-biased, similar to that observed for PS CpG ODN ISS in general. Furthermore, when phosphodiester (PO) ODN is substituted for PS ODN in the SALP formulation cytokine induction is even greater at the early time points, in marked contrast to free PO ODN, which is inactive. These results demonstrate that the immunogenicity of ISS is not only enhanced by encapsulation in lipid particles, which more closely mimic the way ISS DNA would normally be presented to antigen presenting cells by pathogens in vivo, but also SALP enable unmodified PO CpG ODN to be used as immune stimulants.

  11. Enzymatic production of biodiesel from Nannochloropsis gaditana lipids: Influence of operational variables and polar lipid content.

    PubMed

    Navarro López, Elvira; Robles Medina, Alfonso; González Moreno, Pedro A; Jiménez Callejón, María J; Esteban Cerdán, Luis; Martín Valverde, Lorena; Castillo López, Beatriz; Molina Grima, Emilio

    2015-01-01

    Fatty acid methyl esters (FAMEs, biodiesel) were produced from Nannochloropsis gaditana wet biomass (12% saponifiable lipids, SLs) by extraction of SLs and lipase catalyzed transesterification. Lipids were extracted by ethanol (96%)-hexane, and 31% pure SLs were obtained with 85% yield. When the lipids were degummed, SL purity increased to 95%. Novozym 435 was selected from four lipases tested. Both the lipidic composition and the use of t-butanol instead of hexane increased the reaction velocity and the conversion, since both decreased due to the adsorption of polar lipids on the lipase immobilization support. The best FAME yield (94.7%) was attained at a reaction time of 48h and using 10mL of t-butanol/g SL, 0.225gN435/g SL, 11:1 methanol/SL molar ratio and adding the methanol in three steps. In these conditions the FAME conversion decreased by 9.8% after three reaction cycles catalyzed by the same lipase batch. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Nuclear Receptors, Mitochondria, and Lipid Metabolism

    PubMed Central

    Alaynick, William A.

    2009-01-01

    Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome proliferator activated receptors (PPARs) and Liver X receptors (LXRs), acting in concert with PPARγ Coactivator 1α (PGC-1α), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia, and obesity). Recently, additional partners of PGC-1α have moved to the forefront of metabolic research, the Estrogen-related Receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function. PMID:18375192

  13. Effects of dietary lipid sources on performance and apparent total tract digestibility of lipids and energy when fed to nursery pigs.

    PubMed

    Mendoza, S M; van Heugten, E

    2014-02-01

    Acidulated fats and oils are by-products of the fat-refining industry. They contain high levels of FFA and are 10% to 20% less expensive than refined fats and oils. Two studies were designed to measure the effects of dietary lipid sources low or high in FFA on growth performance and apparent total tract digestibility (ATTD) of lipids and GE in nursery pigs. In Exp. 1, 189 pigs at 14 d postweaning (BW of 9.32 ± 0.11 kg) were used for 21 d with 9 replicate pens per treatment and 3 pigs per pen. Dietary treatments consisted of a control diet without added lipids and 6 diets with 6% inclusion of lipids. Four lipid sources were combined to create the dietary treatments with 2 levels of FFA (0.40% or 54.0%) and 3 degrees of fat saturation (iodine value [IV] = 77, 100, or 123) in a 2 × 3 factorial arrangement. Lipid sources were soybean oil (0.3% FFA and IV = 129.4), soybean-cottonseed acid oil blend (70.5% FFA and IV = 112.9), choice white grease (0.6% FFA and IV = 74.8), and choice white acid grease (56.0% FFA and IV = 79.0). Addition of lipid sources decreased ADFI (810 vs. 872 g/d; P = 0.018) and improved G:F (716 vs. 646 g/kg; P < 0.001). Diets high in FFA tended (P = 0.08) to improve final BW (21.35 vs. 21.01 kg) and ADG (576 vs. 560 g/d). Lipid-supplemented diets had greater ATTD of lipids than control diets (67.4% vs. 29.7%; P < 0.001). Apparent total tract digestibility of lipids was greater in diets with low FFA (69.9% vs. 64.9%; P < 0.001) and decreased linearly with increasing IV (73.2%, 69.1%, and 67.2%). For GE, ATTD was greater in diets with low FFA (83.1% vs. 80.9%; P = 0.001). In Exp. 2, 252 pigs at 7 d postweaning (BW of 7.0 ± 0.2 kg) were used for 28 d with 9 replicate pens per treatment and 4 pigs per pen. Diets included a control diet without added lipids and 6 treatments with 2.5%, 5.0%, or 7.5% of lipids from either poultry fat (1.9% FFA) or acidulated poultry fat (37.8% FFA) in a 2 × 3 factorial arrangement. Addition of lipids increased (P < 0

  14. Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-1-dependent signaling.

    PubMed

    Fisher, Kevin E; Pop, Andreia; Koh, Wonshill; Anthis, Nicholas J; Saunders, W Brian; Davis, George E

    2006-12-08

    Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive lipid signaling molecules implicated in tumor dissemination. Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-tethered collagenase thought to be involved in tumor invasion via extracellular matrix degradation. In this study, we investigated the molecular requirements for LPA- and S1P-regulated tumor cell migration in two dimensions (2D) and invasion of three-dimensional (3D) collagen matrices and, in particular, evaluated the role of MT1-MMP in this process. LPA stimulated while S1P inhibited migration of most tumor lines in Boyden chamber assays. Conversely, HT1080 fibrosarcoma cells migrated in response to both lipids. HT1080 cells also markedly invaded 3D collagen matrices (approximatly 700 microm over 48 hours) in response to either lipid. siRNA targeting of LPA1 and Rac1, or S1P1, Rac1, and Cdc42 specifically inhibited LPA- or S1P-induced HT1080 invasion, respectively. Analysis of LPA-induced HT1080 motility on 2D substrates vs. 3D matrices revealed that synthetic MMP inhibitors markedly reduced the distance (approximately 125 microm vs. approximately 45 microm) and velocity of invasion (approximately 0.09 microm/min vs. approximately 0.03 microm/min) only when cells navigated 3D matrices signifying a role for MMPs exclusively in invasion. Additionally, tissue inhibitors of metalloproteinases (TIMPs)-2, -3, and -4, but not TIMP-1, blocked lipid agonist-induced invasion indicating a role for membrane-type (MT)-MMPs. Furthermore, MT1-MMP expression in several tumor lines directly correlated with LPA-induced invasion. HEK293s, which neither express MT1-MMP nor invade in the presence of LPA, were transfected with MT1-MMP cDNA, and subsequently invaded in response to LPA. When HT1080 cells were seeded on top of or within collagen matrices, siRNA targeting of MT1-MMP, but not other MMPs, inhibited lipid agonist-induced invasion establishing a requisite role for MT1-MMP in

  15. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1.

    PubMed

    Joyal, Jean-Sébastien; Sun, Ye; Gantner, Marin L; Shao, Zhuo; Evans, Lucy P; Saba, Nicholas; Fredrick, Thomas; Burnim, Samuel; Kim, Jin Sung; Patel, Gauri; Juan, Aimee M; Hurst, Christian G; Hatton, Colman J; Cui, Zhenghao; Pierce, Kerry A; Bherer, Patrick; Aguilar, Edith; Powner, Michael B; Vevis, Kristis; Boisvert, Michel; Fu, Zhongjie; Levy, Emile; Fruttiger, Marcus; Packard, Alan; Rezende, Flavio A; Maranda, Bruno; Sapieha, Przemyslaw; Chen, Jing; Friedlander, Martin; Clish, Clary B; Smith, Lois E H

    2016-04-01

    Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine. Current dogma suggests that high-energy-consuming photoreceptors depend on glucose. Here we show that the retina also uses fatty acid β-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid. In the retinas of Vldlr(-/-) mice with low fatty acid uptake but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate α-ketoglutarate (α-KG). Low α-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlr(-/-) photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlr(-/-) retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD), which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases.

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

    PubMed

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

    2016-03-01

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

  17. Median barrier crash severity: some new insights.

    PubMed

    Hu, Wen; Donnell, Eric T

    2010-11-01

    Median barrier is used to prevent cross-median crashes on divided highways. Although it is well documented that crash frequencies increase after installing median barrier, little is known about median barrier crash severity outcomes. The present study estimated a nested logit model of median barrier crash severity using 5 years of data from rural divided highways in North Carolina. Vehicle, driver, roadway, and median cross-section design data were factors considered in the model. A unique aspect of the data used to estimate the model was the availability of median barrier placement and median cross-slope data, two elements not commonly included in roadway inventory data files. The estimation results indicate that collisions with a cable median barrier increase the probability of less-severe crash outcomes relative to collisions with a concrete or guardrail median barrier. Increasing the median barrier offset was associated with a lower probability of severe crash outcomes. The presence of a cable median barrier installed on foreslopes that were between 6H:1V and 10H:1V were associated with an increase in severe crash probabilities when compared to cable median barrier installations on foreslopes that were 10H:1V or flatter. 2010 Elsevier Ltd. All rights reserved.

  18. Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

    PubMed Central

    2011-01-01

    Background Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients. In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study. Results In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. Conclusions We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. PMID:22035022

  19. PPARα, PPARγ and SREBP-1 pathways mediated waterborne iron (Fe)-induced reduction in hepatic lipid deposition of javelin goby Synechogobius hasta.

    PubMed

    Chen, Guang-Hui; Luo, Zhi; Chen, Feng; Shi, Xi; Song, Yu-Feng; You, Wen-Jing; Liu, Xu

    2017-07-01

    The 42-day experiment was conducted to investigate the effects and mechanism of waterborne Fe exposure influencing hepatic lipid deposition in Synechogobius hasta. For that purpose, S. hasta were exposed to four Fe concentrations (0 (control), 0.36, 0.72 and 1.07μM Fe) for 42days. On days 21 and 42, morphological parameters, hepatic lipid deposition and Fe contents, and activities and mRNA levels of enzymes and genes related to lipid metabolism, including lipogenic enzymes (6PGD, G6PD, ME, ICDH, FAS and ACC) and lipolytic enzymes (CPTI, HSL), were analyzed. With the increase of Fe concentration, hepatic Fe content tended to increase but HSI and lipid content tended to decrease. On day 21, Fe exposure down-regulated the lipogenic activities of 6PGD, G6PD, ICDH and FAS as well as the mRNA levels of G6PD, ACCa, FAS, SREBP-1 and PPARγ, but up-regulated CPT I, HSLa and PPARα mRNA levels. On day 42, Fe exposure down-regulated the lipogenic activities of 6PGD, G6PD, ICDH and FAS as well as the mRNA levels of 6PGD, ACCa, FAS and SREBP-1, but up-regulated CPT I, HSLa, PPARα and PPARγ mRNA levels. Using primary S. hasta hepatocytes, specific pathway inhibitors (GW6471 for PPARα and fatostatin for SREBP-1) and activator (troglitazone for PPARγ) were used to explore the signaling pathways of Fe reducing lipid deposition. The GW6471 attenuated the Fe-induced down-regulation of mRNA levels of 6PGD, G6PD, ME, FAS and ACCa, and attenuated the Fe-induced up-regulation of mRNA levels of CPT I, HSLa and PPARα. Compared with single Fe-incubated group, the mRNA levels of G6PD, ME, FAS, ACCa, ACCb and PPARγ were up-regulated while the CPT I mRNA levels were down-regulated after troglitazone pre-treatment; fatostatin pre-treatment down-regulated the mRNA levels of 6PGD, ME, FAS, ACCa, ACCb and SREBP-1, and increased the CPT I and HSLa mRNA levels. Based on these results above, our study indicated that Fe exposure reduced hepatic lipid deposition by down-regulating lipogenesis

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

    PubMed

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

    2018-01-01

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

  1. Molecular characterization of Api g 2, a novel allergenic member of the lipid-transfer protein 1 family from celery stalks.

    PubMed

    Gadermaier, Gabriele; Egger, Matthias; Girbl, Tamara; Erler, Anja; Harrer, Andrea; Vejvar, Eva; Liso, Marina; Richter, Klaus; Zuidmeer, Laurian; Mari, Adriano; Ferreira, Fatima

    2011-04-01

    Celery represents a relevant cross-reactive food allergen source in the adult population. As the currently known allergens are not typical elicitors of severe symptoms, we aimed to identify and characterize a non-specific lipid transfer protein (nsLTP). MS and cDNA cloning were applied to obtain the full-length sequence of a novel allergenic nsLTP from celery stalks. The purified natural molecule consisted of a single isoallergen designated as Api g 2.0101, which was recombinantly produced in Escherichia coli Rosetta-gami. The natural and recombinant molecules displayed equivalent physicochemical and immunological properties. Circular dichroism revealed a typical α-helical fold and high thermal stability. Moreover, Api g 2 was highly resistant to simulated gastrointestinal digestion. As assessed by ELISA, thermal denaturation did not affect the IgE binding of Api g 2. Natural and recombinant Api g 2 showed similar allergenic activity in mediator release assays. Api g 2-specific IgE antibodies cross-reacted with peach and mugwort pollen nsLTPs. Based on our results, it can be anticipated that inclusion of recombinant Api g 2 in the current panel of allergens for molecule-based diagnosis will facilitate the evaluation of the clinical relevance of nsLTP sensitization in celery allergy and help clinicians in the management of food allergic patients. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Synthesis of neutral ether lipid monoalkyl-diacylglycerol by lipid acyltransferases[S

    PubMed Central

    Ma, Zhengping; Onorato, Joelle M.; Chen, Luping; Nelson, David W.; Yen, Chi-Liang Eric; Cheng, Dong

    2017-01-01

    In mammals, ether lipids exert a wide spectrum of signaling and structural functions, such as stimulation of immune responses, anti-tumor activities, and enhancement of sperm functions. Abnormal accumulation of monoalkyl-diacylglycerol (MADAG) was found in Wolman’s disease, a human genetic disorder defined by a deficiency in lysosomal acid lipase. In the current study, we found that among the nine recombinant human lipid acyltransferases examined, acyl-CoA:diacylglycerol acyltransferase (DGAT)1, DGAT2, acyl-CoA:monoacylglycerol acyltransferase (MGAT)2, MGAT3, acyl-CoA:wax-alcohol acyltransferase 2/MFAT, and DGAT candidate 3 were able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG). These enzymes demonstrated different enzymatic turnover rates and relative efficiencies for the first and second acylation steps leading to the synthesis of MAMAG and MADAG, respectively. They also exhibited different degrees of substrate preference when presented with 1-monooleoylglycerol versus 1-MAkG. In CHO-K1 cells, treatment with DGAT1 selective inhibitor, XP-620, completely blocked the synthesis of MADAG, indicating that DGAT1 is the predominant enzyme responsible for the intracellular synthesis of MADAG in this model system. The levels of MADAG in the adrenal gland of DGAT1 KO mice were reduced as compared with those of the WT mice, suggesting that DGAT1 is a major enzyme for the synthesis of MADAG in this tissue. Our findings indicate that several of these lipid acyltransferases may be able to synthesize neutral ether lipids in mammals. PMID:28420705

  3. The -675 4G/5G polymorphism at the Plasminogen Activator Inhibitor 1 (PAI-1) gene modulates plasma Plasminogen Activator Inhibitor 1 concentrations in response to dietary fat consumption.

    PubMed

    Pérez-Martínez, P; Adarraga-Cansino, M D; Fernández de la Puebla, R A; Blanco-Molina, A; Delgado-Lista, J; Marín, C; Ordovás, J M; López-Miranda, J; Pérez-Jiménez, F

    2008-04-01

    The objective of the study was to determine whether Plasminogen Activator Inhibitor Type 1 (PAI-1) -675 4G/5G polymorphism is associated with the response of functional plasma PAI-1 concentrations to changes in the amount and quality of dietary fat in healthy subjects. PAI-1 is the major inhibitor of fibrinolysis, and a lower level of fibrinolytic activity could be implicated in an increased risk of IHD. Fifty-nine healthy Spanish volunteers (ten 4G/4G homozygotes, twenty-eight heterozygotes 4G/5G and twenty-one 5G/5G homozygotes) consumed three diets for periods of 4 weeks each: a SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate-rich diet (30 % fat, 55 % carbohydrate) and a MUFA-rich diet (38 % fat, 22 % MUFA) according to a randomized crossover design. At the end of each dietary period plasma lipid and functional plasma PAI-1 concentrations were determined. Subjects carrying the 4G allele (4G/4G and 4G/5G) showed a significant decrease in PAI-1 concentrations after the MUFA diet, compared with the SFA-rich and carbohydrate-rich diets (genotype x diet interaction: P = 0.028). 5G/5G homozygotes had the lowest plasma PAI-1 concentrations compared with 4G/4G and 4G/5G subjects (genotype: P = 0.002), without any changes as a result of the amount and the quality of the dietary fat. In summary, no differences in plasma PAI-1 concentration response were found after changes in dietary fat intake in 5G/5G homozygotes, although these subjects displayed the lowest concentrations of PAI-1. On the other hand, carriers of the 4G allele are more likely to hyper-respond to the presence of MUFA in the diet because of a greater decrease in PAI-1 concentrations.

  4. Neoglycolipid analogues of ganglioside G sub M1 as functional receptors of cholera toxin

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

    Pacuszka, T.; Bradley, R.M.; Fishman, P.H.

    1991-03-12

    The authors synthesized several lipid analogues of ganglioside G{sub M1} by attaching its oligosaccharide moiety (G{sub M1}OS) to aminophospholipids, aliphatic amines, and cholesteryl hemisuccinate. They incubated G{sub M1}-deficient rat glioma C6 cells with each of the derivatives as well as native G{sub M1} and assayed the cells for their ability to bind and respond to cholera toxin. On the basis of the observed increase in binding of {sup 125}I-labeled cholera toxin, it was apparent that the cells took up and initially incorporated most of the derivatives into the plasma membrane. In the case of the aliphatic amine derivatives, the abilitymore » to generate new toxin binding sites was dependent on chain length; whereas the C{sub 10} derivative was ineffective, C{sub 12} and higher analogues were effective. Increased binding was dependent on both the concentration of the neoglycolipid in the medium and the time of exposure. Cells pretreated with the various derivatives accumulated cyclic AMP in response to cholera toxin, but there were differences in their effectiveness. The cholesterol and long-chain aliphatic amine derivatives were more effective than native G{sub M1}, whereas the phospholipid derivatives were less effective. The distance between G{sub M1}OS and the phospholipid also appeared to influence its functional activity. The results indicate that although G{sub M1}OS provides the recognition site for the binding of cholera toxin, the nature of the lipid moiety plays an important role in the action of the toxin.« less

  5. Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

    PubMed

    Zheng, Yingjuan; Zhao, Chao; Zhang, Naijian; Kang, Wenqin; Lu, Rongrong; Wu, Huadong; Geng, Yingxue; Zhao, Yaping; Xu, Xiaoyan

    2018-04-01

    The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR‑206 and the role of miR‑206 on TH‑regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR‑206 on lipid metabolism. Expression of miR‑206 in serum and cells was determined by reverse transcription‑quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR‑206 was performed via transfection with a miR‑206 mimic or miR‑206 inhibitor. Serum miR‑206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR‑206 expression. Inhibition of endogenous miR‑206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR‑206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR‑206 expression is reduced in patients with hyperthyroidism. In addition, miR‑206 is involved in T3‑mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR‑206 in thyroid hormone‑induced disorders of lipid metabolism in the liver.

  6. Optimization of Culture Conditions for Enhanced Growth, Lipid and Docosahexaenoic Acid (DHA) Production of Aurantiochytrium SW1 by Response Surface Methodology.

    PubMed

    Nazir, Yusuf; Shuib, Shuwahida; Kalil, Mohd Sahaid; Song, Yuanda; Hamid, Aidil Abdul

    2018-06-11

    In this study, optimization of growth, lipid and DHA production of Aurantiochytrium SW1 was carried out using response surface methodology (RSM) in optimizing initial fructose concentration, agitation speed and monosodium glutamate (MSG) concentration. Central composite design was applied as the experimental design and analysis of variance (ANOVA) was used to analyze the data. ANOVA analysis revealed that the process which adequately represented by quadratic model was significant (p < 0.0001) for all the response. All the three factors were significant (p < 0.005) in influencing the biomass and lipid data while only two factors (agitation speed and MSG) gave significant effect on DHA production (p < 0.005). The estimated optimal conditions for enhanced growth, lipid and DHA production were 70 g/L fructose, 250 rpm agitation speed and 10 g/L MSG. Consequently, the quadratic model was validated by applying the estimated optimum conditions, which confirmed the model validity where 19.0 g/L biomass, 9.13 g/L lipid and 4.75 g/L of DHA were produced. The growth, lipid and DHA were 28, 36 and 35% respectively higher than that produced in the original medium prior to optimization.

  7. Targeting SREBP-1-driven lipid metabolism to treat cancer

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2009-01-01

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

  10. Molecular dynamics simulations of glyphosate in a DPPC lipid bilayer.

    PubMed

    Frigini, Ezequiel N; López Cascales, J J; Porasso, Rodolfo D

    2018-07-01

    Extensive molecular dynamics simulations have been performed to study the effect of glyphosate (in their neutral and charged forms, GLYP and GLYP 2- , respectively) on fully hydrated DiPalmitoylPhosphatidylCholine (DPPC) lipid bilayer. First, we calculated the free energy profile (using the Umbrella Sampling technique) for both states of charge of glyphosate. The minimum value for the free energy for GLYP is ∼-60 kJ mol -1 located at z = ±1.7 nm (from the lipid bilayer center), and there is almost no maximum at the center of the lipid bilayer. By contrast, the minimum for GLYP 2- is ∼-35 kJ mol -1 located at z = ± 1.4 nm (from the lipid bilayer center), and the maximum reaches ∼35 kJ mol -1 at the center of the lipid bilayer. Then, different lipid bilayer properties were analyzed for different glyphosate:lipid (G:L) ratios. The mean area per lipid was slightly affected, increasing only 5% (in the presence of glyphosate at high concentrations), which is in agreement with the slight decrease in deuterium order parameters. As for the thickness of the bilayer, it is observed that the state of charge produces opposite effects. On one hand, the neutral state produces an increase in the thickness of the lipid bilayer; on the other, the charged form produces a decrease in the thickness, which not depend linearly on the G:L ratios, either. The orientation of the DPPC head groups is practically unaffected throughout the range of the G:L ratios studied. Finally, the mobility of the lipids of the bilayer is strongly affected by the presence of glyphosate, considerably increasing its lateral diffusion coefficient noteworthy (one order of magnitude), with increasing G:L ratio. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Microbial conversion of synthetic and food waste-derived volatile fatty acids to lipids.

    PubMed

    Vajpeyi, Shashwat; Chandran, Kartik

    2015-01-01

    Lipid accumulation in the oleaginous yeast Cryptococcus albidus was evaluated using mixtures of volatile fatty acids (VFA) as substrates. In general, batch growth under nitrogen limitation led to higher lipid accumulation using synthetic VFA. During batch growth, an initial COD:N ratio of 25:1mg COD:mg N led to maximum intracellular lipid accumulation (28.3 ± 0.7% g/g dry cell weight), which is the maximum reported for C. albidus using VFA as the carbon source, without compromising growth kinetics. At this feed COD:N ratio, chemostat cultures fed with synthetic VFA yielded statistically similar intracellular lipid content as batch cultures (29.9 ± 1.9%, g/g). However, batch cultures fed with VFA produced from the fermentation of food waste, yielded a lower lipid content (14.9 ± 0.1%, g/g). The lipid composition obtained with synthetic and food-waste-derived VFA was similar to commercial biodiesel feedstock. We therefore demonstrate the feasibility of linking biochemical waste treatment and biofuel production using VFA as key intermediates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Very large database of lipids: rationale and design.

    PubMed

    Martin, Seth S; Blaha, Michael J; Toth, Peter P; Joshi, Parag H; McEvoy, John W; Ahmed, Haitham M; Elshazly, Mohamed B; Swiger, Kristopher J; Michos, Erin D; Kwiterovich, Peter O; Kulkarni, Krishnaji R; Chimera, Joseph; Cannon, Christopher P; Blumenthal, Roger S; Jones, Steven R

    2013-11-01

    Blood lipids have major cardiovascular and public health implications. Lipid-lowering drugs are prescribed based in part on categorization of patients into normal or abnormal lipid metabolism, yet relatively little emphasis has been placed on: (1) the accuracy of current lipid measures used in clinical practice, (2) the reliability of current categorizations of dyslipidemia states, and (3) the relationship of advanced lipid characterization to other cardiovascular disease biomarkers. To these ends, we developed the Very Large Database of Lipids (NCT01698489), an ongoing database protocol that harnesses deidentified data from the daily operations of a commercial lipid laboratory. The database includes individuals who were referred for clinical purposes for a Vertical Auto Profile (Atherotech Inc., Birmingham, AL), which directly measures cholesterol concentrations of low-density lipoprotein, very low-density lipoprotein, intermediate-density lipoprotein, high-density lipoprotein, their subclasses, and lipoprotein(a). Individual Very Large Database of Lipids studies, ranging from studies of measurement accuracy, to dyslipidemia categorization, to biomarker associations, to characterization of rare lipid disorders, are investigator-initiated and utilize peer-reviewed statistical analysis plans to address a priori hypotheses/aims. In the first database harvest (Very Large Database of Lipids 1.0) from 2009 to 2011, there were 1 340 614 adult and 10 294 pediatric patients; the adult sample had a median age of 59 years (interquartile range, 49-70 years) with even representation by sex. Lipid distributions closely matched those from the population-representative National Health and Nutrition Examination Survey. The second harvest of the database (Very Large Database of Lipids 2.0) is underway. Overall, the Very Large Database of Lipids database provides an opportunity for collaboration and new knowledge generation through careful examination of granular lipid data on

  13. Left-turn lanes at unsignalized median openings.

    DOT National Transportation Integrated Search

    2014-03-01

    Due to the frequent presence of median openings in urban arterial settings, the requirements for the deceleration and : storage of turning vehicles (e.g. AASHTO Green Book) often exceed the available length between two adjacent : openings which leave...

  14. Enhanced lipid accumulation of green microalga Scenedesmus sp. by metal ions and EDTA addition.

    PubMed

    Ren, Hong-Yu; Liu, Bing-Feng; Kong, Fanying; Zhao, Lei; Xie, Guo-Jun; Ren, Nan-Qi

    2014-10-01

    Effects of Fe(3+) (0-0.12 g/L), Mg(2+) (0-0.73 g/L) and Ca(2+) (0-0.98 g/L) on the biomass and lipid accumulation of heterotrophic microalgae were investigated in dark environment. The biomass and lipid production exhibited an increasing trend with increasing the concentrations of metal ions. In cultures with 1.2 × 10(-3) g/L Fe(3+), 7.3 × 10(-3) g/L Mg(2+) and 9.8 × 10(-4) g/L Ca(2+), the maximum biomass, total lipid content and lipid productivity reached 3.49 g/L, 47.4% and 275.7 mg/L/d, respectively. More importantly, EDTA addition (1.0 × 10(-3) g/L) could enhance the solubility of metal ions (iron and calcium) and increase their availability by microalgae, which evidently promote the lipid accumulation. Compared with the control, the total lipid content and lipid productivity increased 28.2% and 29.7%, respectively. These show that appropriate concentrations of metal ions and EDTA in the culture medium were beneficial to lipid accumulation of heterotrophic Scenedesmus sp. cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Switching non-local vector median filter

    NASA Astrophysics Data System (ADS)

    Matsuoka, Jyohei; Koga, Takanori; Suetake, Noriaki; Uchino, Eiji

    2016-04-01

    This paper describes a novel image filtering method that removes random-valued impulse noise superimposed on a natural color image. In impulse noise removal, it is essential to employ a switching-type filtering method, as used in the well-known switching median filter, to preserve the detail of an original image with good quality. In color image filtering, it is generally preferable to deal with the red (R), green (G), and blue (B) components of each pixel of a color image as elements of a vectorized signal, as in the well-known vector median filter, rather than as component-wise signals to prevent a color shift after filtering. By taking these fundamentals into consideration, we propose a switching-type vector median filter with non-local processing that mainly consists of a noise detector and a noise removal filter. Concretely, we propose a noise detector that proactively detects noise-corrupted pixels by focusing attention on the isolation tendencies of pixels of interest not in an input image but in difference images between RGB components. Furthermore, as the noise removal filter, we propose an extended version of the non-local median filter, we proposed previously for grayscale image processing, named the non-local vector median filter, which is designed for color image processing. The proposed method realizes a superior balance between the preservation of detail and impulse noise removal by proactive noise detection and non-local switching vector median filtering, respectively. The effectiveness and validity of the proposed method are verified in a series of experiments using natural color images.

  16. HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells.

    PubMed

    Wei, Shengnan; Zhang, Ming; Yu, Yang; Xue, Huan; Lan, Xiaoxin; Liu, Shuping; Hatch, Grant; Chen, Li

    2016-11-15

    Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells. CPT-1 and phosphorylated ACCα expression were significantly decreased in livers of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. In contrast, expression of miR-122, HNF-4α, PEPCK, G6Pase, SREBP-1, FAS-1 and ACCα were significantly elevated in liver of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. Expression of HNF-4α increased whereas siRNA knockdown of HNF-4α decreased miR-122 levels in HepG2 cells compared to controls. In addition, expression of HNF-4α in HepG2 cells increased PEPCK, G6Pase, SREBP-1, FAS-1, ACCα mRNA and protein expression and decreased CPT-1 and p-ACCα mRNA and protein expression compared to controls. Addition of miR-122 inhibitors attenuated the HNF-4α mediated effect on expression of these gluconeogenic and lipid metabolism proteins. The results indicate that HNF-4α regulated miR-122 contributes to development of the gluconeogenic and lipid metabolism alterations observed in Type 2 diabetic mice and in palmitate-treated HepG2 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Effect of tension and curvature on the chemical potential of lipids in lipid aggregates.

    PubMed

    Grafmüller, Andrea; Lipowsky, Reinhard; Knecht, Volker

    2013-01-21

    Understanding the factors that influence the free energy of lipids in bilayer membranes is an essential step toward understanding exchange processes of lipids between membranes. In general, both lipid composition and membrane geometry can affect lipid exchange rates between bilayer membranes. Here, the free energy change ΔG(des) for the desorption of dipalmitoyl-phosphatidylcholine (DPPC) lipids from different lipid aggregates has been computed using molecular dynamics simulations and umbrella sampling. The value of ΔG(des) is found to depend strongly on the local properties of the aggregate, in that both tension and curvature lead to an increase in ΔG(des). A detailed analysis shows that the increased desorption free energy for tense bilayers arises from the increased conformational entropy of the lipid tails, which reduces the favorable component -TΔS(L) of the desorption free energy.

  18. Investigation of biomass and lipids production with Neochloris oleoabundans in photobioreactor.

    PubMed

    Pruvost, J; Van Vooren, G; Cogne, G; Legrand, J

    2009-12-01

    The fresh water microalga Neochloris oleoabundans was investigated for its ability to accumulate lipids and especially triacylglycerols (TAG). A systematic study was conducted, from the determination of the growth medium to its characterization in an airlift photobioreactor. Without nutrient limitation, a maximal biomass areal productivity of 16.5 g m(-2) day(-1) was found. Effects of nitrogen starvation to induce lipids accumulation was next investigated. Due to initial N. oleoabundans total lipids high content (23% of dry weight), highest productivity was obtained without mineral limitation with a maximal total lipids productivity of 3.8 g m(-2) day(-1). Regarding TAG, an almost similar productivity was found whatever the protocol was: continuous production without mineral limitation (0.5 g m(-2) day(-1)) or batch production with either sudden or progressive nitrogen deprivation (0.7 g m(-2) day(-1)). The decrease in growth rate reduces the benefit of the important lipids and TAG accumulation as obtained in nitrogen starvation (37% and 18% of dry weight, respectively).

  19. Extract from Edible Red Seaweed (Gelidium amansii) Inhibits Lipid Accumulation and ROS Production during Differentiation in 3T3-L1 Cells.

    PubMed

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

    2012-06-01

    Gelidium (G.) amansii is a red alga widely distributed in the shallow waters around East Asian countries. We investigated the effect of G. amansii on lipid accumulation and ROS (Reactive Oxygen Species) production in 3T3-L1 cells. G. amansii extracts dose-dependently inhibited lipid formation and ROS generation in cultured cells. Our results showed that anti-adipogenic effect of G. amansii was due to the reduction in mRNA expressions of PPARγ peroxisome proliferator-activated receptor-γ and aP2 (adipocyte protein 2). G. amansii extracts significantly decreased mRNA levels of a ROS-generator, NOX4 (nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4), and increased the protein levels of antioxidant enzymes including SOD1/2 (superoxide dis-mutases), Gpx (glutathione peroxidase), and GR (glutathione reductase), which can lead to the reduction of ROS in the cell. In addition, the G. amansii extract enhanced mRNA levels of adiponectin, one of the adipokines secreted from adipocytes, and GLUT4, glucose uptake protein. Taken together, our study shows that G. amansii extract inhibited lipid accumulation and ROS production by controlling adipogenic signals and ROS regulating genes.

  20. Extract from Edible Red Seaweed (Gelidium amansii) Inhibits Lipid Accumulation and ROS Production during Differentiation in 3T3-L1 Cells

    PubMed Central

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

    2012-01-01

    Gelidium (G.) amansii is a red alga widely distributed in the shallow waters around East Asian countries. We investigated the effect of G. amansii on lipid accumulation and ROS (Reactive Oxygen Species) production in 3T3-L1 cells. G. amansii extracts dose-dependently inhibited lipid formation and ROS generation in cultured cells. Our results showed that anti-adipogenic effect of G. amansii was due to the reduction in mRNA expressions of PPARγ peroxisome proliferator-activated receptor-γ and aP2 (adipocyte protein 2). G. amansii extracts significantly decreased mRNA levels of a ROS-generator, NOX4 (nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4), and increased the protein levels of antioxidant enzymes including SOD1/2 (superoxide dis-mutases), Gpx (glutathione peroxidase), and GR (glutathione reductase), which can lead to the reduction of ROS in the cell. In addition, the G. amansii extract enhanced mRNA levels of adiponectin, one of the adipokines secreted from adipocytes, and GLUT4, glucose uptake protein. Taken together, our study shows that G. amansii extract inhibited lipid accumulation and ROS production by controlling adipogenic signals and ROS regulating genes. PMID:24471074

  1. Genetic Variations at ABCG5/G8 Genes Modulate Plasma Lipids Concentrations in Patients with Familial Hypercholesterolemia

    PubMed Central

    Garcia-Rios, A; Perez-Martinez, P; Fuentes, F; Mata, P; Lopez-Miranda, J; Alonso, R; Rodriguez, F; Garcia-Olid, A; Ruano, J; Ordovas, JM; Perez-Jimenez, F

    2010-01-01

    Objective To investigate the association of four common single nucleotide polymorphisms (SNPs) at ABCG5 (i7892A>G, i18429C>T, Gln604GluC>G, i11836G>A) and five at ABCG8 (5U145T>G, Tyr54CysA>G, Asp19HisG>C, i14222T>C, and Thr400LysG>T) with plasma lipids concentrations and to explore the interaction between those SNPs and smoking in patients with FH. Methods and Results ABCG5/G8 SNPs were genotyped in 500 subjects with genetic diagnosis of FH. Carriers of the minor A allele at the ABCG5_i11836G>A SNP displayed significantly higher HDL-C concentrations (P=0.023) than G/G subjects. In addition, carriers of the minor G allele at the ABCG5_Gln604GluC>G SNP had significantly lower VLDL-C (P=0.011) and lower TG (P=0.017) concentrations than homozygous C/C. Interestingly, a significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5 (i7892A>G, i18429C>T, i11836G>A) SNPs displayed significantly lower HDL-C, higher TC and higher TG respectively, only in smokers. On the other hand, non-smokers carriers of the minor alleles at ABCG5 (i18429C>T and Gln604GluC>G) SNPs had significantly lower TG concentrations (P=0.012 and P=0.035) compared with homozygous for the major allele. Conclusions Our data support the notion that ABCG5/G8 genetic variants modulate plasma lipids concentrations in patients with FH and confirm that this effect could be influenced by smoking. Therefore, these results suggest that gene-environmental interactions can affect the clinical phenotype of FH. PMID:20172523

  2. Individual and Combined Effects of Fumonisin B1, Deoxynivalenol and Zearalenone on the Hepatic and Renal Membrane Lipid Integrity of Rats

    PubMed Central

    Szabó-Fodor, Judit; Fébel, Hedvig; Mézes, Miklós; Balogh, Krisztián; Bázár, György; Kocsó, Dániel; Kovács, Melinda

    2017-01-01

    (1) Background and (2) Methods: A 14-day in vivo, multitoxic (pure mycotoxins) rat experiment was conducted with zearalenone (ZEA; 15 μg/animal/day), deoxynivalenol (DON; 30 μg/animal/day) and fumonisin B1 (FB1; 150 μg/animal/day), as individual mycotoxins, binary (FD, FZ and DZ) and ternary combinations (FDZ), via gavage in 1 mL water boluses. (3) Results: Body weight was unaffected, while liver (ZEA↑ vs. DON) and kidney weight (ZEA↑ vs. FDZ) increased. Hepatocellular membrane lipid fatty acids (FAs) referred to ceramide synthesis disturbance (C20:0, C22:0), and decreased unsaturation (C22:5 n3 and unsat. index), mainly induced by DON and to a lesser extent by ZEA. The DON-FB1 interaction was additive on C20:0 in liver lipids. In renal phospholipids, ZEA had the strongest effect on the FA profile, affecting the saturated (C18:0) and many n6 FAs; ZEA was in an antagonistic relationship with FB1 (C18:0) or DON (C18:2 n6, C20:1 n9). Hepatic oxidative stress was the most expressed in FD (reduced glutathione and glutathione peroxidase), while the nephrotoxic effect was further supported by lipid peroxidation (malondialdehyde) in the DON treatment. (4) Conclusions: In vivo study results refer to multiple mycotoxin interactions on membrane FAs, antioxidants and lipid peroxidation compounds, needing further testing. PMID:29271890

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

    PubMed Central

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

    2018-01-01

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

  4. Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

    PubMed

    Maki, K C; Geohas, J G; Dicklin, M R; Huebner, M; Udani, J K

    2015-08-01

    This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1.81 mmol/L). Compared to placebo, after eight weeks of treatment, PDL-0101 significantly reduced median TAG (-9.5% vs. 10.6%, p<0.001), while not significantly altering mean LDL-C (-3.0% vs. -8.0% for PDL-0101 and placebo, respectively, p=0.071), mean high-density lipoprotein cholesterol (~3% decrease in both groups, p=0.732), or median oxidized LDL concentrations (5% vs. -5% for PDL-0101 and placebo, respectively, p=0.112). These results demonstrate that PDL-0101 is an effective medical food for the management of elevated TAG. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia type 1

    PubMed Central

    Circelli, Luisa; Ramundo, Valeria; Marotta, Vincenzo; Sciammarella, Concetta; Marciello, Francesca; Del Prete, Michela; Sabatino, Lina; Pasquali, Daniela; Izzo, Francesco; Scala, Stefania; Colao, Annamaria; Faggiano, Antongiulio; Colantuoni, Vittorio

    2015-01-01

    CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype–phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1. PMID:25824098

  6. Identification of a New Class of Lipid Droplet-Associated Proteins in Plants1[C][W][OPEN

    PubMed Central

    Horn, Patrick J.; James, Christopher N.; Gidda, Satinder K.; Kilaru, Aruna; Dyer, John M.; Mullen, Robert T.; Ohlrogge, John B.; Chapman, Kent D.

    2013-01-01

    Lipid droplets in plants (also known as oil bodies, lipid bodies, or oleosomes) are well characterized in seeds, and oleosins, the major proteins associated with their surface, were shown to be important for stabilizing lipid droplets during seed desiccation and rehydration. However, lipid droplets occur in essentially all plant cell types, many of which may not require oleosin-mediated stabilization. The proteins associated with the surface of nonseed lipid droplets, which are likely to influence the formation, stability, and turnover of this compartment, remain to be elucidated. Here, we have combined lipidomic, proteomic, and transcriptomic studies of avocado (Persea americana) mesocarp to identify two new lipid droplet-associated proteins, which we named LDAP1 and LDAP2. These proteins are highly similar to each other and also to the small rubber particle proteins that accumulate in rubber-producing plants. An Arabidopsis (Arabidopsis thaliana) homolog to LDAP1 and LDAP2, At3g05500, was localized to the surface of lipid droplets after transient expression in tobacco (Nicotiana tabacum) cells that were induced to accumulate triacylglycerols. We propose that small rubber particle protein-like proteins are involved in the general process of binding and perhaps the stabilization of lipid-rich particles in the cytosol of plant cells and that the avocado and Arabidopsis protein members reveal a new aspect of the cellular machinery that is involved in the packaging of triacylglycerols in plant tissues. PMID:23821652

  7. Evaluation of the relation between lipid coat, transepidermal water loss, and skin pH.

    PubMed

    Algiert-Zielińska, Barbara; Batory, Mirella; Skubalski, Janusz; Rotsztejn, Helena

    2017-11-01

    The epidermis is an epidermal barrier which accumulates lipid substances and participates in skin moisturizing. An evaluation of the epidermal barrier efficiency can be made, among others, by the measurement of the following values: the lipid coat, the transepidermal water loss (TEWL) index, and pH. The study involved 50 Caucasian, healthy women aged 19-35 years (mean 20.56). Measurements were made using Courage & Khazaka Multi Probe Adapter MPA 580: Tewameter TM 300, pH-Meter PH 905, Sebumeter SM 815. The areas of measurements included forehead, nose, left cheek, right cheek, chin, and thigh. In the T-zone, the lipid coat was in the range between 0 and 270 μg/cm 2 (mean 128 μg/cm 2 ), TEWL between 1 and 55 g/m 2 /h (mean 11.1 g/m 2 /h), and pH 4.0-5.6 (mean 5.39). Lower values of the lipid coat up to 100 μg/cm 2 were accompanied by TEWL greater than 30 g/m 2 /h and less acidic pH of 5.6-9.0. In the U-zone the range of lipid coat was up to 200 μg/cm 2 (mean 65.2 μg/cm 2 ), the skin pH remained 4.0-5.6 (mean 5.47), and TEWL was in the range between 1 and 20 g/m 2 /h (mean 8.7 g/m 2 /h). Lower values of the lipid coat up to 100 μg/cm 2 were accompanied by TEWL between 1 and 20 g/m 2 /h and less acidic pH of 5.6-9.0. High values of the lipid coat between 180 and 200 μg/cm 2 were connected with TEWL of 1-15 g/m 2 /h. On the skin of the thigh, we observed a very thin lipid coat - 35 μg/cm 2 (mean 5.6 μg/cm 2 ), pH (mean 5.37), and TEWL (mean 8.5 g/m 2 /h) were considered by us to be within regular limits. In the T-zone, a thinner lipid coat resulted in relatively high TEWL and pH levels changing toward alkaline. In the U-zone, thinner lipid coat was accompanied by lower TEWL and pH changing toward alkaline. We also observed that lower values of lipid coat up to 100 μg/cm 2 were associated with higher pH values ranging toward the basic character pH 5.6-9.0). © 2017 The International Society of Dermatology.

  8. Kinetic modelling of starch and lipid formation during mixotrophic, nutrient-limited microalgal growth.

    PubMed

    Figueroa-Torres, Gonzalo M; Pittman, Jon K; Theodoropoulos, Constantinos

    2017-10-01

    Microalgal starch and lipids, carbon-based storage molecules, are useful as potential biofuel feedstocks. In this work, cultivation strategies maximising starch and lipid formation were established by developing a multi-parameter kinetic model describing microalgal growth as well as starch and lipid formation, in conjunction with laboratory-scale experiments. Growth dynamics are driven by nitrogen-limited mixotrophic conditions, known to increase cellular starch and lipid contents whilst enhancing biomass growth. Model parameters were computed by fitting model outputs to a range of experimental datasets from batch cultures of Chlamydomonas reinhardtii. Predictive capabilities of the model were established against different experimental data. The model was subsequently used to compute optimal nutrient-based cultivation strategies in terms of initial nitrogen and carbon concentrations. Model-based optimal strategies yielded a significant increase of 261% for starch (0.065gCL -1 ) and 66% for lipid (0.08gCL -1 ) production compared to base-case conditions (0.018gCL -1 starch, 0.048gCL -1 lipids). Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Lipid production of microalga Chlorella sorokiniana CY1 is improved by light source arrangement, bioreactor operation mode and deep-sea water supplements.

    PubMed

    Chen, Chun-Yen; Chang, Hsin-Yueh

    2016-03-01

    Microalgae-based biodiesel has been recognized as a sustainable and promising alternative to fossil diesel. High lipid productivity of microalgae is required for economic production of biodiesel from microalgae. This study was undertaken to enhance the growth and oil accumulation of an indigenous microalga Chlorella sorokiniana CY1 by applying engineering strategies using deep-sea water as the medium. First, the microalga was cultivated using LED as the immersed light source, and the results showed that the immersed LED could effectively enhance the oil/lipid content and final microalgal biomass concentration to 53.8% and 2.5 g/l, respectively. Next, the semi-batch photobioreactor operation with deep-sea water was shown to improve lipid content and microalgal growth over those from using batch and continuous cultures under similar operating conditions. The optimal replacement ratio was 50%, resulting in an oil/lipid content and final biomass concentration of 61.5% and 2.8 g/l, respectively. A long-term semi-batch culture utilizing 50%-replaced medium was carried out for four runs. The final biomass concentration and lipid productivity were 2.5 g/L and 112.2 mg/L/d, respectively. The fatty acid composition of the microalgal lipids was predominant by palmitic acid, stearic acid, oleic acid and linoleic acid, and this lipid quality is suitable for biodiesel production. This demonstrates that optimizing light source arrangement, bioreactor operation and deep-sea water supplements could effectively promote the lipid production of C. sorokiniana CY1 for the applications in microalgae-based biodiesel industry. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT.

    PubMed

    Ajat, Mokrish; Molenaar, Martijn; Brouwers, Jos F H M; Vaandrager, Arie B; Houweling, Martin; Helms, J Bernd

    2017-02-01

    Hepatic stellate cells (HSCs) play an important role in liver physiology and under healthy conditions they have a quiescent and lipid-storing phenotype. Upon liver injury, HSCs are activated and rapidly lose their retinyl ester-containing lipid droplets. To investigate the role of lecithin:retinol acyltransferase (LRAT) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) in retinyl ester synthesis and lipid droplet dynamics, we modified LC-MS/MS procedures by including multiple reaction monitoring allowing unambiguous identification and quantification of all major retinyl ester species. Quiescent primary HSCs contain predominantly retinyl palmitate. Exogenous fatty acids are a major determinant in the retinyl ester species synthesized by activated HSCs and LX-2 cells, indicating that HSCs shift their retinyl ester synthesizing capacity from LRAT to DGAT1 during activation. Quiescent LRAT -/- HSCs retain the capacity to synthesize retinyl esters and to store neutral lipids in lipid droplets ex vivo. The median lipid droplet size in LRAT -/- HSCs (1080nm) is significantly smaller than in wild type HSCs (1618nm). This is a consequence of an altered lipid droplet size distribution with 50.5±9.0% small (≤700nm) lipid droplets in LRAT -/- HSCs and 25.6±1.4% large (1400-2100nm) lipid droplets in wild type HSC cells. Upon prolonged (24h) incubation, the amounts of small (≤700nm) lipid droplets strongly increased both in wild type and in LRAT -/- HSCs, indicating a dynamic behavior in both cell types. The absence of retinyl esters and reduced number of lipid droplets in LRAT-deficient HSCs in vivo will be discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Wrinkled1 Accelerates Flowering and Regulates Lipid Homeostasis between Oil Accumulation and Membrane Lipid Anabolism in Brassica napus.

    PubMed

    Li, Qing; Shao, Jianhua; Tang, Shaohua; Shen, Qingwen; Wang, Tiehu; Chen, Wenling; Hong, Yueyun

    2015-01-01

    Wrinkled1 (WRI1) belongs to the APETALA2 transcription factor family; it is unique to plants and is a central regulator of oil synthesis in Arabidopsis. The effects of WRI1 on comprehensive lipid metabolism and plant development were unknown, especially in crop plants. This study found that BnWRI1 in Brassica napus accelerated flowering and enhanced oil accumulation in both seeds and leaves without leading to a visible growth inhibition. BnWRI1 decreased storage carbohydrates and increased soluble sugars to facilitate the carbon flux to lipid anabolism. BnWRI1 is localized to the nucleus and directly binds to the AW-box at proximal upstream regions of genes involved in fatty acid (FA) synthesis and lipid assembly. The overexpression (OE) of BnWRI1 resulted in the up-regulation of genes involved in glycolysis, FA synthesis, lipid assembly, and flowering. Lipid profiling revealed increased galactolipids monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), and phosphatidylcholine (PC) in the leaves of OE plants, whereas it exhibited a reduced level of the galactolipids DGDG and MGDG and increased levels of PC, phosphatidylethanolamide, and oil [triacylglycerol (TAG)] in the siliques of OE plants during the early seed development stage. These results suggest that BnWRI1 is important for homeostasis among TAG, membrane lipids and sugars, and thus facilitates flowering and oil accumulation in B. napus.

  13. Surface chemistry of lipid raft and amyloid Aβ (1-40) Langmuir monolayer.

    PubMed

    Thakur, Garima; Pao, Christine; Micic, Miodrag; Johnson, Sheba; Leblanc, Roger M

    2011-10-15

    Lipid rafts being rich in cholesterol and sphingolipids are considered to provide ordered lipid environment in the neuronal membranes, where it is hypothesized that the cleavage of amyloid precursor protein (APP) to Aβ (1-40) and Aβ (1-42) takes place. It is highly likely that the interaction of lipid raft components like cholesterol, sphingomylein or GM1 leads to nucleation of Aβ and results in aggregation or accumulation of amyloid plaques. One has investigated surface pressure-area isotherms of the lipid raft and Aβ (1-40) Langmuir monolayer. The compression-decompression cycles and the stability of the lipid raft Langmuir monolayer are crucial parameters for the investigation of interaction of Aβ (1-40) with the lipid raft Langmuir monolayer. It was revealed that GM1 provides instability to the lipid raft Langmuir monolayer. Adsorption of Aβ (1-40) onto the lipid raft Langmuir monolayer containing neutral (POPC) or negatively charged phospholipid (DPPG) was examined. The adsorption isotherms revealed that the concentration of cholesterol was important for adsorption of Aβ (1-40) onto the lipid raft Langmuir monolayer containing POPC whereas for the lipid raft Langmuir monolayer containing DPPG:cholesterol or GM1 did not play any role. In situ UV-vis absorption spectroscopy supported the interpretation of results for the adsorption isotherms. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Supplementation during pregnancy with small-quantity lipid-based nutrient supplements or multiple micronutrients, compared with iron and folic acid, increases women's urinary iodine concentration in semiurban Ghana: A randomized controlled trial.

    PubMed

    Adu-Afarwuah, Seth; Young, Rebecca T; Lartey, Anna; Okronipa, Harriet; Ashorn, Per; Ashorn, Ulla; Zeilani, Mamane; Dewey, Kathryn G

    2018-04-01

    There is little information on whether prenatal multiple micronutrient (MMN) supplements containing iodine affect women's iodine status. In the International Lipid-based Nutrient Supplements DYAD-Ghana trial, we aimed to assess women's urinary iodine concentration (UIC, μg/L) during pregnancy, as one of the planned secondary outcomes. Women (n = 1,320) <20 weeks of gestation were randomized to consume 60 mg iron and 400 μg folic acid per day (iron and folic acid [IFA]); 18 vitamins and minerals including 250 μg iodine per day (MMN); or 20 g/day of small-quantity lipid-based nutrient supplements (LNS) with the same and additional 4 vitamins and minerals as the MMN (LNS). In a subsample (n = 295), we tested differences in groups' geometric mean UICs at 36 weeks of gestation controlling for baseline UIC and compared the geometric means (approximately median UICs) with the World Health Organization (WHO) cut-offs: median UIC <150, 150-249, and ≥500 reflecting low, adequate, and excessive iodine intakes, respectively. At baseline, overall median UIC was 137. At 36 weeks of gestation, controlling for baseline UIC, geometric mean (95% confidence interval) UICs of the MMN (161 [133, 184]) and LNS (158 [132, 185]) groups did not differ; both values were significantly greater (overall p = .004) than that of the IFA group (116 [101, 135]). The median UICs of the MMN and LNS groups were within the WHO "adequate" range, whereas that of the IFA group was below the WHO adequate range. In this setting, supplementation during pregnancy with small-quantity LNS or MMN providing iodine at the WHO-recommended dose, compared with IFA, increases the likelihood of adequate iodine status. © 2017 The Authors. Maternal & Child Nutrition published by John Wiley & Sons, Ltd.

  15. Brassica rapa Has Three Genes That Encode Proteins Associated with Different Neutral Lipids in Plastids of Specific Tissues1

    PubMed Central

    Kim, Hyun Uk; Wu, Sherry S.H.; Ratnayake, Chandra; Huang, Anthony H.C.

    2001-01-01

    Plastid lipid-associated protein (PAP), a predominant structural protein associated with carotenoids and other non-green neutral lipids in plastids, was shown to be encoded by a single nuclear gene in several species. Here we report three PAP genes in the diploid Brassica rapa; the three PAPs are associated with different lipids in specific tissues. Pap1 and Pap2 are more similar to each other (84% amino acid sequence identity) than to Pap3 (46% and 44%, respectively) in the encoded mature proteins. Pap1 transcript was most abundant in the maturing anthers (tapetum) and in lesser amounts in leaves, fruit coats, seeds, and sepals; Pap2 transcript was abundant only in the petals; and Pap3 transcript had a wide distribution, but at minimal levels in numerous organs. Immunoblotting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that most organs had several nanograms of PAP1 or PAP2 per milligram of total protein, the highest amounts being in the anthers (10.9 μg mg−1 PAP1) and petals (6.6 μg mg−1 PAP2), and that they had much less PAP3 (<0.02 μg mg−1). In these organs PAP was localized in isolated plastid fractions. Plants were subjected to abiotic stresses; drought and ozone reduced the levels of the three Pap transcripts, whereas mechanical wounding and altering the light intensity enhanced their levels. We conclude that the PAP gene family consists of several members whose proteins are associated with different lipids and whose expressions are controlled by distinct mechanisms. Earlier reports of the expression of one Pap gene in various organs in a species need to be re-examined. PMID:11351096

  16. Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia type 1.

    PubMed

    Circelli, Luisa; Ramundo, Valeria; Marotta, Vincenzo; Sciammarella, Concetta; Marciello, Francesca; Del Prete, Michela; Sabatino, Lina; Pasquali, Daniela; Izzo, Francesco; Scala, Stefania; Colao, Annamaria; Faggiano, Antongiulio; Colantuoni, Vittorio

    2015-07-01

    CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype-phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  17. pH-sensitive polymer-modified liposome-based immunity-inducing system: Effects of inclusion of cationic lipid and CpG-DNA.

    PubMed

    Yoshizaki, Yuta; Yuba, Eiji; Sakaguchi, Naoki; Koiwai, Kazunori; Harada, Atsushi; Kono, Kenji

    2017-10-01

    Efficient vaccine carriers for cancer immunotherapy require two functions: antigen delivery to dendritic cells (DCs) and the activation of DCs, a so-called adjuvant effect. We previously reported antigen delivery system using liposomes modified with pH-sensitive polymers, such as 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG), for the induction of antigen-specific immune responses. We reported that inclusion of cationic lipids to MGlu-HPG-modified liposomes activates DCs and enhances antitumor effects. In this study, CpG-DNA, a ligand to Toll-like receptor 9 (TLR9) expressing in endosomes of DCs, was introduced to MGlu-HPG-modified liposomes containing cationic lipids using two complexation methods (Pre-mix and Post-mix) for additional activation of antigen-specific immunity. For Pre-mix, thin membrane of lipids and polymers were dispersed by a mixture of antigen/CpG-DNA. For Post-mix, CpG-DNA was added to pre-formed liposomes. Both Pre-mix and Post-mix delivered CpG-DNA to DC endosomes, where TLR9 is expressing, more efficiently than free CpG-DNA solution did. These liposomes promoted cytokine production from DCs and the expression of co-stimulatory molecules in vitro and induced antigen-specific immune responses in vivo. Both Pre-mix and Post-mix exhibited strong antitumor effects compared with conventional pH-sensitive polymer-modified liposomes. Results show that inclusion of multiple adjuvant molecules into pH-sensitive polymer-modified liposomes and suitable CpG-DNA complexation methods are important to design potent vaccine carriers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Phase I Trial of a Pathotropic Retroviral Vector Expressing a Cytocidal Cyclin G1 Construct (Rexin-G) in Patients With Advanced Pancreatic Cancer

    PubMed Central

    Galanis, Evanthia; Carlson, Stephanie K; Foster, Nathan R; Lowe, Val; Quevedo, Fernando; McWilliams, Robert R; Grothey, Axel; Jatoi, Aminah; Alberts, Steven R; Rubin, Joseph

    2009-01-01

    Rexin-G is a pathotropic retroviral vector displaying a von Willebrand factor–targeting motif and expressing a dominant negative cyclin G1 gene. We undertook a phase I trial of intravenous (IV) administration of Rexin-G in patients with gemcitabine refractory, metastatic pancreatic adenocarcinoma. Twelve patients were treated. Dose escalation was performed from a dose of 1 × 1011 colony forming units (CFU) per cycle to 6 × 1011 CFU per cycle. The treatment was well tolerated. One dose-limiting toxicity (DLT) at dose level 2 (1.5 × 1011 CFU per cycle) was observed, consisting of grade 3 transaminitis. There was no detection of replication-competent virus in patients’ peripheral blood mononuclear cells (PBMCs) or viral integration in DNA obtained from PBMCs, and no development of neutralizing antibodies. No evidence of antitumor activity was observed. The best objective response was progressive disease in 11 of the 12 study patients, while 1 patient showed radiographically stable disease with clinical deterioration and increase in the CA19.9 tumor marker. Median time to progression was 32 days. The median duration of survival of the study patients was 3.5 months from treatment initiation. Rexin-G is well tolerated in doses up to 6 × 1011 CFU in patients with recurrent pancreatic cancer, but there was no evidence of clinical antitumor activity. PMID:18388964

  19. The significance of fructose and MSG in affecting lipid and docosahexaenoic acid (DHA) production of Aurantiochytrium sp. SW1

    NASA Astrophysics Data System (ADS)

    Rahman, Shariffah Nurhidayah Syed Abdul; Kalil, Mohd Sahaid; Hamid, Aidil Abdul

    2018-04-01

    Optimization of fermentation medium for the production of docosahexaenoic acid (DHA) by Aurantiochytrium sp. SW1 was carried out. In this study, levels of fructose, monosodium glutamate (MSG) and sea salt were optimized for enhanced lipid and DHA production using response surface methodology (RSM). The design contains a total of 20 runs with 6 central points replication. Cultivation was carried out in 500 mL flasks containing 100 mL nitrogen limited medium at 30°C for 96h. Sequential model sum of squares (SS) revealed that the system was adequately represented by a quadratic model (p<0.0001). ANOVA results showed that fructose and MSG as a single factor has significant positive effect on the DHA content of SW1. The estimated optimal levels of the factors were 100 g/L fructose, 8 g/L MSG and 47% sea salt. Subsequent cultivation employing the suggested values confirmed that the predicted response values were experimentally achievable and reproducible, where 8.82 g/L DHA (51.34% g/g lipid) was achieved.

  20. Th1/Th2 cytokine profiles in G+/G- bacteremia in pediatric hematology/oncology patients.

    PubMed

    Tang, Yongmin; Liao, Chan; Xu, Xiaojun; Song, Hua; Shi, Shuwen; Yang, Shilong

    2012-01-01

    Early diagnosis of infection and appropriate choice of antibiotics are essential not only to improve the prognosis of the patients but also to prevent from the abuse of the antibiotics in hematology/oncology children at the time of neutropenia after intensive chemotherapy. We evaluated the quantification of Th1/Th2 cytokines with flow cytometry bead assay (CBA) in 145 hospitalized febrile hematology/oncology children with positive blood culture to seek for a rapid diagnostic method to determine the type of infection. IL-4, IL-6, IL-10, TNF-α, and IFN-γ levels from both G- and G+ bacteremia groups were significantly higher than those of controls (P < 0.001). The median levels of IL-6, IL-10, TNF-α of Group G- were 525.4, 96.0, and 6.9 pg/ml, respectively, significantly higher than those of Group G+ (150.0, 22.6, and 4.5 pg/ml, respectively, P < 0.001). According to the different degrees of increased IL-6 and IL-10 levels, we named the G- bacterial infection related cytokine profile G- BIRCP and the G+ BIRCP. The specificity and sensitivity of BIRCP prediction for G- and G+ bacteria cultures were 60.2% and 75.4%, 66.8% and 70.1%, respectively. Similar therapeutic efficacy was achieved between BIRCP-based and broad-spectrum antibiotics groups (86.1% vs. 89.3%, P > 0.05), which was significantly increased as compared with that (65.5%, P < 0.05) of empirical group. These results showed the promising use of the IL-6/IL-10/TNF-α determination with CBA technology for the early and rapid diagnosis, evaluation of G+/G- bacteremia in pediatric hematology/oncology patients. Copyright © 2011 Wiley Periodicals, Inc.

  1. Interaction of the Antimicrobial Peptide Aurein 1.2 and Charged Lipid Bilayer

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

    Rai, Durgesh K.; Qian, Shuo

    Aurein 1.2 is a potent antimicrobial peptide secreted by frog Litoria aurea. As a short membrane-active peptide with only 13 amino acids in sequence, it has been found to be residing on the surface of lipid bilayer and permeabilizing bacterial membranes at high concentration. However, the detail at the molecular level is largely unknown. Here in this study, we investigated the action of Aurein 1.2 in charged lipid bilayers composed of DMPC/DMPG. Oriented Circular Dichroism results showed that the peptide was on the surface of lipid bilayer regardless of the charged lipid ratio. Only at a very high peptide-to-lipid ratiomore » (~1/10), the peptide became perpendicular to the bilayer, however no pore was detected by neutron in-plane scattering. To further understand how it interacted with charged lipid bilayers, we employed Small Angle Neutron Scattering to probe lipid distribution across bilayer leaflets in lipid vesicles. The results showed that Aurein 1.2 interacted strongly with negatively charged DMPG, causing strong asymmetry in lipid bilayer. At high concentration, while the vesicles were intact, we found additional structure feature on the bilayer. Finally, our study provides a glimpse into how Aurein 1.2 disturbs anionic lipid-containing membranes without pore formation.« less

  2. Interaction of the Antimicrobial Peptide Aurein 1.2 and Charged Lipid Bilayer

    DOE PAGES

    Rai, Durgesh K.; Qian, Shuo

    2017-06-16

    Aurein 1.2 is a potent antimicrobial peptide secreted by frog Litoria aurea. As a short membrane-active peptide with only 13 amino acids in sequence, it has been found to be residing on the surface of lipid bilayer and permeabilizing bacterial membranes at high concentration. However, the detail at the molecular level is largely unknown. Here in this study, we investigated the action of Aurein 1.2 in charged lipid bilayers composed of DMPC/DMPG. Oriented Circular Dichroism results showed that the peptide was on the surface of lipid bilayer regardless of the charged lipid ratio. Only at a very high peptide-to-lipid ratiomore » (~1/10), the peptide became perpendicular to the bilayer, however no pore was detected by neutron in-plane scattering. To further understand how it interacted with charged lipid bilayers, we employed Small Angle Neutron Scattering to probe lipid distribution across bilayer leaflets in lipid vesicles. The results showed that Aurein 1.2 interacted strongly with negatively charged DMPG, causing strong asymmetry in lipid bilayer. At high concentration, while the vesicles were intact, we found additional structure feature on the bilayer. Finally, our study provides a glimpse into how Aurein 1.2 disturbs anionic lipid-containing membranes without pore formation.« less

  3. Heuristics for the inversion median problem

    PubMed Central

    2010-01-01

    Background The study of genome rearrangements has become a mainstay of phylogenetics and comparative genomics. Fundamental in such a study is the median problem: given three genomes find a fourth that minimizes the sum of the evolutionary distances between itself and the given three. Many exact algorithms and heuristics have been developed for the inversion median problem, of which the best known is MGR. Results We present a unifying framework for median heuristics, which enables us to clarify existing strategies and to place them in a partial ordering. Analysis of this framework leads to a new insight: the best strategies continue to refer to the input data rather than reducing the problem to smaller instances. Using this insight, we develop a new heuristic for inversion medians that uses input data to the end of its computation and leverages our previous work with DCJ medians. Finally, we present the results of extensive experimentation showing that our new heuristic outperforms all others in accuracy and, especially, in running time: the heuristic typically returns solutions within 1% of optimal and runs in seconds to minutes even on genomes with 25'000 genes--in contrast, MGR can take days on instances of 200 genes and cannot be used beyond 1'000 genes. Conclusion Finding good rearrangement medians, in particular inversion medians, had long been regarded as the computational bottleneck in whole-genome studies. Our new heuristic for inversion medians, ASM, which dominates all others in our framework, puts that issue to rest by providing near-optimal solutions within seconds to minutes on even the largest genomes. PMID:20122203

  4. Chlorogenic acid-enriched extract from Eucommia ulmoides leaves inhibits hepatic lipid accumulation through regulation of cholesterol metabolism in HepG2 cells.

    PubMed

    Hao, Shun; Xiao, Yuan; Lin, Yan; Mo, Zhentao; Chen, Yang; Peng, Xiaofeng; Xiang, Canhui; Li, Yiqi; Li, Wenna

    2016-01-01

    Eucommia ulmoides Oliver (Eucommiaceae) leaf exhibits beneficial lipid-lowering and anti-obesity effects. However, the mechanisms remain unknown. The objective of this study is to investigate the lipid-lowering effects of chlorogenic acid (CGA)-enriched extract from this plant (CAEF) in human hepatoma HepG2 cells, focusing on cholesterol metabolism. HepG2 cells were treated with CAEF (10, 20, 25, 40, 60, and 80 mg/L), CGA (0.3, 3, 30, 300, and 600 μmol/L), and simvastatin (0.1, 1, 10, 50, and 100 μmol/L) for 24 or 48 h. The cytotoxicity, Oil red O staining, total cholesterol, and triacylglycerol in supernatants were determined. The mRNA expression of genes involved in cholesterol metabolism was determined with RT-PCR. The protein expression of HMG-CoA reductase (HMGCR) was examined by immunocytochemistry and western-blot. The IC50 values were 59.2 mg/L for CAEF, 335.9 μmol/L for CGA, and 10.5 μmol/L for simvastatin. By treating cells with CAEF (25 mg/L), CGA (30 μmol/L), or simvastatin (10 μmol/L) for 48 h, the efflux of total cholesterol and triacylglycerol was increased (CAEF, 4.06- and 31.00-folds; CGA, 2.94- and 2.17-folds; and simvastatin, 3.94- and 24.67-folds), and the cellular lipid droplets were reduced in Oil red O staining. CAEF and CGA increased mRNA expression of ABCA1, CYP7A1, and AMPKα2, while CAEF and simvastatin decreased SREBP2. However, their effects on LXRα mRNA expression were variable. Importantly, all drugs significantly inhibited protein expression of HMGCR at mRNA and protein levels. CAEF is a promising dietary supplement to prevent obesity and dyslipidemia and the effects appear to be due, at least in part, to regulating cholesterol metabolism through inhibition of HMGCR in HepG2 cells.

  5. Lipids and fatty acids in roasted chickens.

    PubMed

    Souza, S A; Visentainer, J V; Matsushita, M; Souza, N E

    1999-09-01

    Total lipids from meat portions of breast, thigh, wing, side and back with and without skin from 10 roasted chickens were extracted with chloroform and methanol and gravimetrically determined, and their fatty acids were analysed as methyl esters by gaseous chromatography, using a flame ionization detector and capillary column. The main fatty acids found were: C16:0, C18:1 omega 9, and C18:2 omega 6. The average ratio observed between PUFA/SFA was of 0.98, mainly due to the great concentration of the C18:2 omega 6 fatty acid, with an average of 26.75%. Regarding to the lipids content, the skinless breast showed the lowest content, 0.78 g/100 g, while the back with skin was the one with the highest content, 12.13 g/100 g except for the pure skin, with 26.54 grams of lipids by 100 grams.

  6. Biochemical analyses of lipids deposited on silicone hydrogel lenses

    PubMed Central

    Hatou, Shin; Fukui, Masaki; Yatsui, Keiichi; Mochizuki, Hiroshi; Akune, Yoko; Yamada, Masakazu

    2010-01-01

    Purpose This study was performed to determine the levels of lipids deposited on in vivo worn silicone hydrogel lenses. Methods Three silicone hydrogel materials, galyfilcon A, senofilcon A, and asmofilcon A, were worn for 2 weeks by 35 normal subjects. Total lipid deposition was determined by the sulfo-phospho-vanillin reaction. Cholesterol was estimated by a colorimetric probe through enzymatic oxidation. Phospholipid level was estimated by determining phosphorus with ammonium molybdate through enzymatic digestion. Results The total lipid content recovered from galyfilcon A, senofilcon A, and asmofilcon A was 32.9 ± 33.8, 42.1 ± 14.0, and 36.6 ± 31.9 μg/lens, respectively. The cholesterol content recovered from galyfilcon A, senofilcon A, and asmofilcon A was 26.2 ± 26.9, 28.6 ± 19.4, and 31.1 ± 21.1 μg/lens, respectively. There were no statistically significant differences in total lipids and cholesterol among the contact lens types. However, the quantity of phospholipid recovered from the asmofilcon A (7.0 ± 5.5 μg/lens) lenses was significantly higher than from galyfilcon A (1.1 ± 0.8 μg/lens) and senofilcon A (2.4 ± 0.8 mg/lens) lenses (p < 0.05, Mann-Whitney test). Conclusions The quantity of total lipid and cholesterol deposited on the 3 silicone hydrogel lenses tested did not differ. However, there were significant differences in the amounts of phospholipid deposited among the 3 silicone hydrogel lenses, of which clinical significance should be explored in the future study.

  7. GPU Accelerated Vector Median Filter

    NASA Technical Reports Server (NTRS)

    Aras, Rifat; Shen, Yuzhong

    2011-01-01

    Noise reduction is an important step for most image processing tasks. For three channel color images, a widely used technique is vector median filter in which color values of pixels are treated as 3-component vectors. Vector median filters are computationally expensive; for a window size of n x n, each of the n(sup 2) vectors has to be compared with other n(sup 2) - 1 vectors in distances. General purpose computation on graphics processing units (GPUs) is the paradigm of utilizing high-performance many-core GPU architectures for computation tasks that are normally handled by CPUs. In this work. NVIDIA's Compute Unified Device Architecture (CUDA) paradigm is used to accelerate vector median filtering. which has to the best of our knowledge never been done before. The performance of GPU accelerated vector median filter is compared to that of the CPU and MPI-based versions for different image and window sizes, Initial findings of the study showed 100x improvement of performance of vector median filter implementation on GPUs over CPU implementations and further speed-up is expected after more extensive optimizations of the GPU algorithm .

  8. Role of -675 4G/5G in the plasminogen activator inhibitor-1 gene and -308G/A tumor necrosis factor-α gene polymorphisms in obese Argentinean patients.

    PubMed

    Wingeyer, Silvia D Perés; Graffigna, Mabel N; Belli, Susana H; Benetucci, Jorge; de Larrañaga, Gabriela F

    2012-05-01

    Plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor-α (TNF-α) are increased in the circulation of obese persons. Because a direct link between PAI-1 and TNF-α in obesity has been observed, they are candidate genes for the development of obesity. We sought to evaluate the relation between the genotypic and allelic frequencies of the -675 4G/5G PAI-1 and -308 G/A TNF-α polymorphisms and their association with the risk for obesity in an Argentinean population. A group of 110 consecutive obese persons and a group of 111 lean controls were recruited. Polymerase chain reaction was used to determine the frequency of PAI-1 and TNF-α polymorphisms; serum fasting glucose, insulin, and lipid levels were measured by standard methods. Insulin sensitivity was evaluated by using homeostasis model assessment. The -308 TNF-α and -675 4G/5G PAI-1 genotype distribution did not significantly differ between the groups (p=0.544 and p=0.327, respectively). Homeostasis model assessment was the only positive independent determinant of body mass index (R(2)=0.493; p<0.001). The -675 4G/5G PAI-1 and the -308 TNF-α polymorphism variants tested in this study, individually or combined, were not associated with obesity in an Argentinean population.

  9. Prenatal lipid-based nutrient supplements increase cord leptin concentration in pregnant women from rural Burkina Faso.

    PubMed

    Huybregts, Lieven; Roberfroid, Dominique; Lanou, Hermann; Meda, Nicolas; Taes, Youri; Valea, Innocent; D'Alessandro, Umberto; Kolsteren, Patrick; Van Camp, John

    2013-05-01

    In developing countries, prenatal lipid-based nutrient supplements (LNSs) were shown to increase birth size; however, the mechanism of this effect remains unknown. Cord blood hormone concentrations are strongly associated with birth size. Therefore, we hypothesize that LNSs increase birth size through a change in the endocrine regulation of fetal development. We compared the effect of daily prenatal LNSs with multiple micronutrient tablets on cord blood hormone concentrations using a randomized, controlled design including 197 pregnant women from rural Burkina Faso. Insulin-like growth factors (IGF) I and II, their binding proteins IGFBP-1 and IGFBP-3, leptin, cortisol, and insulin were quantified in cord sera using immunoassays. LNS was associated with higher cord blood leptin mainly in primigravidae (+57%; P = 0.02) and women from the highest tertile of BMI at study inclusion (+41%; P = 0.02). We did not find any significant LNS effects on other measured cord hormones. The observed increase in cord leptin was associated with a significantly higher birth weight. Cord sera from small-for-gestational age newborns had lower median IGF-I (-9 μg/L; P = 0.003), IGF-II (-79 μg/L; P = 0.003), IGFBP-3 (-0.7 μg/L; P = 0.007), and leptin (-1.0 μg/L; P = 0.016) concentrations but higher median cortisol (+18 μg/L; P = 0.037) concentrations compared with normally grown newborns. Prenatal LNS resulted in increased cord leptin concentrations in primigravidae and mothers with higher BMI at study inclusion. The elevated leptin concentrations could point toward a higher neonatal fat mass.

  10. Novel Interconnections in Lipid Metabolism Revealed by Overexpression of Sphingomyelin Synthase-1*

    PubMed Central

    Deevska, Gergana M.; Dotson, Patrick P.; Karakashian, Alexander A.; Isaac, Giorgis; Wrona, Mark; Kelly, Samuel B.; Merrill, Alfred H.; Nikolova-Karakashian, Mariana N.

    2017-01-01

    This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1) exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin) but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have fewer triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function. Treatment with 1 mm palmitate increases de novo ceramide synthesis in both cell lines to a similar degree, causing accumulation of C16:0-ceramide (and some C18:0-, C20:0-, and C22:0-ceramides) as well as C16:0- and C18:0-Hex-Cers. In these experiments, the palmitic acid is delivered as a complex with delipidated BSA (2:1, mol/mol) and does not induce significant lipotoxicity. Based on precursor labeling, the flux through SM synthase also increases, which is exacerbated in HepG2-SMS1 cells. In contrast, palmitate-induced lipid droplet formation is significantly reduced in HepG2-SMS1 cells. [14C]Choline and [3H]palmitate tracking shows that SMS1 overexpression apparently affects the partitioning of palmitate-enriched diacylglycerol between the phosphatidylcholine and triacylglycerol pathways, to the benefit of the former. Furthermore, triacylglycerols from HepG2-SMS1 cells are enriched in polyunsaturated fatty acids, which is indicative of active remodeling. Together, these results delineate novel metabolic interactions between glycerolipids and sphingolipids. PMID:28087695

  11. Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.

    PubMed

    Weng, Lu-Chen; Roetker, Nicholas S; Lutsey, Pamela L; Alonso, Alvaro; Guan, Weihua; Pankow, James S; Folsom, Aaron R; Steffen, Lyn M; Pankratz, Nathan; Tang, Weihong

    2018-01-01

    Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and AAA using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-AAA association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical AAA. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of AAA risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with AAA in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of AAA in EAs.

  12. Expression of type 2 diacylglycerol acyltransferse gene DGTT1 from Chlamydomonas reinhardtii enhances lipid production in Scenedesmus obliquus.

    PubMed

    Chen, Chun-Yen; Kao, Ai-Ling; Tsai, Zheng-Chia; Chow, Te-Jin; Chang, Hsin-Yueh; Zhao, Xin-Qing; Chen, Po-Ting; Su, Hsiang-Yen; Chang, Jo-Shu

    2016-03-01

    Microalgal strains of Scenedesmus obliquus have the great potential for the production of biofuels, CO2 fixation, and bioremediation. However, metabolic engineering of S. obliquus to improve their useful phenotypes are still not fully developed. In this study, S. obliquus strain CPC2 was genetically engineered to promote the autotrophic growth and lipid productivity. The overexpression plasmid containing the type 2 diacylglycerol acyltransferse (DGAT) gene DGTT1 from Chlamydomonas reinhardtii was constructed and transformed into S. obliquus CPC2, and the positive transformants were obtained. The expression of DGTT1 gene was confirmed by reverse transcription PCR analysis. Enhanced lipid content of the transformant S. obliquus CPC2-G1 by nearly two-fold was observed. The biomass concentration of the recombinant strains was also 29% higher than that of the wild-type strain. Furthermore, the recombinant strain CPC2-G1 was successfully grown in 40 L tubular type photobioreactor and open pond system in an outdoor environment. The lipid content, biomass concentration, and biomass productivity obtained from 40 L tubular PBR were 127.8% 20.0%, and 232.6% higher than those obtained from the wild-type strain. The major aim of this work is to develop a tool to genetically engineer an isolated S. obliquus strain for the desired purpose. This is the first report that genetic engineering of S. obliquus has been successful employed to improve both the microalgal cell growth and the lipid production. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. ATP binding cassette G1-dependent cholesterol efflux during inflammation.

    PubMed

    de Beer, Maria C; Ji, Ailing; Jahangiri, Anisa; Vaughan, Ashley M; de Beer, Frederick C; van der Westhuyzen, Deneys R; Webb, Nancy R

    2011-02-01

    ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent efflux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A(2) (sPLA(2)-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.

  14. Evaluation of Physarum polycephalum plasmodial growth and lipid production using rice bran as a carbon source.

    PubMed

    Tran, Hanh; Stephenson, Steven; Pollock, Erik

    2015-08-01

    The myxomycete Physarum polycephalum appears to have remarkable potential as a lipid source for biodiesel production. The present study evaluated the use of rice bran as a carbon source and determined the medium components for optimum growth and lipid production for this organism. Optimization of medium components by response surface methodology showed that rice bran and yeast extract had significant influences on lipid and biomass production. The optimum medium consisted of 37.5 g/L rice bran, 0.79 g/L yeast extract and 12.5 g/L agar, and this yielded 7.5 g/L dry biomass and 0.9 g/L lipid after 5 days. The biomass and lipid production profiles revealed that these parameters increased over time and reached their maximum values (10.5 and 1.26 g/L, respectively) after 7 days. Physarum polycephalum growth decreased on the spent medium but using the latter increased total biomass and lipid concentrations to 14.3 and 1.72 g/L, respectively. An effective method for inoculum preparation was developed for biomass and lipid production by P. polycephalum on a low-cost medium using rice bran as the main carbon source. These results also demonstrated the feasibility of scaling up and reusing the medium for additional biomass and lipid production.

  15. [Effects of adiponectin gene SNP45T/G on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy Chinese youth].

    PubMed

    Li, Yu-jia; Fang, Ding-zhi; Gong, Ren-rong; Du, Juan; Huang, Xin

    2010-09-01

    To investigate the effects of adiponectin gene (APM1) SNP45T/G on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy young Chinese. Fifty-six healthy young subjects were given two consecutive diets. The first was control diet (54% carbohydrate, 15% protein, and 31% fat) for 7 days, and the second was HC/LF diet (70% carbohydrate, 15% protein, and 15% fat) for 6 days. Before and after each diet, serum lipids and SNP45T/G were analyzed. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. There was no significant difference of baseline lipid ratios between subjects with TT genotype and subjects carrying G allele (G carriers) in the whole population or in the males and females separately. The G allele was associated with significantly higher TC/HDL-C after HC/LF diet in the males (P < 0.05); and the males with TT genotype had significant decreases of LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.05) after HC/LF diet compared with those before the diet, while G carriers only experienced significant decrease of TC/HDL-C (P < 0.01). In the females, TT genotype was associated with significantly higher TG/HDL-C (P < 0.05) and log (TG/HDL-C) (P < 0.05) both before and after the HC/LF diet. When compared with those before HC/LF diet, elevated TG/HDL-C (P < 0.05) and log (TG/ HDL-C) (P < 0.05) and declined TC/HDL-C (P < 0.01) were observed in the subjects with TT genotype after the diet. In the female subjects of G carriers, LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.01) decreased significantly after the HC/LF diet. G allele of APM1 45T/G could inhibit increase of TG/HDL-C and log (TG/HDL-C) and promote the decrease of LDL-C/HDL-C induced by HC/LF diet in healthy young females. But in the healthy young males, it might eliminate the decline of LDL-C/HDL-C induced by HC/LF diet and increase TC/HDL-C.

  16. AntiClustal: Multiple Sequence Alignment by antipole clustering and linear approximate 1-median computation.

    PubMed

    Di Pietro, C; Di Pietro, V; Emmanuele, G; Ferro, A; Maugeri, T; Modica, E; Pigola, G; Pulvirenti, A; Purrello, M; Ragusa, M; Scalia, M; Shasha, D; Travali, S; Zimmitti, V

    2003-01-01

    In this paper we present a new Multiple Sequence Alignment (MSA) algorithm called AntiClusAl. The method makes use of the commonly use idea of aligning homologous sequences belonging to classes generated by some clustering algorithm, and then continue the alignment process ina bottom-up way along a suitable tree structure. The final result is then read at the root of the tree. Multiple sequence alignment in each cluster makes use of the progressive alignment with the 1-median (center) of the cluster. The 1-median of set S of sequences is the element of S which minimizes the average distance from any other sequence in S. Its exact computation requires quadratic time. The basic idea of our proposed algorithm is to make use of a simple and natural algorithmic technique based on randomized tournaments which has been successfully applied to large size search problems in general metric spaces. In particular a clustering algorithm called Antipole tree and an approximate linear 1-median computation are used. Our algorithm compared with Clustal W, a widely used tool to MSA, shows a better running time results with fully comparable alignment quality. A successful biological application showing high aminoacid conservation during evolution of Xenopus laevis SOD2 is also cited.

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

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

    Mondala, Andro; Hernandez, Rafael; French, Todd

    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%more » 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.« less

  18. [Effect of FABP2 gene G54A polymorphism on lipid and glucose metabolism in simple obesity children].

    PubMed

    Xu, Yunpeng; Rao, Xiaojiao; Hao, Min; Hou, Lijuan; Zhu, Xiaobo; Chang, Xiaotong

    2016-01-01

    To explore the relationship between intestinal fatty acid binding protein (FABP2) gene G54A polymorphism and simple childhood obesity, the effect of mutant 54A FABP2 gene on serum lipids and glucose metabolism. The total of 83 subjects with overweight/obesity and 100 subjects with healthy/normal weight were involved in this study. The G54A FABP2 gene allele and genotype frequencies between control group and overweight/obesity group were detected using polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) technology, and DNA sequences were confirmed by DNA sequencing. The automatic biochemical analyzer was used to detect fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. Plasma insulin (Ins) was detected by radiation immune method, free fatty acids (FFA) was tested by ELISA method, insulin resistance index ( HOMA-IR ) was also calculated. The correlation between FABP2 G54A polymorphism and the development of children' obesity was analyzed. The relation between FABP2 G54A polymorphism and abnormal blood lipid and insulin resistance was assessed. The results of study on FABP2 gene polymorphism revealed as followed. In overweight/obese groups, the frequencies of GG, GA, AA genotypes was 33.7%, 49.4% and 16.9%, respectively. In control group, the frequencies of GG, GA, AA genotypes was 51. 0% , 40. 0% and 9. 0% , respectively. The differences between two groups was statistically significant (Χ2 = 6.27, P < 0.05). In overweight/obesity group, the frequencies of alleles were 58.4% for 54G and 41.6% for 54A. In control group, the frequencies of alleles were 71.0% for 54G and 29.0% for 54A. There was significant differences (Χ2 = 6.32, P < 0.05). The plasma biochemical variables results showed that compared with the normal control group, plasma TG (P < 0.01), Ins (P < 0.05), HOMA-IR (P < 0.05) were elevated in overweight

  19. Cilioretinal artery: Vasculogenesis might be promoted by plasminogen activator inhibitor-1 5G allele.

    PubMed

    Yilmaz, Sarenur; Ardagil, Aylin; Akalin, Ibrahim; Altinel, Meltem Guzin; Dag, Yasar; Kurum, Esra; Koyun, Efe; Ari Yaylali, Sevil; Bayramlar, Huseyin

    2017-01-01

    Cilioretinal arteries (CAs) represent enlargements of microscopic and early established collaterals formed via vasculogenesis between choroidal and retinal circulations. We aimed to investigate whether genetic tendency to thrombosis due to well-known gene polymorphisms may induce CA vasculogenesis in embryonic life. We assessed plasminogen activator inhibitor-1 (PAI-1) 4G/5G, methylenetetrahydrofolatereductase (MTHFR), FACTOR V LEIDEN and PROTHROMBIN gene polymorphisms on 130 patients [82/48 females/males; Median age: 57 (18-84) with visible CAs and 100 (64/36: female/male; Median age: 55 (19-90)] without visible CAs. Using multiple logistic regression models, we found PAI-1 4G/5G; MTHFR (C677T and A1298C) polymorphisms to have significant effects on the probability of visible CAs, that having at least one 5G allele would increase the odds of having visible cilioretinal artery by 98.4% [Odds ratio: 1984 (95% CI: 1.320-3.000, p = 0.001)], and having at least one MTHFR C677T or A1298C allele would decrease the odds of having visible CAs by approximately 38% (OR = 0.618, 95% CI: 0.394-0.961, p = 0.035) or 44% (OR = 0.558, 95% CI: 0.354-0.871, p = 0.011), respectively. This is the first study to test the existence of significant association between presence of enlarged and visible CAs and genetic factors predisposing to thrombosis, according to the literature. Here we suggest that not only the lack of genetic predisposition to thrombosis by MTHFR gene polymorphisms, but also the PAI-1 5G allele might promote vasculogenesis of CAs.

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

    PubMed

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

    2010-09-15

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

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

    PubMed Central

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

    2013-01-01

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

  2. [Evaluation of grip strength in normal and obese Wistar rats submitted to swimming with overload after median nerve compression].

    PubMed

    Coradinia, Josinéia Gresele; Kakihata, Camila Mayumi Martin; Kunz, Regina Inês; Errero, Tatiane Kamada; Bonfleur, Maria Lúcia; Bertolini, Gladson Ricardo Flor

    2015-01-01

    To verify the functionality through muscle grip strength in animals with obesity induced by monosodium glutamate (MSG) and in control animals, which suffered compression of the right median nerve, and treated with swimming with overload. During the first five days of life, neonatal Wistar rats received subcutaneous injections of MSG. The control group received a hypertonic saline solution. Forty-eight rats were divided into six groups: G1 (control); G2 (control + injury); G3 (control + injury + swimming); G4 (obese); G5 (obese + injury); G6 (obese + injury + swimming). The animals in groups G2, G3, G5 and G6 were submitted to compression of the median nerve and G3 and G6 groups were treated, after injury, with swimming exercise with load for three weeks. The swimming exercise had a progressive duration, according to the week, of 20, 30 and 40minutes. Muscle strength was assessed using a grip strength meter preoperatively and on the 3rd, 7th, 14th and 21st days after surgery. The results were expressed and analyzed using descriptive and inferential statistics. When the grip strength was compared among assessments regardless of group, in the second assessment the animals exhibited lower grip strength. G1 and G4 groups had greater grip strength, compared to G2, G3, G4 and G6. The swimming exercise with overload has not been effective in promoting improvement in muscle grip strength after compression injury of the right median nerve in control and in obese-MSG rats. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  3. Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1.

    PubMed

    Svensson, Katrin J; Christianson, Helena C; Wittrup, Anders; Bourseau-Guilmain, Erika; Lindqvist, Eva; Svensson, Lena M; Mörgelin, Matthias; Belting, Mattias

    2013-06-14

    The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signaling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signaling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft-associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signaling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signaling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.

  4. The effect of polyethylene glycol-modified lipids on the interaction of HIV-1 derived peptide-dendrimer complexes with lipid membranes.

    PubMed

    Melikishvili, Sophie; Poturnayova, Alexandra; Ionov, Maksim; Bryszewska, Maria; Vary, Tomáš; Cirak, Julius; Muñoz-Fernández, María Ángeles; Gomez-Ramirez, Rafael; de la Mata, Francisco Javier; Hianik, Tibor

    2016-12-01

    In this study, dendrimers have been purposed as an alternative approach for delivery of HIV peptides to dendritic cells. We have investigated the interaction of dendriplexes formed from polyanionic HIV peptide Nef and cationic carbosilane dendrimer (CBD) with model lipid membranes - large unilamellar vesicles (LUVs), Langmuir monolayers and supported lipid membranes (sBLMs) containing various molar ratio of zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG 2000 ). In our experiments, the lipid membranes represented the model of the plasma membrane of the cell. PEGylated lipids were used in order to model glycocalyx which constitutes the outer leaflet of cellular membranes. The presence of PEGylated lipids resulted in an increase of the phase transition temperature of the lipid bilayer of LUVs, in a decrease of specific volume and adiabatic compressibility. Fluorescence anisotropy study suggests that PEGylated LUVs possessed higher lipid order and decreased fluidity when compared to zwitterionic DMPC vesicles. The interaction of dendriplexes with monolayers was accompanied by the formation of the aggregates as revealed by BAM experiments. This conclusion has been confirmed also by AFM imaging of sBLMs. We have demonstrated that dendriplexes interact with lipid membranes for all types of lipid composition. Moreover, the stronger interaction of cationic dendrimer/peptide complexes with lipid monolayers, vesicles and sBLMs was observed for membranes composed of zwitterionic lipids than for PEGylated lipid membranes. Increased concentration of PEGylated lipids made this interaction weaker. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Lipid and fatty acid compositions of cod ( Gadus morhua), haddock ( Melanogrammus aeglefinus) and halibut ( Hippoglossus hippoglossus)

    NASA Astrophysics Data System (ADS)

    Zeng, Duan; Mai, Kangsen; Ai, Qinghui; Milley, Joyce E.; Lall, Santosh P.

    2010-12-01

    This study was conducted to compare lipid and fatty acid composition of cod, haddock and halibut. Three groups of cod (276 g ± 61 g), haddock (538 g ± 83 g) and halibut (3704 g ± 221 g) were maintained with commercial feeds mainly based on fish meal and marine fish oil for 12 weeks prior to sampling. The fatty acid compositions of muscle and liver were determined by GC/FID after derivatization of extracted lipids into fatty acid methyl esters (FAME). Lipids were also fractionated into neutral and polar lipids using Waters silica Sep-Pak?. The phospholipid fraction was further separated by high-performance thin-layer chromatography (HPTLC) and the FAME profile was obtained. Results of the present study showed that cod and haddock were lean fish and their total muscle lipid contents were 0.8% and 0.7%, respectively, with phospholipid constituting 83.6% and 87.5% of the total muscle lipid, respectively. Halibut was a medium-fat fish and its muscle lipid content was 8%, with 84% of the total muscle lipid being neutral lipid. Total liver lipid contents of cod, haddock and halibut were 36.9%, 67.2% and 30.7%, respectively, of which the neutral lipids accounted for the major fraction (88.1%-97.1%). Polyunsaturated fatty acids were the most abundant in cod and haddock muscle neutral lipid. Monounsaturated fatty acid level was the highest in halibut muscle neutral lipid. Fatty acid compositions of phospholipid were relatively constant. In summary, the liver of cod and haddock as lean fish was the main lipid reserve organ, and structural phospholipid is the major lipid form in flesh. However, as a medium-fat fish, halibut stored lipid in both their liver and muscle.

  6. Salt modulates the stability and lipid binding affinity of the adipocyte lipid-binding proteins

    NASA Technical Reports Server (NTRS)

    Schoeffler, Allyn J.; Ruiz, Carmen R.; Joubert, Allison M.; Yang, Xuemei; LiCata, Vince J.

    2003-01-01

    Adipocyte lipid-binding protein (ALBP or aP2) is an intracellular fatty acid-binding protein that is found in adipocytes and macrophages and binds a large variety of intracellular lipids with high affinity. Although intracellular lipids are frequently charged, biochemical studies of lipid-binding proteins and their interactions often focus most heavily on the hydrophobic aspects of these proteins and their interactions. In this study, we have characterized the effects of KCl on the stability and lipid binding properties of ALBP. We find that added salt dramatically stabilizes ALBP, increasing its Delta G of unfolding by 3-5 kcal/mol. At 37 degrees C salt can more than double the stability of the protein. At the same time, salt inhibits the binding of the fluorescent lipid 1-anilinonaphthalene-8-sulfonate (ANS) to the protein and induces direct displacement of the lipid from the protein. Thermodynamic linkage analysis of the salt inhibition of ANS binding shows a nearly 1:1 reciprocal linkage: i.e. one ion is released from ALBP when ANS binds, and vice versa. Kinetic experiments show that salt reduces the rate of association between ANS and ALBP while simultaneously increasing the dissociation rate of ANS from the protein. We depict and discuss the thermodynamic linkages among stability, lipid binding, and salt effects for ALBP, including the use of these linkages to calculate the affinity of ANS for the denatured state of ALBP and its dependence on salt concentration. We also discuss the potential molecular origins and potential intracellular consequences of the demonstrated salt linkages to stability and lipid binding in ALBP.

  7. Identification of lipid-phosphatidylserine (PS) as the target of unbiasedly selected cancer specific peptide-peptoid hybrid PPS1.

    PubMed

    Desai, Tanvi J; Toombs, Jason E; Minna, John D; Brekken, Rolf A; Udugamasooriya, Damith Gomika

    2016-05-24

    Phosphatidylserine (PS) is an anionic phospholipid maintained on the inner-leaflet of the cell membrane and is externalized in malignant cells. We previously launched a careful unbiased selection targeting biomolecules (e.g. protein, lipid or carbohydrate) distinct to cancer cells by exploiting HCC4017 lung cancer and HBEC30KT normal epithelial cells derived from the same patient, identifying HCC4017 specific peptide-peptoid hybrid PPS1. In this current study, we identified PS as the target of PPS1. We validated direct PPS1 binding to PS using ELISA-like assays, lipid dot blot and liposome based binding assays. In addition, PPS1 recognized other negatively charged and cancer specific lipids such as phosphatidic acid, phosphatidylinositol and phosphatidylglycerol. PPS1 did not bind to neutral lipids such as phosphatidylethanolamine found in cancer and phosphatidylcholine and sphingomyelin found in normal cells. Further we found that the dimeric version of PPS1 (PPS1D1) displayed strong cytotoxicity towards lung cancer cell lines that externalize PS, but not normal cells. PPS1D1 showed potent single agent anti-tumor activity and enhanced the efficacy of docetaxel in mice bearing H460 lung cancer xenografts. Since PS and anionic phospholipid externalization is common across many cancer types, PPS1 may be an alternative to overcome limitations of protein targeted agents.

  8. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

    PubMed Central

    2013-01-01

    Background Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. ANCHOR was a 12-week, phase 3 study that evaluated the efficacy and safety of IPE in patients (N = 702) with residual high fasting TG levels (≥200 and <500 mg/dL) despite having optimized low-density lipoprotein cholesterol (LDL-C) levels (≥40 and <100 mg/dL) on statin therapy. Among patients randomized to IPE (4 g/day or 2 g/day) or placebo, 514 (73%) had diabetes mellitus. Methods A post hoc subgroup analysis of the ANCHOR study was conducted to assess the effects of IPE on median placebo-adjusted percent change from baseline in efficacy end point parameters in 3 subgroups: total (all subjects with diabetes—overall median baseline glycosylated hemoglobin A1c [A1c] = 6.8%), better-controlled diabetes (below median baseline A1c), and less-controlled diabetes (above median baseline A1c). Results Baseline efficacy parameters were similar among all groups except high-sensitivity C-reactive protein (hsCRP), which was higher in the total and less-controlled diabetes groups. Compared with placebo, IPE 4 g/day significantly reduced TG, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein-associated phospholipase A2, apolipoprotein B (Apo B), total cholesterol, high-density lipoprotein cholesterol, VLDL-TG, oxidized LDL, and remnant-like particle cholesterol in all 3 diabetes groups, LDL-C in the total diabetes group, and hsCRP in the total and less-controlled diabetes groups. Decreases in hsCRP and Apo B were much greater in patients with less-controlled diabetes. There were no significant increases in fasting plasma glucose, A1c, insulin, or homeostasis model assessment-estimated insulin resistance in any group. Conclusion IPE 4 g/day significantly improved

  9. Synchronized growth and neutral lipid accumulation in Chlorella sorokiniana FC6 IITG under continuous mode of operation.

    PubMed

    Kumar, Vikram; Muthuraj, Muthusivaramapandian; Palabhanvi, Basavaraj; Das, Debasish

    2016-01-01

    Synchronized growth and neutral lipid accumulation with high lipid productivity under mixotrophic growth of the strain Chlorella sorokiniana FC6 IITG was achieved via manipulation of substrates feeding mode and supplementation of lipid elicitors in the growth medium. Screening and optimization of lipid elicitors resulted in lipid productivity of 110.59mgL(-1)day(-1) under the combined effect of lipid inducers sodium acetate and sodium chloride. Fed-batch cultivation of the strain in bioreactor with intermittent feeding of limiting nutrients and lipid inducer resulted in maximum biomass and lipid productivity of 2.08 and 0.97gL(-1)day(-1) respectively. Further, continuous production of biomass with concomitant lipid accumulation was demonstrated via continuous feeding of BG11 media supplemented with lipid inducers sodium acetate and sodium chloride. The improved biomass and lipid productivity in chemostat was found to be 2.81 and 1.27gL(-1)day(-1) respectively operated at a dilution rate of 0.54day(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Gene polymorphisms of TNF-alpha-308 (G/A), IL-10(-1082) (G/A), IL-6(-174) (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus.

    PubMed

    Settin, Ahmad; Ismail, Azza; El-Magd, Megahed Abo; El-Baz, Rizk; Kazamel, Amira

    2009-01-01

    Type 1 diabetes (T1D) is a genetically conditioned autoimmune disease in which cytokines play an important role. Objectives. To check for the association of polymorphisms of cytokine genes with type 1 diabetes. Subjects. This work included 50 cases with T1D and 98 healthy individuals from the Nile Delta region of Egypt. Cases included 20 males and 30 females with a median age of 25 and range of 15-50 years. DNA was amplified using PCR with sequence-specific primers for detection of polymorphisms related to tumor necrosis factor (TNF)-alpha(- 308) (G/A), interleukin (IL)-10(- 1082) (G/A), IL-6(- 174) (G/C), and IL-1Ra (VNTR). Cases with T1D showed significant higher frequency of genotypes of TNF-alpha(- 308) AA (p < 0.001, odds ratio (OR) = 7.91), IL-6-17CC (p < 0.05, OR = 3.36) and IL-1Ra A1A1 (p < 0.05, OR = 3.68) with significant lower frequencies of TNF-alpha(- 308) GA, and IL-1Ra A1A2 genotypes (p < 0.001 and < 0.05, respectively). They also showed significant higher frequency of TNF-alpha(- 308) allele A (p < 0.05, OR = 2.0), IL-1Ra allele A1 (p < 0.05, OR = 2.98) with a significant lower frequency of TNF-alpha(- 308) G allele and IL-1Ra A2 allele (p < 0.05). No significant difference was detected among cases in relation to IL-10(- 1082) (G/A) genotypes or alleles nor in relation to age, sex, consanguinity or family history of the disease. Polymorphisms related to TNF-alpha and IL-1Ra genes may be considered genetic markers for T1D among Egyptians with a potential impact on family counseling and management.

  11. ApoB-100 secretion by HepG2 cells is regulated by the rate of triglyceride biosynthesis but not by intracellular lipid pools.

    PubMed

    Benoist, F; Grand-Perret, T

    1996-10-01

    Triglycerides (TGs), cholesteryl esters (CEs), cholesterol, and phosphatidylcholine have been independently proposed as playing regulatory roles in apoB-100 secretion; the results depended on the cellular model used. In this study, we reinvestigate the role of lipids in apoB-100 production in HepG2 cells and in particular, we clarify the respective roles of intracellular mass and the biosynthesis of lipids in the regulation of apoB-100 production. In a first set of experiments, the pool size of cholesterol, CEs, and TGs was modulated by a 3-day treatment with either lipid precursors or inhibitors of enzymes involved in lipid synthesis. We used simvastatin (a hydroxymethylglutaryl coenzyme A reductase inhibitor), 58-035 (an acyl coenzyme A cholesterol acyltransferase inhibitor), 5-tetradecyloxy-2-furancarboxylic acid (TOFA, an inhibitor of fatty acid synthesis), and oleic acid. The secretion rate of apoB-100 was not affected by the large modulation of lipid mass induced by these various pre-treatments. In a second set of experiments, the same lipid modulators were added during a 4-hour labeling period. Simvastatin and 58-035 inhibited cholesterol and CE synthesis without affecting apoB-100 secretion. By contrast, treatment of HepG2 cells with TOFA resulted in the inhibition of TG synthesis and apoB-100 secretion. This effect was highly specific for apoB-100 and was reversed by adding oleic acid, which stimulated both TG synthesis and apoB-100 secretion. Moreover, a combination of oleic acid and 58-035 inhibited CE biosynthesis and increased both TG synthesis and apoB-100 secretion. These results show that in HepG2 cells TG biosynthesis regulates apoB-100 secretion, whereas the rate of cholesterol or CE biosynthesis has no effect.

  12. Combination of 1H nuclear magnetic resonance spectroscopy and principal component analysis to evaluate the lipid fluidity of flutamide-encapsulated lipid nanoemulsions.

    PubMed

    Takegami, Shigehiko; Ueyama, Keita; Konishi, Atsuko; Kitade, Tatsuya

    2018-06-06

    The lipid fluidity of various lipid nanoemulsions (LNEs) without and with flutamide (FT) and containing one of two neutral lipids, one of four phosphatidylcholines as a surfactant, and sodium palmitate as a cosurfactant was investigated by the combination of 1 H nuclear magnetic resonance (NMR) spectroscopy and principal component analysis (PCA). In the 1 H NMR spectra, the peaks from the methylene groups of the neutral lipids and surfactants for all LNE preparations showed downfield shifts with increasing temperature from 20 to 60 °C. PCA was applied to the 1 H NMR spectral data obtained for the LNEs. The PCA resulted in a model in which the first two principal components (PCs) extracted 88% of the total spectral variation; the first PC (PC-1) axis and second PC (PC-2) axis accounted for 73 and 15%, respectively, of the total spectral variation. The Score-1 values for PC-1 plotted against temperature revealed the existence of two clusters, which were defined by the neutral lipid of the LNE preparations. Meanwhile, the Score-2 values decreased with rising temperature and reflected the increase in lipid fluidity of each LNE preparation, consistent with fluorescence anisotropy measurements. In addition, the changes of Score-2 values with temperature for LNE preparations with FT were smaller than those for LNE preparations without FT. This indicates that FT encapsulated in LNE particles markedly suppressed the increase in lipid fluidity of LNE particles with rising temperature. Thus, PCA of 1 H NMR spectra will become a powerful tool to analyze the lipid fluidity of lipid nanoparticles. Graphical abstract ᅟ.

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

    PubMed

    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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Temperature induced modulation of lipid oxidation and lipid accumulation in palmitate-mediated 3T3-L1 adipocytes and 3T3-L1 adipocytes.

    PubMed

    Lin, Xiaofen; Li, Yi; Leung, Polly Hangmei; Li, Jiashen; Hu, Junyan; Liu, Xuan; Li, Zhi

    2016-05-01

    Human skin temperature can vary widely depending on anatomical location and ambient temperature. It is also known that local changes in skin and subcutaneous temperature can affect fat metabolism. This study aimed to explore the potential effects of surrounding thermal environment on fat by investigating cell viability, lipid oxidation, and lipid accumulation in 3T3-L1 adipocytes and palmitate-treated adipocytes after 4h incubation. No significant differences of viability in 3T3-L1 adipocytes were detected under different temperature conditions. Despite no significant increase being observed under warm temperature (39°C) conditions, a similarly significant suppression of intracellular reactive oxygen species (ROS) and lipid peroxidation were found in 3T3-L1 adipocytes and palmitate-treated adipocytes under 4h exposure to cooler temperatures of 31-33°C (P<0.01). ROS, chemically reactive molecules containing oxygen, are currently understood to be a major contributor to oxidantive stress in obesity. Additionally, cooler temperatures (31-33°C) could improve the size of lipid droplets in 3T3-L1 adipocytes (P<0.01), but no significant effect was generated by temperature change on lipid droplets in palmitate-treated adipocytes. In the palmitate-induced adiposity model, although excessive ROS and lipid peroxidation has been attenuated by temperature decrease (P<0.01), it still does not positively modulate lipid droplet size (P>0.05) and remedy the palmitate damage induced cell death (P<0.01). These findings provide preliminary support for potential interventions based on temperature manipulation for cell metabolism of adipocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Median barrier placement on six-lane, 46-foot median divided freeways

    DOT National Transportation Integrated Search

    2010-11-01

    This report summarizes the research efforts of using finite element modeling and simulations to evaluate the : performance of W-beam guardrails and cable median barriers on six-lane, 46-foot median divided freeways. A : literature review is included ...

  16. Lipids and collagen matrix restrict the hydraulic permeability within the porous compartment of adult cortical bone

    PubMed Central

    Wen, Demin; Androjna, Caroline; Vasanji, Amit; Belovich, Joanne; Midura, Ronald J.

    2010-01-01

    In vivo the hydraulic permeability of cortical bone influences the transport of nutrients, waste products and signaling molecules, thus influencing the metabolic functions of osteocytes and osteoblasts. In the current study two hypotheses were tested: the presence of (1) lipids and (2) collagen matrix in the porous compartment of cortical bone restricts its permeability. Our approach was to measure the radial permeability of adult canine cortical bone before and after extracting lipids with acetone-methanol, and before and after digesting collagen with bacterial collagenase. Our results showed that the permeability of adult canine cortical bone was below 4.0 × 10−17 m2, a value consistent with prior knowledge. After extracting lipids, permeability increased to a median value of 8.6 × 10−16 m2. After further digesting with collagenase, permeability increased to a median value of 1.4 × 10−14 m2. We conclude that the presence of both lipids and collagen matrix within the porous compartment of cortical bone restricts its radial permeability. These novel findings suggest that the chemical composition of the tissue matrix within the porous compartment of cortical bone influences the transport and exchange of nutrients and waste products, and possibly influences the metabolic functions of osteocytes and osteoblasts. PMID:19967451

  17. Maternal Lipid Provisioning Mirrors Evolution of Reproductive Strategies in Direct-Developing Whelks.

    PubMed

    Carrasco, Sergio A; Phillips, Nicole E; Sewell, Mary A

    2016-06-01

    The energetic input that offspring receive from their mothers is a well-studied maternal effect that can influence the evolution of life histories. Using the offspring of three sympatric whelks: Cominella virgata (one embryo per capsule); Cominella maculosa (multiple embryos per capsule); and Haustrum scobina (multiple embryos per capsule and nurse-embryo consumption), we examined how contrasting reproductive strategies mediate inter- and intraspecific differences in hatchling provisioning. Total lipid content (as measured in μg hatchling(-1) ± SE) was unrelated to size among the 3 species; the hatchlings of H. scobina were the smallest but had the highest lipid content (33.8 ± 8.1 μg hatchling(-1)). In offspring of C. maculosa, lipid content was 6.6 ± 0.4 μg hatchling(-1), and in offspring of C. virgata, it was 21.7 ± 3.2 μg hatchling(-1) The multi-encapsulated hatchlings of C. maculosa and H. scobina were the only species that contained the energetic lipids, wax ester (WE) and methyl ester (ME). However, the overall composition of energetic lipid between hatchlings of the two Cominella species reflected strong affinities of taxonomy, suggesting a phylogenetic evolution of the non-adelphophagic development strategy. Inter- and intracapsular variability in sibling provisioning was highest in H. scobina, a finding that implies less control of allocation to individual hatchlings in this adelphophagic developer. We suggest that interspecific variability of lipids offers a useful approach to understanding the evolution of maternal provisioning in direct-developing species. © 2016 Marine Biological Laboratory.

  18. Autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus is associated with elevated IgG4 but not with low vitamin D.

    PubMed

    Demir, Korcan; Keskin, Mehmet; Kör, Yilmaz; Karaoğlan, Murat; Bülbül, Özlem Gümüştekin

    2014-01-01

    To assess levels of vitamin D and of immunoglobulin G subclasses in children and adolescents with type 1 Diabetes Mellitus with or without autoimmune thyroiditis. Among 213 patients with type 1 diabetes, the cases with thyroid-specific autoantibodies formed Group 1 [n=19, M/F: 7/12, median age 13 years (10.1-14.7)]. Nineteen age-, gender-, and diabetes duration-matched cases with type 1 diabetes without any other systemic disease were designated as controls [Group 2, M/F: 7/12, median age 12.9 years (10.5-14.9)]. Levels of thyroid hormones, vitamin D, total IgG and IgG subclasses, as well as IgG subclasses/total IgG ratios were similar between the groups. Five cases (26%) in Group 1 had IgG4 levels > + 2 SDS, whereas there were no such cases in Group 2 (p=0.046). These five patients had similar clinical features but higher median IgG4 levels and IgG4/Total IgG ratios compared to the subjects with IgG4 levels < + 2 SDS in Group 1 and Group 2. There was no difference of vitamin D levels between the groups. Only a small percentage of patients with type 1 diabetes also having autoimmune thyroiditis had elevated serum IgG4 levels, revealing the heterogeneity of autoimmune thyroiditis and existence of IgG4 thyroiditis in the pediatric age group. Total IgG, the other IgG subclasses, and vitamin D levels did not differ in patients with autoimmune thyroiditis and type 1 diabetes compared to those suffering only from type 1 diabetes.

  19. Detailed Distribution of Lipids in Greenshell™ Mussel (Perna canaliculus)

    PubMed Central

    Miller, Matthew R.; Pearce, Luke; Bettjeman, Bodhi I.

    2014-01-01

    Greenshell™ mussels (GSM–Perna canaliculus) are a source of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). Farmed GSM are considered to be a sustainable source of LC-PUFA as they require no dietary inputs, gaining all of their oil by filter-feeding microorganisms from sea water. GSM oil is a high-value product, with a value as much as 1000 times that of fish oils. GSM oil has important health benefits, for example, anti-inflammatory activity. It also contains several minor lipid components that are not present in most fish oil products, and that have their own beneficial effects on human health. We have shown the lipid content of the female GSM (1.9 g/100 g ww) was significantly greater than that of the male (1.4 g/100 g ww). Compared with male GSM, female GSM contained more n-3 LC-PUFA, and stored a greater proportion of total lipid in the gonad and mantle. The higher lipid content in the female than the male GSM is most likely related to gamete production. This information will be useful to optimize extraction of oils from GSM, a local and sustainable source of n-3 LC-PUFA. PMID:24732016

  20. On the lipid composition of human meibum and tears: comparative analysis of nonpolar lipids.

    PubMed

    Butovich, Igor A

    2008-09-01

    To qualitatively compare the nonpolar lipids present in meibomian gland (MG) secretions (samples T1) with aqueous tears (AT) collected from the lower tear menisci of healthy, non-dry eye volunteers using either glass microcapillaries (samples T2) or Schirmer test strips (samples T3). Samples T1 to T3 were analyzed with the use of high-pressure liquid chromatography/positive ion mode atmospheric pressure chemical ionization mass spectrometry. Where possible, the unknown lipids were compared with known standards. Samples T1 had the simplest lipid composition among all the tested specimens. Samples T2 and T3 were similar to each other but were noticeably different from samples T1. In addition to all the compounds detected in samples T1, lower molecular weight wax esters and other compounds were found in samples T2 and T3. No appreciable amounts of fatty acid amides (e.g., oleamide), ceramides, or monoacyl glycerols were routinely detected. The occasionally observed minor signals of oleamide (m/z 282) in samples T3 were attributed to the contamination of the samples with common plasticizers routinely found in plastic ware extractives and organic solvents. The MG is a prominent source of lipids for the tear film. However, it would have been a mistake to exclude from consideration other likely sources of lipids such as conjunctiva, cornea, and tears produced by the lacrimal glands. These data showed that lipids in AT are more complex than MG secretions, which necessitates more cautious interpretation of the functions of the latter in the tear film.

  1. Aromatic hydrocarbon biodegradation activates neutral lipid biosynthesis in oleaginous yeast.

    PubMed

    Deeba, Farha; Pruthi, Vikas; Negi, Yuvraj S

    2018-05-01

    In this study, the biodegradation ability of oleaginous yeast Cryptococcus psychrotolerans IITRFD for aromatic hydrocarbons (AHs) was investigated. It was found to completely degrade range of AHs such as 1g/L phenol, 0.75 g/L naphthalene, 0.50 g/L anthracene and 0.50 g/L pyrene with lipid productivity (g/L/h) of 0.0444, 0.0441, 0.0394 and 0.0383, respectively. This work demonstrated the ring cleavage pathways of AHs by this yeast which follow ortho route for phenol and naphthalene while meta route for anthracene and pyrene degradation. The end products generated during biodegradation of AHs are feed as precursors for de novo triacylglycerols (TAG) biosynthesis pathway of oleaginous yeast. A high quantity of lipid content (46.54%) was observed on phenol as compared to lipid content on naphthalene (46.38%), anthracene (44.97%) and pyrene (44.16%). The lipid profile revealed by GC-MS analysis shows elevated monounsaturated fatty acid (MUFA) content with improved biodiesel quality. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Comparison of two dose regimens of growth hormone (GH) with different target IGF-1 levels on glucose metabolism, lipid profile, cardiovascular function and anthropometric parameters in gh-deficient adults.

    PubMed

    Cenci, Maria Claudia Peixoto; Soares, Débora Vieira; Spina, Luciana Diniz Carneiro; Brasil, Rosane Resende de Lima Oliveira; Lobo, Priscila Marise; Michmacher, Eduardo; Vaisman, Mario; Boguszewski, Cesar Luiz; Conceição, Flávia Lúcia

    2012-01-01

    To compare the effects of two regimens of GH therapy with different target IGF-1 levels on anthropometric parameters, glucose metabolism, lipid profile and cardiac function in adults with GH deficiency (GHD). Retrospective analysis of 14 GHD adults from Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, who were treated with a GH regimen aimed at maintaining serum IGF-1 levels between the median and upper reference limit (high dose group - HDGH) and 18 GHD adults from Federal University Hospital, Curitiba, Brazil, who received a fixed GH dose of 0.2mg/day in the first year of treatment, followed by titration to maintain serum IGF-1 levels between the median and lower reference limit (low dose group - LDGH). All patients were followed for 2 years with analysis of anthropometric parameters, serum levels of IGF-1, glucose, insulin, HOMA-IR, lipid profile, and transthoracic echocardiography. Changes on weight, BMI and waist circumference were similar between the two groups. Insulin levels increased and HOMA-IR worsened in the LDGH group at 1year and improved thereafter. Total cholesterol and triglycerides did not change with therapy. LDL cholesterol reduced in both groups, while HDL-cholesterol significantly increased only in the HDGH group (p=0.007 vs LDGH). No significant variations on echocardiographic parameters were observed. The HDGH and LDGH regimens resulted in similar changes on anthropometric, echocardiographic, glucose and lipid parameters in GHD adults, except for increase in HDL cholesterol that was only observed in the HDGH regimen. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Medians

    DOT National Transportation Integrated Search

    1996-02-01

    This discussion paper summarizes the literature relating to the use of medians on major roadways. The primary focus is on safety due to the sizable amount of literature in this area and the very limited number of studies relating to such topics as th...

  4. An independent effect of parental lipids on the offspring lipid levels in a cohort of adolescents with type 1 diabetes.

    PubMed

    Marcovecchio, M Loredana; Tossavainen, Paivi H; Heywood, James Jn; Dalton, R Neil; Dunger, David B

    2012-09-01

    Genetic factors modulate lipid levels and an intrafamilial aggregation of abnormal lipid profiles has been reported in the general population. As dyslipidemia is common among people with diabetes and has been related to diabetic nephropathy, we investigated whether parental lipid levels were related to lipids and albumin excretion in young offspring with childhood-onset type 1 diabetes (T1D). Non-fasting blood samples were collected from 895 offspring, 808 mothers and 582 fathers. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C were measured. Three early morning urinary albumin-creatinine ratios (ACR), hemoglobin A1C (HbA1c) and anthropometric parameters were also assessed. The offspring's mean age (±SD) was 14.5 ± 2.2 yr, mean diabetes duration 5.5 ± 3.7 yr; the fathers' age was 45.7 ± 6.1 yr and the mothers' age was 42.8 ± 5.5 yr. After adjusting for the offspring age, gender, body mass index, HbA1c, maternal (TC: β = 0.242; TG: β = 0.152; HDL-C: β = 0.285; LDL-C: β = 0.278; non-HDL-C: β = 0.253; all p < 0.001) and paternal lipid levels (TC: β = 0.188; TG: β = 0.108; HDL-C: β = 0.253; LDL-C: β = 0.187; non-HDL-C: β = 0.173; all p < 0.001) were significantly associated with the offspring's lipid parameters. In contrast, no significant association was found between parental lipid levels and the offspring's ACR. In the present study, parental lipid levels were independently associated with the same traits in the offspring, suggesting a role of genetic influences and/or shared environmental factors in modulating the metabolic profile of adolescents with T1D. In contrast, there was no significant association between parental lipid levels and the offspring's albumin excretion. © 2012 John Wiley & Sons A/S.

  5. Liposomal gD Ectodomain (gD1-306) Vaccine Protects Against HSV2 Genital or Rectal Infection of Female and Male Mice

    PubMed Central

    Olson, K.; Macias, P.; Hutton, S.; Ernst, W. A.; Fujii, G.; Adler-Moore, J. P.

    2009-01-01

    Herpes simplex virus type 2 (HSV2) is the most common causative agent of genital herpes, with infection rates as high as 1 in 6 adults. The present studies were done to evaluate the efficacy of a liposomal HSV2 gD1-306 vaccine (L-gD1-306-HD) in an acute murine HSV2 infection model of intravaginal (female) or intrarectal (male or female) challenge. Two doses of L-gD1-306-HD containing 60μg gD1-306-HD and 15μg monophosphoryl lipid A (MPL) per dose provided protection against HSV2 intravaginal challenge (86-100% survival, P≤0.0003 vs control liposomes; P=0.06 vs L-gD1-306-HD without MPL). Both male and female mice (BALB/c and C57BL/6) immunized with L-gD1-306-HD/MPL were significantly protected against HSV2 intrarectal challenge, with higher survival rates compared to controls (71-100%, P≤0.007). L-gD1-306-HD/MPL also provided increased survival when compared to a liposomal peptide vaccine, L-gD264-285-HD/MPL (male BALB/c, P≤0.001; female BALB/c and male C57BL/6, P=0.06). Mice given L-gD1-306-HD/MPL also had minimal disease signs, reduced viral burden in their spinal cords and elevated neutralizing antibody titers in the females. The vaccine also stimulated gD1-306-HD specific splenocytes of both male and female mice with significantly elevated levels of IFN-γ compared to IL-4 (P≤0.01) indicating that there was an enhanced Th1 response. These results provide the first evidence that the L-gD1-306–HD vaccine can protect both male and female mice against intrarectal HSV2 challenge. PMID:19835825

  6. Structural interactions between lipids, water and S1-S4 voltage-sensing domains.

    PubMed

    Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J

    2012-11-02

    Membrane proteins serve crucial signaling and transport functions, yet relatively little is known about their structures in membrane environments or how lipids interact with these proteins. For voltage-activated ion channels, X-ray structures suggest that the mobile voltage-sensing S4 helix would be exposed to the membrane, and functional studies reveal that lipid modification can profoundly alter channel activity. Here, we use solid-state NMR to investigate structural interactions of lipids and water with S1-S4 voltage-sensing domains and to explore whether lipids influence the structure of the protein. Our results demonstrate that S1-S4 domains exhibit extensive interactions with lipids and that these domains are heavily hydrated when embedded in a membrane. We also find evidence for preferential interactions of anionic lipids with S1-S4 domains and that these interactions have lifetimes on the timescale of ≤ 10(-3)s. Arg residues within S1-S4 domains are well hydrated and are positioned in close proximity to lipids, exhibiting local interactions with both lipid headgroups and acyl chains. Comparative studies with a positively charged lipid lacking a phosphodiester group reveal that this lipid modification has only modest effects on the structure and hydration of S1-S4 domains. Taken together, our results demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close proximity to the hydrophobic interior of the membrane yet are well hydrated, a requirement for carrying charge and driving protein motions in response to changes in membrane voltage. Published by Elsevier Ltd.

  7. Structural interactions between lipids, water and S1-S4 voltage-sensing domains

    PubMed Central

    Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J.

    2012-01-01

    Membrane proteins serve crucial signaling and transport functions, yet relatively little is known about their structures in membrane environments or how lipids interact with these proteins. For voltage-activated ion channels, X-ray structures suggest that the mobile voltage-sensing S4 helix would be exposed to the membrane, and functional studies reveal that lipid modification can profoundly alter channel activity. Here we use solid-state NMR to investigate structural interactions of lipids and water with S1-S4 voltage-sensing domains, and to explore whether lipids influence the structure of the protein. Our results demonstrate that S1-S4 domains exhibit extensive interactions with lipids, and that these domains are heavily hydrated when embedded in a membrane. We also find evidence for preferential interactions of anionic lipids with S1-S4 domains, and that these interactions have lifetimes on the timescale of 10−3s. Arg residues within S1-S4 domains are well-hydrated and are positioned in close proximity to lipids, exhibiting local interactions with both lipid head groups and acyl chains. Comparative studies with a positively charged lipid lacking a phosphodiester group reveal that this lipid modification has only modest effects on the structure and hydration of S1-S4 domains. Taken together, our results demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close proximity to the hydrophobic interior of the membrane, yet are well-hydrated, a requirement for carrying charge and driving protein motions in response to changes in membrane voltage. PMID:22858867

  8. The Contrasting Relationships between Betaine and Homocysteine in Two Clinical Cohorts are Associated with Plasma Lipids and Drug Treatments

    PubMed Central

    Lever, Michael; George, Peter M.; Atkinson, Wendy; Elmslie, Jane L.; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

    2012-01-01

    Background Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease. Methods The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. Principal findings In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion. Conclusions Betaine excretion correlates with homocysteine in subjects with elevated blood lipids. PMID:22396767

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

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

    Malur, Anagha; Huizar, Isham; Wells, Greg

    2011-11-18

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

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

    PubMed

    Huang, Qi; Wang, Ting; Yang, Liu; Wang, He-Yao

    2017-05-19

    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.

  11. Lipid production of Chlorella vulgaris cultured in artificial wastewater medium.

    PubMed

    Feng, Yujie; Li, Chao; Zhang, Dawei

    2011-01-01

    Chlorella vulgaris was used to study algal lipid production with wastewater treatment. Artificial wastewater was used to cultivate C. vulgaris in a column aeration photobioreactor (CAP) under batch and semi-continuous cultivation with various daily culture replacements (0.5l-1.5l per 2l reactor). The cell density was decreased from 0.89 g/l with the daily replacement of 0.5l to 0.28 g/l with 1.5l replacement. However, C. vulgaris culture achieved the highest lipid content (42%, average value of the phase) and the lipid productivity (147 mg/ld(-1)) with daily replacement of 1.0 l. And then the nutrient removal efficiency were 86% (COD), 97% (NH(4)(+)) and 96% (TP), respectively. Analyses of energy efficiency showed that the net energy ratio (NER) for lipid production with daily replacement of 1.0 l (1.25) was higher than the other volume replacement protocols. And cost analyses showed that the algal biomass can be competitive with petroleum at US$ 63.97 per barrel with the potential credit for wastewater treatment. According to the above results, it is concluded that the present research will lead to an economical technology of algal lipid production. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Heterotrophy of filamentous oleaginous microalgae Tribonema minus for potential production of lipid and palmitoleic acid.

    PubMed

    Zhou, Wenjun; Wang, Hui; Chen, Lin; Cheng, Wentao; Liu, Tianzhong

    2017-09-01

    Heterotrophic fermentation and high valuable co-product producing are thought to be effective ways to improve the economic viability and feasibility of commercial production of microalgae biofuels. This work reported the heterotrophic cultivation of Tribonema minus for lipid and palmitoleic acid (a novel functional fatty acid) production. Firstly, the heterotrophic ability of T. minus was identified for the first time with significant promotion in biomass and lipid productivity, and glucose and urea were then selected as the optimal carbon and nitrogen sources. Moreover, nutrient concentrations and culture conditions were optimized. Highest biomass and lipid productivity of 30.8gL -1 and 730mgL -1 d -1 were obtained respectively by adding 80gL -1 glucose at once. In addition, 2gL -1 urea, 0.8gL -1 K 2 HPO 4 , 24mgL -1 ammonium ferric citrate, initial pH of 6, and temperature of 27°C were determined as the appropriate conditions for heterotrophic growth and lipid production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Lipid-coated mannitol core microparticles for sustained release of protein.

    PubMed

    Wang, Bifeng; Friess, Wolfgang

    2018-07-01

    Parenteral sustained release systems for proteins which provide therapeutic levels over a longer period avoiding frequent administration, which preserve protein stability during manufacturing, storage and application and which are biodegradable and highly biocompatible in the body are intensively sought after. The aim of this study was to generate and study mannitol core microparticles loaded with a monoclonal antibody IgG1 and coated with lipid either hard fat or glyceryl stearate at different coating levels. The protein was stabilized with 22.5 mg/mL sucrose, 0.1% PS 80, 10 mM methionine in 10 mM His buffer pH 7.2 during the spray loading process. 30 g protein-loaded mannitol carrier microparticles were coated with 5 g, 10 g, 20 g and 30 g of lipid, respectively. Placing more lipid onto the protein-loaded microparticles reduced both burst and release rate, and the particles maintained their geometric form during the release test. The IgG1 release from microparticles covered with a hard fat layer extended up to 6 weeks. The IgG1 was released in its monomeric form and maintained its secondary structure as shown by FTIR. Incomplete release of IgG1 from glyceryl stearate-coated microparticles was observed, which may be due to the small pore sizes of the glyceryl stearate layer or a detrimental surfactant character of glyceryl stearate to protein. Hence, these hard fat-coated mannitol core microparticles have high potential for protein delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Loss of CTRP1 disrupts glucose and lipid homeostasis

    PubMed Central

    Rodriguez, Susana; Lei, Xia; Petersen, Pia S.; Tan, Stefanie Y.; Little, Hannah C.

    2016-01-01

    C1q/TNF-related protein 1 (CTRP1) is a conserved plasma protein of the C1q family with notable metabolic and cardiovascular functions. We have previously shown that CTRP1 infusion lowers blood glucose and that transgenic mice with elevated circulating CTRP1 are protected from diet-induced obesity and insulin resistance. Here, we used a genetic loss-of-function mouse model to address the requirement of CTRP1 for metabolic homeostasis. Despite similar body weight, food intake, and energy expenditure, Ctrp1 knockout (KO) mice fed a low-fat diet developed insulin resistance and hepatic steatosis. Impaired glucose metabolism in Ctrp1 KO mice was associated with increased hepatic gluconeogenic gene expression and decreased skeletal muscle glucose transporter glucose transporter 4 levels and AMP-activated protein kinase activation. Loss of CTRP1 enhanced the clearance of orally administered lipids but did not affect intestinal lipid absorption, hepatic VLDL-triglyceride export, or lipoprotein lipase activity. In contrast to triglycerides, hepatic cholesterol levels were reduced in Ctrp1 KO mice, paralleling the reduced expression of cholesterol synthesis genes. Contrary to expectations, when challenged with a high-fat diet to induce obesity, Ctrp1 KO mice had increased physical activity and reduced body weight, adiposity, and expression of lipid synthesis and fibrotic genes in adipose tissue; these phenotypes were linked to elevated FGF-21 levels. Due in part to increased hepatic AMP-activated protein kinase activation and reduced expression of lipid synthesis genes, Ctrp1 KO mice fed a high-fat diet also had reduced liver and serum triglyceride and cholesterol levels. Taken together, these results provide genetic evidence to establish the significance of CTRP1 to systemic energy metabolism in different metabolic and dietary contexts. PMID:27555298

  15. Liposomal gD ectodomain (gD1-306) vaccine protects against HSV2 genital or rectal infection of female and male mice.

    PubMed

    Olson, K; Macias, P; Hutton, S; Ernst, W A; Fujii, G; Adler-Moore, J P

    2009-12-11

    Herpes simplex virus type 2 (HSV2) is the most common causative agent of genital herpes, with infection rates as high as 1 in 6 adults. The present studies were done to evaluate the efficacy of a liposomal HSV2 gD(1-306) vaccine (L-gD(1-306)-HD) in an acute murine HSV2 infection model of intravaginal (female) or intrarectal (male or female) challenge. Two doses of L-gD(1-306)-HD containing 60 microg gD(1-306)-HD and 15 microg monophosphoryl lipid A (MPL) per dose provided protection against HSV2 intravaginal challenge (86-100% survival, P< or =0.0003 vs. control liposomes; P=0.06 vs. L-gD(1-306)-HD without MPL). Both male and female mice (BALB/c and C57BL/6) immunized with L-gD(1-306)-HD/MPL were significantly protected against HSV2 intrarectal challenge, with higher survival rates compared to controls (71-100%, P< or =0.007). L-gD(1-306)-HD/MPL also provided increased survival when compared to a liposomal peptide vaccine, L-gD(264-285)-HD/MPL (male BALB/c, PgD(1-306)-HD/MPL also had minimal disease signs, reduced viral burden in their spinal cords and elevated neutralizing antibody titers in the females. The vaccine also stimulated gD(1-306)-HD specific splenocytes of both male and female mice with significantly elevated levels of IFN-gamma compared to IL-4 (P< or =0.01) indicating that there was an enhanced Th1 response. These results provide the first evidence that the L-gD(1-306)-HD vaccine can protect both male and female mice against intrarectal HSV2 challenge.

  16. Fast ultrasound-assisted extraction of polar (phenols) and nonpolar (lipids) fractions in Heterotheca inuloides Cass.

    PubMed

    Ricárdez, O F Mijangos; Ruiz-Jiménez, J; Lagunez-Rivera, L; de Castro, M D Luque

    2011-01-01

    Heterotheca inuloides Cass., also known as "arnica", is used in traditional medicine in Mexico. Development of fast methods for the extraction of lipidic and phenolic fractions from arnica plants and their subsequent characterization. Ultrasound was applied to accelerate extraction of the target compounds from this plant and reduce the use of organic solvents as compared with conventional methods. Gas chromatography-ion trap mass spectrometry and liquid chromatography with diode-array detection were used for the characterization of the lipidic and phenolic fractions, respectively. Under optimal extraction conditions, 9 and 55 min were necessary to complete extraction of the lipidic and phenolic fractions, respectively. The fatty acids present at the highest concentrations in H. inuloides were eicosatetraenoic n3 (24.6 μg/g), cis-9-hexadecenoic n7 (23.1 μg/g), exacosanoic (22.7 μg/g) and cis-9-octadecenoic acid (21.3 μg/g), while the rest were in the range 7.6-1.3 μg/g. The most concentrated phenols were guaiacol (41.5 μg/g), catechin (38.7 μg/g), ellagic acid (35.9 μg/g), carbolic acid (24.2 μg/g) and p-coumaric acid (19.5 μg/g), while the rest were in the range 5.1-0.4 μg/g. Ultrasound reduces the time necessary to complete the extraction 160 and 26 times, the extraction volume 2.5 and 4 times, and increases the extraction efficiency 5 and 3 times for lipidic and phenolic fractions, respectively, in comparison with conventional extraction methods. In addition, the characterization of the lipidic and phenolic fractions constitutes a first approach to the H. inuloides metabolome. Copyright © 2011 John Wiley & Sons, Ltd.

  17. Lipid composition of Castanea sativa Mill. and Aesculus hippocastanum fruit oils.

    PubMed

    Zlatanov, Magdalen D; Antova, Ginka A; Angelova-Romova, Maria J; Teneva, Olga T

    2013-02-01

    Sweet and horse chestnut fruit contain carbohydrates, fibers, proteins, lipids, vitamins, glycosides and coumarin. The lipids are rich in biologically active substances as fatty acids, phospholipids, sterols and tocopherols. The fruit has been used as food, and for medicinal purposes to treat inflammatory and vascular problems. The fruits of sweet and horse chestnut contain 20 and 81 g kg(-1) glyceride oil respectively. The content of phospholipids in the oils was 49 and 3 g kg(-1). Sterols were found to be 8 and 12 g kg(-1). In the tocopherol fraction (1920 and 627 mg kg(-1)) γ-tocopherol predominated in the sweet chestnut oil (927 g kg(-1)); γ-tocopherol (591 g kg(-1)) and α-tocopherol (402 g kg(-1)) in horse chestnut oil. Palmitic, oleic and linoleic acids predominated in the triacylglycerols. Higher quantities of palmitic and oleic acids were established in the phospholipids and sterol esters. The fruits of horse and sweet chestnut have a close lipid composition. The oils are rich in essential fatty acids, such as linoleic and linolenic, as well as biologically active substances: phospholipids, sterols and tocopherols. This fact determines the good food value of sweet chestnut fruit and the possibilities for use of horse chestnuts in pharmacy and for technical purposes. © 2012 Society of Chemical Industry.

  18. Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1.

    PubMed

    Zheng, Quan; Cao, Ying; Chen, Yalan; Wang, Jiqiu; Fan, Qiuju; Huang, Xian; Wang, Yiping; Wang, Tianshi; Wang, Xiuzhi; Ma, Jiao; Cheng, Jinke

    2018-06-01

    One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is associated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2 diabetes. In this study, we observed the overexpression of SUMO-specific protease 2 (Senp2) in adipose tissues during obesity. Adipocyte Senp2 deficiency resulted in less adipose lipid storage accompanied by an ectopic fat accumulation and insulin resistance under high-fat diet feeding. We further found that SET domain bifurcated 1 (Setdb1) was a SUMOylated protein and that SUMOylation promoted Setdb1 occupancy on the promoter locus of Pparg and Cebpa genes to suppress their expressions by H3K9me3. Senp2 could suppress Setdb1 function by de-SUMOylation. In adipocyte Senp2-deficiency mice, accumulation of the SUMOylated Setdb1 suppressed the expression of Pparg and Cebpa genes as well as lipid metabolism-related target genes, which would decrease the ability of lipid storage in adipocytes. These results revealed the crucial role of Senp2-Setdb1 axis in controlling adipose lipid storage.

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

    PubMed Central

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

    2008-01-01

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

  20. Characterization of Two Unique Cholesterol-Rich Lipid Particles Isolated from Human Atherosclerotic Lesions

    PubMed Central

    Chao, Fei-Fei; Blanchette-Mackie, E. Joan; Chen, Ya-Jun; Dickens, Benjamin F.; Berlin, Elliott; Amende, Lynn M.; Skarlatos, Sonia I.; Gamble, Wilbert; Resau, James H.; Mergner, Wolfgang T.; Kruth, Howard S.

    1990-01-01

    The authors' laboratory, using histochemicalmethods, previously identified two types of cholesterol-containing lipid particles in the extracellular spaces of human atherosclerotic lesions, one particle enriched in esterified cholesterol and the other particle enriched in unesterified cholesterol. The authors isolated and characterized these lipid particles. The esterified cholesterol-rich lipid particle was a small lipid droplet and differed from intracellular lipid dropletsfound in foam cells with respect to size and chemical composition. It had an esterified cholesterol core surrounded by aphospholipidunesterified cholesterol monolayer. Some aqueous spaces were seen within the particle core. Unesterified cholesterol-rich lipid particles were multilamellated, solid structures and vesicles comprised of single or multiple lamellas. The esterified cholesterol-rich particle had a density <1.01 g/ml, whereas the unesterified cholesterol-rich particle had a density between 1.03 and 1.05 g/ml. Both particles were similar in size fraction, whereas palmitate, stearate, oleate, and linoleate were predominant in the phospholipid fraction. The origins and the role of these two unusual lipid particles in vessel wall cholesterol metabolism remain to be determined. ImagesFigure 1Figure 3Figure 4Figure 5 PMID:2297045

  1. Membrane Binding of HIV-1 Matrix Protein: Dependence on Bilayer Composition and Protein Lipidation

    PubMed Central

    Barros, Marilia; Nanda, Hirsh

    2016-01-01

    ABSTRACT By assembling in a protein lattice on the host's plasma membrane, the retroviral Gag polyprotein triggers formation of the viral protein/membrane shell. The MA domain of Gag employs multiple signals—electrostatic, hydrophobic, and lipid-specific—to bring the protein to the plasma membrane, thereby complementing protein-protein interactions, located in full-length Gag, in lattice formation. We report the interaction of myristoylated and unmyristoylated HIV-1 Gag MA domains with bilayers composed of purified lipid components to dissect these complex membrane signals and quantify their contributions to the overall interaction. Surface plasmon resonance on well-defined planar membrane models is used to quantify binding affinities and amounts of protein and yields free binding energy contributions, ΔG, of the various signals. Charge-charge interactions in the absence of the phosphatidylinositide PI(4,5)P2 attract the protein to acidic membrane surfaces, and myristoylation increases the affinity by a factor of 10; thus, our data do not provide evidence for a PI(4,5)P2 trigger of myristate exposure. Lipid-specific interactions with PI(4,5)P2, the major signal lipid in the inner plasma membrane, increase membrane attraction at a level similar to that of protein lipidation. While cholesterol does not directly engage in interactions, it augments protein affinity strongly by facilitating efficient myristate insertion and PI(4,5)P2 binding. We thus observe that the isolated MA protein, in the absence of protein-protein interaction conferred by the full-length Gag, binds the membrane with submicromolar affinities. IMPORTANCE Like other retroviral species, the Gag polyprotein of HIV-1 contains three major domains: the N-terminal, myristoylated MA domain that targets the protein to the plasma membrane of the host; a central capsid-forming domain; and the C-terminal, genome-binding nucleocapsid domain. These domains act in concert to condense Gag into a membrane

  2. In vitro antitumor efficacy of berberine: solid lipid nanoparticles against human HepG2, Huh7 and EC9706 cancer cell lines

    NASA Astrophysics Data System (ADS)

    Meng, Xiang-Ping; Wang, Xiao; Wang, Huai-ling; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Hepatocarcinoma and esophageal squamous cell carcinomas threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma and esophageal carcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma and antiesophageal carcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded solid lipid nanoparticles (Ber-SLN) was prepared by hot melting and then high pressure homogenization technique. The in vitro anti-hepatocarcinoma and antiesophageal carcinoma effects of Ber-SLN relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-SLN were 154.3 ± 4.1 nm and -11.7 ± 1.8 mV, respectively. MTT assay showed that Ber-SLN effectively inhibited the proliferation of human HepG2 and Huh7 and EC9706 cells, and the corresponding IC50 value was 10.6 μg/ml, 5.1 μg/ml, and 7.3 μg/ml (18.3μg/ml, 6.5μg/ml, and 12.4μg/ml μg/ml of bulk Ber solution), respectively. These results suggest that the delivery of Ber-SLN is a promising approach for treating tumors.

  3. Electrostatic interactions of colicin E1 with the surface of Escherichia coli total lipid.

    PubMed

    Tian, Chunhong; Tétreault, Elaine; Huang, Christopher K; Dahms, Tanya E S

    2006-06-01

    The surface properties of colicin E1, a 522-amino acid protein, and its interaction with monolayers of Escherichia coli (E. coli) total lipid and 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DOPC) were studied using the Langmuir-Blodgett (LB) technique. Colicin E1 is amphiphilic, forming a protein monolayer at the air/buffer interface. The protein is thought to interact with the E. coli total lipid head groups through electrostatic interactions, followed by its insertion into the lipid monolayers. Supported lipid bilayers (SLBs) of E. coli total lipid and DOPC, deposited onto mica at the cell membrane equivalence pressure for E. coli and incubated with colicin E1, were imaged by contact mode atomic force microscopy (CM-AFM). Colicin E1 formed protein aggregates on DOPC SLBs, while E. coli total lipid SLB was deformed following its incubation with colicin E1. Corresponding lateral force images, along with electrostatic surface potentials for colicin E1 P190, imply a direct interaction of colicin E1 with lipid head groups facilitating their charge neutralization.

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

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

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

    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 exposuremore » 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.

  5. On the Lipid Composition of Human Meibum and Tears: Comparative Analysis of Nonpolar Lipids

    PubMed Central

    Butovich, Igor A.

    2009-01-01

    PURPOSE To qualitatively compare the nonpolar lipids present in meibomian gland (MG) secretions (samples T1) with aqueous tears (AT) collected from the lower tear menisci of healthy, non-dry eye volunteers using either glass microcapillaries (samples T2) or Schirmer test strips (samples T3). METHODS Samples T1 to T3 were analyzed with the use of high-pressure liquid chromatography/positive ion mode atmospheric pressure chemical ionization mass spectrometry. Where possible, the unknown lipids were compared with known standards. RESULTS Samples T1 had the simplest lipid composition among all the tested specimens. Samples T2 and T3 were similar to each other but were noticeably different from samples T1. In addition to all the compounds detected in samples T1, lower molecular weight wax esters and other compounds were found in samples T2 and T3. No appreciable amounts of fatty acid amides (e.g., oleamide), ceramides, or monoacyl glycerols were routinely detected. The occasionally observed minor signals of oleamide (m/z 282) in samples T3 were attributed to the contamination of the samples with common plasticizers routinely found in plastic ware extractives and organic solvents. CONCLUSIONS The MG is a prominent source of lipids for the tear film. However, it would have been a mistake to exclude from consideration other likely sources of lipids such as conjunctiva, cornea, and tears produced by the lacrimal glands. These data showed that lipids in AT are more complex than MG secretions, which necessitates more cautious interpretation of the functions of the latter in the tear film. PMID:18487374

  6. Clustering of Rac1: Selective Lipid Sorting Drives Signaling.

    PubMed

    Maxwell, Kelsey N; Zhou, Yong; Hancock, John F

    2018-02-01

    The ability of lipid-anchored small GTPases to form nanometer-scale lipid domains on the cell plasma membrane (PM) is precipitating exciting new insights into membrane-anchored protein regulation. A recent article by Remorino et al. demonstrates that Rac1, similar to Ras, forms nanoclusters on the PM. The implications of these findings are discussed herein. Copyright © 2017. Published by Elsevier Ltd.

  7. Entropic Anomaly Observed in Lipid Polymorphisms Induced by Surfactant Peptide SP-B(1-25).

    PubMed

    Tran, Nhi; Kurian, Justin; Bhatt, Avni; McKenna, Robert; Long, Joanna R

    2017-10-05

    The N-terminal 25 amino-acid residues of pulmonary surfactant protein B (SP-B 1-25 ) induces unusual lipid polymorphisms in a model lipid system, 4:1 DPPC/POPG, mirroring the lipid composition of native pulmonary surfactant. It is widely suggested that SP-B 1-25 -induced lipid polymorphisms within the alveolar aqueous subphase provide a structural platform for rapid lipid adsorption to the air-water interface. Here, we characterize in detail the phase behavior of DPPC and POPG in hydrated lipid assemblies containing therapeutic levels of SP-B 1-25 using 2 H and 31 P solid state NMR spectroscopy. The appearance of a previously observed isotropic lipid phase is found to be highly dependent on the thermal cycling of the samples. Slow heating of frozen samples leads to phase separation of DPPC into a lamellar phase whereas POPG lipids interact with the peptide to form an isotropic phase at physiologic temperature. Rapid heating of frozen samples to room temperature leads to strongly isotropic phase behavior for both DPPC and POPG lipids, with DPPC in exchange between isotropic and interdigitated phases. 31 P T 2 relaxation times confirm the isotropic phase to be consistent with a lipid cubic phase. The observed phases exhibit thermal stability up to physiologic temperature (37 °C) and are consistent with the formation of a ripple phase containing a large number of peptide-induced membrane structural defects enabling rapid transit of lipids between lipid lamellae. The coexistance of a lipid cubic phase with interdigitated lipids suggests a specific role for the highly conserved N-terminus of SP-B in stabilizing this unusual lipid polymorphism.

  8. Anti-hepatocarcinoma effects of berberine-nanostructured lipid carriers against human HepG2, Huh7, and EC9706 cancer cell lines

    NASA Astrophysics Data System (ADS)

    Meng, Xiang-Ping; Fan, Hua; Wang, Yi-fei; Wang, Zhi-ping; Chen, Tong-sheng

    2016-10-01

    Hepatocarcinoma and esophageal squamous cell carcinomas threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma and esophageal carcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma and antiesophageal carcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded nanostructured lipid carriers (Ber-NLC) was prepared by hot melting and then high pressure homogenization technique. The in vitro anti-hepatocarcinoma and antiesophageal carcinoma effects of Ber-NLC relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-NLC were 189.3 +/- 3.7 nm and -19.3 +/- 1.4 mV, respectively. MTT assay showed that Ber-NLC effectively inhibited the proliferation of human HepG2 and Huh7 and EC9706 cells, and the corresponding IC50 value was 9.1 μg/ml, 4.4 μg/ml, and 6.3 μg/ml (18.3μg/ml, 6.5μg/ml, and 12.4μg/ml μg/ml of bulk Ber solution), respectively. These results suggest that the delivery of Ber-NLC is a promising approach for treating tumors.

  9. Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.

    PubMed

    Tarr, Philip E; Taffé, Patrick; Bleiber, Gabriela; Furrer, Hansjakob; Rotger, Margalida; Martinez, Raquel; Hirschel, Bernard; Battegay, Manuel; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Rickenbach, Martin; Ledergerber, Bruno; Telenti, Amalio

    2005-05-01

    Single-nucleotide polymorphisms in genes involved in lipoprotein and adipocyte metabolism may explain why dyslipidemia and lipoatrophy occur in some but not all antiretroviral therapy (ART)-treated individuals. We evaluated the contribution of APOC3 -482C-->T, -455T-->C, and 3238C-->G; epsilon 2 and epsilon 4 alleles of APOE; and TNF -238G-->A to dyslipidemia and lipoatrophy by longitudinally modeling >2600 lipid determinations and 2328 lipoatrophy assessments in 329 ART-treated patients during a median follow-up period of 3.4 years. In human immunodeficiency virus (HIV)-infected individuals, the effects of variant alleles of APOE on plasma cholesterol and triglyceride levels and of APOC3 on plasma triglyceride levels were comparable to those reported in the general population. However, when treated with ritonavir, individuals with unfavorable genotypes of APOC3 and [corrected] APOE were at risk of extreme hypertriglyceridemia. They had median plasma triglyceride levels of 7.33 mmol/L, compared with 3.08 mmol/L in the absence of ART. The net effect of the APOE*APOC3*ritonavir interaction was an increase in plasma triglyceride levels of 2.23 mmol/L. No association between TNF -238G-->A and lipoatrophy was observed. Variant alleles of APOE and APOC3 contribute to an unfavorable lipid profile in patients with HIV. Interactions between genotypes and ART can lead to severe hyperlipidemia. Genetic analysis may identify patients at high risk for severe ritonavir-associated hypertriglyceridemia.

  10. EVALUATION OF RECOVERABLE FUNCTIONAL LIPID COMPONENTS OF SEVERAL BROWN SEAWEEDS (PHAEOPHYTA) FROM JAPAN WITH SPECIAL REFERENCE TO FUCOXANTHIN AND FUCOSTEROL CONTENTS(1).

    PubMed

    Terasaki, Masaru; Hirose, Atsushi; Narayan, Bhaskar; Baba, Yuta; Kawagoe, Chikara; Yasui, Hajime; Saga, Naotsune; Hosokawa, Masashi; Miyashita, Kazuo

    2009-08-01

    Fucoxanthin (Fx) and fucosterol (Fs) are characteristic lipid components of brown seaweeds that afford several health benefits to humans. This article describes the quantitative evaluation of lipids of 15 species of brown seaweeds with specific reference to Fx, Fs, and functional long-chain omega-6/omega-3 polyunsaturated fatty acids (PUFAs). In addition, fatty-acid composition of selected species was also accomplished in the study. Major omega-3 PUFAs in the brown seaweeds analyzed were α-linolenic acid (18:3n-3), octadecatetraenoic acid (18:4n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3). Both Fx (mg · g(-1) dry weight [dwt]) and Fs (mg · g(-1) dwt) were determined to be relatively abundant in Sargassum horneri (Turner) C. Agardh (Fx, 3.7 ± 1.6; Fs, 13.4 ± 4.4) and Cystoseira hakodatensis (Yendo) Fensholt (Fx, 2.4 ± 0.9; Fs, 8.9 ± 2.0), as compared with other brown seaweed species. Studies related to seasonal variation in Fx, Fs, and total lipids of six brown algae [S. horneri, C. hakodatensis, Sargassum fusiforme (Harv.) Setch., Sargassum thunbergii (Mertens ex Roth) Kuntze, Analipus japonicus (Harv.) M. J. Wynne, and Melanosiphon intestinalis (D. A. Saunders) M. J. Wynne] indicated that these functional lipid components reached maximum during the period between January and March. The functional lipid components present in these seaweeds have the potential for application as nutraceuticals and novel functional ingredients after their recovery. © 2009 Phycological Society of America.

  11. LipidPedia: a comprehensive lipid knowledgebase.

    PubMed

    Kuo, Tien-Chueh; Tseng, Yufeng Jane

    2018-04-10

    Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

  12. Rubber particle proteins REF1 and SRPP1 interact differently with native lipids extracted from Hevea brasiliensis latex.

    PubMed

    Wadeesirisak, Kanthida; Castano, Sabine; Berthelot, Karine; Vaysse, Laurent; Bonfils, Frédéric; Peruch, Frédéric; Rattanaporn, Kittipong; Liengprayoon, Siriluck; Lecomte, Sophie; Bottier, Céline

    2017-02-01

    Rubber particle membranes from the Hevea latex contain predominantly two proteins, REF1 and SRPP1 involved in poly(cis-1,4-isoprene) synthesis or rubber quality. The repartition of both proteins on the small or large rubber particles seems to differ, but their role in the irreversible coagulation of the rubber particle is still unknown. In this study we highlighted the different modes of interactions of both recombinant proteins with different classes of lipids extracted from Hevea brasiliensis latex, and defined as phospholipids (PL), glycolipids (GL) and neutral lipids (NL). We combined two biophysical methods, polarization modulated-infrared reflection adsorption spectroscopy (PM-IRRAS) and ellipsometry to elucidate their interactions with monolayers of each class of lipids. REF1 and SRPP1 interactions with native lipids are clearly different; SRPP1 interacts mostly in surface with PL, GL or NL, without modification of its structure. In contrast REF1 inserts deeply in the lipid monolayers with all lipid classes. With NL, REF1 is even able to switch from α-helice conformation to β-sheet structure, as in its aggregated form (amyloid form). Interaction between REF1 and NL may therefore have a specific role in the irreversible coagulation of rubber particles. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study.

    PubMed

    Casas-Agustench, Patricia; Serra, Mercè; Pérez-Heras, Ana; Cofán, Montserrat; Pintó, Xavier; Trautwein, Elke A; Ros, Emilio

    2012-06-01

    Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P < 0·015, both) in the PS-SM and PS-VFM periods, respectively. Serum lathosterol:cholesterol (C) ratios increased by 11-25 %, while sitosterol:C and campesterol:C ratios increased by 70-120 % with both the PS-fortified milk. Adjusted LDL-C reductions were variably enhanced in participants with basal low serum lathosterol/C or conversely high sitosterol/C and campesterol/C. Subjects with post-treatment serum PS:C ratios above the median showed mean LDL-C changes of - 5·9 to - 10·4 %, compared with 1·7 to - 2·9 % below the median. In conclusion, consumption of 2 g/d of PS as PS-SM and PS-VFM lowered LDL-C in hypercholesterolaemic subjects to a similar extent. Basal and post-treatment changes in markers of cholesterol metabolism indicating low cholesterol synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.

  14. Methylation on the Circadian Gene BMAL1 Is Associated with the Effects of a Weight Loss Intervention on Serum Lipid Levels.

    PubMed

    Samblas, Mirian; Milagro, Fermin I; Gómez-Abellán, Purificación; Martínez, J Alfredo; Garaulet, Marta

    2016-06-01

    The circadian clock system has been linked to the onset and development of obesity and some accompanying comorbidities. Epigenetic mechanisms, such as DNA methylation, are putatively involved in the regulation of the circadian clock system. The aim of this study was to investigate the influence of a weight loss intervention based on an energy-controlled Mediterranean dietary pattern in the methylation levels of 3 clock genes, BMAL1, CLOCK, and NR1D1, and the association between the methylation levels and changes induced in the serum lipid profile with the weight loss treatment. The study sample enrolled 61 women (body mass index = 28.6 ± 3.4 kg/m(2); age: 42.2 ± 11.4 years), who followed a nutritional program based on a Mediterranean dietary pattern. DNA was isolated from whole blood obtained at the beginning and end point. Methylation levels at different CpG sites of BMAL1, CLOCK, and NR1D1 were analyzed by Sequenom's MassArray. The energy-restricted intervention modified the methylation levels of different CpG sites in BMAL1 (CpGs 5, 6, 7, 9, 11, and 18) and NR1D1 (CpGs 1, 10, 17, 18, 19, and 22). Changes in cytosine methylation in the CpG 5 to 9 region of BMAL1 with the intervention positively correlated with the eveningness profile (p = 0.019). The baseline methylation of the CpG 5 to 9 region in BMAL1 positively correlated with energy (p = 0.047) and carbohydrate (p = 0.017) intake and negatively correlated with the effect of the weight loss intervention on total cholesterol (p = 0.032) and low-density lipoprotein cholesterol (p = 0.005). Similar significant and positive correlations were found between changes in methylation levels in the CpG 5 to 9 region of BMAL1 due to the intervention and changes in serum lipids (p < 0.05). This research describes apparently for the first time an association between changes in the methylation of the BMAL1 gene with the intervention and the effects of a weight loss intervention on blood lipids levels. © 2016 The Author(s).

  15. The effects of coconut oil supplementation on the body composition and lipid profile of rats submitted to physical exercise.

    PubMed

    Resende, Nathália M; Félix, Henrique R; Soré, Murillo R; M M, Aníbal; Campos, Kleber E; Volpato, Gustavo T

    2016-05-13

    This study aims to verify the effects of coconut oil supplementation (COS) in the body composition and lipid profile of rats submitted to physical exercise. The animals (n=6 per group) were randomly assigned to: G1=Sedentary and Non-supplemented (Control Group), G2=Sedentary and Supplemented, G3=Exercised and Non-supplemented and G4=Exercised and Supplemented. The COS protocol used was 3 mL/Kg of body mass by gavage for 28 days. The physical exercise was the vertical jumping training for 28 days. It was determined the body mass parameters, Lee Index, blood glucose and lipid profile. The COS did not interfere with body mass, but the lean body mass was lower in G3 compared to G2. The final Lee Index classified G1 and G2 as obese (>30g/cm). The lipid profile showed total cholesterol was decreased in G3, LDL-c concentration was decreased in G2, triglycerides, VLDL-c and HDL-c concentrations were increased in G2 and G4 in relation to G1 and G3. The COS decreased LDL-c/HDL-c ratio. In conclusion, the COS associated or not to physical exercise worsen others lipid parameters, like triglycerides and VLDL-c level, showing the care with the use of lipid supplements.

  16. Anaerobic digestion of cattle offal: protein and lipid-rich substrate degradation and population dynamics of acidogens and methanogens.

    PubMed

    Lee, Joonyeob; Koo, Taewoan; Han, Gyuseong; Shin, Seung Gu; Hwang, Seokhwan

    2015-12-01

    Anaerobic digestion of cattle offal was investigated in batch reactors at 35 °C to determine the feasibility of using cattle offal as a feedstock. The organic content [i.e., volatile solids (VS)] of the cattle offal was mainly composed of protein (33.9%) and lipids (46.1%). Hydrolysis along with acidogenesis was monitored to investigate the substrate degradation and generation of intermediate products (e.g., volatile fatty acids, ammonia). Acetate (2.03 g/L), propionate (0.60 g/L), n-butyrate (0.39 g/L), and iso-valerate (0.37 g/L) were major acidogenesis products (91% of total volatile fatty acid concentration). Overall protein and lipid degradation were 82.9 and 81.8%, respectively. Protein degraded first, and four times faster (0.28 day(-1)) than lipid (0.07 day(-1)). Methane yields were 0.52 L CH4/g VSadded and 0.65 L CH4/g VSremoved, indicating that anaerobic digestion of the offal was feasible. A quantitative QPCR assay was conducted to understand the microbial dynamics. The variation patt erns in the gene concentrations successfully indicated the population dynamics of proteolytic and lipolytic acidogens. A fourth-order Runge-Kutta approximation was used to determine the kinetics of the acidogens. The molecular biotechnology approach was appropriate for the evaluation of the acidogenic biokinetics. The maximum growth rate, μ m, halfsaturation coefficients, K s, microbial yield coefficient, Y, cell mass decay rate coefficient, k d, of the proteolytic acidogens were 9.9 day(-1), 37.8 g protein/L, 1.1 × 10(10) copies/g protein, and 3.8 × 10(-1), respectively. Those for the lipolytic acidogens were 1.2 × 10(-1) day(-1), 8.3 g lipid/L, 1.5 × 10(9) copies/g lipid, and 9.9 × 10(-3) day(-1), respectively.

  17. Serum levels of brominated flame retardants (BFRs: PBDE, HBCD) and influence of dietary factors in a population-based study on Swedish adults.

    PubMed

    Bjermo, Helena; Aune, Marie; Cantillana, Tatiana; Glynn, Anders; Lind, P Monica; Ridefelt, Peter; Darnerud, Per Ola

    2017-01-01

    The aim of this study was to investigate associations between serum concentrations of brominated flame retardants and personal characteristics, including diet, in adults participating in a population-based study in Sweden 2010-11. Moreover, observed concentrations were used in a health risk assessment, using published health-based reference values. Serum samples of 170 adult individuals of both sexes were analyzed for 10 PBDE congeners and HBCD by GC-MS. When including concentrations between LOD and LOQ, highest median serum concentration was observed for BDE-153 (1.2 ng/g serum lipid), followed by BDE-209 (0.95 ng/g lipid), BDE-47 (0.49 ng/g lipid) and BDE-100 (0.21 ng/g lipid). Median concentration of HBCD was 0.10 ng/g lipid. A few markedly elevated concentrations of BDE-209, HBCD (77-78 ng/g lipid) and BDE-47 (44 ng/g lipid) were observed. The only statistical significant findings were higher BDE-153 concentrations in men than in women, and positive associations between serum BDE-153 concentrations and consumption of fish (total), beef, mutton and poultry. PBDE concentrations were in accordance with concentrations reported in other European countries but generally lower than those found in North America. Median PBDE serum concentrations observed in adults from Sweden suggest sufficient health protection, when compared with published health-based reference values, although some outliers with high serum concentrations had lower safety margins. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

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

    Zhang, Wanlu; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province; Tang, Zhuqi

    High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion ofmore » TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. - Highlights: • TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling. • Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells. • Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.« less

  19. Threonine supplementation reduces dietary protein and improves lipid metabolism in Pekin ducks.

    PubMed

    Jiang, Y; Tang, J; Xie, M; Wen, Z G; Qiao, S Y; Hou, S S

    2017-12-01

    1. This study was conducted to investigate the efficiency of threonine (Thr) supplementation on reducing dietary crude protein (CP) content and the effects of Thr on lipid metabolism in Pekin ducks. The effects of dietary CP concentration (160, 190 and 220 g/kg) and Thr supplemental concentration (0, 0.7, 1.4, 2.1 and 2.8 g/kg) on growth performance, carcass, liver lipid and plasma profiles were determined in Pekin ducks from 1-21 d of age. 2. A total of 720-d-old male Pekin ducks were randomly allotted to 1 of 15 dietary treatments with 6 replicate cages of 8 birds per cage for each treatment according to average body weight. 3. Dietary Thr supplementation improved growth performance and breast muscle percentage at all CP diets, and ducks fed Thr-supplemented diets had higher plasma concentrations of some plasma amino acids. Thr supplementation reduced the concentrations of total lipid, triglyceride, cholesterol in liver, and plasma low density lipoprotein cholesterin concentration at 160 and 190 g/kg CP, whereas it increased triglyceride concentration at 160 g/kg CP. 4. Thr requirements based on quadratic broken-line model estimation were 6.6 and 7.0 g/kg for optimal average daily gain (ADG), and 6.7 and 7.3 g/kg for breast muscle percentage of Pekin ducks from 1-21 d of age at 190 and 220 g/kg CP, respectively. The dietary Thr requirements and estimated ADG (55.18 vs. 55.86 g/d/bird) and breast muscle percentage (2.79% vs. 2.75%) of Pekin ducks did not differ between 190 and 220 g/kg CP according to the t-test results. 5. Dietary CP level could be reduced to 190 g/kg in Pekin ducks from 1-21 d of age with Thr supplementation to balance dietary amino acids, and Thr supplementation prevented excess liver lipid deposition in this instance.

  20. 4G/5G Polymorphism of Plasminogen Activator Inhibitor -1 Gene Is Associated with Mortality in Intensive Care Unit Patients with Severe Pneumonia

    PubMed Central

    Sapru, Anil; Hansen, Helen; Ajayi, Temitayo; Brown, Ron; Garcia, Oscar; Zhuo, HanJing; Wiemels, Joseph; Matthay, Michael A.; Wiener-Kronish, Jeanine

    2011-01-01

    Background Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. Methods The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. Results A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. Conclusions The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia. PMID:19387177

  1. 4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with mortality in intensive care unit patients with severe pneumonia.

    PubMed

    Sapru, Anil; Hansen, Helen; Ajayi, Temitayo; Brown, Ron; Garcia, Oscar; Zhuo, HanJing; Wiemels, Joseph; Matthay, Michael A; Wiener-Kronish, Jeanine

    2009-05-01

    Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia.

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

    PubMed

    Zhang, Jianguo; Hu, Bo

    2012-02-01

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

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

    PubMed

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

    2017-09-01

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

  4. Excretion of extracellular lipids by Streptococcus mutans BHT and FA-1.

    PubMed Central

    Cabacungan, E; Pieringer, R A

    1980-01-01

    Streptococcus mutans BHT and FA-1, when grown to log phase on chemically defined medium containing [14C]glycerol, excreted 15% of the total biosynthesized 14C-lipid into the medium. When grown to early stationary phase, 28 to 33% of the 14C-lipid was found in the medium. The radioactive lipids of these varieties of S. mutans were identified as diacylglycerol, diglucosyl diacylglycerol (DGD), monoglucosyl diacylglycerol, diphosphatidylglycerol, phosphatidylglycerol (PG), and smaller amounts of two other lipids tentatively were identified as amino acyl-PG and glycerol phosphoryl-DGD. All lipids were found as extracellular and intracellular components from cells grown to either log or stationary phase. However, there were some shifts in the relative percentage of these lipids as the cells changed from log to stationary phase. For example, the intracellular lipid content of log-phase S. mutans BHT was composed of 49% PG and 19% DGD, but these percents shifted to 18% PG and 57% DGD when the cells were grown to stationary phase. However, the extracellular lipids of this organism contained 50 to 60% PG and 20% DGD in both log and stationary phases. PMID:7380539

  5. Association of Plasminogen Activator Inhibitor-Type 1 (-675 4G/5G) Polymorphism with Pre-Eclampsia: Systematic Review

    PubMed Central

    Morgan, Jessie A.; Bombell, Sarah; McGuire, William

    2013-01-01

    Background and Aims Excessive generation of plasminogen activator inhibitor-type 1 (PAI-1) is implicated in the pathogenesis of pre-eclampsia and related conditions. The PAI-1 (−675 4G/5G) promoter polymorphism (rs1799889) affects transcriptional activity and is a putative genetic risk factor for pre-eclampsia. The aim of this study was identify, appraise and synthesise the available evidence for the association of the PAI-1 (−675 4G/5G) polymorphism with pre-eclampsia. Methods Systematic review and random effects meta-analysis of genetic association studies. Results We found 12 eligible genetic association studies in which a total of 1511 women with pre-eclampsia, eclampsia or HELLP syndrome and 3492 controls participated. The studies were generally small (median number of cases 102, range 24 to 403) and underpowered to detect plausible association sizes. Meta-analysis of all of the studies detected statistically significant gene-disease associations in the recessive [pooled odds ratio 1.28 (95% confidence interval 1.09, 1.50); population attributable risk 7.7%] and dominant [pooled odds ratio 1.21 (95% confidence interval 1.01, 1.44); population attributable risk 13.7%] models. We did not find evidence of statistical heterogeneity, funnel plot asymmetry or small study bias. Conclusions These data suggest that the fibrinolytic pathway regulated by the PAI-1 gene may contribute to the pathogenesis of pre-eclampsia and related conditions. This association, if confirmed in larger genetic association studies, may inform research efforts to develop novel interventions or help to prioritise therapeutic targets that merit evaluation in randomised clinical trials. PMID:23457639

  6. Effects of molten-salt/ionic-liquid mixture on extraction of docosahexaenoic acid (DHA)-rich lipids from Aurantiochytrium sp. KRS101.

    PubMed

    Choi, Sun-A; Jung, Joo-Young; Kim, Kyochan; Kwon, Jong-Hee; Lee, Jin-Suk; Kim, Seung Wook; Park, Ji-Yeon; Yang, Ji-Won

    2014-11-01

    In this study, lipid extraction from Aurantiochytrium sp. was performed using a molten-salt/ionic-liquid mixture. The total fatty acid content of Aurantiochytrium sp. was 478.8 mg/g cell, from which 145 mg/g cell (30.3% of total fatty acids) of docosahexaenoic acid (DHA) was obtained. FeCl3·6H2O showed a high lipid extraction yield (207.9 mg/g cell), when compared with that of [Emim]OAc, which was only 118.1 mg/g cell; notably however, when FeCl3·6H2O was mixed with [Emim]OAc (5:1, w/w), the yield was increased to 478.6 mg/g cell. When lipid was extracted by the FeCl3·6H2O/[Emim]OAc mixture at a 5:1 (w/w) blending ratio under 90 °C, 30 min reaction conditions, the fatty acid content of the extracted lipid was a high purity 997.7 mg/g lipid, with most of the DHA having been extracted (30.2% of total fatty acids). Overall, lipid extraction from Aurantiochytrium sp. was enhanced by the synergistic effects of the molten-salt/ionic-liquid mixture with different ions.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27502578

  9. Incidence of hypertriglyceridemia in critically ill neonates receiving lipid injectable emulsions in glass versus plastic containers: a retrospective analysis.

    PubMed

    Martin, Camilia R; Dumas, Gregory J; Shoaie, Claire; Zheng, Zheng; Mackinnon, Brenda; Al-Aweel, Issa; Bistrian, Bruce R; Pursley, DeWayne M; Driscoll, David F

    2008-02-01

    To evaluate plasma clearance of lipid injectable emulsions packaged in either glass or plastic containers in neonates from 2 7-month periods, 1 year apart. Clinical records from June 1 to December 31, 2003 (glass [G] period) and the same months in 2004 (plastic [P] period) were assessed. Neonates who received lipid injectable emulsions were studied. Lipid container (glass vs plastic) was the independent variable. Of the 197 patients studied, 122 (G, 50/81; P, 72/116) had evaluable triglyceride (TG) levels, for an overall rate of 62%. Only birth weight (G, 1.09 +/- 0.32 kg vs P, 1.23 +/- .45 kg) and birth length (G, 36.4 +/- 3.5 cm vs P, 37.9 +/- 3.5 cm) were significantly different between the 2 groups (P = .047 and .028, respectively). There were no differences in the day of life on which lipid injection was started, the lipid dose, or the timing of TG measurements. The incidence of hypertriglyceridemia was significantly higher in the P period (G, 3/50 vs P, 19/72; P = .004). Administration of the same lipid formulation in plastic bags compared with glass containers is associated with higher rates of hypertriglyceridemia. The poorer clearance of lipids could be due to a higher proportion of large-diameter fat globules in plastic bags compared with those in glass containers.

  10. The CD1 family: serving lipid antigens to T cells since the Mesozoic era.

    PubMed

    Zajonc, Dirk M

    2016-08-01

    Class I-like CD1 molecules are in a family of antigen-presenting molecules that bind lipids and lipopeptides, rather than peptides for immune surveillance by T cells. Since CD1 lacks the high degree of polymorphism found in their major histocompatibility complex (MHC) class I molecules, different species express different numbers of CD1 isotypes, likely to be able to present structurally diverse classes of lipid antigens. In this review, we will present a historical overview of the structures of the different human CD1 isotypes and also discuss species-specific adaptations of the lipid-binding groove. We will discuss how single amino acid changes alter the shape and volume of the CD1 binding groove, how these minor changes can give rise to different numbers of binding pockets, and how these pockets affect the lipid repertoire that can be presented by any given CD1 protein. We will compare the structures of various lipid antigens and finally, we will discuss recognition of CD1-presented lipid antigens by antigen receptors on T cells (TCRs).

  11. The CD1 family: serving lipid antigens to T cells since the Mesozoic era

    PubMed Central

    Zajonc, Dirk M.

    2016-01-01

    Class I-like CD1 molecules are in a family of antigen-presenting molecules that bind lipids and lipopeptides, rather than peptides for immune surveillance by T cells. Since CD1 lacks the high degree of polymorphism found in their major histocompatibility complex (MHC) class I molecules, different species express different numbers of CD1 isotypes, likely to be able to present structurally diverse classes of lipid antigens. In this review, we will present a historical overview of the structures of the different human CD1 isotypes and also discuss species-specific adaptations of the lipid-binding groove. We will discuss how single amino acid changes alter the shape and volume of the CD1 binding groove, how these minor changes can give rise to different numbers of binding pockets, and how these pockets affect the lipid repertoire that can be presented by any given CD1 protein. We will compare the structures of various lipid antigens and finally, we will discuss recognition of CD1-presented lipid antigens by antigen receptors on T cells (TCRs). PMID:27368414

  12. Photosynthesis-fermentation hybrid system to produce lipid feedstock for algal biofuel.

    PubMed

    Lu, Yue; Dai, Junbiao; Wu, Qingyu

    2013-01-01

    To avoid bacterial contamination due to medium replacement in the expanded application of a photosynthesis-fermentation model, an integrated photosynthesis-fermentation hybrid system was set up and evaluated for algal lipid production using Chlorella protothecoides. In this system, the CO2-rich off-gas from the fermentation process was recycled to agitate medium in thephotobioreactor, which could provide initial cells for the heterotrophic fermentation. The cell concentration reached 1.03 +/- 0.07 g/L during photoautotrophic growth and then the concentrated green cells were switched to heterotrophic fermentation after removing over 99.5% ofnitrogen in the medium by a nitrogen removal device. At the end offermentation in the system, the cell concentration could reach as high as 100.51 +/- 2.03 g/L, and 60.05 +/- 1.38% lipid content was achieved simultaneously. The lipid yield (60.36 +/- 2.63 g/L) in the hybrid system was over 700 times higher than that in a photobioreactor and exceeded that by fermentation alone (47.56 +/- 7.31 g/L). The developed photosynthesis-fermentation hybrid system in this study was not only a feasible option to enhance microalgal lipid production, but also an environment-friendly approach to produce biofuel feedstock through concurrent utilization of ammonia nitrogen, CO2, and organic carbons.

  13. The effect of amino acids on lipid production and nutrient removal by Rhodotorula glutinis cultivation in starch wastewater.

    PubMed

    Liu, Meng; Zhang, Xu; Tan, Tianwei

    2016-10-01

    In this paper, the components of amino acids in mixed starch wastewater (corn steep water/corn gluten water=1/3, v/v) were analyzed by GC-MS. Effects of amino acids on lipid production by Rhodotorula glutinis and COD removal were studied. The results showed that mixed starch wastewater contained 9 kinds of amino acids and these amino acids significantly improved the biomass (13.63g/L), lipid yield (2.48g/L) and COD removal compared to the basic medium (6.23g/L and 1.56g/L). In a 5L fermentor containing mixed starch wastewater as substrate to culture R. glutinis, the maximum biomass, lipid content and lipid yield reached 26.38g/L, 28.90% and 7.62g/L, with the associated removal rates of COD, TN and TP reaching 77.41%, 69.12% and 73.85%, respectively. The results revealed a promising approach for lipid production with using amino acids present in starch wastewater as an alternative nitrogen source. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Lipid composition of thermophilic Geobacillus sp. strain GWE1, isolated from sterilization oven.

    PubMed

    Shah, Siddharth P; Jansen, Susan A; Taylor, Leeandrew Jacques-Asa; Chong, Parkson Lee-Gau; Correa-Llantén, Daniela N; Blamey, Jenny M

    2014-05-01

    GWE1 strain is an example of anthropogenic thermophilic bacterium, recently isolated from dark crusty material from sterilization ovens by Correa-Llantén et al. (Kor. J. Microb. Biotechnol. 2013. 41(3):278-283). Thermostability is likely to arise from the adaptation of macromolecules such as proteins, lipids and nucleic acids. Complex lipid arrangement and/or type in the cell membrane are known to affect thermostability of microorganisms and efforts were made to understand the chemical nature of the polar lipids of membrane. In this work, we extracted total lipids from GWE1 cell membrane, separated them by TLC into various fractions and characterize the lipid structures of certain fractions with analytical tools such as (1)H, (13)C, (31)P and 2D NMR spectroscopy, ATR-FTIR spectroscopy and MS(n) spectrometry. We were able to identify glycerophosphoethanolamine, glycerophosphate, glycerophosphocholine, glycerophosphoglycerol and cardiolipin lipid classes and an unknown glycerophospholipid class with novel MS/MS spectra pattern. We have also noticed the presence of saturated iso-branched fatty acids with NMR spectra in individual lipid classes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Lipid structure does not modify incorporation of EPA and DHA into blood lipids in healthy adults: a randomised-controlled trial.

    PubMed

    West, Annette L; Burdge, Graham C; Calder, Philip C

    2016-09-01

    Dietary supplementation is an effective means to improve EPA and DHA status. However, it is unclear whether lipid structure affects EPA+DHA bioavailability. We determined the effect of consuming different EPA and DHA lipid structures on their concentrations in blood during the postprandial period and during dietary supplementation compared with unmodified fish oil TAG (uTAG). In a postprandial cross-over study, healthy men (n 9) consumed in random order test meals containing 1·1 g EPA+0·37 g DHA as either uTAG, re-esterified TAG, free fatty acids (FFA) or ethyl esters (EE). In a parallel design supplementation study, healthy men and women (n 10/sex per supplement) consumed one supplement type for 12 weeks. Fatty acid composition was determined by GC. EPA incorporation over 6 h into TAG or phosphatidylcholine (PC) did not differ between lipid structures. EPA enrichment in NEFA was lower from EE than from uTAG (P=0·01). Plasma TAG, PC or NEFA DHA incorporation did not differ between lipid structures. Lipid structure did not affect TAG or NEFA EPA incorporation and PC or NEFA DHA incorporation following dietary supplementation. Plasma TAG peak DHA incorporation was greater (P=0·02) and time to peak shorter (P=0·02) from FFA than from uTAG in men. In both studies, the order of EPA and DHA incorporation was PC>TAG>NEFA. In conclusion, EPA and DHA lipid structure may not be an important consideration in dietary interventions.

  16. RKIP phosphorylation–dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3

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

    Hahm, Jong Ryeal; Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27; Ahmed, Mahmoud

    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 wasmore » 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

  17. Factors influencing particulate lipid production in the East Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Gašparović, B.; Frka, S.; Koch, B. P.; Zhu, Z. Y.; Bracher, A.; Lechtenfeld, O. J.; Neogi, S. B.; Lara, R. J.; Kattner, G.

    2014-07-01

    Extensive analyses of particulate lipids and lipid classes were conducted to gain insight into lipid production and related factors along the biogeochemical provinces of the Eastern Atlantic Ocean. Data are supported by particulate organic carbon (POC), chlorophyll a (Chl a), phaeopigments, Chl a concentrations and carbon content of eukaryotic micro-, nano- and picophytoplankton, including cell abundances for the latter two and for cyanobacteria and prokaryotic heterotrophs. We focused on the productive ocean surface (2 m depth and deep Chl a maximum (DCM). Samples from the deep ocean provided information about the relative reactivity and preservation potential of particular lipid classes. Surface and DCM particulate lipid concentrations (3.5-29.4 μg L-1) were higher than in samples from deep waters (3.2-9.3 μg L-1) where an increased contribution to the POC pool was observed. The highest lipid concentrations were measured in high latitude temperate waters and in the North Atlantic Tropical Gyral Province (13-25°N). Factors responsible for the enhanced lipid synthesis in the eastern Atlantic appeared to be phytoplankton size (micro, nano, pico) and the low nutrient status with microphytoplankton having the most expressed influence in the surface and eukaryotic nano- and picophytoplankton in the DCM layer. Higher lipid to Chl a ratios suggest enhanced lipid biosynthesis in the nutrient poorer regions. The various lipid classes pointed to possible mechanisms of phytoplankton adaptation to the nutritional conditions. Thus, it is likely that adaptation comprises the replacement of membrane phospholipids by non-phosphorus containing glycolipids under low phosphorus conditions. The qualitative and quantitative lipid compositions revealed that phospholipids were the most degradable lipids, and their occurrence decreased with increasing depth. In contrast, wax esters, possibly originating from zooplankton, survived downward transport probably due to the fast sinking

  18. Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population.

    PubMed

    Zhi, Xueyuan; Yang, Boyi; Fan, Shujun; Wang, Yanxun; Wei, Jian; Zheng, Quanmei; Sun, Guifan

    2016-10-28

    Little is known regarding the interactions of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with overweight/obesity on serum lipid profiles. The aim of the current study was to explore interactions between the two polymorphisms and overweight/obesity on four common lipid levels in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity. A total of 2239 participants (750 females and 1489 males) were enrolled into this study. The genotypes of the MTHFR C677T and MTRR A66G were determined by a TaqMan assay. Overweight and obesity were defined as a body mass index between 24 and 27.99 and ≥ 28 kg/m 2 , respectively. The interactions were examined by factorial design covariance analysis, and further multiple comparisons were conducted by Bonferroni correction. There was no significant difference in the genotypic and allelic frequencies between females and males (MTHFR 677 T allele: 54.47 % for females and 54.40 % for males; MTRR 66G allele: 24.73 % for females and 24.71 % for males). Interaction between the MTHFR C677T polymorphism and overweight/obesity on serum triglyceride levels, and interaction between the MTRR A66G polymorphism and overweight/obesity on serum high-density lipoprotein cholesterol levels were detected in women (P = 0.015 and P = 0.056, respectively). For female subjects with overweight/obesity, the serum triglyceride levels in MTHFR 677TT genotype [1.09 (0.78-1.50) mmol/L] were significantly higher as compared with MTHFR 677CC genotype [0.90 (0.60-1.15) mmol/L, P = 0.007], and the MTRR 66GG genotype carriers had higher serum high-density lipoprotein cholesterol levels than those with MTRR 66AG genotype (1.46 ± 0.50 vs. 1.19 ± 0.31 mmol/L, P = 0.058). Furthermore, in male subjects with overweight/obesity, the MTHFR 677CT genotype carriers had higher low-density lipoprotein cholesterol levels than those

  19. Relationship between CYP1A2 Localization and Lipid Microdomain Formation as a Function of Lipid Composition

    PubMed Central

    Brignac-Huber, Lauren M.; Reed, James R.; Eyer, Marilyn K.

    2013-01-01

    Cytochrome P450 (P450) function requires the interaction of P450 and NADPH-cytochrome P450 reductase (CPR) in membranes, and is frequently studied using reconstituted systems composed solely of phosphatidylcholine. There is increasing evidence that other endoplasmic reticulum (ER) lipids can affect P450 structure, activity, and interactions with CPR. Some of these lipid effects have been attributed to the formation of organized liquid-ordered (lo) domains. The goal of this study was to determine if lo domains were formed in P450 reconstituted systems mimicking the ER membrane. CYP1A2, when incorporated in “ER-like” lipid vesicles, displayed detergent insolubility after treatment with Brij 98 and centrifugation in a sucrose gradient. Lipid probes were employed to identify domain formation in both ER-like vesicles and model membranes known to form lo domains. Changes in fluorescence resonance energy transfer (FRET) using an established donor/acceptor FRET pair in both ER-like and model lo-forming systems demonstrated the coexistence of lo- and liquid-disordered domains as a function of cholesterol and sphingomyelin content. Similarly, 6-dodecanoyl-2-dimethylaminonaphthalene (laurdan), a probe that reports on membrane organization, showed that cholesterol and sphingomyelin increased membrane order. Finally, brominated-phosphatidylcholine allowed for monitoring of the location of both CPR and CYP1A2 within the lo regions of ER-like systems. Taken together, the results demonstrate that ER-like vesicles generate microdomains, and both CYP1A2 and CPR predominantly localize into lo membrane regions. Probe fluorescent responses suggest that lipid microdomains form in these vesicles whether or not enzymes are included in the reconstituted systems. Thus, it does not appear that the proteins are critical for stabilizing lo domains. PMID:23963955

  20. LRH-1 regulates hepatic lipid homeostasis and maintains arachidonoyl phospholipid pools critical for phospholipid diversity

    PubMed Central

    Miranda, Diego A.; Krause, William C.; Suzawa, Miyuki; Escusa, Hazel; Foo, Juat Chin; Shihadih, Diyala S.; Stahl, Andreas; Nyangau, Edna; Hellerstein, Marc; Wenk, Markus R.; Silver, David L.; Ingraham, Holly A.

    2018-01-01

    Excess lipid accumulation is an early signature of nonalcoholic fatty liver disease (NAFLD). Although liver receptor homolog 1 (LRH-1) (encoded by NR5A2) is suppressed in human NAFLD, evidence linking this phospholipid-bound nuclear receptor to hepatic lipid metabolism is lacking. Here, we report an essential role for LRH-1 in hepatic lipid storage and phospholipid composition based on an acute hepatic KO of LRH-1 in adult mice (LRH-1AAV8-Cre mice). Indeed, LRH-1–deficient hepatocytes exhibited large cytosolic lipid droplets and increased triglycerides (TGs). LRH-1–deficient mice fed high-fat diet displayed macrovesicular steatosis, liver injury, and glucose intolerance, all of which were reversed or improved by expressing wild-type human LRH-1. While hepatic lipid synthesis decreased and lipid export remained unchanged in mutants, elevated circulating free fatty acid helped explain the lipid imbalance in LRH-1AAV8-Cre mice. Lipidomic and genomic analyses revealed that loss of LRH-1 disrupts hepatic phospholipid composition, leading to lowered arachidonoyl (AA) phospholipids due to repression of Elovl5 and Fads2, two critical genes in AA biosynthesis. Our findings reveal a role for the phospholipid sensor LRH-1 in maintaining adequate pools of hepatic AA phospholipids, further supporting the idea that phospholipid diversity is an important contributor to healthy hepatic lipid storage. PMID:29515023

  1. Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.

    PubMed

    Mostad, Ingrid L; Bjerve, Kristian S; Basu, Samar; Sutton, Pauline; Frayn, Keith N; Grill, Valdemar

    2009-12-01

    Fatty acids (FA) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA. Here we tested for acute effects of marine n-3 FA on insulin sensitivity, insulin secretion, energy metabolism, and oxidative stress. This was a randomized, double-blind, crossover study in 11 subjects with type 2 diabetes mellitus. A 4-hour lipid infusion (Intralipid [Fresenius Kabi, Halden, Norway], total of 384 mL) was compared with a similar lipid infusion partly replaced by Omegaven (Fresenius Kabi) that contributed a median of 0.1 g fish oil per kilogram body weight, amounting to 0.04 g/kg of marine n-3 FA. Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps; insulin secretion (measured after the clamps), by C-peptide glucagon tests; and energy metabolism, by indirect calorimetry. Infusion of Omegaven increased the proportion of n-3 FA in plasma nonesterified fatty acids (NEFA) compared with Intralipid alone (20:5n-3: median, 1.5% [interquartile range, 0.6%] vs -0.2% [0.2%], P = .001; 22:6n-3: 0.8% [0.4%] vs -0.7% [0.2%], P = .001). However, glucose utilization was not affected; neither was insulin secretion or total energy production (P = .966, .210, and .423, respectively, for the differences between the lipid clamps). Omegaven tended to lower oxidation of fat (P = .062) compared with Intralipid only, correlating with the rise in individual n-3 NEFA (r = 0.627, P = .039). The effects of clamping on phospholipid FA composition, leptin, adiponectin, or F(2)-isoprostane concentrations were not affected by Omegaven. Enrichment of NEFA with n-3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.

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

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

    Yu, Jung Hwan; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752; Lee, Yoo Jeong

    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 ofmore » 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.« less

  3. Persistent organic pollutants in red-crowned cranes (Grus japonensis) from Hokkaido, Japan.

    PubMed

    Kakimoto, Kensaku; Akutsu, Kazuhiko; Nagayoshi, Haruna; Konishi, Yoshimasa; Kajimura, Keiji; Tsukue, Naomi; Yoshino, Tomoo; Matsumoto, Fumio; Nakano, Takeshi; Tang, Ning; Hayakawa, Kazuichi; Toriba, Akira

    2018-01-01

    The red-crowned crane (Grus japonensis) from eastern Hokkaido is classified as a Special Natural Monument in Japan. In this study, we determined the concentrations of persistent organic pollutants (POPs) in red-crowned crane muscle tissues (n = 47). Polychlorinated biphenyls (PCBs) had the highest median concentration (240ng/g lipid weight), followed by dichlorodiphenyltrichloroethane and its metabolites (DDTs) (150ng/g lipid weight), chlordane-related compounds (CHLs) (36ng/g lipid weight), hexachlorobenzene (HCB) (16ng/g lipid weight), hexachlorocyclohexanes (HCHs) (4.4ng/g lipid weight), polybrominated diphenyl ethers (PBDEs) (1.8ng/g lipid weight), and finally, Mirex (1.5ng/g lipid weight). Additionally, a positive correlation was found among POP concentrations. No sex differences beyond body parameters were observed. Additionally, red-crowned cranes exhibited a high enantiomeric excess of (+)-alpha-HCH, with enantiomer fractions varying from 0.51 to 0.87 (average: 0.69). Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Associations of genetic variants for adult lipid levels with lipid levels in children. The Generation R Study.

    PubMed

    Latsuzbaia, Ardashel; Jaddoe, Vincent W V; Hofman, Albert; Franco, Oscar H; Felix, Janine F

    2016-12-01

    Lipid concentrations are heritable traits. Recently, the number of known genetic loci associated with lipid levels in adults increased from 95 to 157. The effects of these 157 loci have not been tested in children. Considering that lipid levels track from childhood to adulthood, we studied to determine whether these variants already affected lipid concentrations in a large group of 2,645 children with a median age of 6.0 years (95% range 5.7-7.3 years) from the population-based Generation R Study. Twenty-eight SNPs associated with TGs, 39 SNPs associated with total cholesterol (TC), 28 SNPs associated with LDL cholesterol (LDL-C), and 56 SNPs associated with HDL cholesterol (HDL-C) were analyzed individually and combined into genetic risk scores (GRSs). All risk scores were associated with their specific outcomes. The differences in mean absolute lipid and lipoprotein values between the 10% of children with the highest lipid or lipoprotein GRS versus the 10% with the lowest score were 0.28, 0.25, 0.32, and 0.30 mmol/l for TGs, TC, LDL-C, and HDL-C, respectively. In conclusion, we show for the first time that GRSs based on 157 SNPs associated with adult lipid concentrations are associated with lipid levels in children. The genetic background of these phenotypes at least partly overlaps between children and adults. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Lipid catabolism via CPT1 as a therapeutic target for prostate cancer

    PubMed Central

    Schlaepfer, Isabel R.; Rider, Leah; Rodrigues, Lindsey Ulkus; Gijón, Miguel A.; Pac, Colton T.; Romero, Lina; Cimic, Adela; Sirintrapun, S. Joseph; Glodé, L. Michael; Eckel, Robert H.; Cramer, Scott D.

    2014-01-01

    Prostate cancer (PCa) is the most commonly diagnosed malignancy among western men and accounts for the second leading cause of cancer-related deaths. PCa tends to grow slowly and recent studies suggest that it relies on lipid fuel more than on aerobic glycolysis. However, the biochemical mechanisms governing the relationships between lipid synthesis, lipid utilization, and cancer growth remain unknown. To address the role of lipid metabolism in PCa we have used Etomoxir and Orlistat, clinically safe drugs that block lipid oxidation and lipid synthesis/lipolysis, respectively. Etomoxir is an irreversible inhibitor of the carnitine palmitoyltransferase (CPT1) enzyme that decreases beta oxidation in the mitochondria. Combinatorial treatments using Etomoxir and Orlistat resulted in synergistic decreased viability in LNCaP, VCaP and patient-derived benign and PCa cells. These effects were associated with decreased androgen receptor (AR) expression, decreased mammalian target of Rapamycin (mTOR) signaling and increased caspase-3 activation. Knockdown of CPT1A enzyme in LNCaP cells resulted in decreased palmitate oxidation but increased sensitivity to Etomoxir, with inactivation of AKT kinase and activation of caspase-3. Systemic treatment with Etomoxir in nude nice resulted in decreased xenograft growth over 21 days, underscoring the therapeutic potential of blocking lipid catabolism to decrease PCa tumor growth. PMID:25122071

  6. Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemia LOX-1 ligand and IMT in Japanese.

    PubMed

    Okamura, Tomonori; Miura, Katsuyuki; Sawamura, Tatsuya; Kadota, Aya; Hisamatsu, Takashi; Fujiyoshi, Akira; Miyamatsu, Naomi; Takashima, Naoyuki; Miyagawa, Naoko; Kadowaki, Takashi; Ohkubo, Takayoshi; Murakami, Yoshitaka; Nakamura, Yasuyuki; Ueshima, Hirotsugu

    2016-01-01

    The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations. A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. Serum LAB levels (median [interquartile range], μg cs/L) were 5341 μg cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 μm) compared with the first quartile (797 μm) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC ≥ 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 μm (12.7), 856 μm (16.7) in the low LAB/hypercholesterolemia group, and 833 μm (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication. Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  7. Role of skeletal muscle mitochondrial density on exercise-stimulated lipid oxidation.

    PubMed

    Galgani, Jose E; Johannsen, Neil M; Bajpeyi, Sudip; Costford, Sheila R; Zhang, Zhengyu; Gupta, Alok K; Ravussin, Eric

    2012-07-01

    Reduced skeletal muscle mitochondrial density is proposed to lead to impaired muscle lipid oxidation and increased lipid accumulation in sedentary individuals. We assessed exercise-stimulated lipid oxidation by imposing a prolonged moderate-intensity exercise in men with variable skeletal muscle mitochondrial density as measured by citrate synthase (CS) activity. After a 2-day isoenergetic high-fat diet, lipid oxidation was measured before and during exercise (650 kcal at 50% VO(2)max) in 20 healthy men with either high (HI-CS = 24 ± 1; mean ± s.e.) or low (LO-CS = 17 ± 1 nmol/min/mg protein) muscle CS activity. Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Respiratory exchange data and blood samples were collected at rest and throughout the exercise. HI-CS subjects had higher VO(2)max (50 ± 1 vs. 44 ± 2 ml/kg fat free mass/min; P = 0.01), lower fasting respiratory quotient (RQ) (0.81 ± 0.01 vs. 0.85 ± 0.01; P = 0.04) and higher ex vivo muscle palmitate oxidation (866 ± 168 vs. 482 ± 78 nmol/h/mg muscle; P = 0.05) compared to LO-CS individuals. However, whole-body exercise-stimulated lipid oxidation (20 ± 2 g vs. 19 ± 1 g; P = 0.65) and plasma glucose, lactate, insulin, and catecholamine responses were similar between the two groups. In conclusion, in response to the same energy demand during a moderate prolonged exercise bout, reliance on lipid oxidation was similar in individuals with high and low skeletal muscle mitochondrial density. This data suggests that decreased muscle mitochondrial density may not necessarily impair reliance on lipid oxidation over the course of the day since it was normal under a high-lipid oxidative demand condition. Twenty-four-hour lipid oxidation and its relationship with mitochondrial density need to be assessed.

  8. Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children.

    PubMed

    Rosewich, M; Schulze, J; Eickmeier, O; Telles, T; Rose, M A; Schubert, R; Zielen, S

    2010-06-01

    Specific immunotherapy (SIT) is a well-established and clinically effective treatment for allergic diseases. A pollen allergoid formulated with the T helper type 1 (Th1)-inducing adjuvant monophosphoryl lipid A (MPL) facilitates short-term SIT. Little is known about mechanisms of tolerance induction in this setting. In a prospective study, 34 patients allergic to grass pollen (25 male, nine female, median age 10.2 years) received a total of 44 SIT courses (20 in the first, 24 in the second) with MPL-adjuvanted pollen allergoids. Immunogenicity was measured by levels of specific immunoglobulin G (IgG(grass)) and IgG4(grass) by antibody blocking properties on basophil activation, and by induction of CD4(+), CD25(+) and forkhead box P3 (FoxP3(+)) regulatory T cells (T(reg)). Specific IgG and IgG4 levels increased only slightly in the first year of SIT. In the second year these changes reached significance (P < 0.0001). In keeping with these findings, we were able to show an increase of T(reg) cells and a decreased release of leukotrienes after the second year of treatment. In the first year of treatment we found little evidence for immunological changes. A significant antibody induction was seen only after the second course of SIT. Short-course immunotherapy with pollen allergoids formulated with the Th1-inducing adjuvant MPL needs at least two courses to establish tolerance.

  9. Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study.

    PubMed

    Isotton, Ana Lúcia; Wender, Maria Celeste Osorio; Casagrande, Alessandra; Rollin, Guilherme; Czepielewski, Mauro Antônio

    2012-02-01

    To evaluate the effects of oral estradiol and transdermal 17β-estradiol on serum concentrations of IGF1 and its binding proteins in women with hypopituitarism. Prospective, comparative study. Eleven patients with hypopituitarism were randomly allocated to receive 2 mg oral estradiol (n=6) or 50 μg/day of transdermal 17β-estradiol (n=5) for 3 months. The oral estrogen group showed a significant reduction in IGF1 levels (mean: 42.7%±41.4, P=0.046); no difference was observed in the transdermal estrogen group. There was a significant increase in IGFBP1 levels (mean: 170.2%±230.9, P=0.028) in the oral group, but not in the transdermal group. There was no significant difference within either group in terms of median IGFBP3 levels. In relation to lipid profiles, there was a significant increase in mean high-density lipoprotein cholesterol levels in the oral group after 3 months of treatment, (27.8±9.3, P=0.003). We found no differences in the anthropometric measurements, blood pressure, heart rate, glucose, insulin, C-peptide, or the homeostasis model assessment index after treatment. Our preliminary data indicate that different estrogen administration routes can influence IGF1 and IGFBP1 levels. These findings in patients with hypopituitarism have an impact on their response to treatment with GH, since patients receiving oral estrogen require increased GH dosage. These results suggest that oral estrogens may reduce the beneficial effects of GH replacement on fat and protein metabolism, body composition, and quality of life.

  10. Lamin B1 mediated demyelination: Linking Lamins, Lipids and Leukodystrophies

    PubMed Central

    Padiath, Quasar S.

    2016-01-01

    ABSTRACT Autosomal Dominant Leukodystrophy (ADLD), a fatal adult onset demyelinating disorder, is the only human disease that has been linked to mutations of the nuclear lamina protein, lamin B1, and is primarily caused by duplications of the LMNB1 gene. Why CNS myelin is specifically targeted and the mechanisms underlying ADLD are unclear. Recent work from our group has demonstrated that over expression of lamin B1 in oligodendrocytes, the myelin producing cells in the CNS, resulted in age dependent epigenetic modifications, transcriptional down-regulation of lipogenic gene expression and significant reductions of myelin-enriched lipids. Given the high lipid content of meylin, we hypothesize that lipid loss is one of the primary drivers of the demyelination phenotype. These results can, at least partially, explain the age dependence and cell type specificity in ADLD and are discussed in the context of the existing literature, in an attempt to delineate potential pathways underlying the disease phenotype. PMID:27854160

  11. ToF-SIMS observation for evaluating the interaction between amyloid β and lipid membranes.

    PubMed

    Aoyagi, Satoka; Shimanouchi, Toshinori; Kawashima, Tomoko; Iwai, Hideo

    2015-04-01

    The adsorption behaviour of amyloid beta (Aβ), thought to be a key peptide for understanding Alzheimer's disease, was investigated by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS). Aβ aggregates depending on the lipid membrane condition though it has not been fully understood yet. In this study, Aβ samples on different lipid membranes, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), were observed with ToF-SIMS and the complex ToF-SIMS data of the Aβ samples was interpreted using data analysis techniques such as principal component analysis (PCA), gentle-SIMS (G-SIMS) and g-ogram. DOPC and DMPC are liquid crystal at room temperature, while DPPC is gel at room temperature. As primary ion beams, Bi3(+) and Ar cluster ion beams were used and the effect of an Ar cluster ion for evaluating biomolecules was also studied. The secondary ion images of the peptide fragment ions indicated by G-SIMS and g-ogram were consistent with the PCA results. It is suggested that Aβ is adsorbed homogeneously on the liquid-crystalline-phase lipid membranes, while it aggregates along the lipid on the gel-phase lipid membrane. Moreover, in the results using the Ar cluster, the influence of contamination was reduced.

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

    PubMed

    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.

  13. Ratiometric imaging of gastrodermal lipid bodies in coral-dinoflagellate endosymbiosis

    NASA Astrophysics Data System (ADS)

    Luo, Y.-J.; Wang, L.-H.; Chen, W.-N. U.; Peng, S.-E.; Tzen, J. T.-C.; Hsiao, Y.-Y.; Huang, H.-J.; Fang, L.-S.; Chen, C.-S.

    2009-03-01

    Cnidaria-dinoflagellate endosymbiosis is the phenomenon of autotrophic symbionts living inside the gastrodermal cells of their animal hosts. The molecular mechanism that regulates this association remains unclear. Using quantitative microscopy, we now provide evidence that the dynamic lipid changes in gastrodermal “lipid bodies” (LBs) reflect the symbiotic status of the host cell and its symbiont in the hermatypic coral Euphyllia glabrescens. By dual-emission ratiometric imaging with a solvatochromic fluorescent probe, Nile red (9-diethylamino-5H-benzo[α]phenoxazine-5-one), we showed that the in situ distribution of polar versus neutral lipids in LBs in living gastrodermal cells and symbionts can be analyzed. The ratio of Nile red fluorescence at red (R) versus green (G) wavelength region (i.e., R/G ratio) correlated with the relative molar ratio of polar (P) versus neutral (NP) lipids (i.e., P/NP ratio). The R/G ratio in host LBs increased after bleaching, indicating a decrease in neutral lipid accumulation in gastrodermal cells. On the other hand, neutral lipid accumulation inside the symbiont LBs resulted in gradual decreases of the R/G ratio as a result of bleaching. In comparison with the bleaching event, there was no relative lipid concentration change in host LBs under continual light or dark treatments as shown by insignificant R/G ratio shift. Patterns of R/G ratio shift in symbiont LBs were also different between corals undergoing bleaching and continual light/dark treatment. In the latter, there was little lipid accumulation in symbionts, with no resulting R/G ratio decrease. These results, demonstrating that the symbiotic status positively correlated with morphological and compositional changes of lipid bodies, not only highlight the pivotal role of LBs, but also implicate an involvement of lipid trafficking in regulating the endosymbiosis.

  14. Liver-specific expression of carboxylesterase 1g/esterase-x reduces hepatic steatosis, counteracts dyslipidemia and improves insulin signaling.

    PubMed

    Bahitham, Wesam; Watts, Russell; Nelson, Randal; Lian, Jihong; Lehner, Richard

    2016-05-01

    Ces1g/Es-x deficiency in mice results in weight gain, insulin resistance, fatty liver and hyperlipidemia through upregulation of de novo lipogenesis and oversecretion of triacylglycerol (TG)-rich lipoproteins. Here, we show that restoration of Ces1g/Es-x expression only in the liver significantly reduced hepatic TG concentration accompanied by decreased size of lipid droplets, reduced secretion of very low-density lipoproteins and improved insulin-mediated signal transduction in the liver. Collectively, these results demonstrate that hepatic Ces1g/Es-x plays a critical role in limiting hepatic steatosis, very low-density lipoprotein assembly and in augmenting insulin sensitivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Update on the healthful lipid constituents of commercially important tree nuts.

    PubMed

    Robbins, Katherine S; Shin, Eui-Cheol; Shewfelt, Robert L; Eitenmiller, Ronald R; Pegg, Ronald B

    2011-11-23

    Uncharacteristic of most whole foods, the major component of tree nuts is lipid; surprisingly, information on the lipid constituents in tree nuts has been sporadic and, for the most part, not well reported. Most published papers focus on only one nut type, or those that report a cultivar lack a quality control program, thus making data comparisons difficult. The present study was designed to quantify the healthful lipid constituents of 10 different types of commercially important tree nuts (i.e., almonds, black walnuts, Brazil nuts, cashews, English walnuts, hazelnuts, macadamias, pecans, pine nuts, and pistachios) according to standardized, validated methods. The total lipid content of each nut type ranged from 44.4 ± 1.9% for cashews to 77.1 ± 1.7% for macadamias. As expected, the major fatty acids present in the tree nuts were unsaturated: oleic (18:1 ω9) and linoleic (18:2 ω6) acids. A majority of the lipid extracts contained <10% saturated fatty acids with the exceptions of Brazil nuts (24.5%), cashews (20.9%), macadamias (17.1%), and pistachios (13.3%). The total tocopherol (T) content ranged from 1.60 ± 1.27 mg/100 g nutmeat in macadamias to 32.99 ± 0.78 in black walnuts. The predominant T isomers in the nut types were α- and γ-T. Tocotrienols were also detected, but only in 6 of the 10 nut types (i.e., Brazil nut, cashews, English walnuts, macadamias, pine nuts, and pistachios). In most cases, total phytosterol contents were greater in the present study than reported in peer-reviewed journal papers and the USDA National Nutrient Database for Standard Reference, which is attributed to total lipid extraction and the inclusion of steryl glucosides in the analysis; the levels were highest for pistachios (301.8 ± 15.4 mg/100 g nutmeat) and pine nuts (271.7 ± 9.1 mg/100 g nutmeat). Minor sterols were also quantified and identified using GC-FID and GC-MS techniques.

  16. Optimization of lipids production by Cryptococcus laurentii 11 using cheese whey with molasses.

    PubMed

    Castanha, Rodrigo Fernandes; Mariano, Adriano Pinto; de Morais, Lilia Aparecida Salgado; Scramin, Shirlei; Monteiro, Regina Teresa Rosim

    2014-01-01

    This study aimed the optimization of culture condition and composition for production of Cryptococcus laurentii 11 biomass and lipids in cheese whey medium supplemented with sugarcane molasses. The optimization of pH, fermentation time, and molasses concentration according to a full factorial statistical experimental design was followed by a Plackett-Burman experimental design, which was used to determine whether the supplementation of the culture medium by yeast extract and inorganic salts could provide a further enhancement of lipids production. The following conditions and composition of the culture medium were found to optimize biomass and lipids production: 360 h fermentation, 6.5 pH and supplementation of (g L(-1)): 50 molasses, 0.5 yeast extract, 4 KH2PO4, 1 Na2HPO4, 0.75 MgSO4 · 7H2O and 0.002 ZnSO4 · H2O. Additional supplementation with inorganic salts and yeast extract was essential to optimize the production, in terms of product concentration and productivity, of neutral lipids by C. laurentii 11. Under this optimized condition, the production of total lipids increased by 133% in relation to control experiment (from 1.27 to 2.96 g L(-1)). The total lipids indicated a predominant (86%) presence of neutral lipids with high content of 16- and 18-carbon-chain saturated and monosaturated fatty acids. This class of lipids is considered especially suitable for the production of biodiesel.

  17. Evaluation of the membrane lipid selectivity of the pea defensin Psd1.

    PubMed

    Gonçalves, Sónia; Teixeira, Alexandre; Abade, João; de Medeiros, Luciano Neves; Kurtenbach, Eleonora; Santos, Nuno C

    2012-05-01

    Psd1, a 46 amino acid residues defensin isolated from the pea Pisum sativum seeds, exhibits anti-fungal activity by a poorly understood mechanism of action. In this work, the interaction of Psd1 with biomembrane model systems of different lipid compositions was assessed by fluorescence spectroscopy. Partition studies showed a marked lipid selectivity of this antimicrobial peptide (AMP) toward lipid membranes containing ergosterol (the main sterol in fungal membranes) or specific glycosphingolipid components, with partition coefficients (K(p)) reaching uncommonly high values of 10(6). By the opposite, Psd1 does not partition to cholesterol-enriched lipid bilayers, such as mammalian cell membranes. The Psd1 mutants His36Lys and Gly12Glu present a membrane affinity loss relative to the wild type. Fluorescence quenching data obtained using acrylamide and membrane probes further clarify the mechanism of action of this peptide at the molecular level, pointing out the potential therapeutic use of Psd1 as a natural antimycotic agent. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Gravity susception by buoyancy: floating lipid globules in sporangiophores of Phycomyces.

    PubMed

    Grolig, F; Herkenrath, H; Pumm, T; Gross, A; Galland, P

    2004-02-01

    To elucidate the mechanisms of gravity susception that operate in the sporangiophore of Phycomyces blakesleeanus, we characterized the function and topography of a large apical complex of lipid globules. Stage-1 sporangiophores (without sporangium) possess a roughly spherical complex of 100-200 large lipid globules whose center is localized 110 microm below the apex. The complex of lipid globules (CLG) is rather stable and is kept in place by positioning forces that resist centrifugal accelerations of up to 150 g. The lipid globules possess an average diameter of 2 to 2.5 microm and a density of 0.791 g cm(-3), which is below that of typical plant oleosomes. The potential energy which is generated by the buoyancy of a CLG of 100 globules is in the order of 10(-17) to 10(-16) J, which is 4 to 5 orders of magnitude above thermal noise. The formation of lipid globules can be suppressed by raising stage-1 sporangiophores for 24 hs at 5 degrees C. Sporangiophores with a reduced number of lipid globules display gravitropic bending angles that are 3 to 4 times smaller than those of sporangiophores with the normal number of lipid globules. The results suggest that the lipid globules function as gravisusceptors of Phycomyces and that buoyancy is the physical principle for their mode of action. The globules contain beta-carotene and two distinct fluorescing pigments that are, however, dispensable for graviperception.

  19. T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.

    PubMed

    Wun, Kwok S; Reijneveld, Josephine F; Cheng, Tan-Yun; Ladell, Kristin; Uldrich, Adam P; Le Nours, Jérôme; Miners, Kelly L; McLaren, James E; Grant, Emma J; Haigh, Oscar L; Watkins, Thomas S; Suliman, Sara; Iwany, Sarah; Jimenez, Judith; Calderon, Roger; Tamara, Kattya L; Leon, Segundo R; Murray, Megan B; Mayfield, Jacob A; Altman, John D; Purcell, Anthony W; Miles, John J; Godfrey, Dale I; Gras, Stephanie; Price, David A; Van Rhijn, Ildiko; Moody, D Branch; Rossjohn, Jamie

    2018-04-01

    The hallmark function of αβ T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses.

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

    PubMed Central

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

    2015-01-01

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

  1. Boosting accumulation of neutral lipids in Rhodosporidium kratochvilovae HIMPA1 grown on hemp (Cannabis sativa Linn) seed aqueous extract as feedstock for biodiesel production.

    PubMed

    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. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  2. Production of added value bacterial lipids through valorisation of hydrocarbon-contaminated cork waste.

    PubMed

    Castro, A R; Guimarães, M; Oliveira, J V; Pereira, M A

    2017-12-15

    This work demonstrates that cork used as oil-spill sorbents, contaminated with liquid hydrocarbons, herein demonstrated with hexadecane, can be biologically treated by Rhodococcus opacus B4 with concomitant lipids production. R. opacus B4 consumed up to 96% of hexadecane (C16) impregnated in natural and regranulated cork sorbents after 48h incubation, producing 0.59±0.06g of triacylglycerol (TAG) g -1 of C16 consumed with a TAG content of 0.60±0.06gg -1 of cellular dry weight (CDW) and 0.54±0.05g TAG g -1 of C16 consumed with a TAG content of 0.77±0.04gg -1 (CDW), respectively. TAG was mainly composed by fatty acids of 16 and 18 carbon chains demonstrating the feasibility of using it as raw material for biodiesel production. In addition, the obtained lipid-rich biomass (whole cells) can be used for biomethane production, at a yield of 0.4L CH 4 g -1 (CDW). The obtained results support a novel approach for management of oil-spill contaminated cork sorbents through its valorisation by producing bacterial lipids, which can be used as feedstocks for biofuels production. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Converting lignin derived phenolic aldehydes into microbial lipid by Trichosporon cutaneum.

    PubMed

    Hu, Mingshan; Wang, Juan; Gao, Qiuqiang; Bao, Jie

    2018-06-18

    Lignin is one of the major components of lignocellulose biomass and chemically degrades into phenolic aldehydes including 4-hydroxybenzaldehyde, vanillin, and syringaldehyde. No lipid accumulation from the phenolic aldehydes by oleaginous microbes had been succeeded. Compared with vanillin and syringaldehyde, T. cutaneum ACCC 20271 have better tolerance to 4-hydroxybenzaldehyde. 4-Hydroxybenzaldehyde was found to be able as the substrate for lipid accumulation, while vanillin and syringaldehyde were only converted to less toxic phenolic alcohols and acids without observable lipid accumulation, perhaps due to the space shelling of methoxyl group(s) in the structures. A long term fed batch fermentation of 4-hydroxybenzaldehyde accumulated 0.85 g L -1 of lipid, equivalent to 0.039 g lipid per gram of 4-hydroxybenzaldehyde substrate, approximately 3.7 folds greater than the control without 4-hydroxybenzaldehyde addition. The fatty acid composition well met the need for biodiesel synthesis. The preliminary pathway from 4-hydroxybenzaldehyde to lipid was predicted. This study took the first experimental trial on utilizing phenolic aldehydes as the sole carbon sources for microbial lipid accumulation by T. cutaneum ACCC 20271. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT.

    PubMed

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

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1. Copyright © 2016 National Lipid Association. All rights reserved.

  5. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY.

    PubMed

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

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2-part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1. Copyright © 2016 National Lipid Association. All rights reserved.

  6. Intravenous lipid emulsion only minimally influences bupivacaine and mepivacaine distribution in plasma and does not enhance recovery from intoxication in pigs.

    PubMed

    Litonius, Erik S; Niiya, Tomohisa; Neuvonen, Pertti J; Rosenberg, Per H

    2012-04-01

    The reported successful use of IV lipid emulsions in local anesthetic intoxications is thought to be due to lipid sequestration of local anesthetics. However, controlled efficacy studies were lacking, and other mechanisms of action have also been suggested. We investigated the effect of lipid infusion on plasma concentrations and cardiovascular effects of 2 local anesthetics differing in lipophilicity, bupivacaine, and mepivacaine. Bupivacaine (n = 20) or mepivacaine (n = 20) was infused into a central vein of anesthetized (isoflurane 1%, Fio(2) 0.21) pigs until mean arterial blood pressure decreased to 50% from baseline. Isoflurane was discontinued and Fio(2) was increased to 1.0. Ten pigs in each local anesthetic group were treated with 20% lipid emulsion (ClinOleic®), and 10 pigs with Ringer's solution: 1.5 mL/kg in 1 minute followed by an infusion of 0.25 mL · kg(-1) · min(-1) for 29 minutes. Five additional pigs were infused bupivacaine and Intralipid®. Total and nonlipid-bound local anesthetic concentrations were determined from repeated blood samples. There were no overall differences in total or nonlipid-bound plasma local anesthetic concentrations between the lipid and Ringer's groups. However, plasma median total bupivacaine concentration was 21% and 23% higher at 20 and 30 minutes, respectively, in the lipid group (P = 0.016 without Holm-Bonferroni correction). There was also no overall difference between lipid and Ringer's groups in the rate of recovery of hemodynamic and electrocardiographic variables. Median mean arterial blood pressure in the lipid group with bupivacaine intoxication was 16 mm Hg and 15 mm Hg higher than in the corresponding Ringer's group at 10 and 15 minutes, respectively (P = 0.016 and P = 0.021, respectively, without Holm-Bonferroni correction). Intralipid® also caused no difference between total plasma and nonlipid-bound concentrations of bupivacaine with no apparent enhancement of recovery. Lipid emulsion neither had any

  7. YALI0E32769g (DGA1) and YALI0E16797g (LRO1) encode major triacylglycerol synthases of the oleaginous yeast Yarrowia lipolytica.

    PubMed

    Athenstaedt, Karin

    2011-10-01

    The oleaginous yeast Yarrowia lipolytica has an outstanding capacity to produce and store triacylglycerols resembling adipocytes of higher eukaryotes. Here, the identification of two genes YALI0E32769g (DGA1) and YALI0E16797g (LRO1) encoding major triacylglycerol synthases of Yarrowia lipolytica is reported. Heterologous expression of either DGA1 or LRO1 in a mutant of the budding yeast Saccharomyces cerevisiae defective in triacylglycerol synthesis restores the formation of this neutral lipid. Whereas Dga1p requires acyl-CoA as a substrate for acylation of diacylglycerol, Lro1p is an acyl-CoA independent triacylglycerol synthase using phospholipids as acyl-donor. Growth of Yarrowia lipolytica strains deleted of DGA1 and/or LRO1 on glucose containing medium significantly decreases triacylglycerol accumulation. Most interestingly, when oleic acid serves as the carbon source the ratio of triacylglycerol accumulation in mutants to wild-type is significantly increased in strains defective in DGA1 but not in lro1Δ. In vitro experiments revealed that under these conditions an additional acyl-CoA dependent triacylglycerol synthase contributes to triacylglycerol synthesis in the respective mutants. Taken together, evidence is provided that Yarrowia lipolytica contains at least four triacylglycerol synthases, namely Lro1p, Dga1p and two additional triacylglycerol synthases whereof one is acyl-CoA dependent and specifically induced upon growth on oleic acid. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Two ATP Binding Cassette G Transporters, Rice ATP Binding Cassette G26 and ATP Binding Cassette G15, Collaboratively Regulate Rice Male Reproduction1[OPEN

    PubMed Central

    Zhao, Guochao; Shi, Jianxin; Liang, Wanqi; Xue, Feiyang; Luo, Qian; Zhu, Lu; Qu, Guorun; Chen, Mingjiao; Schreiber, Lukas; Zhang, Dabing

    2015-01-01

    Male reproduction in higher plants requires the support of various metabolites, including lipid molecules produced in the innermost anther wall layer (the tapetum), but how the molecules are allocated among different anther tissues remains largely unknown. Previously, rice (Oryza sativa) ATP binding cassette G15 (ABCG15) and its Arabidopsis (Arabidopsis thaliana) ortholog were shown to be required for pollen exine formation. Here, we report the significant role of OsABCG26 in regulating the development of anther cuticle and pollen exine together with OsABCG15 in rice. Cytological and chemical analyses indicate that osabcg26 shows reduced transport of lipidic molecules from tapetal cells for anther cuticle development. Supportively, the localization of OsABCG26 is on the plasma membrane of the anther wall layers. By contrast, OsABCG15 is polarly localized in tapetal plasma membrane facing anther locules. osabcg26 osabcg15 double mutant displays an almost complete absence of anther cuticle and pollen exine, similar to that of osabcg15 single mutant. Taken together, we propose that OsABCG26 and OsABCG15 collaboratively regulate rice male reproduction: OsABCG26 is mainly responsible for the transport of lipidic molecules from tapetal cells to anther wall layers, whereas OsABCG15 mainly is responsible for the export of lipidic molecules from the tapetal cells to anther locules for pollen exine development. PMID:26392263

  9. MALDI mass spectrometry imaging of bioactive lipids in mouse brain with a Synapt G2-S mass spectrometer operated at elevated pressure: improving the analytical sensitivity and the lateral resolution to ten micrometers.

    PubMed

    Kettling, Hans; Vens-Cappell, Simeon; Soltwisch, Jens; Pirkl, Alexander; Haier, Jörg; Müthing, Johannes; Dreisewerd, Klaus

    2014-08-05

    Mass spectrometers from the Synapt-G1/G2 family (Waters) are widely employed for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). A lateral resolution of about 50 μm is typically achieved with these instruments, that is, however, below the often desired cellular resolution. Here, we show the first MALDI-MSI examples demonstrating a lateral resolution of about ten micrometers obtained with a Synapt G2-S HDMS mass spectrometer without oversampling. This improvement became possible by laser beam shaping using a 4:1 beam expander and a circular aperture for spatial mode filtering and by replacement of the default focusing lens. We used dithranol as an effective matrix for imaging of acidic lipids such as sulfatides, gangliosides, and phosphatidylinositols in the negative ion mode. At the same time, the matrix enables MS imaging of more basic lipids in the positive ion mode. Uniform matrix coatings with crystals having average dimensions between 0.5 and 3 μm were obtained upon spraying a chloroform/methanol matrix solution. Increasing the cooling gas pressure in the MALDI ion source after adding an additional gas line was furthermore found to increase the ion abundances of labile lipids such as gangliosides. The combined characteristics are demonstrated with the MALDI-MSI analysis of fine structures in coronal mouse brain slices.

  10. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes

    PubMed Central

    Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

    2018-01-01

    Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows. PMID:29593725

  11. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes.

    PubMed

    Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

    2018-01-01

    Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

  12. Microwave-assisted extraction of lipid from fish waste

    NASA Astrophysics Data System (ADS)

    Rahimi, M. A.; Omar, R.; Ethaib, S.; Siti Mazlina, M. K.; Awang Biak, D. R.; Nor Aisyah, R.

    2017-06-01

    Processing fish waste for extraction of value added products such as protein, lipid, gelatin, amino acids, collagen and oil has become one of the most intriguing researches due to its valuable properties. In this study the extraction of lipid from sardine fish waste was carried out using microwave-assisted extraction (MAE) and compared with Soxhlets and Hara and Radin methods. A mixture of two organic solvents isopropanol/hexane and distilled water were used for MAE and Hara and Radin methods. Meanwhile, Soxhlet method utilized only hexane as solvent. The results show that the higher yield of lipid 80.5 mg/g was achieved using distilled water in MAE method at 10 min extraction time. Soxhlet extraction method only produced 46.6 mg/g of lipid after 4 hours of extraction time. Lowest yield of lipid was found at 15.8 mg/g using Hara and Radin method. Based on aforementioned results, it can be concluded MAE method is superior compared to the Soxhlet and Hara and Radin methods which make it an attractive route to extract lipid from fish waste.

  13. Lipid raft-associated β-adducin is required for PSGL-1-mediated neutrophil rolling on P-selectin.

    PubMed

    Xu, Tingshuang; Liu, Wenai; Yang, Chen; Ba, Xueqing; Wang, Xiaoguang; Jiang, Yong; Zeng, Xianlu

    2015-02-01

    Lipid rafts, a liquid-ordered plasma membrane microdomain, are related to cell-surface receptor function. PSGL-1, a major surface receptor protein for leukocyte, also acts as a signaling receptor in leukocyte rolling. To investigate the role of lipid raft in PSGL-1 signaling in human neutrophils, we quantitatively analyzed lipid raft proteome of human promyelocytic leukemia cell line HL-60 cells and identified a lipid raft-associated protein β-adducin. PSGL-1 ligation induced dissociation of the raft-associated protein β-adducin from lipid rafts and actin, as well as phosphorylation of β-adducin, indicating a transient uncoupling of lipid rafts from the actin cytoskeleton. Knockdown of β-adducin greatly attenuated HL-60 cells rolling on P-selectin. We also showed that Src kinase is crucial for PSGL-1 ligation-induced β-adducin phosphorylation and relocation. Taken together, these results show that β-adducin is a pivotal lipid raft-associated protein in PSGL-1-mediated neutrophil rolling on P-selectin. © Society for Leukocyte Biology.

  14. Biotechnological conversion of waste cooking olive oil into lipid-rich biomass using Aspergillus and Penicillium strains.

    PubMed

    Papanikolaou, S; Dimou, A; Fakas, S; Diamantopoulou, P; Philippoussis, A; Galiotou-Panayotou, M; Aggelis, G

    2011-05-01

    In this study, we have investigated the biochemical behaviour of Aspergillus sp. (five strains) and Penicillium expansum (one strain) fungi cultivated on waste cooking olive oil. The production of lipid-rich biomass was the main target of the work. In parallel, the biosynthesis of other extracellular metabolites (organic acids) and enzyme (lipase) and the substrate fatty acid specificity of the strains were studied. Carbon-limited cultures were performed on waste oil, added in the growth medium at 15g l(-1) , and high biomass quantities were produced (up to c.18g l(-1) , conversion yield of c. 1·0 g of dry biomass formed per g of fat consumed or higher). Cellular lipids were accumulated in notable quantities in almost all cultures. Aspergillus sp. ATHUM 3482 accumulated lipid up to 64·0% (w/w) in dry fungal mass. In parallel, extracellular lipase activity was quantified, and it was revealed to be strain and fermentation time dependent, with a maximum quantity of 645 U ml(-1) being obtained by Aspergillus niger NRRL 363. Storage lipid content significantly decreased at the stationary growth phase. Some differences in the fatty acid composition of both cellular and residual lipids when compared with the initial substrate fat used were observed; in various cases, cellular lipids more saturated and enriched with arachidic acid were produced. Aspergillus strains produced oxalic acid up to 5·0 g l(-1) . Aspergillus and Penicillium strains are able to convert waste cooking olive oil into high-added-value products.   Increasing fatty wastes amounts are annually produced. The current study provided an alternative way of biovalourization of these materials, by using them as substrates, to produce added-value compounds. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

  15. Ginseng (Panax quinquefolius) Reduces Cell Growth, Lipid Acquisition and Increases Adiponectin Expression in 3T3-L1 Cells

    PubMed Central

    Yeo, Chia-Rou; Lee, Sea-Ming; Popovich, David G.

    2011-01-01

    An American ginseng (Panax quinquefolius) extract (GE) that contained a quantifiable amount of ginsenosides was investigated for the potential to inhibit proliferation, affect the cell cycle, influence lipid acquisition and adiponectin expression in 3T3-L1 cells. Six fingerprint ginsenosides were quantified by high performance liquid chromatography and the respective molecular weights were confirmed by LC-ESI-MS analysis. The extract contained Rg1 (347.3 ± 99.7 μg g−1, dry weight), Re (8280.4 ± 792.3 μg g−1), Rb1 (1585.8 ± 86.8 μg g−1), Rc (32.9 ± 8 μg g−1), Rb2 (62.6 ± 10.6 μg g−1) and Rd (90.4 ± 3.2 μg g−1). The GE had a dose-dependent effect on 3T3-L1 cell growth, the LC50 value was determined to be 40.3 ± 5 μg ml−1. Cell cycle analysis showed modest changes in the cell cycle. No significant changes observed in both G1 and G2/M phases, however there was a significant decrease (P < .05) in the S phase after 24 and 48 h treatment. Apoptotic cells were modest but significantly (P < .05) increased after 48 h (3.2 ± 1.0%) compared to untreated control cells (1.5 ± 0.1%). Lipid acquisition was significantly reduced (P < .05) by 13 and 22% when treated at concentrations of 20.2 and 40.3 μg ml−1 compared to untreated control cells. In relation to adiponectin activation, western blot analysis showed that the protein expression was significantly (P < .05) increased at concentrations tested. A quantified GE reduced the growth of 3T3-L1 cells, down-regulated the accumulation of lipid and up-regulated the expression of adiponectin in the 3T3-L1 adipocyte cell model. PMID:21799682

  16. Nitrogen starvation strategies and photobioreactor design for enhancing lipid content and lipid production of a newly isolated microalga Chlorella vulgaris ESP-31: implications for biofuels.

    PubMed

    Yeh, Kuei-Ling; Chang, Jo-Shu

    2011-11-01

    Microalgae are recognized for serving as a sustainable source for biodiesel production. This study investigated the effect of nitrogen starvation strategies and photobioreactor design on the performance of lipid production and of CO(2) fixation of an indigenous microalga Chlorella vulgaris ESP-31. Comparison of single-stage and two-stage nitrogen starvation strategies shows that single-stage cultivation on basal medium with low initial nitrogen source concentration (i.e., 0.313 g/L KNO(3)) was the most effective approach to enhance microalgal lipid production, attaining a lipid productivity of 78 mg/L/d and a lipid content of 55.9%. The lipid productivity of C. vulgaris ESP-31 was further upgraded to 132.4 mg/L/d when it was grown in a vertical tubular photobioreactor with a high surface to volume ratio of 109.3 m(2)/m(3) . The high lipid productivity was also accompanied by fixation of 6.36 g CO(2) during the 10-day photoautotrophic growth with a CO(2) fixation rate of 430 mg/L/d. Analysis of fatty acid composition of the microalgal lipid indicates that over 65% of fatty acids in the microalgal lipid are saturated [i.e., palmitic acid (C16:0) and stearic acid (C18:0)] and monounsaturated [i.e., oleic acid (C18:1)]. This lipid quality is suitable for biodiesel production. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Median and ulnar neuropathies in university guitarists.

    PubMed

    Kennedy, Rachel H; Hutcherson, Kimberly J; Kain, Jennifer B; Phillips, Alicia L; Halle, John S; Greathouse, David G

    2006-02-01

    Descriptive study. To determine the presence of median and ulnar neuropathies in both upper extremities of university guitarists. Peripheral nerve entrapment syndromes of the upper extremities are well documented in musicians. Guitarists and plucked-string musicians are at risk for entrapment neuropathies in the upper extremities and are prone to mild neurologic deficits. Twenty-four volunteer male and female guitarists (age range, 18-26 years) were recruited from the Belmont University School of Music and the Vanderbilt University Blair School of Music. Individuals were excluded if they were pregnant or had a history of recent upper extremity or neck injury. Subjects completed a history form, were interviewed, and underwent a physical examination. Nerve conduction status of the median and ulnar nerves of both upper extremities was obtained by performing motor, sensory, and F-wave (central) nerve conduction studies. Descriptive statistics of the nerve conduction study variables were computed using Microsoft Excel. Six subjects had positive findings on provocative testing of the median and ulnar nerves. Otherwise, these guitarists had normal upper extremity neural and musculoskeletal function based on the history and physical examinations. When comparing the subjects' nerve conduction study values with a chart of normal nerve conduction studies values, 2 subjects had prolonged distal motor latencies (DMLs) of the left median nerve of 4.3 and 4.7 milliseconds (normal, < 4.2 milliseconds). Prolonged DMLs are compatible with median neuropathy at or distal to the wrist. Otherwise, all electrophysiological variables were within normal limits for motor, sensory, and F-wave (central) values. However, comparison studies of median and ulnar motor latencies in the same hand demonstrated prolonged differences of greater than 1.0 milliseconds that affected the median nerve in 2 additional subjects, and identified contralateral limb involvement in a subject with a prolonged

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

    PubMed

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

    2012-11-01

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

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

    PubMed

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

    2016-05-01

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

  20. Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children

    PubMed Central

    Rosewich, M; Schulze, J; Eickmeier, O; Telles, T; Rose, M A; Schubert, R; Zielen, S

    2010-01-01

    Specific immunotherapy (SIT) is a well-established and clinically effective treatment for allergic diseases. A pollen allergoid formulated with the T helper type 1 (Th1)-inducing adjuvant monophosphoryl lipid A (MPL) facilitates short-term SIT. Little is known about mechanisms of tolerance induction in this setting. In a prospective study, 34 patients allergic to grass pollen (25 male, nine female, median age 10·2 years) received a total of 44 SIT courses (20 in the first, 24 in the second) with MPL-adjuvanted pollen allergoids. Immunogenicity was measured by levels of specific immunoglobulin G (IgGgrass) and IgG4grass by antibody blocking properties on basophil activation, and by induction of CD4+, CD25+ and forkhead box P3 (FoxP3+) regulatory T cells (Treg). Specific IgG and IgG4 levels increased only slightly in the first year of SIT. In the second year these changes reached significance (P < 0·0001). In keeping with these findings, we were able to show an increase of Treg cells and a decreased release of leukotrienes after the second year of treatment. In the first year of treatment we found little evidence for immunological changes. A significant antibody induction was seen only after the second course of SIT. Short-course immunotherapy with pollen allergoids formulated with the Th1-inducing adjuvant MPL needs at least two courses to establish tolerance. PMID:20345983

  1. Identification of superior lipid producing Lipomyces and Myxozyma yeasts

    USDA-ARS?s Scientific Manuscript database

    Oleaginous yeasts are of interest for production of single cell oils from sugars. Here 17 members of the Lipomyces and Myxozyma clade were screened for lipid production when cultured on glucose. The highest ranking yeasts included L. tetrasporus (21 g/l), L. kononenkoae (19.6 g/l), and L. lipofer (1...

  2. Enhanced lipid productivity and photosynthesis efficiency in a Desmodesmus sp. mutant induced by heavy carbon ions.

    PubMed

    Hu, Guangrong; Fan, Yong; Zhang, Lei; Yuan, Cheng; Wang, Jufang; Li, Wenjian; Hu, Qiang; Li, Fuli

    2013-01-01

    The unicellular green microalga Desmodesmus sp. S1 can produce more than 50% total lipid of cell dry weight under high light and nitrogen-limitation conditions. After irradiation by heavy (12)C(6+) ion beam of 10, 30, 60, 90 or 120 Gy, followed by screening of resulting mutants on 24-well microplates, more than 500 mutants were obtained. One of those, named D90G-19, exhibited lipid productivity of 0.298 g L(-1)⋅d(-1), 20.6% higher than wild type, likely owing to an improved maximum quantum efficiency (Fv/Fm) of photosynthesis under stress. This work demonstrated that heavy-ion irradiation combined with high-throughput screening is an effective means for trait improvement. The resulting mutant D90G-19 may be used for enhanced lipid production.

  3. Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells

    PubMed Central

    Hao, Lei; Ito, Kyoko; Huang, Kuan-Hsun; Sae-tan, Sudathip; Lambert, Joshua D.; Ross, A. Catharine

    2014-01-01

    Objective Patatin-like phospholipase domain containing 3 (PNPLA3, adiponutrin) has been identified as a modifier of lipid metabolism. To better understand the physiological role of PNPLA3/adiponutrin, we have investigated its regulation in intact mice and human hepatocytes under various nutritional/metabolic conditions. Material/Methods PNPLA3 gene expression was determined by real-time PCR in liver of C57BL/6 mice after dietary treatments and in HepG2 cells exposed to various nutritional/metabolic stimuli. Intracellular lipid content was determined in HepG2 cells after siRNA-mediated knockdown of PNPLA3. Results In vivo, mice fed a high-carbohydrate (HC) liquid diet had elevated hepatic lipid content, and PNPLA3 mRNA and protein expression, compared to chow-fed mice. Elevated expression was completely abrogated by addition of unsaturated lipid emulsion to the HC diet. By contrast, in mice with high-fat diet-induced steatosis, Pnpla3 expression did not differ compared to low-fat fed mice. In HepG2 cells, Pnpla3 expression was reversibly suppressed by glucose depletion and increased by glucose refeeding, but unchanged by addition of insulin and glucagon. Several unsaturated fatty acids each significantly decreased Pnpla3 mRNA, similar to lipid emulsion in vivo. However, Pnpla3 knockdown in HepG2 cells did not alter total lipid content in high glucose- or oleic acid-treated cells. Conclusions Our results provide evidence that PNPLA3 expression is an early signal/signature of carbohydrate-induced lipogenesis, but its expression is not associated with steatosis per se. Under lipogenic conditions due to high-carbohydrate feeding, certain unsaturated fatty acids can effectively suppress both lipogenesis and PNPLA3 expression, both in vivo and in a hepatocyte cell line. PMID:25060692

  4. Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells.

    PubMed

    Hao, Lei; Ito, Kyoko; Huang, Kuan-Hsun; Sae-tan, Sudathip; Lambert, Joshua D; Ross, A Catharine

    2014-10-01

    Patatin-like phospholipase domain containing 3 (PNPLA3, adiponutrin) has been identified as a modifier of lipid metabolism. To better understand the physiological role of PNPLA3/adiponutrin, we have investigated its regulation in intact mice and human hepatocytes under various nutritional/metabolic conditions. PNPLA3 gene expression was determined by real-time PCR in liver of C57BL/6 mice after dietary treatments and in HepG2 cells exposed to various nutritional/metabolic stimuli. Intracellular lipid content was determined in HepG2 cells after siRNA-mediated knockdown of PNPLA3. In vivo, mice fed a high-carbohydrate (HC) liquid diet had elevated hepatic lipid content, and PNPLA3 mRNA and protein expression, compared to chow-fed mice. Elevated expression was completely abrogated by addition of unsaturated lipid emulsion to the HC diet. By contrast, in mice with high-fat diet-induced steatosis, Pnpla3 expression did not differ compared to low-fat fed mice. In HepG2 cells, Pnpla3 expression was reversibly suppressed by glucose depletion and increased by glucose refeeding, but unchanged by addition of insulin and glucagon. Several unsaturated fatty acids each significantly decreased Pnpla3 mRNA, similar to lipid emulsion in vivo. However, Pnpla3 knockdown in HepG2 cells did not alter total lipid content in high glucose- or oleic acid-treated cells. Our results provide evidence that PNPLA3 expression is an early signal/signature of carbohydrate-induced lipogenesis, but its expression is not associated with steatosis per se. Under lipogenic conditions due to high-carbohydrate feeding, certain unsaturated fatty acids can effectively suppress both lipogenesis and PNPLA3 expression, both in vivo and in a hepatocyte cell line. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Response of pigeon guillemots to variable abundance of high-lipid and low-lipid prey

    USGS Publications Warehouse

    Litzow, Michael A.; Piatt, John F.; Prichard, A.K.; Roby, D.D.

    2002-01-01

    Populations of the pigeon guillemot (Cepphus columba) and other piscivores have been in decline for several decades in the Gulf of Alaska and Bering Sea, and a decline in abundance of lipid-rich schooling fishes is hypothesized as the major cause. We tested this hypothesis by studying the breeding biology of pigeon guillemots during 1995-1999 while simultaneously measuring prey abundance with beach seines and bottom trawls. Our study area (Kachemak Bay, Alaska) comprises two oceanographically distinct areas. Populations of a lipid-rich schooling fish, Pacific sand lance (Ammodytes hexapterus), were higher in the warmer Inner Bay than in the colder Outer Bay, and sand lance abundance was higher during warm years. Populations of low-lipid content demersal fishes were similar between areas. Chick survival to age 15 days was 47% higher in the Inner Bay (high-lipid diet) than in the Outer Bay (low-lipid diet), and estimated reproductive success (chicks fledged nest-1) was 62% higher in the Inner Bay than in the Outer Bay. Chick provisioning rate (kJ chick-1 h-1) increased with the proportion of sand lance in the diet (r2=0.21), as did growth rate (g day-1) of younger (beta) chicks in two-chick broods (r2=0.14). Pigeon guillemots in the Inner Bay switched to demersal prey during years of below-average sand lance abundance, and these birds reacted to 38-fold interannual changes in sand lance abundance with reductions in beta chick growth rates, with no decline in beta chick survival. In contrast, the proportion of nests experiencing brood reduction in the Outer Bay (demersal diet) increased >300% during years of below-average demersal abundance, although demersal fish abundance varied only 4-fold among years. Our results support the hypothesis that recovery of pigeon guillemot populations from the effects of the Exxon Valdez oil spill is limited by availability of lipid-rich prey.

  6. High-density lipoprotein and apolipoprotein A-I inhibit palmitate-induced translocation of toll-like receptor 4 into lipid rafts and inflammatory cytokines in 3T3-L1 adipocytes

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

    Yamada, Hodaka; Umemoto, Tomio; Kawano, Mikihiko

    Saturated fatty acids (SFAs) activate toll-like receptor 4 (TLR4) signal transduction in macrophages and are involved in the chronic inflammation accompanying obesity. High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) produce anti-inflammatory effects via reverse cholesterol transport. However, the underlying mechanisms by which HDL and apoA-I inhibit inflammatory responses in adipocytes remain to be determined. Here we examined whether palmitate increases the translocation of TLR4 into lipid rafts and whether HDL and apoA-I inhibit inflammation in adipocytes. Palmitate exposure (250 μM, 24 h) increased interleukin-6 and tumor necrosis factor-α gene expressions and translocation of TLR4 into lipid rafts in 3T3-L1 adipocytes. Pretreatment withmore » HDL and apoA-I (50 μg/mL, 6 h) suppressed palmitate-induced inflammatory cytokine expression and TLR4 translocation into lipid rafts. Moreover, HDL and apoA-I inhibited palmitate-induced phosphorylation of nuclear factor-kappa B. HDL showed an anti-inflammatory effect via ATP-binding cassette transporter G1 and scavenger receptor class B, member 1, whereas apoA-I showed an effect via ATP-binding cassette transporter A1. These results demonstrated that HDL and apoA-I reduced palmitate-potentiated TLR4 trafficking into lipid rafts and its related inflammation in adipocytes via these specific transporters. - Highlights: • Palmitate induces TLR4 translocation into lipid rafts in 3T3-L1 adipocytes. • Raft disruption by MβCD inhibits lipid raft formation. • HDL and apoA-I inhibit palmitate-induced translocation of TLR4 into lipid rafts. • Anti-inflammatory effects of HDL and apoA-I occur via specific transporters.« less

  7. Ethanol Enhances TGF-β Activity by Recruiting TGF-β Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non-Lipid Raft Microdomains.

    PubMed

    Huang, Shuan Shian; Chen, Chun-Lin; Huang, Franklin W; Johnson, Frank E; Huang, Jung San

    2016-04-01

    Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF-β-stimulated luciferase activity with a maximum of 0.5-1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2-dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-β signaling sensor, by ∼ 2-3-fold. Ethanol (0.5%) increases cell-surface expression of the type II TGF-β receptor (TβR-II) by ∼ 2-3-fold from its intracellular pool, as determined by I(125) -TGF-β-cross-linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface TβR-I and TβR-II from lipid rafts/caveolae and facilitates translocation of these receptors to non-lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF-β signaling by increasing non-lipid raft microdomain localization of the TGF-β receptors. Since TGF-β plays a protective role in ASCVD but can also cause ALD, the TGF-β enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein-coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues. © 2015 Wiley Periodicals, Inc.

  8. Fasting-induced G0/G1 switch gene 2 and FGF21 expression in the liver are under regulation of adipose tissue derived fatty acids

    PubMed Central

    Jaeger, Doris; Schoiswohl, Gabriele; Hofer, Peter; Schreiber, Renate; Schweiger, Martina; Eichmann, Thomas O.; Pollak, Nina M.; Poecher, Nadja; Grabner, Gernot F.; Zierler, Kathrin A.; Eder, Sandra; Kolb, Dagmar; Radner, Franz P.W.; Preiss-Landl, Karina; Lass, Achim; Zechner, Rudolf; Kershaw, Erin E.; Haemmerle, Guenter

    2015-01-01

    Background & Aims Adipose tissue (AT)-derived fatty acids (FAs) are utilized for hepatic triacylglycerol (TG) generation upon fasting. However, their potential impact as signaling molecules is not established. Herein we examined the role of exogenous AT-derived FAs in the regulation of hepatic gene expression by investigating mice with a defect in AT-derived FA supply to the liver. Methods Plasma FA levels, tissue TG hydrolytic activities and lipid content were determined in mice lacking the lipase co-activator comparative gene identification-58 (CGI-58) selectively in AT (CGI-58-ATko) applying standard protocols. Hepatic expression of lipases, FA oxidative genes, transcription factors, ER stress markers, hormones and cytokines were determined by qRT-PCR, Western blotting and ELISA. Results Impaired AT-derived FA supply upon fasting of CGI-58-ATko mice causes a marked defect in liver PPARα-signaling and nuclear CREBH translocation. This severely reduced the expression of respective target genes such as the ATGL inhibitor G0/G1 switch gene-2 (G0S2) and the endocrine metabolic regulator FGF21. These changes could be reversed by lipid administration and raising plasma FA levels. Impaired AT-lipolysis failed to induce hepatic G0S2 expression in fasted CGI-58-ATko mice leading to enhanced ATGL-mediated TG-breakdown strongly reducing hepatic TG deposition. On high fat diet, impaired AT-lipolysis counteracts hepatic TG accumulation and liver stress linked to improved systemic insulin sensitivity. Conclusions AT-derived FAs are a critical regulator of hepatic fasting gene expression required for the induction of G0S2-expression in the liver to control hepatic TG-breakdown. Interfering with AT-lipolysis or hepatic G0S2 expression represents an effective strategy for the treatment of hepatic steatosis. PMID:25733154

  9. Sudden appearance of anti-protein IgG1-forming cell precursors early during primary immunization.

    PubMed

    Nossal, G J; Riedel, C

    1989-06-01

    The anti-keyhole limpet hemocyanin (KLH) B-cell repertoire of unimmunized adult mice was examined by culture of splenocytes (generally 100-3000) at limiting dilution. Cells were polyclonally stimulated with Escherichia coli lipopolysaccharide (LPS) and an interleukin-4-containing lymphokine mixture in the presence of 3T3 fibroblast filler cells. After 7 days of culture, supernatants were examined for their content of anti-KLH IgM and IgG1 antibody by an enzyme-linked immunosorbent assay (ELISA). Parallel cultures of smaller numbers (generally 1-15) of splenocytes were examined to determine the cloning efficiency of B cells in terms of total IgM and IgG1 production. Whereas one spleen cell in 370 produced clones secreting anti-KLH IgM, only 1% of these produced IgG1 that could bind to KLH, despite the fact that about half of the clones switched to IgG1 production with these stimuli. In mice immunized with KLH, this situation did not change until day 5, when there was a sudden, explosive emergence of B cells that could form clones secreting anti-KLH IgG1. The absolute number of such cells in the spleen was found to rise by a factor of 350 between days 3 and 7 of immunization. Moreover, the median amount of IgG1 antibody formed per clone and binding to KLH also rose markedly. In contrast, neither the numbers nor the median KLH-binding antibody content of anti-KLH IgM clones changed significantly after immunization. The results show that the repertoire of anti-protein B cells detected through IgM formation in ELISA consists chiefly of cells producing antibody of low avidity and of doubtful in vivo significance. Assuming that the small proportion of these cells making antibody that is of sufficient avidity to bind as the IgG1 isotype are the ancestors of the many such cells found on day 7 of the primary immune response, one would have to postulate a very high recruitment and/or division rate to account for the increase in numbers and avidity that occurs. It is possible

  10. Lipid, Detergent, and Coomassie Blue G-250 Affect the Migration of Small Membrane Proteins in Blue Native Gels

    PubMed Central

    Crichton, Paul G.; Harding, Marilyn; Ruprecht, Jonathan J.; Lee, Yang; Kunji, Edmund R. S.

    2013-01-01

    Blue native gel electrophoresis is a popular method for the determination of the oligomeric state of membrane proteins. Studies using this technique have reported that mitochondrial carriers are dimeric (composed of two ∼32-kDa monomers) and, in some cases, can form physiologically relevant associations with other proteins. Here, we have scrutinized the behavior of the yeast mitochondrial ADP/ATP carrier AAC3 in blue native gels. We find that the apparent mass of AAC3 varies in a detergent- and lipid-dependent manner (from ∼60 to ∼130 kDa) that is not related to changes in the oligomeric state of the protein, but reflects differences in the associated detergent-lipid micelle and Coomassie Blue G-250 used in this technique. Higher oligomeric state species are only observed under less favorable solubilization conditions, consistent with aggregation of the protein. Calibration with an artificial covalent AAC3 dimer indicates that the mass observed for solubilized AAC3 and other mitochondrial carriers corresponds to a monomer. Size exclusion chromatography of purified AAC3 in dodecyl maltoside under blue native gel-like conditions shows that the mass of the monomer is ∼120 kDa, but appears smaller on gels (∼60 kDa) due to the unusually high amount of bound negatively charged dye, which increases the electrophoretic mobility of the protein-detergent-dye micelle complex. Our results show that bound lipid, detergent, and Coomassie stain alter the behavior of mitochondrial carriers on gels, which is likely to be true for other small membrane proteins where the associated lipid-detergent micelle is large when compared with the mass of the protein. PMID:23744064

  11. Improvement of lipid content of Chlorella minutissima MCC 5 for biodiesel production.

    PubMed

    Chakraborty, Sourabh; Mohanty, Debabrata; Ghosh, Supratim; Das, Debabrata

    2016-09-01

    Lipids extracted from microalgae have been considered as a potential source for the production of biodiesel. Enhancement of lipid has the limitations of low biomass productivity. So, the main objective of the present study was to deduce suitable conditions for the improvement of biomass production followed by enhancement of lipid content. After optimization, a strategy for two stage cultivation was utilized where high lipid content was obtained with a high biomass concentration. Optimization of biomass production of Chlorella minutissima MCC 5 was carried out under different intensities of light, temperatures, concentrations of nitrate and phosphate using Taguchi model. A suitable synergy of the four parameters yielded maximum biomass (1.93 g L(-1)) in airlift reactor. Temperature was found to be relatively effective than other parameters for higher biomass production. Activation energy for the cell growth was determined (47.95 kJ mol(-1)). Among the various (photo, thermal, nitrate and phosphate) stress conditions studied, nitrate limitation (1 mM) was found to be suitable for the enhancement of lipid resulting highest yield (48.26% w/w). Two stage cultivation of the microalgae yielded a maximum lipid content of 46% w/w with a biomass concentration of 2.2 g L(-1). Additionally, FAME analysis exhibited significant increase of oleic acid in the biodiesel. So, C. minutissima MCC 5 cultivated under nitrate stress could be a possible feedstock for biodiesel production. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  12. Effects of some inhibitors on the growth and lipid accumulation of oleaginous yeast Rhodosporidium toruloides and preparation of biodiesel by enzymatic transesterification of the lipid.

    PubMed

    Zhao, Xuebing; Peng, Feng; Du, Wei; Liu, Canming; Liu, Dehua

    2012-08-01

    Microbial lipid produced using yeast fermentation with inexpensive carbon sources such as lignocellulosic hydrolyzate can be an alternative feedstock for biodiesel production. Several inhibitors that can be generated during acid hydrolysis of lignocellulose were added solely or together into the culture medium to study their individual inhibitory actions and their synergistic effects on the growth and lipid accumulation of oleaginous yeast Rhodosporidium toruloides. When the inhibitors were present in isolation in the medium, to obtain a high cell biomass accumulation, the concentrations of formic acid, acetic acid, furfural and vanillin should be lower than 2, 5, 0.5 and 1.5 g/L, respectively. However, the synergistic effects of these compounds could dramatically decrease the minimum critical inhibitory concentrations leading to significant growth and lipid production inhibitions. Unlike the above-cited inhibitors, sodium lignosulphonate had no negative influence on biomass accumulation when its concentration was in the range of 0.5-2.0 g/L; in effect, it was found to facilitate cell growth and sugar-to-lipid conversion. The fatty acid compositional profile of the yeast lipid was in the compositional range of various plant oils and animal tallow. Finally, the crude yeast lipid from bagasse hydrolyzate could be well converted into fatty acid methyl ester (FAME, biodiesel) by enzymatic transesterification in a tert-butanol system with biodiesel yield of 67.2% and lipid-to-biodiesel conversion of 88.4%.

  13. Effects of dietary phospholipid level in cobia (Rachycentron canadum) larvae: growth, survival, plasma lipids and enzymes of lipid metabolism.

    PubMed

    Niu, J; Liu, Y J; Tian, L X; Mai, K S; Yang, H J; Ye, C X; Zhu, Y

    2008-03-01

    A study was conducted to determine the effects of dietary phospholipid (PL) levels in cobia (Rachycentron canadum) larvae with regard to growth, survival, plasma lipids and enzymes of lipid metabolism. Fish with an average weight of 0.4 g were fed diets containing four levels of PL (0, 20, 40 and 80 g kg(-1)dry matter: purity 97%) for 42 days. Final body weight (FBW), weight gain (WG) and survival ratio were highest in the 8% PL diet group and mortality was highest in PL-free diet group. We examined the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in liver, lecithin-cholesterolacyltransferase (LCAT) in plasma as well as plasma lipids and lipoprotein. LCAT activity showed a decrease of more than two-fold in PL-supplemented diet groups compared with the PL-free diet group. HL activity was highest in the 8% PL diet group and the other three groups showed no difference. LPL activity was significantly higher in the PL-supplemented diet groups than in the PL-free diet group. The dietary intervention significantly increased plasma phospholipids and total cholesterol (TC) levels, and the higher free cholesterol (FC) level contributed to the TC level. However, the fish fed PL exhibited a significantly decreased plasma triglyceride (TG) level. The lipoprotein fractions were also affected significantly by the PL. The PL-supplemented diet groups had significantly higher high-density lipoprotein (HDL) compared with the PL-free diet group, but showed a marked decrease in very low-density lipoprotein (VLDL). The results suggested that PL could modify plasma lipoprotein metabolism and lipid profile, and that the optimal dietary PL level may well exceed 80 g kg(-1) for cobia larvae according to growth and survival.

  14. Interactions between HIV-1 Neutralizing Antibodies and Model Lipid Membranes imaged with AFM

    NASA Astrophysics Data System (ADS)

    Zauscher, Stefan; Hardy, Gregory; Alam, Munir; Shapter, Joseph

    2012-02-01

    Lipid membrane interactions with rare, broadly neutralizing antibodies (NAbs), 2F5 and 4E10, play a critical role in HIV-1 neutralization. Our research is motivated by recent immunization studies that have shown that induction of antibodies that avidly bind the gp41-MPER antigen is not sufficient for neutralization. Rather, it is required that antigen designs induce polyreactive antibodies that recognize MPER antigens as well as the viral lipid membrane. However, the mechanistic details of how membrane properties influence NAb-lipid and NAb-antigen interactions remain unknown. Furthermore, it is well established that the native viral membrane is heterogeneous, representing a mosaic of lipid rafts and protein clustering. However, the size, physical properties, and dynamics of these regions are poorly characterized and their potential roles in HIV-1 neutralization are also unknown. To understand how membrane properties contribute to 2F5/4E10 membrane interactions, we have engineered biomimetic supported lipid bilayers (SLBs) and use atomic force microscopy to visualize membrane domains, antigen clustering, and antibody-membrane interactions at sub-nanometer z-resolution. Our results show that localized binding of HIV-1 antigens and NAbs occur preferentially with the most fluid membrane domain. This supports the theory that NAbs may interact with regions of low lateral lipid forces that allow antibody insertion into the bilayer.

  15. A lipid-binding loop of botulinum neurotoxin serotypes B, DC and G is an essential feature to confer their exquisite potency

    PubMed Central

    Le Blanc, Alexander; Mahrhold, Stefan; Piesker, Janett; Luppa, Peter B.

    2018-01-01

    The exceptional toxicity of botulinum neurotoxins (BoNTs) is mediated by high avidity binding to complex polysialogangliosides and intraluminal segments of synaptic vesicle proteins embedded in the presynaptic membrane. One peculiarity is an exposed hydrophobic loop in the toxin’s cell binding domain HC, which is located between the ganglioside- and protein receptor-binding sites, and that is particularly pronounced in the serotypes BoNT/B, DC, and G sharing synaptotagmin as protein receptor. Here, we provide evidence that this HC loop is a critical component of their tripartite receptor recognition complex. Binding to nanodisc-embedded receptors and toxicity were virtually abolished in BoNT mutants lacking residues at the tip of the HC loop. Surface plasmon resonance experiments revealed that only insertion of the HC loop into the lipid-bilayer compensates for the entropic penalty inflicted by the dual-receptor binding. Our results represent a new paradigm of how BoNT/B, DC, and G employ ternary interactions with a protein, ganglioside, and lipids to mediate their extraordinary neurotoxicity. PMID:29718991

  16. ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics

    PubMed Central

    Barratt, Daniel T; Coller, Janet K; Hallinan, Richard; Byrne, Andrew; White, Jason M; Foster, David JR; Somogyi, Andrew A

    2012-01-01

    Background: Genetic variability in ABCB1, encoding the P-glycoprotein efflux transporter, has been linked to altered methadone maintenance treatment dose requirements. However, subsequent studies have indicated that additional environmental or genetic factors may confound ABCB1 pharmacogenetics in different methadone maintenance treatment settings. There is evidence that genetic variability in OPRM1, encoding the mu opioid receptor, and ABCB1 may interact to affect morphine response in opposite ways. This study aimed to examine whether a similar gene-gene interaction occurs for methadone in methadone maintenance treatment. Methods: Opioid-dependent subjects (n = 119) maintained on methadone (15–300 mg/day) were genotyped for five single nucleotide polymorphisms of ABCB1 (61A > G; 1199G > A; 1236C > T; 2677G > T; 3435C > T), as well as for the OPRM1 118A > G single nucleotide polymorphism. Subjects’ methadone doses and trough plasma (R)-methadone concentrations (Ctrough) were compared between ABCB1 haplotypes (with and without controlling for OPRM1 genotype), and between OPRM1 genotypes (with and without controlling for ABCB1 haplotype). Results: Among wild-type OPRM1 subjects, an ABCB1 variant haplotype group (subjects with a wild-type and 61A:1199G:1236C:2677T:3435T haplotype combination, or homozygous for the 61A:1199G:1236C:2677T:3435T haplotype) had significantly lower doses (median ± standard deviation 35 ± 5 versus 180 ± 65 mg/day, P < 0.01) and Ctrough (78 ± 22 versus 177 ± 97 ng/mL, P < 0.05) than ABCB1 wild-type subjects. Among subjects with the most common ABCB1 haplotype combination (wild-type with 61A:1199G:1236T:2677T:3435T), the OPRM1 118 A/G genotype was associated with a significantly higher Ctrough than 118 A/A (250 ± 126 versus 108 ± 36 ng/mL, P = 0.016). No ABCB1 haplotype group or OPRM1 genotype was associated with dose or Ctrough without taking into account confounding genetic variability at the other locus. Therefore, two

  17. Effects of imidazolium-based ionic liquids on the stability and dynamics of gramicidin A and lipid bilayers at different salt concentrations.

    PubMed

    Lee, Hwankyu; Kim, Sun Min; Jeon, Tae-Joon

    2015-09-01

    Gramicidin A (gA) dimers with bilayers, which consist of phospholipids and ionic liquids (ILs) at different molar ratios, were simulated at different salt concentrations of 0.15 and 1M NaCl. Bilayer thickness is larger than the length of a gA dimer, and hence lipids around the gA dimer are significantly disordered to adapt to the gA dimer, yielding membrane curvature. As the IL concentration increases, the bilayer thickness decreases and becomes closer to the gA length, leading to less membrane curvature. Also, ILs significantly increase lateral diffusivities of the gA dimer and lipids at 0.15M NaCl, but not at 1M NaCl because strong electrostatic interactions between salt ions and lipid head groups suppress an increase in the lateral mobility of the bilayer at high salt concentration. These findings help explain the conflicting experimental results that showed the increased ion permeability in electrophysiological experiments at 1M NaCl, but the reduced ion permeability in fluorescent experiments at 0.15M NaCl. ILs disorder lipids and make bilayers thinner, which yields less membrane curvature around the gA dimer and thus stabilizes the gA dimer, leading to the increased ion permeability. This IL effect predominantly occurs at 1M NaCl, where ILs only slightly increase the bilayer dynamics because of the strong electrostatic interactions between salt ions and lipids. In contrast, at 0.15M NaCl, ILs do not only stabilize the curved bilayer but also significantly increase the lateral mobility of gA dimers and lipids, which can reduce gA-induced pore formation, leading to the decreased ion permeability. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation

    PubMed Central

    Dias, Irundika H.K.; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M.; Polidori, Maria C.; Lip, Gregory Y.H.; Griffiths, Helen R.

    2014-01-01

    Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4 μg oxLDL and 25 µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells. PMID:25048970

  19. Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif.

    PubMed

    Molinos-Albert, Luis M; Bilbao, Eneritz; Agulló, Luis; Marfil, Silvia; García, Elisabet; Rodríguez de la Concepción, Maria Luisa; Izquierdo-Useros, Nuria; Vilaplana, Cristina; Nieto-Garai, Jon A; Contreras, F-Xabier; Floor, Martin; Cardona, Pere J; Martinez-Picado, Javier; Clotet, Bonaventura; Villà-Freixa, Jordi; Lorizate, Maier; Carrillo, Jorge; Blanco, Julià

    2017-01-13

    The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants.

  20. Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif

    PubMed Central

    Molinos-Albert, Luis M.; Bilbao, Eneritz; Agulló, Luis; Marfil, Silvia; García, Elisabet; Concepción, Maria Luisa Rodríguez de la; Izquierdo-Useros, Nuria; Vilaplana, Cristina; Nieto-Garai, Jon A.; Contreras, F.-Xabier; Floor, Martin; Cardona, Pere J.; Martinez-Picado, Javier; Clotet, Bonaventura; Villà-Freixa, Jordi; Lorizate, Maier; Carrillo, Jorge; Blanco, Julià

    2017-01-01

    The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants. PMID:28084464

  1. Switching non-local median filter

    NASA Astrophysics Data System (ADS)

    Matsuoka, Jyohei; Koga, Takanori; Suetake, Noriaki; Uchino, Eiji

    2015-06-01

    This paper describes a novel image filtering method for removal of random-valued impulse noise superimposed on grayscale images. Generally, it is well known that switching-type median filters are effective for impulse noise removal. In this paper, we propose a more sophisticated switching-type impulse noise removal method in terms of detail-preserving performance. Specifically, the noise detector of the proposed method finds out noise-corrupted pixels by focusing attention on the difference between the value of a pixel of interest (POI) and the median of its neighboring pixel values, and on the POI's isolation tendency from the surrounding pixels. Furthermore, the removal of the detected noise is performed by the newly proposed median filter based on non-local processing, which has superior detail-preservation capability compared to the conventional median filter. The effectiveness and the validity of the proposed method are verified by some experiments using natural grayscale images.

  2. Water extract of gromwell (Lithospermum erythrorhizon) enhances migration of human keratinocytes and dermal fibroblasts with increased lipid synthesis in an in vitro wound scratch model.

    PubMed

    Kim, H; Kim, J; Park, J; Kim, S H; Uchida, Y; Holleran, W M; Cho, Y

    2012-01-01

    Although organic extracts of gromwell (Lithospermum erythrorhizon) have been shown to promote wound healing, the wound healing effects of water extracts of gromwell (WG) that are commonly used in traditional remedies have not been elucidated. We investigated whether WG promotes the migration and/or proliferation of cultured human keratinocytes (CHK) or dermal fibroblasts in parallel with increases in lipid synthesis during in vitro wound healing. CHK or fibroblasts were treated with 1-1,000 μg/ml WG for up to 48 h following scratch wound formation. Cell migration was assessed by measuring coverage (in percent) from the wound margin, while cell proliferation and lipid synthesis were determined by [(3)H]thymidine incorporation into DNA fractions, and [(3)H]palmitate or [(3)H]serine incorporation into lipid fractions, respectively. Low-dose WG (1 μg/ml) enhanced the wound coverage for both CHK and fibroblasts at 24 h, while cell proliferation was not altered in either cell types. Synthesis of both total lipids and individual lipid classes, including phospholipids, sphingolipids and neutral lipids, were found to be increased at 24 h in CHK treated with 1 μg/ml WG; in similarly treated fibroblasts, only the syntheses of sphingolipids (such as ceramides and glucosylceramides), but not other lipid species, were significantly increased. In contrast, a higher dose of WG (10-1,000 μg/ml) did not enhance wound coverage, and 100 μg/ml WG neither altered cell proliferation nor lipid synthesis in both CHK and fibroblasts. Low-dose WG (1 μg/ml) enhances the migration of both CHK and fibroblasts with increased lipid synthesis in an in vitro wound scratch model. Copyright © 2011 S. Karger AG, Basel.

  3. ABCA1 gene variants regulate postprandial lipid metabolism in healthy men

    PubMed Central

    Delgado-Lista, Javier; Perez-Martinez, Pablo; Perez-Jimenez, Francisco; Garcia-Rios, Antonio; Fuentes, Francisco; Marin, Carmen; Gómez-Luna, Purificación; Camargo, Antonio; Parnell, Laurence D; Ordovas, Jose Maria; Lopez-Miranda, Jose

    2010-01-01

    Objective Genetic variants of ABCA1, an ATP-binding cassette (ABC) transporter, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly high density lipoproteins (HDL) and Apolipoprotein A1 (APOA1), but results from different studies have been inconsistent. Methods and results In order to further characterize the effects of ABCA1 variants in human postprandial lipid metabolism, we studied the influence of three single nucleotide polymorphisms (SNPs) [i27943 (rs2575875); i48168 (rs4149272); R219K (rs2230806)] in the postprandial lipemia of 88 normolipidemic young men, who were given a fatty meal. For i27943 and i48168 SNPs, fasting and postprandial values of APOA1 were higher, and postprandial lipemia was much lower in homozygotes for the major alleles, for total triglycerides in plasma, and large-triglyceride rich lipoproteins (TRL) triglycerides. These persons also showed higher APOA1/APOB ratio. Major allele homozygotes for i48168 and i27943 showed additionally higher HDL and lower postprandial Apolipoprotein B (ApoB). Conclusions Our work shows that major allele homozygotes for ABCA1 SNPs i27943 and i48168 have a lower postprandial response as compared to minor allele carriers. This finding may further characterize the role of ABCA1 in lipid metabolism. PMID:20185793

  4. Dual pathology proximal median nerve compression of the forearm.

    PubMed

    Murphy, Siun M; Browne, Katherine; Tuite, David J; O'Shaughnessy, Michael

    2013-12-01

    We report an unusual case of synchronous pathology in the forearm- the coexistence of a large lipoma of the median nerve together with an osteochondroma of the proximal ulna, giving rise to a dual proximal median nerve compression. Proximal median nerve compression neuropathies in the forearm are uncommon compared to the prevalence of distal compression neuropathies (eg Carpal Tunnel Syndrome). Both neural fibrolipomas (Refs. 1,2) and osteochondromas of the proximal ulna (Ref. 3) in isolation are rare but well documented. Unlike that of a distal compression, a proximal compression of the median nerve will often have a definite cause. Neural fibrolipoma, also called fibrolipomatous hamartoma are rare, slow-growing, benign tumours of peripheral nerves, most often occurring in the median nerve of younger patients. To our knowledge, this is the first report of such dual pathology in the same forearm, giving rise to a severe proximal compression of the median nerve. In this case, the nerve was being pushed anteriorly by the osteochondroma, and was being compressed from within by the intraneural lipoma. This unusual case highlights the advantage of preoperative imaging as part of the workup of proximal median nerve compression. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  5. 26 CFR 1.475(g)-1 - Effective dates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Effective dates. 1.475(g)-1 Section 1.475(g)-1...) INCOME TAXES (CONTINUED) Inventories § 1.475(g)-1 Effective dates. (a)-(b) [Reserved] (c) Section 1.475(a...) applies on and after August 13, 1996 (the effective date of § 1.1275-6). (g) [Reserved] (h) Section 1.475...

  6. 26 CFR 1.475(g)-1 - Effective dates.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Effective dates. 1.475(g)-1 Section 1.475(g)-1...) INCOME TAXES (CONTINUED) Inventories § 1.475(g)-1 Effective dates. (a)-(b) [Reserved] (c) Section 1.475(a...) applies on and after August 13, 1996 (the effective date of § 1.1275-6). (g) [Reserved] (h) Section 1.475...

  7. 26 CFR 1.475(g)-1 - Effective dates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Effective dates. 1.475(g)-1 Section 1.475(g)-1...) INCOME TAXES (CONTINUED) Inventories § 1.475(g)-1 Effective dates. (a)-(b) [Reserved] (c) Section 1.475(a...) applies on and after August 13, 1996 (the effective date of § 1.1275-6). (g) [Reserved] (h) Section 1.475...

  8. 26 CFR 1.475(g)-1 - Effective dates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Effective dates. 1.475(g)-1 Section 1.475(g)-1...) INCOME TAXES (CONTINUED) Inventories § 1.475(g)-1 Effective dates. (a)-(b) [Reserved] (c) Section 1.475(a...) applies on and after August 13, 1996 (the effective date of § 1.1275-6). (g) [Reserved] (h) Section 1.475...

  9. IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal

    PubMed Central

    2012-01-01

    Background Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low. Methods One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district. Results Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to Anopheles gambiae bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and Anopheles mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to Anopheles bites between different exposure groups of districts. Conclusions Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the

  10. Flexible Charged Macromolecules on Mixed Fluid Lipid Membranes: Theory and Monte Carlo Simulations

    PubMed Central

    Tzlil, Shelly; Ben-Shaul, Avinoam

    2005-01-01

    Fluid membranes containing charged lipids enhance binding of oppositely charged proteins by mobilizing these lipids into the interaction zone, overcoming the concomitant entropic losses due to lipid segregation and lower conformational freedom upon macromolecule adsorption. We study this energetic-entropic interplay using Monte Carlo simulations and theory. Our model system consists of a flexible cationic polyelectrolyte, interacting, via Debye-Hückel and short-ranged repulsive potentials, with membranes containing neutral lipids, 1% tetravalent, and 10% (or 1%) monovalent anionic lipids. Adsorption onto a fluid membrane is invariably stronger than to an equally charged frozen or uniform membrane. Although monovalent lipids may suffice for binding rigid macromolecules, polyvalent counter-lipids (e.g., phosphatidylinositol 4,5 bisphosphate), whose entropy loss upon localization is negligible, are crucial for binding flexible macromolecules, which lose conformational entropy upon adsorption. Extending Rosenbluth's Monte Carlo scheme we directly simulate polymer adsorption on fluid membranes. Yet, we argue that similar information could be derived from a biased superposition of quenched membrane simulations. Using a simple cell model we account for surface concentration effects, and show that the average adsorption probabilities on annealed and quenched membranes coincide at vanishing surface concentrations. We discuss the relevance of our model to the electrostatic-switch mechanism of, e.g., the myristoylated alanine-rich C kinase substrate protein. PMID:16126828

  11. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    PubMed

    Xu, Jialin; Donepudi, Ajay C; Moscovitz, Jamie E; Slitt, Angela L

    2013-01-01

    The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD), regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting). Male C57BL/6 (WT) and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase) and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36) and Fatty acid transport protein (FATP) 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar) α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK) phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  12. Bioaccumulation of PCBs in liver tissue of dusky Carcharhinus obscurus, sandbar C. plumbeus and white Carcharodon carcharias sharks from south-eastern Australian waters.

    PubMed

    Gilbert, Jann M; Baduel, Christine; Li, Yan; Reichelt-Brushett, Amanda J; Butcher, Paul A; McGrath, Shane P; Peddemors, Victor M; Hearn, Laurence; Mueller, Jochen; Christidis, Les

    2015-12-30

    Polychlorinated biphenyls (PCBs) are ubiquitous pollutants in the marine environment that are known to accumulate in apex predators such as sharks. Liver samples from dusky Carcharhinus obscurus, sandbar Carcharhinus plumbeus, and white Carcharodon carcharias sharks from south-eastern Australian waters were analysed for the seven indicator PCBs 28, 52, 101, 118, 138, 153 and 180. Median ∑PCBs were significantly higher in white than sandbar sharks (3.35 and 0.36 μg g(-1) lipid, respectively, p=0.05) but there were no significant differences between dusky sharks (1.31 μg g(-1) lipid) and the other two species. Congener concentrations were also significantly higher in white sharks. Significant differences in PCB concentrations between mature and immature dusky (3.78 and 0.76 μg g(-1) lipid, respectively) and sandbar (1.94 and 0.18 μg g(-1) lipid, respectively) sharks indicated that PCB concentrations in these species increased with age/growth. Higher-chlorinated congeners (hexa and heptachlorobiphenyls) dominated results, accounting for ~90% of ∑PCBs. Copyright © 2015. Published by Elsevier Ltd.

  13. Direct bioconversion of rice residue from canteen waste into lipids by new amylolytic oleaginous yeast Sporidiobolus pararoseus KX709872.

    PubMed

    Chaiyaso, Thanongsak; Srisuwan, Wimada; Techapun, Charin; Watanabe, Masanori; Takenaka, Shinji

    2018-04-21

    The new amylolytic oleaginous red yeast, Sporidiobolus pararoseus KX709872, produced both α-amylase (540 ± 0.09 mU/mL) and amyloglucosidase (23 ± 0.00 mU/mL) and showed good ability to directly convert rice residue from canteen waste to biomass and lipids. Effects of medium composition and cultivation conditions on growth and lipid accumulation for strain KX709872 were investigated under shaking flask and upscaling levels. At C : N ratio of 25 : 1, pH 5.45, 22.36°C, and 199.40 rpm for 7 days, volumetric production of biomass and lipids, lipid content, and lipid productivity reached 17.69 ± 0.44, 8.35 ± 0.19 g/L, 49.48 ± 0.41% (w/w), and 1.67 ± 0.11 g/L/day, respectively. Production of lipids was also implemented in 5.0-L stirred tank bioreactor with 2.5 L of optimized medium at 300 rpm and 3.0 vvm for 5 days. Volumetric production of biomass and lipids, lipid content, and lipid productivity were 16.33 ± 0.49, 8.75 ± 0.13 g/L, 56.61 ± 0.04% (w/w), and 2.19 ± 0.03 g/L/day, respectively. Meanwhile, the fatty acids of lipids from strain KX709872 had high oleic acid content (60-62%) which was similar to those of vegetable oils, indicating that these lipids are promising as an alternative biodiesel feedstock. Moreover, the biodiesel derived from lipids of strain KX709872 had properties satisfying the criteria of ASTM D6751 and EN 14214 standards.

  14. G protein-coupled estrogen receptor 1 (GPER 1) mediates estrogen-induced, proliferation of leiomyoma cells.

    PubMed

    Jiang, Xiuxiu; Ye, Xiaolei; Ma, Junyan; Li, Wen; Wu, Ruijin; Jun, Lin

    2015-01-01

    G protein-coupled estrogen receptor 1 (GPER-1, formerly known as GPR30) has been proposed as the receptor for estrogen-induced, growth of leiomyomas though its precise mechanisms of action are not clear. We obtained leiomyoma cells (LC) and normal smooth muscle cells from 28 women (n = 28, median age 38 years, median parity 1.0). We incubated them with 17-β estradiol (E(2)), after blocking, or upregulating, expression of GPER-1 with ICI182,780 (a GPER-1 agonist) and siGPR30, respectively. We evaluated the role of GPER-1 in the mitogen-activated protein kinase (MAPK) signaling pathway using Western blot analysis. We studied cell proliferation with 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and, mitotic activity with phosphohistone H3 (PPH3) expression in leiomyoma, and, matched, normal, smooth muscle tissues using standard immunohistochemistry. Downregulation of GPER-1 expression with siGPR30 partially attenuated the E(2)-activated MAPK signaling pathway (p < 0.01). Upregulation of GPER-1 with ICI182,780 enhanced the E(2)-activated MAPK signaling pathway (p < 0.01). ICI182,780 enhanced E(2)-induced proliferation of LC (p < 0.01), while knock down of the GPER-1 gene with GPER-1 small interfering RNA partially inhibited E(2)-induced cell proliferation (p < 0.01). There were no significant differences in PPH3 expression between LCs and normal smooth muscle tissues (p > 0.05). Neither ICI182,780 nor siGPR30 increased mitosis in LCs (p > 0.05). Our results indicate that GPER-1 mediates proliferation of estrogen-induced, LC by activating the MAPK pathway, and, not by promoting mitosis.

  15. 26 CFR 1.149(g)-1 - Hedge bonds.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Hedge bonds. 1.149(g)-1 Section 1.149(g)-1...) INCOME TAXES (CONTINUED) Tax Exemption Requirements for State and Local Bonds § 1.149(g)-1 Hedge bonds... for purposes of section 149(g) and this section. In addition, the following terms have the following...

  16. 26 CFR 1.149(g)-1 - Hedge bonds.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Hedge bonds. 1.149(g)-1 Section 1.149(g)-1...) INCOME TAXES (CONTINUED) Tax Exemption Requirements for State and Local Bonds § 1.149(g)-1 Hedge bonds... for purposes of section 149(g) and this section. In addition, the following terms have the following...

  17. 26 CFR 1.149(g)-1 - Hedge bonds.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Hedge bonds. 1.149(g)-1 Section 1.149(g)-1...) INCOME TAXES (CONTINUED) Tax Exemption Requirements for State and Local Bonds § 1.149(g)-1 Hedge bonds... for purposes of section 149(g) and this section. In addition, the following terms have the following...

  18. 26 CFR 1.149(g)-1 - Hedge bonds.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Hedge bonds. 1.149(g)-1 Section 1.149(g)-1...) INCOME TAXES (CONTINUED) Tax Exemption Requirements for State and Local Bonds § 1.149(g)-1 Hedge bonds... for purposes of section 149(g) and this section. In addition, the following terms have the following...

  19. 26 CFR 1.149(g)-1 - Hedge bonds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Hedge bonds. 1.149(g)-1 Section 1.149(g)-1...) INCOME TAXES (CONTINUED) Tax Exemption Requirements for State and Local Bonds § 1.149(g)-1 Hedge bonds... for purposes of section 149(g) and this section. In addition, the following terms have the following...

  20. 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.

    PubMed

    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. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Lipid monitoring in patients with schizophrenia prescribed second-generation antipsychotics.

    PubMed

    Weissman, Ellen M; Zhu, Carolyn W; Schooler, Nina R; Goetz, Raymond R; Essock, Susan M

    2006-09-01

    Treatment with second-generation antipsychotic (SGA) medications has been linked with increased rates of the metabolic syndrome (i.e., dyslipidemia, obesity, and hyperglycemia). Several sets of published recommendations now provide clinicians with guidelines for monitoring metabolic parameters in individuals with schizophrenia treated with SGAs. However, few data are available regarding actual metabolic monitoring practices in this patient population. The objectives of the study were to determine baseline lipid monitoring rates for individuals with schizophrenia prescribed SGAs during the period prior to the publication of monitoring guidelines and to determine whether individuals with abnormal lipid levels received follow-up monitoring sooner than individuals with normal levels. Lipid monitoring rates for 408 individuals with schizophrenia who were prescribed SGAs from October 1999 to October 2003 were examined using administrative data from a Veterans Affairs facility. Survival analysis was used to examine time to follow-up lipid measurement and to compare time to follow-up measure for individuals with normal initial lipid levels versus those with elevated initial lipid levels. Eighty-five percent of individuals had at least 1 measurement for total cholesterol or triglycerides in a 4-year period. Abnormal initial measurements predicted significantly earlier follow-up monitoring (p < .005 for total cholesterol, p < .05 for triglycerides, p < .001 for low-density lipoprotein cholesterol). However, median time to follow-up measure was 304 days (approximately 10 months) for individuals with elevated total cholesterol levels, which is too long for optimal clinical follow-up. Program managers and clinicians should assess adequacy of monitoring and support quality improvement initiatives in this area.

  2. Scavenging amphipods: sentinels for penetration of mercury and persistent organic chemicals into food webs of the deep Arctic Ocean.

    PubMed

    Bidleman, Terry F; Stern, Gary A; Tomy, Gregg T; Hargrave, Barry T; Jantunen, Liisa M; Macdonald, Robie W

    2013-06-04

    Archived specimens of the scavenging amphipod Eurythenes gryllus, collected from 2075 to 4250 m below the surface on five expeditions to the western and central Arctic Ocean between 1983 and 1998, were analyzed for total mercury (∑Hg), methyl mercury (MeHg), polychlorinated biphenyls (PCBs) and other industrial or byproduct organochlorines (chlorobenzenes, pentachloroanisole, octachlorostyrene), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs). Median ∑Hg concentrations ranged from 70 to 366 ng g(-1) wet weight (ww). MeHg concentrations (3.55 to 23.5 ng g(-1) ww) accounted for 1.7 to 20.1% (median 3.7%) of ∑Hg. ∑Hg and MeHg were positively and significantly correlated with ww (∑Hg r(2) = 0.18, p = 0.0004, n = 63; MeHg r(2) = 0.42, p = 0.0004, n = 25), but not significantly with δ(13)C nor δ(15)N. Median concentrations of total persistent organic pollutants (POPs) ranged from 9750 to 156,000 ng g(-1) lipid weight, with order of abundance: ∑TOX (chlorobornanes quantified as technical toxaphene) > ∑PCBs > ∑DDTs > ∑chlordanes > ∑mirex compounds > ∑BDEs ∼ ∑chlorobenzenes ∼ octachlorostyrene > α-hexachlorocyclohexane ∼ hexachlorobenzene ∼ pentachloroanisole. Enantioselective accumulation was found for the chiral OCPs o,p'-DDT, cis- and trans-chlordane, nonachlor MC6 and oxychlordane. Lipid-normalized POPs concentrations were elevated in amphipods with lipid percentages ≤10%, suggesting that utilization of lipids resulted in concentration of POPs in the remaining lipid pool. Multidimensional Scaling (MDS) analysis using log-transformed physiological variables and lipid-normalized organochlorine concentrations distinguished amphipods from the central vs western arctic stations. This distinction was also seen for PCB homologues, whereas profiles of other compound classes were more related to specific stations rather than central-west differences.

  3. Fluorescence lifetime imaging of lipids during 3T3-L1 cell differentiation

    NASA Astrophysics Data System (ADS)

    Song, Young Sik; Won, Young Jae; Lee, Sang-Hak; Kim, Dug Young

    2014-03-01

    Obesity is becoming a big health problem in these days. Since increased body weight is due to increased number and size of the triglyceride-storing adipocytes, many researchers are working on differentiation conditions and processes of adipocytes. Adipocytes also work as regulators of whole-body energy homeostasis by secreting several proteins that regulate processes as diverse as haemostasis, blood pressure, immune function, angiogenesis and energy balance. 3T3-L1 cells are widely used cell line for studying adipogenesis because it can differentiate into an adipocyte-like phenotype under appropriate conditions. In this paper, we propose an effective fluorescence lifetime imaging technique which can easily distinguish lipids in membrane and those in lipid droplets. Nile red dyes are attached to lipids in 3T3-L1 cells. Fluorescence lifetime images were taken for 2 week during differentiation procedure of 3T3-L1 cells into adipocytes. We used 488 nm pulsed laser with 5MHz repetition rate and emission wavelength is 520 nm of Nile Red fluorescent dye. Results clearly show that the lifetime of Nile red in lipid droplets are smaller than those in cell membrane. Our results suggest that fluorescence lifetime imaging can be a very powerful tool to monitor lipid droplet formation in adipocytes from 3T3-L1 cells.

  4. [Prospective study of gluco-lipidic hormone and peptide levels in morbidly obese patients after sleeve gastrectomy].

    PubMed

    Bruna, Marcos; Gumbau, Verónica; Guaita, Marcos; Canelles, Enrique; Mulas, Claudia; Basés, Carla; Celma, Isabel; Puche, José; Marcaida, Goitzane; Oviedo, Miguel; Vázquez, Antonio

    2014-03-01

    Different hormones and peptides involved in lipid and carbohydrate metabolism have been studied in relation to morbid obesity and its variation after bariatric surgery. The aim of this study is toevaluate variations in different molecules related to glico-lipidic metabolism during the first year after sleeve gastrectomy in morbidly obese patients. Prospective study in patients undergoing sleeve gastrectomy between November 2009 and January 2011. We analyzed changes in different clinical, anthropometric and analytic parameters related with glico-lipidic metabolism in all patients in the preoperative period, first postoperative day, fifth day, one month, 6 months and one year after surgery. Statistical analysis was performed using SPSS 20.0. We included 20 patients, 60% were women with a median of age of 45 years. Median of body mass index (IMC) was 48,5 kg/m(2) and 70% had obstructive sleep apnea syndrome (SAOS), 65% arterial hypertension (HTA), 45% dyslipidemia and 40% diabetes mellitus. One year after surgery, the percentage of excess of BMI loss was 72% and the rate of cure or improvement of dyslipidemia was 100%, diabetes 87,5%, HTA 84,6% and SAOS 57,1%. At this time, glycemia levels decreased significantly (P<.001), and levels of IGF-1 and HDL-cholesterol increased significantly. Levels of adiponectine increased and leptine (P=.003), insulin (P=.004) and triglycerides (P=.016) decreased significantly one year after the surgery. ACTH levels (that decreased during first 6 months after surgery), glycosilated hemoglobin, total cholesterol and LDL-cholesterol had no changes one year after surgery. Sleeve gastrectomy is a surgical technique with good results of weight loss and cure of comorbidities. This procedure induces significant modifications in blood levels of glico-lipidic metabolism related peptides and hormones, such as glucose, IGF-1, insulin, leptin, triglycerides and HDL-cholesterol. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

  5. Lipid and carotenoid production by Rhodotorula glutinis under irradiation/high-temperature and dark/low-temperature cultivation.

    PubMed

    Zhang, Zhiping; Zhang, Xu; Tan, Tianwei

    2014-04-01

    The capacity of lipid and carotenoid production by Rhodotorula glutinis was investigated under different irradiation conditions, temperatures and C/N ratios. The results showed that dark/low-temperature could enhance lipid content, while irradiation/high-temperature increased the yields of biomass and carotenoid. The optimum C/N ratio for production was between 80 and 100. A two-stage cultivation strategy was used for lipid and carotenoid production in a 5L fermenter. In the first stage, the maximum biomass reached 28.1g/L under irradiation/high-temperature. Then, the cultivation condition was changed to dark/low-temperature, and C/N ratio was adjusted to 90. After the second stage, the biomass, lipid content and carotenoid reached 86.2g/L, 26.7% and 4.2mg/L, respectively. More significantly, the yields of biomass and lipid were 43.1% and 11.5%, respectively. Lipids contained 79.7% 18C and 16.8% 16C fatty acids by GC analysis. HPLC quantified the main carotenoids were β-carotene (68.4%), torularhodin (21.5%) and torulene (10.1%). Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  6. Myo1c regulates lipid raft recycling to control cell spreading, migration and Salmonella invasion.

    PubMed

    Brandstaetter, Hemma; Kendrick-Jones, John; Buss, Folma

    2012-04-15

    A balance between endocytosis and membrane recycling regulates the composition and dynamics of the plasma membrane. Internalization and recycling of cholesterol- and sphingolipid-enriched lipid rafts is an actin-dependent process that is mediated by a specialized Arf6-dependent recycling pathway. Here, we identify myosin1c (Myo1c) as the first motor protein that drives the formation of recycling tubules emanating from the perinuclear recycling compartment. We demonstrate that the single-headed Myo1c is a lipid-raft-associated motor protein that is specifically involved in recycling of lipid-raft-associated glycosylphosphatidylinositol (GPI)-linked cargo proteins and their delivery to the cell surface. Whereas Myo1c overexpression increases the levels of these raft proteins at the cell surface, in cells depleted of Myo1c function through RNA interference or overexpression of a dominant-negative mutant, these tubular transport carriers of the recycling pathway are lost and GPI-linked raft markers are trapped in the perinuclear recycling compartment. Intriguingly, Myo1c only selectively promotes delivery of lipid raft membranes back to the cell surface and is not required for recycling of cargo, such as the transferrin receptor, which is mediated by parallel pathways. The profound defect in lipid raft trafficking in Myo1c-knockdown cells has a dramatic impact on cell spreading, cell migration and cholesterol-dependent Salmonella invasion; processes that require lipid raft transport to the cell surface to deliver signaling components and the extra membrane essential for cell surface expansion and remodeling. Thus, Myo1c plays a crucial role in the recycling of lipid raft membrane and proteins that regulate plasma membrane plasticity, cell motility and pathogen entry.

  7. Imaging lipid droplets in Arabidopsis mutants

    USDA-ARS?s Scientific Manuscript database

    Confocal fluorescence microscopy was adapted for the imaging of neutral lipids in plant leaves with defects in normal lipid metabolism using two different fluorescent dyes. Disruptions in a gene locus, At4g24160, yielded Arabidopsis thaliana plants with a preponderance of oil bodies in their leaves ...

  8. Structure-function insights into direct lipid transfer between membranes by Mmm1-Mdm12 of ERMES.

    PubMed

    Kawano, Shin; Tamura, Yasushi; Kojima, Rieko; Bala, Siqin; Asai, Eri; Michel, Agnès H; Kornmann, Benoît; Riezman, Isabelle; Riezman, Howard; Sakae, Yoshitake; Okamoto, Yuko; Endo, Toshiya

    2018-03-05

    The endoplasmic reticulum (ER)-mitochondrial encounter structure (ERMES) physically links the membranes of the ER and mitochondria in yeast. Although the ER and mitochondria cooperate to synthesize glycerophospholipids, whether ERMES directly facilitates the lipid exchange between the two organelles remains controversial. Here, we compared the x-ray structures of an ERMES subunit Mdm12 from Kluyveromyces lactis with that of Mdm12 from Saccharomyces cerevisiae and found that both Mdm12 proteins possess a hydrophobic pocket for phospholipid binding. However in vitro lipid transfer assays showed that Mdm12 alone or an Mmm1 (another ERMES subunit) fusion protein exhibited only a weak lipid transfer activity between liposomes. In contrast, Mdm12 in a complex with Mmm1 mediated efficient lipid transfer between liposomes. Mutations in Mmm1 or Mdm12 impaired the lipid transfer activities of the Mdm12-Mmm1 complex and furthermore caused defective phosphatidylserine transport from the ER to mitochondrial membranes via ERMES in vitro. Therefore, the Mmm1-Mdm12 complex functions as a minimal unit that mediates lipid transfer between membranes. © 2018 Kawano et al.

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

    PubMed Central

    Neumann, Steffen; Schmitt-Kopplin, Philippe

    2017-01-01

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

  10. Miscibility, chain packing, and hydration of 1-palmitoyl-2-oleoyl phosphatidylcholine and other lipids in surface phases.

    PubMed

    Smaby, J M; Brockman, H L

    1985-11-01

    The miscibility of 1-palmitoyl-2-oleoyl phosphatidylcholine with triolein, 1,2-diolein, 1,3-diolein, 1(3)-monoolein, oleyl alcohol, methyl oleate, oleic acid, and oleyl cyanide (18:1 lipids) was studied at the argon-water interface. The isothermal phase diagrams for the mixtures at 24 degrees were characterized by two compositional regions. At the limit of miscibility with lower mol fractions of 18:1 lipid, the surface pressure was composition-independent, but above a mixture-specific stoichiometry, surface pressure at the limit of miscibility was composition-dependent. From the two-dimensional phase rule, it was determined that at low mol fractions of 18:1 lipids, the surface consisted of phospholipid and a preferred packing array or complex of phospholipid and 18:1 lipid, whereas, above the stoichiometry of the complex, the surface phase consisted of complex and excess 18:1 lipids. In both regions of the phase diagram, mixing along the phase boundary was apparently ideal allowing application of an equation of state described earlier (J. M. Smaby and H. L. Brockman, 1984, Biochemistry, 23:3312-3316). From such analysis, apparent partial molecular areas and hydrations for phospholipid, complex, and 18:1 lipid were obtained. Comparison of these calculated parameters for the complexed and uncomplexed states shows that the aliphatic moieties behave independently of polar head group. The transition of each 18:1 chain to the complexed state involves the loss of about one interfacial water molecule and its corresponding area. For 18:1 lipids with more than one chain another two water molecules per additional chain are present in both states but contribute little to molecular area. In contrast to 18:1 lipids, the phospholipid area and hydration change little upon complexation. The uniformity of chain packing and hydration behavior among 18:1 lipid species contrasts with complex stoichiometries that vary from 0.04 to 0.65. This suggests that the stoichiometry of the

  11. Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids

    PubMed Central

    Teslovich, Tanya M.; Musunuru, Kiran; Smith, Albert V.; Edmondson, Andrew C.; Stylianou, Ioannis M.; Koseki, Masahiro; Pirruccello, James P.; Ripatti, Samuli; Chasman, Daniel I.; Willer, Cristen J.; Johansen, Christopher T.; Fouchier, Sigrid W.; Isaacs, Aaron; Peloso, Gina M.; Barbalic, Maja; Ricketts, Sally L.; Bis, Joshua C.; Aulchenko, Yurii S.; Thorleifsson, Gudmar; Feitosa, Mary F.; Chambers, John; Orho-Melander, Marju; Melander, Olle; Johnson, Toby; Li, Xiaohui; Guo, Xiuqing; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C.; Lange, Leslie A.; Smith, Joshua D.; Song, Kijoung; Zhao, Jing Hua; Yuan, Xin; Luan, Jian'an; Lamina, Claudia; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y.L.; Wright, Alan F.; Witteman, Jacqueline C.M.; Wilson, James F.; Willemsen, Gonneke; Wichmann, H-Erich; Whitfield, John B.; Waterworth, Dawn M.; Wareham, Nicholas J.; Waeber, Gérard; Vollenweider, Peter; Voight, Benjamin F.; Vitart, Veronique; Uitterlinden, Andre G.; Uda, Manuela; Tuomilehto, Jaakko; Thompson, John R.; Tanaka, Toshiko; Surakka, Ida; Stringham, Heather M.; Spector, Tim D.; Soranzo, Nicole; Smit, Johannes H.; Sinisalo, Juha; Silander, Kaisa; Sijbrands, Eric J.G.; Scuteri, Angelo; Scott, James; Schlessinger, David; Sanna, Serena; Salomaa, Veikko; Saharinen, Juha; Sabatti, Chiara; Ruokonen, Aimo; Rudan, Igor; Rose, Lynda M.; Roberts, Robert; Rieder, Mark; Psaty, Bruce M.; Pramstaller, Peter P.; Pichler, Irene; Perola, Markus; Penninx, Brenda W.J.H.; Pedersen, Nancy L.; Pattaro, Cristian; Parker, Alex N.; Pare, Guillaume; Oostra, Ben A.; O'Donnell, Christopher J.; Nieminen, Markku S.; Nickerson, Deborah A.; Montgomery, Grant W.; Meitinger, Thomas; McPherson, Ruth; McCarthy, Mark I.; McArdle, Wendy; Masson, David; Martin, Nicholas G.; Marroni, Fabio; Mangino, Massimo; Magnusson, Patrik K.E.; Lucas, Gavin; Luben, Robert; Loos, Ruth J. F.; Lokki, Maisa; Lettre, Guillaume; Langenberg, Claudia; Launer, Lenore J.; Lakatta, Edward G.; Laaksonen, Reijo; Kyvik, Kirsten O.; Kronenberg, Florian; König, Inke R.; Khaw, Kay-Tee; Kaprio, Jaakko; Kaplan, Lee M.; Johansson, Åsa; Jarvelin, Marjo-Riitta; Janssens, A. Cecile J.W.; Ingelsson, Erik; Igl, Wilmar; Hovingh, G. Kees; Hottenga, Jouke-Jan; Hofman, Albert; Hicks, Andrew A.; Hengstenberg, Christian; Heid, Iris M.; Hayward, Caroline; Havulinna, Aki S.; Hastie, Nicholas D.; Harris, Tamara B.; Haritunians, Talin; Hall, Alistair S.; Gyllensten, Ulf; Guiducci, Candace; Groop, Leif C.; Gonzalez, Elena; Gieger, Christian; Freimer, Nelson B.; Ferrucci, Luigi; Erdmann, Jeanette; Elliott, Paul; Ejebe, Kenechi G.; Döring, Angela; Dominiczak, Anna F.; Demissie, Serkalem; Deloukas, Panagiotis; de Geus, Eco J.C.; de Faire, Ulf; Crawford, Gabriel; Collins, Francis S.; Chen, Yii-der I.; Caulfield, Mark J.; Campbell, Harry; Burtt, Noel P.; Bonnycastle, Lori L.; Boomsma, Dorret I.; Boekholdt, S. Matthijs; Bergman, Richard N.; Barroso, Inês; Bandinelli, Stefania; Ballantyne, Christie M.; Assimes, Themistocles L.; Quertermous, Thomas; Altshuler, David; Seielstad, Mark; Wong, Tien Y.; Tai, E-Shyong; Feranil, Alan B.; Kuzawa, Christopher W.; Adair, Linda S.; Taylor, Herman A.; Borecki, Ingrid B.; Gabriel, Stacey B.; Wilson, James G.; Stefansson, Kari; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Krauss, Ronald M.; Mohlke, Karen L.; Ordovas, Jose M.; Munroe, Patricia B.; Kooner, Jaspal S.; Tall, Alan R.; Hegele, Robert A.; Kastelein, John J.P.; Schadt, Eric E.; Rotter, Jerome I.; Boerwinkle, Eric; Strachan, David P.; Mooser, Vincent; Holm, Hilma; Reilly, Muredach P.; Samani, Nilesh J; Schunkert, Heribert; Cupples, L. Adrienne; Sandhu, Manjinder S.; Ridker, Paul M; Rader, Daniel J.; van Duijn, Cornelia M.; Peltonen, Leena; Abecasis, Gonçalo R.; Boehnke, Michael; Kathiresan, Sekar

    2010-01-01

    Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. PMID:20686565

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

    PubMed

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

    2017-02-01

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

  13. Fat emulsions based on structured lipids (1,3-specific triglycerides): an investigation of the in vivo fate.

    PubMed

    Hedeman, H; Brøndsted, H; Müllertz, A; Frokjaer, S

    1996-05-01

    Structured lipids (1,3-specific triglycerides) are new chemical entities made by enzymatic transesterification of the fatty acids in the 1,3 positions of the triglyceride. The purpose of this study is to characterize structured lipids with either short chain fatty acids or medium chain fatty acids in the 1,3 positions with regard to their hydrophobicity, and investigate the in vivo fate in order to evaluate the potential of structured lipids as core material in fat emulsions used as parenteral drug delivery system. The lipids were characterized by employing reversed phase high performance liquid chromatography. The biodistribution of radioactively labeled emulsions was studied in rats. By employing high performance liquid chromatography a rank order of the hydrophobicities of the lipids could be given, with the triglycerides containing long chain fatty acids being the most hydrophobic and the structured lipid with short chain fatty acids in the 1,3 positions the least. When formulated as fat emulsions, the emulsion based on structured lipids with short fatty acids in the 1,3 positions was removed slower from the general blood circulation compared to emulsions based on lipids with long chain fatty acids in the 1,3 positions. The type of core material influences the in vivo circulation time of fat emulsions.

  14. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    NASA Astrophysics Data System (ADS)

    Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

    2010-03-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  15. Low-cost production of green microalga Botryococcus braunii biomass with high lipid content through mixotrophic and photoautotrophic cultivation.

    PubMed

    Yeesang, Chittra; Cheirsilp, Benjamas

    2014-09-01

    Botryococcus braunii is a microalga that is regarded as a potential source of renewable fuel because of its ability to produce large amounts of lipid that can be converted into biodiesel. Agro-industrial by-products and wastes are of great interest as cultivation medium for microorganisms because of their low cost, renewable nature, and abundance. In this study, two strategies for low-cost production of B. braunii biomass with high lipid content were performed: (i) the mixotrophic cultivation using molasses, a cheap by-product from the sugar cane plant as a carbon source, and (ii) the photoautotrophic cultivation using nitrate-rich wastewater supplemented with CO2 as a carbon source. The mixotrophic cultivation added with 15 g L(-1) molasses produced a high amount of biomass of 3.05 g L(-1) with a high lipid content of 36.9 %. The photoautotrophic cultivation in nitrate-rich wastewater supplemented with 2.0 % CO2 produced a biomass of 2.26 g L(-1) and a lipid content of 30.3 %. The benefits of this photoautotrophic cultivation are that this cultivation would help to reduce accumulation of atmospheric carbon dioxide and more than 90 % of the nitrate could be removed from the wastewater. When this cultivation was scaled up in a stirred tank photobioreactor and run with semi-continuous cultivation regime, the highest microalgal biomass of 5.16 g L(-1) with a comparable lipid content of 32.2 % was achieved. These two strategies could be promising ways for producing cheap lipid-rich microalgal biomass that can be used as biofuel feedstocks and animal feeds.

  16. [Proximal composition, lipid and cholesterol content of meat from pigs fed peach-palm meal (Bactris gasipaes Kunth) and synthetic lysine].

    PubMed

    Jerez-Timaure, Nancy; Rivero, Janeth Colina; Araque, Humberto; Jiménez, Paola; Velazco, Mariela; Colmenares, Ciolys

    2011-03-01

    Two experiments were conducted to evaluate the proximal composition, lipids and cholesterol content of meat from pigs fed diets with peach-palm meal (PPM), with or without addition of synthetic lysine (LYS). In experiment 1, 24 pigs were randomly allotted into six treatments with three levels of PPM (0.16 and 32%) and two levels of LYS (0 and 0.27%). In experiment II, 16 finishing pigs were fed with two levels of PPM (0 and 17.50%) and two levels of LYS (0 and 0.27%). At the end of each experiment (42 and 35 d, respectively), pigs were slaughtered and loin samples were obtained to determine crude protein, dry matter, moisture, ash, total lipids, and cholesterol content. In experiment I, pork loin from 16% PPM had more dry matter (26.45 g/100 g) and less moisture (73.49 g/100g) than pork loin from 32% PPM (25.11 y 75.03 g/100g, respectively). Meat samples from pigs without LYS had higher (p < 0.05) content of lipids (2.11 g/100 g) than meat from pigs that consumed LYS (1.72 g/100 g). In experiment II, the proximal, lipids and cholesterol content were similar among treatments. The PPM addition to pig diets did not affect the proximal composition of pork, while LYS addition indicated a reduction of total lipids, which could result as an alternative to obtain leaner meat.

  17. Engineering strategies for enhancing C. vulgaris ESP-31 lipid production using effluents of coke-making wastewater.

    PubMed

    Chen, Chun-Yen; Chang, Yu-Han

    2018-06-01

    Microalgae cultivation using wastewater is an approach for simultaneous wastewater treatment and biofuels/chemicals productions. In this study, three microalgae species Chorella vulgaris ESP-31, Chorella sorokiniana CY-1 and Scenedesmus sp. were cultivated using coke-making wastewater generated from a steel-making company. Of these, C.vulgaris ESP-31 had the best tolerance towards wastewater, with maximal biomass concentration of 2.82 g/l and lipid productivity of 32.3 mg/l/d. The highest biomass concentration 3.98 g/l and lipid productivity of 47.1 mg/l/d was obtained in 20% wastewater. Immobilization approach was applied to boost biomass growth and lipid production. Both maximal biomass growth (5.17 g/l) and lipid productivity (68.4 mg/l/d) was significantly enhanced with activated charcoal addition. Semi-batch cultivation resulted in stable biomass production and lipid productivity of 5.18 g/l and 77.3 mg/l/d, respectively. This study has revealed that C. vulgaris ESP-31 is a potential candidate for growth in coke making wastewater and biofuel production. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. Chemical composition, mineral content and amino acid and lipid profiles in bones from various fish species.

    PubMed

    Toppe, Jogeir; Albrektsen, Sissel; Hope, Britt; Aksnes, Anders

    2007-03-01

    The chemical composition, content of minerals and the profiles of amino acids and fatty acids were analyzed in fish bones from eight different species of fish. Fish bones varied significantly in chemical composition. The main difference was lipid content ranging from 23 g/kg in cod (Gadus morhua) to 509 g/kg in mackerel (Scomber scombrus). In general fatty fish species showed higher lipid levels in the bones compared to lean fish species. Similarly, lower levels of protein and ash were observed in bones from fatty fish species. Protein levels differed from 363 g/kg lipid free dry matter (dm) to 568 g/kg lipid free dm with a concomitant inverse difference in ash content. Ash to protein ratio differed from 0.78 to 1.71 with the lowest level in fish that naturally have highest swimming and physical activity. Saithe (Pollachius virens) and salmon (Salmo salar) were found to be significantly different in the levels of lipid, protein and ash, and ash/protein ratio in the bones. Only small differences were observed in the level of amino acids although species specific differences were observed. The levels of Ca and P in lipid free fish bones were about the same in all species analyzed. Fatty acid profile differed in relation to total lipid levels in the fish bones, but some minor differences between fish species were observed.

  19. Purification of family B G protein-coupled receptors using nanodiscs: Application to human glucagon-like peptide-1 receptor.

    PubMed

    Cai, Yingying; Liu, Yuting; Culhane, Kelly J; DeVree, Brian T; Yang, Yang; Sunahara, Roger K; Yan, Elsa C Y

    2017-01-01

    Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL) particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

  20. Purification of family B G protein-coupled receptors using nanodiscs: Application to human glucagon-like peptide-1 receptor

    PubMed Central

    Cai, Yingying; Liu, Yuting; Culhane, Kelly J.; DeVree, Brian T.; Yang, Yang; Sunahara, Roger K.; Yan, Elsa C. Y.

    2017-01-01

    Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL) particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms. PMID:28609478

  1. The effects of fasting in Ramadan. 1. Serum uric acid and lipid concentrations.

    PubMed

    Gumaa, K A; Mustafa, K Y; Mahmoud, N A; Gader, A M

    1978-11-01

    1. The changes in serum levels of uric acid and lipids during 1 month of starvation-refeeding were measured in sixteen male volunteers. 2. Uric acid levels increased linearly with the duration of the experiment. The increase was positively correlated with the increase in serum triglycerides but not with cholesterol or phospholipids. 3. Triglycerides increased at a faster rate than uric acid implying that the increase in uric acid was secondary to that of the lipid. 4. It was concluded that the purine and lipid synthetic pathways are linked through a common small-molecular-weight effector rather than through the sharing of a common enzyme.

  2. Lipid raft regulates the initial spreading of melanoma A375 cells by modulating β1 integrin clustering.

    PubMed

    Wang, Ruifei; Bi, Jiajia; Ampah, Khamal Kwesi; Zhang, Chunmei; Li, Ziyi; Jiao, Yang; Wang, Xiaoru; Ba, Xueqing; Zeng, Xianlu

    2013-08-01

    Cell adhesion and spreading require integrins-mediated cell-extracellular matrix interaction. Integrins function through binding to extracellular matrix and subsequent clustering to initiate focal adhesion formation and actin cytoskeleton rearrangement. Lipid raft, a liquid ordered plasma membrane microdomain, has been reported to play major roles in membrane motility by regulating cell surface receptor function. Here, we identified that lipid raft integrity was required for β1 integrin-mediated initial spreading of melanoma A375 cells on fibronectin. We found that lipid raft disruption with methyl-β-cyclodextrin led to the inability of focal adhesion formation and actin cytoskeleton rearrangement by preventing β1 integrin clustering. Furthermore, we explored the possible mechanism by which lipid raft regulates β1 integrin clustering and demonstrated that intact lipid raft could recruit and modify some adaptor proteins, such as talin, α-actinin, vinculin, paxillin and FAK. Lipid raft could regulate the location of these proteins in lipid raft fractions and facilitate their binding to β1 integrin, which may be crucial for β1 integrin clustering. We also showed that lipid raft disruption impaired A375 cell migration in both transwell and wound healing models. Together, these findings provide a new insight for the relationship between lipid raft and the regulation of integrins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Blockade of lipid accumulation by silibinin in adipocytes and zebrafish.

    PubMed

    Suh, Hyung Joo; Cho, So Young; Kim, Eun Young; Choi, Hyeon-Son

    2015-02-05

    Silibinin is a compound present mainly in milk thistle. In this study, we investigated the mechanism by which silibinin suppresses adipogenesis of 3T3-L1 cells, and evaluated the anti-adipogenic effect of silibinin in zebrafish. Silibinin reduced lipid accumulation by downregulating adipogenic factors, such as, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer binding protein α (C/EBPα), and fatty acid-binding protein 4 (FABP4). The reduction of these adipogenic protein levels was associated with the regulation of early adipogenic factors, such as, C/EBPβ and Krüppel-like factor 2 (KLF2), and was reflected in downregulation of lipid synthetic enzymes. Silibinin arrested cells in the G0/G1 phase of the cell cycle, accompanied by downregulation of cyclins and upregulation of p27, a cell cycle inhibitor. These results correlated with the finding of deactivation of extracellular signal-regulated kinase (ERK) and AKT, a serine/threonine-specific kinase. In addition, silibinin activated AMP-activated protein kinase α (AMPKα) to inhibit fatty acid synthesis. As observed in 3T3-L1 cells, silibinin inhibited lipid accumulation in zebrafish with the reduction of adipogenic factors and triglyceride levels. Our data revealed that silibinin inhibited lipid accumulation in 3T3-L1 cells and zebrafish, and this inhibitory effect was associated with abrogation of early adipogenesis via regulation of cell cycle and AMPKα signaling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Dietary docosahexaenoic acid-induced generation of liver lipid peroxides is not suppressed further by elevated levels of glutathione in ODS rats.

    PubMed

    Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

    2006-04-01

    We examined the effects of ascorbic acid (AsA) and glutathione (GSH; experiment 1) and of GSH in acetaminophen-fed rats (experiment 2) on dietary docosahexaenoic acid (DHA)-induced tissue lipid peroxidation. In experiment 1, AsA-requiring Osteogenic Disorder Shionogi/Shi-od/od (ODS) rats were fed soybean protein diets containing DHA (10.0% total energy) and AsA at 50 (low) or 300 (normal) mg/kg without (low) or with (normal) methionine at 2 g/kg for 32 d. In experiment 2, ODS rats were fed diets containing DHA (7.8% total energy) and acetaminophen (4 g/kg) with different levels of dietary methionine (low, moderate, high, and excessive at 0, 3, 6, and 9 g/kg, respectively) for 30 d. Tissue lipid peroxides and antioxidant levels were determined. In experiment 1, liver lipid peroxide levels in the low-AsA group were lower than those in the normal-AsA group, but kidney and testis lipid peroxide levels in the low-AsA group were higher than those in the normal-AsA group. Dietary methionine tended to decrease tissue lipid peroxide levels but did not decrease vitamin E (VE) consumption. In experiment 2, a high level of methionine (6 g/kg) decreased liver lipid peroxide levels and VE consumption. However, generation of tissue lipid peroxides and VE consumption were not decreased further by a higher dose of methionine (9 g/kg). Higher than normal levels of dietary methionine are not necessarily associated with decreased dietary DHA-induced generation of tissue lipid peroxides and VE consumption except that the GSH requirement is increased in a condition such as acetaminophen feeding.

  5. Spatial variation in the accumulation of POPs and mercury in bottlenose dolphins of the Lower Florida Keys and the coastal Everglades (South Florida).

    PubMed

    Damseaux, France; Kiszka, Jeremy J; Heithaus, Michael R; Scholl, George; Eppe, Gauthier; Thomé, Jean-Pierre; Lewis, Jennifer; Hao, Wensi; Fontaine, Michaël C; Das, Krishna

    2017-01-01

    The bottlenose dolphin (Tursiops truncatus) is an upper trophic level predator and the most common cetacean species found in nearshore waters of southern Florida, including the Lower Florida Keys (LFK) and the Florida Coastal Everglades (FCE). The objective of this study was to assess contamination levels of total mercury (T-Hg) in skin and persistent organic pollutants (PCBs, PBDEs, DDXs, HCHs, HCB, Σ PCDD/Fs and Σ DL-PCBs) in blubber samples of bottlenose dolphins from LFK (n = 27) and FCE (n = 24). PCBs were the major class of compounds found in bottlenose dolphin blubber and were higher in individuals from LFK (Σ 6 PCBs LFK males: 13,421 ± 7730 ng g -1 lipids, Σ 6 PCBs LFK females: 9683 ± 19,007 ng g -1 lipids) than from FCE (Σ 6 PCBs FCE males: 5638 ng g -1  ± 3627 lipids, Σ 6 PCBs FCE females: 1427 ± 908 ng g -1 lipids). These levels were lower than previously published data from the southeastern USA. The Σ DL-PCBs were the most prevalent pollutants of dioxin and dioxin like compounds (Σ DL-PCBs LFK: 739 ng g -1 lipids, Σ DL-PCBs FCE: 183 ng g -1 lipids) since PCDD/F concentrations were low for both locations (mean 0.1 ng g -1 lipids for LFK and FCE dolphins). The toxicity equivalences of PCDD/Fs and DL-PCBs expressed as TEQ in LFK and FCE dolphins is mainly expressed by DL-PCBs (81% LFK - 65% FCE). T-Hg concentrations in skin were significantly higher in FCE (FCE median 9314 ng g -1 dw) compared to LFK dolphins (LFK median 2941 ng g -1 dw). These concentrations are the highest recorded in bottlenose dolphins in the southeastern USA, and may be explained, at least partially, by the biogeochemistry of the Everglades and mangrove sedimentary habitats that create favourable conditions for the retention of mercury and make it available at high concentrations for aquatic predators. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Cancer Cells Differentially Activate and Thrive on De Novo Lipid Synthesis Pathways in a Low-Lipid Environment

    PubMed Central

    Daniëls, Veerle W.; Smans, Karine; Royaux, Ines; Chypre, Melanie

    2014-01-01

    Increased lipogenesis is a hallmark of a wide variety of cancers and is under intense investigation as potential antineoplastic target. Although brisk lipogenesis is observed in the presence of exogenous lipids, evidence is mounting that these lipids may adversely affect the efficacy of inhibitors of lipogenic pathways. Therefore, to fully exploit the therapeutic potential of lipid synthesis inhibitors, a better understanding of the interrelationship between de novo lipid synthesis and exogenous lipids and their respective role in cancer cell proliferation and therapeutic response to lipogenesis inhibitors is of critical importance. Here, we show that the proliferation of various cancer cell lines (PC3M, HepG2, HOP62 and T24) is attenuated when cultured in lipid-reduced conditions in a cell line-dependent manner, with PC3M being the least affected. Interestingly, all cell lines - lipogenic (PC3M, HepG2, HOP62) as well as non-lipogenic (T24) - raised their lipogenic activity in these conditions, albeit to a different degree. Cells that attained the highest lipogenic activity under these conditions were best able to cope with lipid reduction in term of proliferative capacity. Supplementation of the medium with very low density lipoproteins, free fatty acids and cholesterol reversed this activation, indicating that the mere lack of lipids is sufficient to activate de novo lipogenesis in cancer cells. Consequently, cancer cells grown in lipid-reduced conditions became more dependent on de novo lipid synthesis pathways and were more sensitive to inhibitors of lipogenic pathways, like Soraphen A and Simvastatin. Collectively, these data indicate that limitation of access to exogenous lipids, as may occur in intact tumors, activates de novo lipogenesis is cancer cells, helps them to thrive under these conditions and makes them more vulnerable to lipogenesis inhibitors. These observations have important implications for the design of new antineoplastic strategies targeting

  7. Myo1c regulates lipid raft recycling to control cell spreading, migration and Salmonella invasion

    PubMed Central

    Brandstaetter, Hemma; Kendrick-Jones, John; Buss, Folma

    2012-01-01

    A balance between endocytosis and membrane recycling regulates the composition and dynamics of the plasma membrane. Internalization and recycling of cholesterol- and sphingolipid-enriched lipid rafts is an actin-dependent process that is mediated by a specialized Arf6-dependent recycling pathway. Here, we identify myosin1c (Myo1c) as the first motor protein that drives the formation of recycling tubules emanating from the perinuclear recycling compartment. We demonstrate that the single-headed Myo1c is a lipid-raft-associated motor protein that is specifically involved in recycling of lipid-raft-associated glycosylphosphatidylinositol (GPI)-linked cargo proteins and their delivery to the cell surface. Whereas Myo1c overexpression increases the levels of these raft proteins at the cell surface, in cells depleted of Myo1c function through RNA interference or overexpression of a dominant-negative mutant, these tubular transport carriers of the recycling pathway are lost and GPI-linked raft markers are trapped in the perinuclear recycling compartment. Intriguingly, Myo1c only selectively promotes delivery of lipid raft membranes back to the cell surface and is not required for recycling of cargo, such as the transferrin receptor, which is mediated by parallel pathways. The profound defect in lipid raft trafficking in Myo1c-knockdown cells has a dramatic impact on cell spreading, cell migration and cholesterol-dependent Salmonella invasion; processes that require lipid raft transport to the cell surface to deliver signaling components and the extra membrane essential for cell surface expansion and remodeling. Thus, Myo1c plays a crucial role in the recycling of lipid raft membrane and proteins that regulate plasma membrane plasticity, cell motility and pathogen entry. PMID:22328521

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

    PubMed

    Cuschieri, Joseph

    2004-08-01

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

  9. ELISA-based assay of immunoglobulin G antibodies against mammalian cell entry 1A (Mce1A) protein: a novel diagnostic approach for leprosy.

    PubMed

    Lima, Filipe R; Takenami, Iukary; Cavalcanti, Maurílio Al; Riley, Lee W; Arruda, Sérgio

    2017-12-01

    Leprosy is a chronic infectious disease caused by the obligate intracellular bacillus Mycobacterium leprae. Because leprosy diagnosis is complex and requires professional expertise, new tools and methodologies are needed to detect cases in early stages and prevent transmission. The M. leprae genome contains mce1A, which encodes a putative mammalian cell entry protein (Mce1A). We hypothesised that the presence of Mce1A on the cell surface could be detected by the host's immune system. The aim of this study was to evaluate antibody responses against the Mce1A protein in leprosy patients, household contacts of patients, and the general population to present an addition tool for leprosy diagnosis. A cross-sectional study involving 89 volunteers [55 leprosy cases, 12 household contacts (HHC) and 22 endemic controls (EC)] was conducted at Couto Maia Hospital, in Salvador, Bahia (BA), Brazil. The median anti-Mce1A IgA was significantly higher in multibacillary (MB) and paucibacillary (PB) cases than in EC (p < 0.0001). A similar trend was observed in IgM levels, which were significantly higher in both MB (p < 0.0001) and PB (p = 0.0006) groups compared to in EC individuals. The greatest differences were observed for IgG class-specific antibodies against Mce1A. The median levels of MB and PB were significantly higher compared to both controls HHC and EC (MB or PB vs EC, MB vs HHC p < 0.0001; PB vs HHC, p = 0.0013). Among leprosy cases, IgG enzyme-linked immunosorbent assay sensitivity and specificity were 92.7% and 97.1%, respectively. IgG positivity was confirmed in 92.1% and 94.1% of MB and PB patients, respectively. This novel diagnostic approach presents an easy, non-invasive, and inexpensive method for leprosy screening, which may be applicable in endemic areas.

  10. Lipotoxicity in HepG2 cells triggered by free fatty acids

    PubMed Central

    Yao, Hong-Rui; Liu, Jun; Plumeri, Daniel; Cao, Yong-Bing; He, Ting; Lin, Ling; Li, Yu; Jiang, Yuan-Ying; Li, Ji; Shang, Jing

    2011-01-01

    The goal of this study was to investigate the lipid accumulation and lipotoxicity of free fatty acids (FFAs) induced in HepG2 cells. HepG2 cells were co-incubated with various concentrations of FFAs for 24h and the intracellular lipid contents were observed by Oil Red O and Nile Red staining methods. The lipotoxicity of HepG2 cells were then detected by Hoechest 33342/PI, Annexin V-FITC/PI double-staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide (MTT) experiment tests. The experiments showed a lipid accumulation and lipotoxicity by increasing FFA concentration gradients. Through cell morphological observation and quantitative analysis, FFAs have shown to increase in a dose-dependent manner compared with the control group. The data collected from hoechst 33342/PI, annexin V-FITC/PI double staining and also MTT experiments showed that cell apoptosis and necrosis significantly increased with increasing FFA concentrations. Apoptosis was not obvious in the 1 mM FFAs-treated group compared to the other two groups. In a certain concentration range, FFAs induced intracellular lipid accumulation and lipotoxicity of HepG2 cells in a dose-dependent manner. PMID:21654881

  11. Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity.

    PubMed

    Zhang, Yongxian; Gu, Jin; Wang, Lin; Zhao, Zilong; Pan, Yi; Chen, Yan

    2017-01-05

    Glycogen and triglyceride are two major forms of energy storage in the body and provide the fuel during different phases of food deprivation. However, how glycogen metabolism is linked to fat deposition in adipose tissue has not been clearly characterized. We generated a mouse model with whole-body deletion of PPP1R3G, a glycogen-targeting subunit of protein phosphatase-1 required for glycogen synthesis. Upon feeding with high-fat diet, the body weight and fat composition are significantly reduced in the PPP1R3G -/- mice compared to the wild type controls. The metabolic rate of the mice as measured by O 2 consumption and CO 2 production is accelerated by PPP1R3G deletion. The high-fat diet-induced liver steatosis is also slightly relieved by PPP1R3G deletion. The glycogen level in adipose tissue is reduced by PPP1R3G deletion. In 3T3L1 cells, overexpression of PPP1R3G leads to increases of both glycogen and triglyceride levels. In conclusion, our study indicates that glycogen is actively involved in fat accumulation in adipose tissue and obesity development upon high-fat diet. Our study also suggests that PPP1R3G is an important player that links glycogen metabolism to lipid metabolism in vivo. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. MeCP2 co-ordinates liver lipid metabolism with the NCoR1/HDAC3 corepressor complex

    PubMed Central

    Kyle, Stephanie M.; Saha, Pradip K.; Brown, Hannah M.; Chan, Lawrence C.; Justice, Monica J.

    2016-01-01

    Rett syndrome (RTT; OMIM 312750), a progressive neurological disorder, is caused by mutations in methyl-CpG-binding protein 2 (MECP2; OMIM 300005), a ubiquitously expressed factor. A genetic suppressor screen designed to identify therapeutic targets surprisingly revealed that downregulation of the cholesterol biosynthesis pathway improves neurological phenotypes in Mecp2 mutant mice. Here, we show that MeCP2 plays a direct role in regulating lipid metabolism. Mecp2 deletion in mice results in a host of severe metabolic defects caused by lipid accumulation, including insulin resistance, fatty liver, perturbed energy utilization, and adipose inflammation by macrophage infiltration. We show that MeCP2 regulates lipid homeostasis by anchoring the repressor complex containing NCoR1 and HDAC3 to its lipogenesis targets in hepatocytes. Consistently, we find that liver targeted deletion of Mecp2 causes fatty liver disease and dyslipidemia similar to HDAC3 liver-specific deletion. These findings position MeCP2 as a novel component in metabolic homeostasis. Rett syndrome patients also show signs of peripheral dyslipidemia; thus, together these data suggest that RTT should be classified as a neurological disorder with systemic metabolic components. We previously showed that treatment of Mecp2 mice with statin drugs alleviated motor symptoms and improved health and longevity. Lipid metabolism is a highly treatable target; therefore, our results shed light on new metabolic pathways for treatment of Rett syndrome. PMID:27288453

  13. Safety performance evaluation of cable median barriers on freeways in Florida.

    PubMed

    Alluri, Priyanka; Haleem, Kirolos; Gan, Albert; Mauthner, John

    2016-07-03

    This article aims to evaluate the safety performance of cable median barriers on freeways in Florida. The safety performance evaluation was based on the percentages of barrier and median crossovers by vehicle type, crash severity, and cable median barrier type (Trinity Cable Safety System [CASS] and Gibraltar system). Twenty-three locations with cable median barriers totaling about 101 miles were identified. Police reports of 6,524 crashes from years 2005-2010 at these locations were reviewed to verify and obtain detailed crash information. A total of 549 crashes were determined to be barrier related (i.e., crashes involving vehicles hitting the cable median barrier) and were reviewed in further detail to identify crossover crashes and the manner in which the vehicles crossed the barriers; that is, by either overriding, underriding, or penetrating the barriers. Overall, 2.6% of vehicles that hit the cable median barrier crossed the median and traversed into the opposite travel lane. Overall, 98.1% of cars and 95.5% of light trucks that hit the barrier were prevented from crossing the median. In other words, 1.9% of cars and 4.5% of light trucks that hit the barrier had crossed the median and encroached on the opposite travel lanes. There is no significant difference in the performance of cable median barrier for cars versus light trucks in terms of crossover crashes. In terms of severity, overrides were more severe compared to underrides and penetrations. The statistics showed that the CASS and Gibraltar systems performed similarly in terms of crossover crashes. However, the Gibraltar system experienced a higher proportion of penetrations compared to the CASS system. The CASS system resulted in a slightly higher percentage of moderate and minor injury crashes compared to the Gibraltar system. Cable median barriers are successful in preventing median crossover crashes; 97.4% of the cable median barrier crashes were prevented from crossing over the median. Of all of

  14. Growth, fatty acid profile in major lipid classes and lipid fluidity of Aurantiochytrium mangrovei SK-02 As a function of growth temperature.

    PubMed

    Chodchoey, Kanokwan; Verduyn, Cornelis

    2012-01-01

    Aurantiochytrium mangrovei Sk-02 was grown in a medium containing glucose (40 g/l), yeast extract (10 g/L) and sea salts (15 g/L) at temperatures ranging from 12 to 35°C. The fastest growth (µmax= 0.15 h(-1)) and highest fatty acid content of 415 mg/g-dry cell weight were found in the cells grown at 30°C. However, the cells grown at 12°C showed the highest percentage of polyunsaturated fatty acid (PUFA) (48.6% of total fatty acid). The percentage of docosahexaenoic acid (DHA) and pentadecanoic acid (C15:0) decreased with an increase in the growth temperature, whereas, palmitic acid (C16:0), stearic acid (C18:0) and DPA (C22:5n6) increased with an increase in the growth temperature. The composition of the major lipid class (%w/w) was slightly affected by the growth temperature. The fluidity of the organelle membrane or intracellular lipid (by DPH measurement) decreased with an increase in the growth temperatures, while the plasma membrane fluidity (by TMA-DPH measurement) could still maintain its fluidity in a wide range of temperatures (15 - 37°C). Furthermore, the distribution of DHA was found to be higher (36 - 54%) in phospholipid (PL) as compared to neutral lipid (NL) (20 - 41%).

  15. E4orf1 improves lipid and glucose metabolism in hepatocytes: a template to improve steatosis & hyperglycemia.

    PubMed

    Dhurandhar, Emily J; Krishnapuram, Rashmi; Hegde, Vijay; Dubuisson, Olga; Tao, Rongya; Dong, X Charlie; Ye, Jianping; Dhurandhar, Nikhil V

    2012-01-01

    Hepatic steatosis often accompanies obesity and insulin resistance. The cornerstones of steatosis treatment include reducing body weight and dietary fat intake, which are marginally successful over the long term. Ad36, a human adenovirus, may offer a template to overcome these limitations. In vitro and in vivo studies collectively indicate that via its E4orf1 protein, Ad36 improves hyperglycemia, and attenuates hepatic steatosis, despite a high fat diet and without weight loss. Considering that hepatic insulin sensitivity, or the synthesis, oxidation, or export of fatty acid by hepatocytes are the key determinant of hepatic lipid storage, we determined the role of E4orf1 protein in modulating these physiological pathways. For this study, HepG2 cells, or mouse primary hepatocytes were transfected with E4orf1 or the null vector. Glucose output by hepatocytes was determined under gluconeogenic conditions (cAMP and dexamethasone, or glucagon exposure). Also, de-novo lipogenesis, palmitate oxidation, and lipid export as determined by apoB secretion were measured 48 h post transfection. Results show that compared to null vector transfected cells, E4orf1 significantly reduced glucose output in basal and gluconeogenic conditions. E4orf1 reduced de-novo lipogenesis by about 35%, increased complete fatty acid oxidation 2-fold (p<0.0001), and apoB secretion 1.5 fold(p<0.003). Response of key signaling molecules to E4orf1 transfection was in agreement with these findings. Thus, E4orf1 offers a valuable template to exogenously modulate hepatic glucose and lipid metabolism. Elucidating the underlying molecular mechanism may help develop therapeutic approaches for treating diabetes or non-alcoholic fatty liver disease(NAFLD).

  16. E4orf1 Improves Lipid and Glucose Metabolism in Hepatocytes: A Template to Improve Steatosis & Hyperglycemia

    PubMed Central

    Dhurandhar, Emily J.; Krishnapuram, Rashmi; Hegde, Vijay; Dubuisson, Olga; Tao, Rongya; Dong, X. Charlie; Ye, Jianping; Dhurandhar, Nikhil V.

    2012-01-01

    Hepatic steatosis often accompanies obesity and insulin resistance. The cornerstones of steatosis treatment include reducing body weight and dietary fat intake, which are marginally successful over the long term. Ad36, a human adenovirus, may offer a template to overcome these limitations. In vitro and in vivo studies collectively indicate that via its E4orf1 protein, Ad36 improves hyperglycemia, and attenuates hepatic steatosis, despite a high fat diet and without weight loss. Considering that hepatic insulin sensitivity, or the synthesis, oxidation, or export of fatty acid by hepatocytes are the key determinant of hepatic lipid storage, we determined the role of E4orf1 protein in modulating these physiological pathways. For this study, HepG2 cells, or mouse primary hepatocytes were transfected with E4orf1 or the null vector. Glucose output by hepatocytes was determined under gluconeogenic conditions (cAMP and dexamethasone, or glucagon exposure). Also, de-novo lipogenesis, palmitate oxidation, and lipid export as determined by apoB secretion were measured 48 h post transfection. Results show that compared to null vector transfected cells, E4orf1 significantly reduced glucose output in basal and gluconeogenic conditions. E4orf1 reduced de-novo lipogenesis by about 35%, increased complete fatty acid oxidation 2-fold (p<0.0001), and apoB secretion 1.5 fold(p<0.003). Response of key signaling molecules to E4orf1 transfection was in agreement with these findings. Thus, E4orf1 offers a valuable template to exogenously modulate hepatic glucose and lipid metabolism. Elucidating the underlying molecular mechanism may help develop therapeutic approaches for treating diabetes or non-alcoholic fatty liver disease(NAFLD). PMID:23110104

  17. Keap1-Knockdown Decreases Fasting-Induced Fatty Liver via Altered Lipid Metabolism and Decreased Fatty Acid Mobilization from Adipose Tissue

    PubMed Central

    Xu, Jialin; Donepudi, Ajay C.; Moscovitz, Jamie E.; Slitt, Angela L.

    2013-01-01

    Aims The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD), regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting). Methods and Results Male C57BL/6 (WT) and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase) and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36) and Fatty acid transport protein (FATP) 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar) α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK) phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters — CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. Conclusion Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation. PMID:24224011

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

    PubMed

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

    2018-06-01

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

  19. Changes in lipid fluidity and fatty acid composition with altered culture temperature in Tetrahymena pyriformis-NT1.

    PubMed

    Connolly, J G; Brown, I D; Lee, A G; Kerkut, G A

    1985-01-01

    Cultures of T. pyriformis-NT1 were grown at 20 degrees C (Tg 20 degrees C) and 38 degrees C (Tg 38 degrees C). G.L.C. analysis and D.P.H. fluorescence polarization measurements in extracted phospholipids indicated that there was increased saturation of fatty acids and relatively reduced fluidity as growth temperature was increased. Breakpoints occurred in the Arrhenius plots of fluorescence polarization at 16 degrees C for Tg 38 degrees C total extracted phospholipids and 9 degrees C for Tg 20 degrees C lipids.

  20. Optimization of Medium Using Response Surface Methodology for Lipid Production by Scenedesmus sp.

    PubMed Central

    Yang, Fangfang; Long, Lijuan; Sun, Xiumei; Wu, Hualian; Li, Tao; Xiang, Wenzhou

    2014-01-01

    Lipid production is an important indicator for assessing microalgal species for biodiesel production. In this work, the effects of medium composition on lipid production by Scenedesmus sp. were investigated using the response surface methodology. The results of a Plackett–Burman design experiment revealed that NaHCO3, NaH2PO4·2H2O and NaNO3 were three factors significantly influencing lipid production, which were further optimized by a Box–Behnken design. The optimal medium was found to contain 3.07 g L−1 NaHCO3, 15.49 mg L−1 NaH2PO4·2H2O and 803.21 mg L−1 NaNO3. Using the optimal conditions previously determined, the lipid production (304.02 mg·L−1) increased 54.64% more than that using the initial medium, which agreed well with the predicted value 309.50 mg L−1. Additionally, lipid analysis found that palmitic acid (C16:0) and oleic acid (C18:1) dominantly constituted the algal fatty acids (about 60% of the total fatty acids) and a much higher content of neutral lipid accounted for 82.32% of total lipids, which strongly proved that Scenedesmus sp. is a very promising feedstock for biodiesel production. PMID:24663113

  1. Effects of 2.0-g 1.75-g and 1.5-g Hypergravity on Pregnancy Outcome in Rats (Rattus norvegicus)

    NASA Technical Reports Server (NTRS)

    Mills, Nicole A.; Baer, Lisa A.; Ronca, April E.

    2001-01-01

    In 1995, ten pregnant female rats were launched on the Space Shuttle (STS-70) on Gestational day(G) 11 of their 22-day pregnancy as part of the NASA/NIH.Rodent (R)2 Experiment. Following landing on G20, fetuses were harvested from half of the dams, while the remaining five dams underwent birth. Spaceflight did not interrupt pregnancy, alter litter sizes, or affect body weights or gender ratios of the fetuses or neonates. In the present study we used the NASA/NIH.R2 experimental paradigm to analyze the effects of hypergravity on pregnancy outcome. On G10, time-bred Sprague-Dawley rat dams were assigned to either G20 or Birth conditions, then further assigned to Hypergravity (HG) 2.0-g, HG 1.75-g, HG 1.5-g, Rotational Control (RC, 1.03), or Stationary Control (SC, 1.0-g) treatments. Dams were exposed to continuous centrifugation from G11 through G20, with brief daily stops for animal health checks and maintenance. For both the G20 and Birth dams, comparable litter sizes and litter gender ratios were observed across gravity conditions. However, centrifugation-exposed (HG and RC) fetuses and neonates showed significantly lower body masses (p less than 0.05) relative to SC offspring. HG 2.0-g offspring weighed significantly less than those in all other gravity conditions (p less than 0.05). The observed reductions in offspring body mass at 1.5-g and 1.75-g, can be attributed to the rotational component of centrifugation, rather than to increased gravitational load, whereas 2.0-g hypergravity exposure further exacerbated the gravity centrifugation effect on offspring body mass. Pregnant dams exposed to centrifugation weighed significantly less than SC dams (p less than 0.05), suggesting that centrifugation effects on maternal body mass may contribute to reduced size of the developing offspring. These findings are consistent with previous reports of non-pregnant adult animals suggesting that, whereas spaceflight has virtually no effect on body mass, centrifugation is

  2. Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

    PubMed

    Cruz-Garcia, Lourdes; Schlegel, Amnon

    2014-09-01

    Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  3. Intramyocellular lipid quantification: repeatability with 1H MR spectroscopy.

    PubMed

    Torriani, Martin; Thomas, Bijoy J; Halpern, Elkan F; Jensen, Megan E; Rosenthal, Daniel I; Palmer, William E

    2005-08-01

    To prospectively determine the repeatability and variability of tibialis anterior intramyocellular lipid (IMCL) quantifications performed by using 1.5-T hydrogen 1 (1H) magnetic resonance (MR) spectroscopy in healthy subjects. Institutional review board approval and written informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant study. The authors examined the anterior tibial muscles of 27 healthy subjects aged 19-48 years (12 men, 15 women; mean age, 25 years) by using single-voxel short-echo-time point-resolved 1H MR spectroscopy. During a first visit, the subjects underwent 1H MR spectroscopy before and after being repositioned in the magnet bore, with voxels carefully placed on the basis of osseous landmarks. Measurements were repeated after a mean interval of 12 days. All spectra were fitted by using Java-based MR user interface (jMRUI) and LCModel software, and lipid peaks were scaled to the unsuppressed water peak (at 4.7 ppm) and the total creatine peak (at approximately 3.0 ppm). A one-way random-effects variance components model was used to determine intraday and intervisit coefficients of variation (CVs). A power analysis was performed to determine the detectable percentage change in lipid measurements for two subject sample sizes. Measurements of the IMCL methylene protons peak at a resonance of 1.3 ppm scaled to the unsuppressed water peak (IMCL(W)) that were obtained by using jMRUI software yielded the lowest CVs overall (intraday and intervisit CVs, 13.4% and 14.4%, respectively). The random-effects variance components model revealed that nonbiologic factors (equipment and repositioning) accounted for 50% of the total variability in IMCL quantifications. Power analysis for a sample size of 20 subjects revealed that changes in IMCL(W) of greater than 15% could be confidently detected between 1H MR spectroscopic measurements obtained on different days. 1H MR spectroscopy is feasible for repeatable

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

    PubMed

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

    2017-02-01

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

  5. Intramyocellular lipid stores increase markedly in athletes after 1.5 days lipid supplementation and are utilized during exercise in proportion to their content.

    PubMed

    Zehnder, Monica; Christ, Emanuel R; Ith, Michael; Acheson, Kevin J; Pouteau, Etienne; Kreis, Roland; Trepp, Roman; Diem, Peter; Boesch, Chris; Décombaz, Jacques

    2006-11-01

    Intramyocellular lipids (IMCL) and muscle glycogen provide local energy during exercise (EX). The objective of this study was to clarify the role of high versus low IMCL levels at equal initial muscle glycogen on fuel selection during EX. After 3 h of depleting exercise, 11 endurance-trained males consumed in a crossover design a high-carbohydrate (7 g kg(-1) day(-1)) low-fat (0.5 g kg(-1) day(-1)) diet (HC) for 2.5 days or the same diet with 3 g kg(-1) day(-1) more fat provided during the last 1.5 days of diet (four meals; HCF). Respiratory exchange, thigh muscle substrate breakdown by magnetic resonance spectroscopy, and plasma FFA oxidation ([1-(13)C]palmitate) were measured during EX (3 h, 50% W (max)). Pre-EX IMCL concentrations were 55% higher after HCF. IMCL utilization during EX in HCF was threefold greater compared with HC (P < 0.001) and was correlated with aerobic power and highly correlated (P < 0.001) with initial content. Glycogen values and decrements during EX were similar. Whole-body fat oxidation (Fat(ox)) was similar overall and plasma FFA oxidation smaller (P < 0.05) during the first EX hour after HCF. Myocellular fuels contributed 8% more to whole-body energy demands after HCF (P < 0.05) due to IMCL breakdown (27% Fat(ox)). After EX, when both IMCL and glycogen concentrations were again similar across trials, a simulated 20-km time-trial showed no difference in performance between diets. In conclusion, IMCL concentrations can be increased during a glycogen loading diet by consuming additional fat for the last 1.5 days. During subsequent exercise, IMCL decrease in proportion to their initial content, partly in exchange for peripheral fatty acids.

  6. A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed vacuoles.

    PubMed

    Chen, J; Hong, D; Wang, Z; Yuan, Y

    2010-01-01

    Neutral lipid storage disease with myopathy (NLSDM) is a type of lipid storage myopathy arising due to a mutation in the PNPLA2 gene encoding an adipose triglyceride lipase responsible for the degradation of intracellular triglycerides. Herein, we report the cases of two siblings manifesting slowly progressive proximal and distal limb weakness in adulthood. One of the patients had dilated cardiomyopathy, hearing loss and short stature. Muscle specimens of the 2 patients revealed muscular dystrophic features with massive lipid droplets and numerous rimmed vacuoles in the fibers. A novel homozygous mutation IVS2+1G > A in the PNPLA2 gene was identified in the 2 cases, but not in the healthy familial individuals. The presence of massive lipid droplets with muscular dystrophic changes and rimmed vacuoles in muscle fibers might be one of the characteristic pathological changes of NLSDM.

  7. Rhodopsin-lipid interactions studied by NMR.

    PubMed

    Soubias, Olivier; Gawrisch, Klaus

    2013-01-01

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

  8. Thermodynamic study of benzocaine insertion into different lipid bilayers

    NASA Astrophysics Data System (ADS)

    Cascales, J. J. López; Costa, S. D. Oliveira; Porasso, R. D.

    2011-10-01

    Despite the general consensus concerning the role played by sodium channels in the molecular mechanism of local anesthetics, the potency of anaesthetic drugs also seems to be related with their solubility in lipid bilayers. In this respect, this work represents a thermodynamic study of benzocaine insertion into lipid bilayers of different compositions by means of molecular dynamics simulation. Thus, the free energy profiles associated with benzocaine insertion into symmetric lipid bilayers composed of different proportions of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine were studied. From the simulation results, a maximum in the free energy (ΔG) profile was measured in the region of the lipid/solution interface. This free energy barrier appears to be very much dependent on the lipid composition of the membrane. On the other hand, the minimum free energy (ΔG) within the bilayer remained almost independent of the lipid composition of the bilayer. By repeating the study at different temperatures, it was seen how the spontaneity of benzocaine insertion into the lipid bilayer is due to an increase in the entropy associated with the process.

  9. Thermodynamic study of benzocaine insertion into different lipid bilayers.

    PubMed

    Cascales, J J López; Costa, S D Oliveira; Porasso, R D

    2011-10-07

    Despite the general consensus concerning the role played by sodium channels in the molecular mechanism of local anesthetics, the potency of anaesthetic drugs also seems to be related with their solubility in lipid bilayers. In this respect, this work represents a thermodynamic study of benzocaine insertion into lipid bilayers of different compositions by means of molecular dynamics simulation. Thus, the free energy profiles associated with benzocaine insertion into symmetric lipid bilayers composed of different proportions of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine were studied. From the simulation results, a maximum in the free energy (ΔG) profile was measured in the region of the lipid/solution interface. This free energy barrier appears to be very much dependent on the lipid composition of the membrane. On the other hand, the minimum free energy (ΔG) within the bilayer remained almost independent of the lipid composition of the bilayer. By repeating the study at different temperatures, it was seen how the spontaneity of benzocaine insertion into the lipid bilayer is due to an increase in the entropy associated with the process. © 2011 American Institute of Physics

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

    PubMed

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

    2018-03-29

    Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids. We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequence analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for activities of caspases 3 and 7. In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids. We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal

  11. A Comparison among Worker Types Using a Composites Approach and Median Splits

    ERIC Educational Resources Information Center

    Aziz, Shahnaz; Wuensch, Karl L.; Brandon, Howard R.

    2010-01-01

    The current study examined Spence and Robbins' (1992) worker types in terms of correlates of workaholism (e.g., work-life imbalance, obsessive-compulsive behavior). A survey was administered to professionals, who were then classified into different worker types following the traditional median-split technique. The data were also analyzed with…

  12. Phosphatidylserine lipids and membrane order precisely regulate the activity of Polybia-MP1 peptide.

    PubMed

    Alvares, Dayane S; Ruggiero Neto, João; Ambroggio, Ernesto E

    2017-06-01

    Polybia-MP1 (IDWKKLLDAAKQIL-NH 2 ) is a lytic peptide from the Brazilian wasp venom with known anti-cancer properties. Previous evidence indicates that phosphatidylserine (PS) lipids are relevant for the lytic activity of MP1. In agreement with this requirement, phosphatidylserine lipids are translocated to the outer leaflet of cells, and are available for MP1 binding, depending on the presence of liquid-ordered domains. Here, we investigated the effect of PS on MP1 activity when this lipid is reconstituted in membranes of giant or large liposomes with different lipid-phase states. By monitoring the membrane and soluble luminal content of giant unilamellar vesicles (GUVs), using fluorescence confocal microscopy, we were able to determine that MP1 has a pore-forming activity at the membrane level. Liquid-ordered domains, which were phase-separated within the membrane of GUVs, influenced the pore-forming activity of MP1. Experiments evaluating the membrane-binding and lytic activity of MP1 on large unilamellar vesicles (LUVs), with the same lipid composition as GUVs, demonstrated that there was synergy between liquid-ordered domains and PS, which enhanced both activities. Based on our findings, we propose that the physicochemical properties of cancer cell membranes, which possess a much higher concentration of PS than normal cells, renders them susceptible to MP1 binding and lytic pore formation. These results can be correlated with MP1's potent and selective anti-cancer activity and pave the way for future research to develop cancer therapies that harness and exploit the properties of MP1. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Immobilized oleaginous microalgae for production of lipid and phytoremediation of secondary effluent from palm oil mill in fluidized bed photobioreactor.

    PubMed

    Cheirsilp, Benjamas; Thawechai, Tipawan; Prasertsan, Poonsuk

    2017-10-01

    Oleaginous microalga Nannochloropsis sp. was immobilized in alginate gel beads and cultivated under optimal conditions that their growth and lipid production were comparable to those of free cells. The immobilized cells were used in phytoremediation of secondary effluent from palm oil mill and easily recovered by simple sieving method. The immobilized cells contributed to removal of nitrogen and phosphorus >90% and CO 2 mitigation >99%. They also gave the biomass and lipid production of 1.300±0.050g/L and 0.356±0.097g/L, respectively. The repeated-batch cultivation improved the biomass and lipid production by 2.66 folds and 1.41 folds, respectively. The scale up in 3L-fluidized bed photobioreactor gave the maximum biomass of 3.280±0.049g/L and lipid production of 0.362±0.010g/L. Fatty acid compositions of Nannochloropsis sp. lipids showed their suitability as biodiesel feedstocks. This system not only contributes as tertiary treatment of industrial effluent and CO 2 mitigation but also low-cost production of renewable energy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Mobilizing peripheral blood stem cells with high-dose G-CSF alone is as effective as with Dexa-BEAM plus G-CSF in lymphoma patients.

    PubMed

    Kröger, N; Zeller, W; Fehse, N; Hassan, H T; Krüger, W; Gutensohn, K; Lölliger, C; Zander, A R

    1998-09-01

    We compared retrospectively the efficacy of granulocyte colony stimulating factor (G-CSF) alone with chemotherapy plus G-CSF in mobilizing CD34-positive cells in patients with malignant lymphoma. 35 patients underwent peripheral blood stem cell (PBSC) collection following mobilization either with 24 microg/kg G-CSF for 4 consecutive days (n = 18) or Dexa-BEAM chemotherapy plus 5 microg/kg G-CSF (n = 17). High-dose G-CSF was well tolerated with only slight bone pain and/or myalgia. The Dexa-BEAM therapy required hospitalization with a median duration of 21 d. The median number of apheresis procedures in both groups was two (range two to four), resulting in a median of 5.3 and 5.1 x 10(6) CD34+ cells/kg. No patients in the G-CSF group, but one in the Dexa-BEAM group, failed to reach the target of collecting >2.0 x 10(6) CD34+ cells/kg. The number of CFU-GM (10.4 v 6.0 x 10(5)/kg) and of BFU-E (10.6 v 4.5 x 10(5)/kg; P = 0.04) was higher in the G-CSF group than in the Dexa-BEAM group. A subset analysis of CD34+ cells was performed in 16 patients showing a higher mean of Thy-1 (CD90w) coexpression in the G-CSF than in the Dexa-BEAM group (4.8 v 1.8%, P = 0.12). Additionally the percentage of CD34+/CD38- cells was higher in the G-CSF group (10.66% v 8.8%). However, these differences were not statistically significant. The median time to leucocyte and platelet engraftment after high-dose chemotherapy was slightly shorter in the G-CSF than in the Dexa-BEAM group (9 v 10 and 12 v 13.5 d, respectively). These results demonstrate that high-dose G-CSF is as effective as Dexa-BEAM plus G-CSF in mobilizing peripheral blood stem cells and produces prompt engraftment. The major advantages of G-CSF mobilization were the safe outpatient self-application and the fixed-day apheresis.

  15. Application and expression of HSV gG1 protein from a recombinant strain.

    PubMed

    Yan, Hua; Yan, Huishen; Huang, Tao; Li, Guocai; Gong, Weijuan; Jiao, Hongmei; Chen, Hongju; Ji, Mingchun

    2010-11-01

    According to the homologous sequence of glycoprotein G1 (gG1) genes from different strains of herpes simplex virus type 1 (HSV-1), a pair of primers was designed to amplify the gG1 gene fragment by PCR. Both the PCR product and the pGEX-4T-1 vector were digested with EcoR I and Sal I. The gG1 gene fragment was subcloned into the digested pGEX-4T-1 vector to construct a recombinant plasmid (pGEX-4T-1-gG1). The resultant plasmid was identified by dual-enzyme digestion and sequence analysis, and then transformed into Escherichia coli BL21 for expression under the induction of isopropyl β-D-1-thiogalactoside (IPTG). The expressed GST-gG1 fragment was detected by SDS-PAGE and purified by affinity chromatography. The properties of GST-gG1 fragment were evaluated by immunoblot analysis. Enzyme-linked immunosorbent assays (ELISAs) based on the GST-gG1 fragment were used for determining IgG or IgM to HSV-1. The GST-gG1 fragment-specific ELISA was also compared with ELISA with whole-HSV-1 antigen and commercial ELISA kits. The gG1-specific IgG and IFN-γ producing CD8+ T cells were induced in mice immunized with the GST-gG1 fragment. These results indicated that the GST-gG1 fragment could be used for replacing whole-virus antigen to detect IgM and IgG to HSV-1 in human sera, which provided a strategy for developing vaccines to protect HSV-1 infection using gG1 fragment. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. In Vivo Inhibition of Lipid Accumulation in Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Sulistiyani; Purwakusumah, E. P.; Andrianto, D.

    2017-03-01

    This is a preliminary research report on the use of Caenorhabditis elegans as a model to establish anti-obesity screening assay of the natural plant resources. Nematode C. elegans has been used as experimental animal model for understanding lipid accumulation. The objective of this research was to investigate the effect of selected plant extracts on lipid accumulation in C. elegans. Currently no report could be found regarding lipid accumulation in C.elegans treated with ethanolic leaf extracts of jabon merah (Anthocephalus macrophyllus), jati belanda (Guazuma ulmifolia), and Mindi (Melia Azedarach) plants. Lipid accumulation was determined qualitatively using lipid staining method and quantitatively by colorimetry using sulpho-phospho-vanillin reagent. Data showed that lipid accumulation was inhibited up to 72% by extract of M. azedarach, about 35% by both of A. macrophyllus and G. ulmifolia extracts, and up to 25% by orlistat (a synthetic slimming drug). Ethanolic extract of A. macrophyllus, G. ulmifolia, and M. azedarach leaves were shown to inhibit lipid accumulation in C. elegans and M. azedarach leaves extracts was the most effective inhibitor. C.elegans were shown to be an effective model for in vivo lipid accumulation mechanism and potential to be used as a rapid screening assay for bioactive compounds with lipid accumulation inhibitory activity.

  17. Adaptive marginal median filter for colour images.

    PubMed

    Morillas, Samuel; Gregori, Valentín; Sapena, Almanzor

    2011-01-01

    This paper describes a new filter for impulse noise reduction in colour images which is aimed at improving the noise reduction capability of the classical vector median filter. The filter is inspired by the application of a vector marginal median filtering process over a selected group of pixels in each filtering window. This selection, which is based on the vector median, along with the application of the marginal median operation constitutes an adaptive process that leads to a more robust filter design. Also, the proposed method is able to process colour images without introducing colour artifacts. Experimental results show that the images filtered with the proposed method contain less noisy pixels than those obtained through the vector median filter.

  18. 17 CFR 240.12g-1 - Exemption from section 12(g).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... pursuant to section 12(g)(1) if on the last day of its most recent fiscal year the issuer had total assets...). 240.12g-1 Section 240.12g-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Securities Exchange Act of 1934 Extensions and Temporary Exemptions; Definitions § 240.12g-1 Exemption from...

  19. 17 CFR 240.12g-1 - Exemption from section 12(g).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... pursuant to section 12(g)(1) if on the last day of its most recent fiscal year the issuer had total assets...). 240.12g-1 Section 240.12g-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Securities Exchange Act of 1934 Extensions and Temporary Exemptions; Definitions § 240.12g-1 Exemption from...

  20. 17 CFR 240.12g-1 - Exemption from section 12(g).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... pursuant to section 12(g)(1) if on the last day of its most recent fiscal year the issuer had total assets...). 240.12g-1 Section 240.12g-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Securities Exchange Act of 1934 Extensions and Temporary Exemptions; Definitions § 240.12g-1 Exemption from...

  1. 17 CFR 240.12g-1 - Exemption from section 12(g).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pursuant to section 12(g)(1) if on the last day of its most recent fiscal year the issuer had total assets...). 240.12g-1 Section 240.12g-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Securities Exchange Act of 1934 Extensions and Temporary Exemptions; Definitions § 240.12g-1 Exemption from...

  2. 17 CFR 240.12g-1 - Exemption from section 12(g).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... pursuant to section 12(g)(1) if on the last day of its most recent fiscal year the issuer had total assets...). 240.12g-1 Section 240.12g-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Securities Exchange Act of 1934 Extensions and Temporary Exemptions; Definitions § 240.12g-1 Exemption from...

  3. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

    PubMed

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

    2016-01-01

    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

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

    PubMed

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

    2017-10-01

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

  5. Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative injuries.

    PubMed

    Liu, Qingsheng; Pan, Ran; Ding, Lei; Zhang, Fuli; Hu, Linfeng; Ding, Bin; Zhu, Linwensi; Xia, Yongliang; Dou, Xiaobing

    2017-08-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Rutin is a natural flavonoid with significant roles in combating cellular oxidative stress and regulating lipid metabolism. The current study aims to investigate the molecular mechanisms underlying rutin's hypolipidemic and hepatoprotective effects in nonalcoholic fatty liver disease. Rutin treatment was applied to male C57BL/6 mice maintained on a high-fat diet and HepG2 cells challenged with oleic acid. Hepatic lipid accumulation was evaluated by triglyceride assay and Oil Red O staining. Oxidative hepatic injury was assessed by malondialdehyde assay, superoxide dismutase assay and reactive oxygen species assay. The expression levels of various lipogenic and lipolytic genes were determined by quantitative real-time polymerase chain reactions. In addition, liver autophagy was investigated by enzyme-linked immunosorbent assay. In both fat-challenged murine liver tissues and HepG2 cells, rutin treatment was shown to significantly lower triglyceride content and the abundance of lipid droplets. Rutin was also found to reduce cellular malondialdehyde level and restore superoxide dismutase activity in hepatocytes. Among the various lipid-related genes, rutin treatment was able to restore the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its downstream targets, carnitine palmitoyltransferase 1 and 2 (CPT-1 and CPT-2), while suppressing those of sterol regulatory element-binding protein 1c (SREBP-1c), diglyceride acyltransfase 1 and 2 (DGAT-1 and 2), as well as acyl-CoA carboxylase (ACC). In addition, rutin was shown to repress the autophagic function of liver tissues by down-regulating key autophagy biomarkers, including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β). The experimental data demonstrated that rutin could reduce triglyceride content and mitigate oxidative injuries in fat

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

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

    Huang, Haibo; Long, Stephen; Singh, Vijay

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

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

    DOE PAGES

    Huang, Haibo; Long, Stephen; Singh, Vijay

    2016-03-07

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

  8. Polymorphism 4G/5G of the plasminogen activator inhibitor 1 gene as a risk factor for the development of allergic rhinitis symptoms in patients with asthma.

    PubMed

    Lampalo, Marina; Jukic, Irena; Bingulac-Popovic, Jasna; Marunica, Ivona; Petlevski, Roberta; Pavlisa, Gordana; Popovic-Grle, Sanja

    2017-06-01

    Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein which has a role in tissue remodelling after inflammatory processes. The objective is to investigate the frequency of PAI-1 gene polymorphism (4G/5G) in patients with a lung ventilation dysfunction in asthma and allergic rhinitis. Genomic DNA was isolated and genotypes of polymorphism of PAI-1 4G/5G and ABO were determined using the methods of RT-PCR and PCR-SSP. Study group includes 145 adult patients diagnosed with chronic asthma, with all clinically relevant parameters and the laboratory markers of pO 2 , IgE and eosinophils in sputum and nasal swab. In the processing of data, appropriate statistical tests (Kolmogorov-Smirnov test, median, interquartile ranges, χ 2 and Mann-Whitney U tests) were used. Patients with symptoms of allergic rhinitis were significantly younger and had an almost four time higher levels of IgE (P = 0.001), higher pO 2 (P = 0.002) and PEF (P = 0.036), compared to those who do not have these symptoms. Genotype PAI 4G/4G is significantly more common in patients with allergic rhinitis (28.1% vs. 16.1%; P = 0.017) compared to the genotype 5G/5G. Carriers of the genotype 4G/5G also have a borderline statistical significance. There were no statistically significant difference in the incidence of allergic rhinitis in the carriers of any ABO genotypes. The frequency of PAI genotype 4G/4G is significantly more common in patients with allergic rhinitis. The results suggest that the carriers of at least one 4G allele are at a higher risk for developing symptoms of allergic rhinitis in asthma.

  9. Imaging of Lipids in Microalgae with Coherent Anti-Stokes Raman Scattering Microscopy1[OPEN

    PubMed Central

    Cavonius, Lillie; Fink, Helen; Kiskis, Juris; Albers, Eva; Undeland, Ingrid; Enejder, Annika

    2015-01-01

    Microalgae have great prospects as a sustainable resource of lipids for refinement into nutraceuticals and biodiesel, which increases the need for detailed insights into their intracellular lipid synthesis/storage mechanisms. As an alternative strategy to solvent- and label-based lipid quantification techniques, we introduce time-gated coherent anti-Stokes Raman scattering (CARS) microscopy for monitoring lipid contents in living algae, despite strong autofluorescence from the chloroplasts, at approximately picogram and subcellular levels by probing inherent molecular vibrations. Intracellular lipid droplet synthesis was followed in Phaeodactylum tricornutum algae grown under (1) light/nutrient-replete (control [Ctrl]), (2) light-limited (LL), and (3) nitrogen-starved (NS) conditions. Good correlation (r2 = 0.924) was found between lipid volume data yielded by CARS microscopy and total fatty acid content obtained from gas chromatography-mass spectrometry analysis. In Ctrl and LL cells, micron-sized lipid droplets were found to increase in number throughout the growth phases, particularly in the stationary phase. During more excessive lipid accumulation, as observed in NS cells, promising commercial harvest as biofuels and nutritional lipids, several micron-sized droplets were present already initially during cultivation, which then fused into a single giant droplet toward stationary phase alongside with new droplets emerging. CARS microspectroscopy further indicated lower lipid fluidity in NS cells than in Ctrl and LL cells, potentially due to higher fatty acid saturation. This agreed with the fatty acid profiles gathered by gas chromatography-mass spectrometry. CARS microscopy could thus provide quantitative and semiqualitative data at the single-cell level along with important insights into lipid-accumulating mechanisms, here revealing two different modes for normal and excessive lipid accumulation. PMID:25583924

  10. Isothermal lipid phase transitions.

    PubMed

    Cevc, G

    1991-03-01

    In liotropic lipid systems phase transitions can be induced isothermally by changing the solvent concentration or composition; alternatively, lipid composition can be modified by (bio)chemical means. The probability for isothermal phase transitions increases with the decreasing transition entropy; it is proportional to the magnitude of the transition temperature shift caused by transformation-inducing system variation. Manipulations causing large thermodynamic effects, such as lipid (de)hydration, binding of protons or divalent ions and macromolecular adsorption, but also close bilayer approach are, therefore, likely to cause structural lipid change(s) at a constant temperature. Net lipid charges enhance the membrane susceptibility to salt-induced isothermal phase transitions; a large proportion of this effect is due to the bilayer dehydration, however, rather than being a consequence of the decreased Coulombic electrostatic interactions. Membrane propensity for isothermal phase transitions, consequently, always increases with the hydrophilicity of the lipid heads, as well as with the desaturation and shortening of the lipid chains. Upon a phase change at a constant temperature, some of the interfacially bound solutes (e.g. protons or calcium) are released in the solution. Membrane permeability and fusogenicity simultaneously increase. In mixed systems, isothermal phase transitions, moreover, may result in lateral phase separation. All this opens up ways for the involvement of isothermal phase transitions in the regulation of biological processes.

  11. Recovery of lipid metabolic alterations in hepatitis C patients after viral clearance: Incomplete restoration with accelerated ω-oxidation.

    PubMed

    Chang, Su-Wei; Cheng, Mei-Ling; Shiao, Ming-Shi; Yeh, Chau-Ting; Wang, Chao-Hung; Fan, Chun-Ming; Chiu, Cheng-Tang; Chang, Ming-Ling

    2018-03-02

    How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. The aforementioned recovery pattern was investigated. In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR

  12. Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.

    PubMed

    Harding, Peter J; Attrill, Helen; Boehringer, Jonas; Ross, Simon; Wadhams, George H; Smith, Eleanor; Armitage, Judith P; Watts, Anthony

    2009-02-01

    Neurotensin receptor 1 (NTS1), a Family A G-protein coupled receptor (GPCR), was expressed in Escherichia coli as a fusion with the fluorescent proteins eCFP or eYFP. A fluorophore-tagged receptor was used to study the multimerization of NTS1 in detergent solution and in brain polar lipid bilayers, using fluorescence resonance energy transfer (FRET). A detergent-solubilized receptor was unable to form FRET-competent complexes at concentrations of up to 200 nM, suggesting that the receptor is monomeric in this environment. When reconstituted into a model membrane system at low receptor density, the observed FRET was independent of agonist binding, suggesting constitutive multimer formation. In competition studies, decreased FRET in the presence of untagged NTS1 excludes the possibility of fluorescent protein-induced interactions. A simulation of the experimental data indicates that NTS1 exists predominantly as a homodimer, rather than as higher-order multimers. These observations suggest that, in common with several other Family A GPCRs, NTS1 forms a constitutive dimer in lipid bilayers, stabilized through receptor-receptor interactions in the absence of other cellular signaling components. Therefore, this work demonstrates that well-characterized model membrane systems are useful tools for the study of GPCR multimerization, allowing fine control over system composition and complexity, provided that rigorous control experiments are performed.

  13. Molecular Mechanism of Betaine on Hepatic Lipid Metabolism: Inhibition of Forkhead Box O1 (FoxO1) Binding to Peroxisome Proliferator-Activated Receptor Gamma (PPARγ).

    PubMed

    Kim, Dae Hyun; Lee, Bonggi; Kim, Min Jo; Park, Min Hi; An, Hye Jin; Lee, Eun Kyeong; Chung, Ki Wung; Park, June Whoun; Yu, Byung Pal; Choi, Jae Sue; Chung, Hae Young

    2016-09-14

    Betaine is a major water-soluble component of Lycium chinensis. Although there are reports about the protective effects of betaine on hepatic steatosis, the underlying mechanisms are unclear. We used db/db mice and HepG2 cells to examine the mechanism underlying betaine-mediated protection against hepatic steatosis. Here, we showed increased hepatic lipid accumulation in db/db mice, which is associated with increased activation of lipogenic transcription factors including forkhead box O1 (FoxO1) and peroxisome proliferator-activated receptor gamma (PPARγ), whereas betaine administration by oral gavage reversed these characteristics. We investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO1/PPARγ signaling in HepG2 cells. Although adenovirus-mediated FoxO1 overexpression notably increased mRNA expression levels of PPARγ and its target genes including FAS and ACC, betaine treatment reversed them. Furthermore, betaine inhibited FoxO1 binding to the PPARγ promoter and PPARγ transcriptional activity in HepG2 cells, which was previously shown to induce hepatic steatosis. We concluded that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the FoxO1 binding to PPARγ and their downstream lipogenic signaling cascade.

  14. [Effects of furfural on the growth and lipid production of oleaginous yeast Rhodotorula glutinis].

    PubMed

    Yong, Zihan; Zhang, Xu; Tan, Tianwei

    2015-10-01

    In order to illustrate the effects of furfural, one of the most common inhibitory compounds in lignocellulosic hydrolysate, on oleaginous yeast Rhodotorula glutinis, we investigated the effects of different concentrations of furfural (0.1, 0.4, 0.6 and 1.5 g/L) on the biomass and lipid production of R. glutinis, as well as the effects of 1.0 g/L furfural on the utilization of glucose and xylose. Results showed that: when the furfural concentration reached 1.5 g/L, the lag phrase time was extended to 96 h, and the residual glucose was up to 17.7 g/L, with maximum biomass of only 6.6 g/L, which accounted for 47% of that in the basic medium (furfural-free), and the corresponding lipid content was reduced about 50%. Furfural showed lighter inhibitory degree on R. glutinis when xylose acted as the carbon source than glucose was the carbon source; more C18 fatty acids or unsaturated C18 fatty acids were generated in the presence of furfural.

  15. Lipid Droplet-Associated Proteins (LDAPs) Are Required for the Dynamic Regulation of Neutral Lipid Compartmentation in Plant Cells1

    PubMed Central

    Park, Sunjung; Wu, Peng

    2016-01-01

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols in seeds, their biogenesis and function in nonseed tissues are poorly understood. Recently, we identified a class of plant-specific, lipid droplet-associated proteins (LDAPs) that are abundant components of LDs in nonseed cell types. Here, we characterized the three LDAPs in Arabidopsis (Arabidopsis thaliana) to gain insight to their targeting, assembly, and influence on LD function and dynamics. While all three LDAPs targeted specifically to the LD surface, truncation analysis of LDAP3 revealed that essentially the entire protein was required for LD localization. The association of LDAP3 with LDs was detergent sensitive, but the protein bound with similar affinity to synthetic liposomes of various phospholipid compositions, suggesting that other factors contributed to targeting specificity. Investigation of LD dynamics in leaves revealed that LD abundance was modulated during the diurnal cycle, and characterization of LDAP misexpression mutants indicated that all three LDAPs were important for this process. LD abundance was increased significantly during abiotic stress, and characterization of mutant lines revealed that LDAP1 and LDAP3 were required for the proper induction of LDs during heat and cold temperature stress, respectively. Furthermore, LDAP1 was required for proper neutral lipid compartmentalization and triacylglycerol degradation during postgerminative growth. Taken together, these studies reveal that LDAPs are required for the maintenance and regulation of LDs in plant cells and perform nonredundant functions in various physiological contexts, including stress response and postgerminative growth. PMID:26896396

  16. Influence of cationic lipid concentration on properties of lipid-polymer hybrid nanospheres for gene delivery.

    PubMed

    Bose, Rajendran J C; Arai, Yoshie; Ahn, Jong Chan; Park, Hansoo; Lee, Soo-Hong

    2015-01-01

    Nanoparticles have been widely used for nonviral gene delivery. Recently, cationic hybrid nanoparticles consisting of two different materials were suggested as a promising delivery vehicle. In this study, nanospheres with a poly(D,L-lactic-co-glycolic acid) (PLGA) core and cationic lipid shell were prepared, and the effect of cationic lipid concentrations on the properties of lipid polymer hybrid nanocarriers investigated. Lipid-polymer hybrid nanospheres (LPHNSs) were fabricated by the emulsion-solvent evaporation method using different concentrations of cationic lipids and characterized for size, surface charge, stability, plasmid DNA-binding capacity, cytotoxicity, and transfection efficiency. All LPHNSs had narrow size distribution with positive surface charges (ζ-potential 52-60 mV), and showed excellent plasmid DNA-binding capacity. In vitro cytotoxicity measurements with HEK293T, HeLa, HaCaT, and HepG2 cells also showed that LPHNSs exhibited less cytotoxicity than conventional transfection agents, such as Lipofectamine and polyethyleneimine-PLGA. As cationic lipid concentrations increased, the particle size of LPHNSs decreased while their ζ-potential increased. In addition, the in vitro transfection efficiency of LPHNSs increased as lipid concentration increased.

  17. Iterative dip-steering median filter

    NASA Astrophysics Data System (ADS)

    Huo, Shoudong; Zhu, Weihong; Shi, Taikun

    2017-09-01

    Seismic data are always contaminated with high noise components, which present processing challenges especially for signal preservation and its true amplitude response. This paper deals with an extension of the conventional median filter, which is widely used in random noise attenuation. It is known that the standard median filter works well with laterally aligned coherent events but cannot handle steep events, especially events with conflicting dips. In this paper, an iterative dip-steering median filter is proposed for the attenuation of random noise in the presence of multiple dips. The filter first identifies the dominant dips inside an optimized processing window by a Fourier-radial transform in the frequency-wavenumber domain. The optimum size of the processing window depends on the intensity of random noise that needs to be attenuated and the amount of signal to be preserved. It then applies median filter along the dominant dip and retains the signals. Iterations are adopted to process the residual signals along the remaining dominant dips in a descending sequence, until all signals have been retained. The method is tested by both synthetic and field data gathers and also compared with the commonly used f-k least squares de-noising and f-x deconvolution.

  18. Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects.

    PubMed

    Woo, Hye In; Kim, Suk Ran; Huh, Wooseong; Ko, Jae-Wook; Lee, Soo-Youn

    2017-01-01

    Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals. Atorvastatin 80 mg was given to 50 healthy Korean male volunteers. Blood samples were collected to measure plasma atorvastatin and lipid concentrations up to 48 hours after atorvastatin administration. Subjects were genotyped for 1,936 drug metabolism and transporter genetic polymorphisms using the Affymetrix DMET plus array. The pharmacokinetics and lipid-lowering effect of atorvastatin showed remarkable interindividual variation. Three polymorphisms in the SLCO1B1 , SLCO1B3 , and ABCC2 genes were associated with either the maximum concentration (C max ) of atorvastatin or changes in total cholesterol or low-density lipoprotein cholesterol (LDL-C). Minor homozygotes (76.5 ng/mL) of SLCO1B1 c.-910G>A showed higher C max than heterozygotes (34.0 ng/mL) and major homozygotes (33.5 ng/mL, false discovery rate P =0.040). C max and the area under the plasma concentration curve from hour 0 to infinity (AUC ∞ ) were higher in carriers of the SLCO1B1 *17 haplotype that included c.-910G>A than in noncarriers (46.1 vs 32.8 ng/mL for C max ; 221.5 vs 154.2 ng/mL for AUC ∞ ). SLCO1B3 c.334G>T homozygotes (63.0 ng/mL) also showed higher C max than heterozygotes (34.7 ng/mL) and major homozygotes (31.4 ng/mL, FDR P =0.037). A nonsynonymous ABCC2 c.1249G>A was associated with small total cholesterol and LDL-C responses (0.23% and -0.70% for G/A vs -11.9% and -17.4% for G/G). The C max tended to increase according to the increase in the number of minor allele of SLCO1B1 c. -910G>A and SLCO1B3 c.334G>T. Genetic polymorphisms in transporter genes, including SLCO1B1 , SLCO1B3 , and ABCC2 , may influence the pharmacokinetics and lipid-lowering response to

  19. Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects

    PubMed Central

    Woo, Hye In; Kim, Suk Ran; Huh, Wooseong; Ko, Jae-Wook; Lee, Soo-Youn

    2017-01-01

    Background Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals. Methods Atorvastatin 80 mg was given to 50 healthy Korean male volunteers. Blood samples were collected to measure plasma atorvastatin and lipid concentrations up to 48 hours after atorvastatin administration. Subjects were genotyped for 1,936 drug metabolism and transporter genetic polymorphisms using the Affymetrix DMET plus array. Results The pharmacokinetics and lipid-lowering effect of atorvastatin showed remarkable interindividual variation. Three polymorphisms in the SLCO1B1, SLCO1B3, and ABCC2 genes were associated with either the maximum concentration (Cmax) of atorvastatin or changes in total cholesterol or low-density lipoprotein cholesterol (LDL-C). Minor homozygotes (76.5 ng/mL) of SLCO1B1 c.-910G>A showed higher Cmax than heterozygotes (34.0 ng/mL) and major homozygotes (33.5 ng/mL, false discovery rate P=0.040). Cmax and the area under the plasma concentration curve from hour 0 to infinity (AUC∞) were higher in carriers of the SLCO1B1*17 haplotype that included c.-910G>A than in noncarriers (46.1 vs 32.8 ng/mL for Cmax; 221.5 vs 154.2 ng/mL for AUC∞). SLCO1B3 c.334G>T homozygotes (63.0 ng/mL) also showed higher Cmax than heterozygotes (34.7 ng/mL) and major homozygotes (31.4 ng/mL, FDR P=0.037). A nonsynonymous ABCC2 c.1249G>A was associated with small total cholesterol and LDL-C responses (0.23% and −0.70% for G/A vs −11.9% and −17.4% for G/G). The Cmax tended to increase according to the increase in the number of minor allele of SLCO1B1 c. −910G>A and SLCO1B3 c.334G>T. Conclusion Genetic polymorphisms in transporter genes, including SLCO1B1, SLCO1B3, and ABCC2, may influence the pharmacokinetics and lipid

  20. Overview of Shipyard coast line with Piers G1, G2, G3, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Overview of Shipyard coast line with Piers G-1, G-2, G-3, G-4, and G-5 in view, view facing east-southeast - U.S. Naval Base, Pearl Harbor, Pier & Quay Walls, Entrance to Dry Dock No. 2 & Repair Wharfs, east & west sides of Dry Dock No. 2 & west side of Dry Dock No. 3, Pearl City, Honolulu County, HI

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

    PubMed

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

    2016-10-01

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

  2. Separation, hydrolysis and fermentation of pyrolytic sugars to produce ethanol and lipids.

    PubMed

    Lian, Jieni; Chen, Shulin; Zhou, Shuai; Wang, Zhouhong; O'Fallon, James; Li, Chun-Zhu; Garcia-Perez, Manuel

    2010-12-01

    This paper describes a new scheme to convert anhydrosugars found in pyrolysis oils into ethanol and lipids. Pyrolytic sugars were separated from phenols by solvent extraction and were hydrolyzed into glucose using sulfuric acid as a catalyst. Toxicological studies showed that phenols and acids were the main species inhibiting growth of the yeast Saccharomyces cerevisiae. The sulfuric acids, and carboxylic acids from the bio-oils, were neutralized with Ba(OH)(2). The phase rich in sugar was further detoxified with activated carbon. The resulting aqueous phase rich in glucose was fermented with three different yeasts: S. cerevisiae to produce ethanol, and Cryptococcus curvatus and Rhodotorula glutinis to produce lipids. Yields as high as 0.473 g ethanol/g glucose and 0.167 g lipids/g sugar (0.266 g ethanol equivalent/g sugar), were obtained. These results confirm that pyrolytic sugar fermentation to produce ethanol is more efficient than for lipid production. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  4. Bioconversion of volatile fatty acids derived from waste activated sludge into lipids by Cryptococcus curvatus.

    PubMed

    Liu, Jia; Liu, Jia-Nan; Yuan, Ming; Shen, Zi-Heng; Peng, Kai-Ming; Lu, Li-Jun; Huang, Xiang-Feng

    2016-07-01

    Pure volatile fatty acid (VFA) solution derived from waste activated sludge (WAS) was used to produce microbial lipids as culture medium in this study, which aimed to realize the resource recovery of WAS and provide low-cost feedstock for biodiesel production simultaneously. Cryptococcus curvatus was selected among three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by struvite precipitation. The lipid content further increased to 39.6% and the biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA solution contained nearly 50% of monounsaturated fatty acids, including palmitic acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic acid, which showed the adequacy of biodiesel production. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Fatty acid methyl ester profiles of bat wing surface lipids.

    PubMed

    Pannkuk, Evan L; Fuller, Nathan W; Moore, Patrick R; Gilmore, David F; Savary, Brett J; Risch, Thomas S

    2014-11-01

    Sebocytes are specialized epithelial cells that rupture to secrete sebaceous lipids (sebum) across the mammalian integument. Sebum protects the integument from UV radiation, and maintains host microbial communities among other functions. Native glandular sebum is composed primarily of triacylglycerides (TAG) and wax esters (WE). Upon secretion (mature sebum), these lipids combine with minor cellular membrane components comprising total surface lipids. TAG and WE are further cleaved to smaller molecules through oxidation or host enzymatic digestion, resulting in a complex mixture of glycerolipids (e.g., TAG), sterols, unesterified fatty acids (FFA), WE, cholesteryl esters, and squalene comprising surface lipid. We are interested if fatty acid methyl ester (FAME) profiling of bat surface lipid could predict species specificity to the cutaneous fungal disease, white nose syndrome (WNS). We collected sebaceous secretions from 13 bat spp. using Sebutape(®) and converted them to FAME with an acid catalyzed transesterification. We found that Sebutape(®) adhesive patches removed ~6× more total lipid than Sebutape(®) indicator strips. Juvenile eastern red bats (Lasiurus borealis) had significantly higher 18:1 than adults, but 14:0, 16:1, and 20:0 were higher in adults. FAME profiles among several bat species were similar. We concluded that bat surface lipid FAME profiling does not provide a robust model predicting species susceptibility to WNS. However, these results provide baseline data that can be used for lipid roles in future ecological studies, such as life history, diet, or migration.

  6. Function of Lipid Storage Droplet 1 (Lsd1) in Wing Development of Drosophila melanogaster.

    PubMed

    Men, Tran Thanh; Binh, Tran Duy; Yamaguchi, Masamitsu; Huy, Nguyen Tien; Kamei, Kaeko

    2016-04-29

    Perilipins are evolutionarily conserved from Drosophila to humans, the lipid storage droplet 1 (Lsd1) is a Drosophila homolog of human perilipin 1. The function of Lsd1 as a regulator of lipolysis in Drosophila has been demonstrated, as the Lsd1 mutant causes an increase of lipid droplet size. However, the functions of this gene during development are still under investigation. In order to determine the function of Lsd1 during development, Lsd1 was knocked down in Drosophila using the GAL4-UAS system. Selective knockdown of Lsd1 in the dorsal wing disc caused an atrophied wing phenotype. The generation of reactive oxygen species in the wing pouch compartment of the Lsd1-knockdown flies was significantly higher than in the control. Immunostaining with caspase-3 antibody revealed a greater number of apoptotic cells in Lsd1-knockdown wing discs than in the control. Cell death by autophagy was also induced in the knockdown flies. Moreover, cells deprived of Lsd1 showed mitochondrial expansion and decreased ATP levels. These results strongly suggest that knockdown of Lsd1 induces mitochondrial stress and the production of reactive oxygen species that result in cell death, via apoptosis and the autophagy pathway. These results highlight the roles of Drosophila Lsd1 during wing development.

  7. Utilization of methanol in crude glycerol to assist lipid production in non-sterilized fermentation from Trichosporon oleaginosus.

    PubMed

    Chen, Jiaxin; Zhang, Xiaolei; Tyagi, Rajeshwar Dayal; Drogui, Patrick

    2018-04-01

    In this work, methanol in crude glycerol solution was used to assist the lipid production with oleaginous yeast Trichosporon oleaginosus cultivated under non-sterilized conditions. The investigated methanol concentration was 0%, 1.4%, 2.2%, 3.3% and 4.4% (w/v). The results showed that methanol played a significant role in the non-sterilized fermentation for lipid production. The optimal methanol concentration was around 1.4% (w/v) in which the growth of T. oleaginosus was promoted and overcame that of the contaminants. The non-sterilized fed-batch fermentation with initial methanol concentration of 1.4% (w/v) was then performed and high biomass production (43.39 g/L) and lipid production (20.42 g/L) were achieved. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Characterization of Yeasts and Filamentous Fungi using MALDI Lipid Phenotyping.

    PubMed

    Stübiger, Gerald; Wuczkowski, Michael; Mancera, Luis; Lopandic, Ksenija; Sterflinger, Katja; Belgacem, Omar

    2016-11-01

    Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) becomes the method of choice for the rapid identification of microorganisms (i.e. protein biotyping). Although bacterial identification is already quite advanced, biotyping of other microbes including yeasts and fungi are still under development. In this context, lipids (e.g. membrane phospholipids) represent a very important group of molecules with essential functions for cell survival and adaptation to specific environments and habitats of the microorganisms. Therefore, lipids show the potential to serve as additional molecular parameters to be used for biotyping purposes. In this paper we present a molecular characterisation of yeasts and filamentous fungi based on the analysis of lipid composition by MALDI-MS (i.e. MALDI lipid phenotyping). Using a combination of Principal Component Analysis (PCA) and Hierarchical Clustering we could demonstrate that this approach allowed a classification and differentiation of several groups of yeasts (e.g. Saccharomyces) and filamentous fungi (e.g. Aspergillus, Penicillium, Trichoderma) at the species/strain level. By analysing the MALDI lipid profiles we were able to differentiate 26 closely related yeast strains, for which discrimination via genotypic methods like AFLP in this case are relatively more elaborate. Moreover, employing statistical analysis we could identify those lipid parameters (e.g. PCs and LPCs), which were responsible for the differentiation of the strains, thus providing insights into the molecular basis of our results. In summary, MALDI lipid phenotyping represents a suitable method for fungal characterization and shows the potential to be used as companion tool to genotyping and/or protein biotyping for the characterization and identification of yeasts and fungi in diverse areas (e.g. environmental, pharmaceutical, clinical applications, etc.). Copyright © 2016 Elsevier B.V. All rights reserved.

  9. The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.

    PubMed

    Fujisawa, Yasuko; Yamaguchi, Rie; Nagata, Eiko; Satake, Eiichiro; Sano, Shinichiro; Matsushita, Rie; Kitsuta, Kazunobu; Nakashima, Shinichi; Nakanishi, Toshiki; Nakagawa, Yuichi; Ogata, Tsutomu

    2013-09-01

    The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Tris(1,3-dichloro-2-propyl) phosphate perturbs the expression of genes involved in immune response and lipid and steroid metabolism in chicken embryos

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

    Farhat, Amani; National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3; Buick, Julie K.

    We previously demonstrated that in ovo exposure to the flame retardant tris(1,3-dichloro-2-propyl) phosphate (TDCPP) decreased plasma thyroxine levels, reduced growth parameters, and decreased gallbladder size in chicken embryos. In the current study DNA microarrays were used to evaluate global mRNA expression in liver tissue of male chicken embryos that exhibited the above mentioned effects. Injected doses were dimethyl sulfoxide vehicle control, 7.6 or 45 μg TDCPP/g egg. TDCPP caused significant changes in the expression of five genes at the low dose and 47 genes at the high dose (False Discovery Rate p ≤ 0.1, fold change ≥ 1.5). The genemore » expression analysis suggested a compromised immune function, a state of cholestatic liver/biliary fibrosis, and disrupted lipid and steroid metabolism. Circulating bile acid levels were elevated, which is an indication of liver dysfunction, and plasma cholesterol levels were reduced; however, hepatic bile acid and cholesterol levels were unaltered. Interactome analyses identified apolipoprotein E, hepatocyte nuclear factor 4 alpha, and peroxisome proliferator-activated receptor alpha as key regulatory molecules involved in the effects of TDCPP. Our results demonstrate a targeted effect of TDCPP toxicity on lipid metabolism, including cholesterol, that helps explain the aforementioned phenotypic effects, as chicken embryos are highly dependent on yolk lipids for growth and maintenance throughout development. Finally, our results are in concordance with the literature that describes TDCPP as a cancer-causing agent, since the majority of dysregulated genes were involved in cancer pathways. - Highlights: • TDCPP dysregulates genes involved in immune function and lipid metabolism. • A targeted effect of TDCPP toxicity on cholesterol metabolism is apparent. • A state of cholestatic liver fibrosis is suggested by the expression profile. • Elevated plasma bile acids suggest that TDCPP causes liver dysfunction.« less

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

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

    Song, Jun; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX; Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX

    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)more » 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.« less

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

    PubMed

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

    2016-08-01

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

  13. Improved outcome in neonatal short bowel syndrome using parenteral fish oil in combination with ω-6/9 lipid emulsions.

    PubMed

    Angsten, Gertrud; Finkel, Yigael; Lucas, Steven; Kassa, Ann-Marie; Paulsson, Mattias; Lilja, Helene Engstrand

    2012-09-01

    Newborn infants with short bowel syndrome (SBS) represent a high-risk group of developing intestinal failure-associated liver disease (IFALD), which may be fatal. However, infants have a great capacity for intestinal growth and adaptation if IFALD can be prevented or reversed. A major contributing factor to IFALD may be the soybean oil-based intravenous lipid emulsions used since the introduction of parenteral nutrition (PN) 40 years ago. This retrospective study compares the outcome in 20 neonates with SBS treated with parenteral fish oil (Omegaven) in combination with ω-6/9 lipid emulsions (ClinOleic) with the outcome in a historical cohort of 18 patients with SBS who received a soybean oil-based intravenous lipid emulsion (Intralipid). Median gestational age was 26 weeks in the treatment group and 35.5 weeks in the historical group. All patients were started on PN containing Intralipid that was switched to ClinOleic/Omegaven in the treatment group at a median age of 39 gestational weeks. In the treatment group, direct bilirubin levels were reversed in all 14 survivors with cholestasis (direct bilirubin >50 umol/L). Median time to reversal was 2.9 months. Only 2 patients died of liver failure (10%). In the historical cohort, 6 patients (33%) died of liver failure, and only 2 patients showed normalization of bilirubin levels. Parenteral fish oil in combination with ω-6/9 lipid emulsions was associated with improved outcome in premature neonates with SBS. When used instead of traditional soybean-based emulsions, this mixed lipid emulsion may facilitate intestinal adaptation by increasing the IFALD-free period.

  14. Wavelet median denoising of ultrasound images

    NASA Astrophysics Data System (ADS)

    Macey, Katherine E.; Page, Wyatt H.

    2002-05-01

    Ultrasound images are contaminated with both additive and multiplicative noise, which is modeled by Gaussian and speckle noise respectively. Distinguishing small features such as fallopian tubes in the female genital tract in the noisy environment is problematic. A new method for noise reduction, Wavelet Median Denoising, is presented. Wavelet Median Denoising consists of performing a standard noise reduction technique, median filtering, in the wavelet domain. The new method is tested on 126 images, comprised of 9 original images each with 14 levels of Gaussian or speckle noise. Results for both separable and non-separable wavelets are evaluated, relative to soft-thresholding in the wavelet domain, using the signal-to-noise ratio and subjective assessment. The performance of Wavelet Median Denoising is comparable to that of soft-thresholding. Both methods are more successful in removing Gaussian noise than speckle noise. Wavelet Median Denoising outperforms soft-thresholding for a larger number of cases of speckle noise reduction than of Gaussian noise reduction. Noise reduction is more successful using non-separable wavelets than separable wavelets. When both methods are applied to ultrasound images obtained from a phantom of the female genital tract a small improvement is seen; however, a substantial improvement is required prior to clinical use.

  15. Enhancement of carotenoids and lipids production by oleaginous red yeast Sporidiobolus pararoseus KM281507.

    PubMed

    Chaiyaso, Thanongsak; Manowattana, Atchara

    2018-01-02

    Bioconversion of biodiesel-derived crude glycerol into carotenoids and lipids was investigated by a microbial conversion of an oleaginous red yeast Sporidiobolus pararoseus KM281507. The methanol content in crude glycerol (0.5%, w/v) did not show a significant effect on biomass production by strain KM281507. However, demethanolized crude glycerol significantly supported the production of biomass (8.64 ± 0.13 g/L), lipids (2.92 ± 0.03 g/L), β-carotene (15.76 ± 0.85 mg/L), and total carotenoids (33.67 ± 1.28 mg/L). The optimal conditions suggested by central composite design were crude glycerol concentration (55.04 g/L), initial pH of medium (pH 5.63) and cultivation temperature (24.01°C). Under these conditions, the production of biomass, lipids, β-carotene, and total carotenoids were elevated up to 8.83 ± 0.05, 4.00 ± 0.06 g/L, 27.41 ± 0.20, and 53.70 ± 0.48 mg/L, respectively. Moreover, an addition of olive oil (0.5 - 2.0%) dramatically increased the production of biomass (14.47 ± 0.15 g/L), lipids (6.40 ± 0.09 g/L), β-carotene (54.43 ± 0.95 mg/L), and total carotenoids (70.92 ± 0.51 mg/L). The oleic acid content in lipids was also increased to 75.1% (w/w) of total fatty acids, indicating a good potential to be an alternative biodiesel feedstock. Meanwhile, the β-carotene content in total carotenoids was increased to 76.7% (w/w). Hence, strain KM281507 could be a good potential source of renewable biodiesel feedstock and natural carotenoids.

  16. Lamellar Biogels: Fluid-Membrane-Based Hydrogels Containing Polymer Lipids

    NASA Astrophysics Data System (ADS)

    Warriner, Heidi E.; Idziak, Stefan H. J.; Slack, Nelle L.; Davidson, Patrick; Safinya, Cyrus R.

    1996-02-01

    A class of lamellar biological hydrogels comprised of fluid membranes of lipids and surfactants with small amounts of low molecular weight poly(ethylene glycol)-derived polymer lipids (PEG-lipids) were studied by x-ray diffraction, polarized light microscopy, and rheometry. In contrast to isotropic hydrogels of polymer networks, these membrane-based birefringent liquid crystalline biogels, labeled Lα,g, form the gel phase when water is added to the liquid-like lamellar L_α phase, which reenters a liquid-like mixed phase upon further dilution. Furthermore, gels with larger water content require less PEG-lipid to remain stable. Although concentrated (~50 weight percent) mixtures of free PEG (molecular weight, 5000) and water do not gel, gelation does occur in mixtures containing as little as 0.5 weight percent PEG-lipid. A defining signature of the Lα,g regime as it sets in from the fluid lamellar L_α phase is the proliferation of layer-dislocation-type defects, which are stabilized by the segregation of PEG-lipids to the defect regions of high membrane curvature that connect the membranes.

  17. Detection of superlattice domain formation in ternary lipid mixtures using fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Mutlu, Burcin; Lopez, Stephanie; Vaughn, Mark; Huang, Juyang; Cheng, K.

    2011-10-01

    Multicomponent lipid bilayers represent an important model system for studying the structures and functions of cell membranes. At present, the lateral organization of lipid components, particularly the formation of regular distribution, in lipid membranes containing charged lipid, e.g., phosphatidylserine, is not clear. Using a ternary phosphatidylcholine/phosphatidylserine/cholesterol lipid bilayer system, the presence of ordered domain formation was examined by measuring the fluorescence anisotropy of the embedded fluorescent probe, 22-(N-(7-nitrobenz-2-oxa-1,3-diazol- 4-yl)amino)-23,24-bisnor-5-cholen-3β- ol (NBD-CHOL), with structure similar to that of a cholesterol, as a function of phospatidylserine composition. The plot of the anisotropy vs. phosphatidylserine revealed abrupt changes at certain critical compositions of phosphatidylserine. Some of these critical compositions agree favorably with those predicted by the headgroup superlattice model suggesting that the charged phosphatidylserine lipid molecules adopt a superlattice-like distribution in the lipid bilayer at some predicted compositions. The ordered distribution of charged lipids may play an important role in the regulation of the composition of the biological membranes.

  18. Dietary lipid and gross energy affect protein utilization in the rare minnow Gobiocypris rarus

    NASA Astrophysics Data System (ADS)

    Wu, Benli; Xiong, Xiaoqin; Xie, Shouqi; Wang, Jianwei

    2016-07-01

    An 8-week feeding trial was conducted to detect the optimal dietary protein and energy, as well as the effects of protein to energy ratio on growth, for the rare minnow ( Gobiocypris rarus), which are critical to nutrition standardization for model fish. Twenty-four diets were formulated to contain three gross energy (10, 12.5, 15 kJ/g), four protein (20%, 25%, 30%, 35%), and two lipid levels (3%, 6%). The results showed that optimal dietary E/P was 41.7-50 kJ/g for maximum growth in juvenile rare minnows at 6% dietary crude lipid. At 3% dietary lipid, specific growth rate (SGR) increased markedly when E/P decreased from 62.5 kJ/g to 35.7 kJ/g and gross energy was 12.5 kJ/g, and from 75 kJ/g to 42.9 kJ/g when gross energy was 15.0 kJ/g. The optimal gross energy was estimated at 12.5 kJ/g and excess energy decreased food intake and growth. Dietary lipid exhibited an apparent protein-sparing effect. Optimal protein decreased from 35% to 25%-30% with an increase in dietary lipid from 3% to 6% without adversely effecting growth. Dietary lipid level affects the optimal dietary E/P ratio. In conclusion, recommended dietary protein and energy for rare minnow are 20%-35% and 10-12.5 kJ/g, respectively.

  19. Evaluation of median barrier safety issues.

    DOT National Transportation Integrated Search

    2008-01-01

    The objective of this study was to evaluate the effectiveness of the Brifen TL-4 and Trinity CASS median cable barrier systems in preventing cross-median collisions on sections of I-64, I-71, and I-265 (Brifen system) and I-265 (Trinity system) in Je...

  20. Selection and evaluation of CO2 tolerant indigenous microalga Scenedesmus dimorphus for unsaturated fatty acid rich lipid production under different culture conditions.

    PubMed

    Vidyashankar, S; Deviprasad, K; Chauhan, V S; Ravishankar, G A; Sarada, R

    2013-09-01

    Five indigenous microalgal strains of Scenedesmus, Chlorococcum, Coelastrum, and Ankistrodesmus genera, isolated from Indian fresh water habitats, were studied for carbon-dioxide tolerance and its effect on growth, lipid and fatty acid profile. Scenedesmus dimorphus strain showed maximum growth (1.5 g/L) and lipid content (17.83% w/w) under CO2 supplementation, hence selected for detailed evaluation. The selected strain was alkaline adapted but tolerated (i) wide range of pH (5-11); (ii) elevated salinity levels (up to 100 mM, NaCl) with low biomass yields and increased carotenoids (19.34 mg/g biomass); (iii) elevated CO2 levels up to 15% v/v with enhancement in specific growth rate (0.137 d(-1)), biomass yield (1.57 g/L), lipid content (19.6% w/w) and CO2 biofixation rate (0.174 g L(-1) d(-1)). Unsaturated fatty acid content (alpha linolenic acid) increased with CO2 supplementation in the strain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Effects of ligand binding on the dynamics of rice nonspecific lipid transfer protein 1: a model from molecular simulations.

    PubMed

    Lai, Yen-Ting; Cheng, Chao-Sheng; Liu, Yu-Nan; Liu, Yaw-Jen; Lyu, Ping-Chiang

    2008-09-01

    Plant nonspecific lipid transfer proteins (nsLTPs) are small, basic proteins constituted mainly of alpha-helices and stabilized by four conserved disulfide bridges. They are characterized by the presence of a tunnel-like hydrophobic cavity, capable of transferring various lipid molecules between lipid bilayers in vitro. In this study, molecular dynamics (MD) simulations were performed at room temperature to investigate the effects of lipid binding on the dynamic properties of rice nsLTP1. Rice nsLTP1, either in the free form or complexed with one or two lipids was subjected to MD simulations. The C-terminal loop was very flexible both before and after lipid binding, as revealed by calculating the root-mean-square fluctuation. After lipid binding, the flexibility of some residues that were not in direct contact with lipid molecules increased significantly, indicating an increase of entropy in the region distal from the binding site. Essential dynamics analysis revealed clear differences in motion between unliganded and liganded rice nsLTP1s. In the free form of rice nsLTP1, loop1 exhibited the largest directional motion. This specific essential motion mode diminished after binding one or two lipid molecules. To verify the origin of the essential motion observed in the free form of rice nsLTP1, we performed multiple sequence alignments to probe the intrinsic motion encoded in the primary sequence. We found that the amino acid sequence of loop1 is highly conserved among plant nsLTP1s, thus revealing its functional importance during evolution. Furthermore, the sequence of loop1 is composed mainly of amino acids with short side chains. In this study, we show that MD simulations, together with essential dynamics analysis, can be used to determine structural and dynamic differences of rice nsLTP1 upon lipid binding. 2008 Wiley-Liss, Inc.

  2. Unexpected roles of plastoglobules (plastid lipid droplets) in vitamin K1 and E metabolism.

    PubMed

    Spicher, Livia; Kessler, Felix

    2015-06-01

    Tocopherol (vitamin E) and phylloquinone (vitamin K1) are lipid-soluble antioxidants that can only be synthesized by photosynthetic organisms. These compounds function primarily at the thylakoid membrane but are also present in chloroplast lipid droplets, also known as plastoglobules (PG). Depending on environmental conditions and stage of plant development, changes in the content, number and size of PG occur. PG are directly connected to the thylakoid membrane via the outer lipid leaflet. Apart from storage, PG are active in metabolism and likely trafficking of diverse lipid species. This review presents recent advances on how plastoglobules are implicated in the biosynthesis and metabolism of vitamin E and K. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

    PubMed

    Dzneladze, Irakli; Woolley, John F; Rossell, Carla; Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D; Salmena, Leonardo

    2018-01-01

    Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher's exact P values). In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

  4. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML

    PubMed Central

    Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D.; Salmena, Leonardo

    2018-01-01

    Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher’s exact P values). In our study, Fisher’s exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B’s prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene. PMID:29415082

  5. REGRESSION ON MEDIANS OF PROBABILITY DISTRIBUTIONS

    EPA Science Inventory

    The median is a fundamental parameter in the area of lifetime and survival statistics. n toxicodynamics the LD50, lethal dose that results in 50% mortality, is frequently used. he median is also used to describe the incidence of cancer and other disease states. Factors such as nu...

  6. Tripterygium regelii decreases the biosynthesis of triacylglycerol and cholesterol in HepG2 cells.

    PubMed

    Kang, Myung-Ji; Kwon, Eun-Bin; Yuk, Heung Joo; Ryu, Hyung Won; Kim, Soo-Yeon; Lee, Mi-Kyeong; Moon, Dong-Oh; Lee, Su Ui; Oh, Sei-Ryang; Lee, Hyun-Sun; Kim, Mun-Ock

    2017-12-01

    In the course of screening to find a plant material decreasing the activity of triacylglycerol and cholesterol, we identified Tripterygium regelii (TR). The methanol extract of TR leaves (TR-LM) was shown to reduce the intracellular lipid contents consisting of triacylglycerol (TG) and cholesterol in HepG2 cells. TR-LM also downregulated the mRNA and protein expression of the lipogenic genes such as SREBP-1 and its target enzymes. Consequently, TR-LM reduced the TG biosynthesis in HepG2 cells. In addition, TR-LM decreased SREBP2 and its target enzyme HMG-CoA reductase, which is involved in cholesterol synthesis. In this study, we evaluated that TR-LM attenuated cellular lipid contents through the suppression of de novo TG and cholesterol biosynthesis in HepG2 cells. All these taken together, TR-LM could be beneficial in regulating lipid metabolism and useful preventing the hyperlipidemia and its complications, in that liver is a crucial tissue for the secretion of serum lipids.

  7. Proteome Analysis of Cytoplasmatic and Plastidic β-Carotene Lipid Droplets in Dunaliella bardawil1[OPEN

    PubMed Central

    Davidi, Lital; Levin, Yishai; Ben-Dor, Shifra; Pick, Uri

    2015-01-01

    The halotolerant green alga Dunaliella bardawil is unique in that it accumulates under stress two types of lipid droplets: cytoplasmatic lipid droplets (CLD) and β-carotene-rich (βC) plastoglobuli. Recently, we isolated and analyzed the lipid and pigment compositions of these lipid droplets. Here, we describe their proteome analysis. A contamination filter and an enrichment filter were utilized to define core proteins. A proteome database of Dunaliella salina/D. bardawil was constructed to aid the identification of lipid droplet proteins. A total of 124 and 42 core proteins were identified in βC-plastoglobuli and CLD, respectively, with only eight common proteins. Dunaliella spp. CLD resemble cytoplasmic droplets from Chlamydomonas reinhardtii and contain major lipid droplet-associated protein and enzymes involved in lipid and sterol metabolism. The βC-plastoglobuli proteome resembles the C. reinhardtii eyespot and Arabidopsis (Arabidopsis thaliana) plastoglobule proteomes and contains carotene-globule-associated protein, plastid-lipid-associated protein-fibrillins, SOUL heme-binding proteins, phytyl ester synthases, β-carotene biosynthesis enzymes, and proteins involved in membrane remodeling/lipid droplet biogenesis: VESICLE-INDUCING PLASTID PROTEIN1, synaptotagmin, and the eyespot assembly proteins EYE3 and SOUL3. Based on these and previous results, we propose models for the biogenesis of βC-plastoglobuli and the biosynthesis of β-carotene within βC-plastoglobuli and hypothesize that βC-plastoglobuli evolved from eyespot lipid droplets. PMID:25404729

  8. Years Versus Days Between Successive Surgeries, After an Initial Outpatient Procedure, for the Median Patient Versus the Median Surgeon in the State of Iowa.

    PubMed

    Dexter, Franklin; Jarvie, Craig; Epstein, Richard H

    2018-03-01

    Previously, we studied the relative importance of different institutional interventions that the largest hospital in Iowa could take to grow the anesthesia department's outpatient surgical care. Most (>50%) patients having elective surgery had not previously had surgery at the hospital. Patient perioperative experience was unimportant for influencing total anesthesia workload and numbers of patients. More important was the availability of surgical clinic appointments within several days. These results would be generalizable if the median time from surgery to a patient's next surgical procedure was large (eg, >2 years), among all hospitals in Iowa with outpatient surgery, and without regard to the hospital where the next procedure was performed. There were 37,172 surgical cases at hospital outpatient departments of any of the 117 hospitals in Iowa from July 1, 2013, to September 30, 2013. Data extracted about each case included its intraoperative work relative value units. The 37,172 cases were matched to all inpatient and outpatient records for the next 2 years statewide using patient linkage identifiers; from these were determined whether the patient had surgery again within 2 years. Furthermore, the cases' 1820 surgeons were matched to the surgeon's next outpatient or inpatient case, both including and excluding other cases performed on the date of the original case. By patient, the median time to their next surgical case, either outpatient or inpatient, exceeded 2 years, tested with weighting by intraoperative relative value units and repeated when unweighted (both P < .0001). Specifically, with weighting, 65.9% (99% confidence interval [CI], 65.2%-66.5%) of the patients had no other surgery within 2 years, at any hospital in the state. The median time exceeded 2 years for multiple categories of patients and similar measures of time to next surgery (all P < .01). In comparison, by surgeon, the median time to the next outpatient surgical case was 1 calendar day

  9. Lipid reserve dynamics and magnification of persistent organic pollutants in spawning sockeye salmon (Oncorhynchus nerka) from the Fraser River, British Columbia.

    PubMed

    Kelly, Barry C; Gray, Samantha L; Ikonomou, Michael G; Macdonald, J Steve; Bandiera, Stelvio M; Hrycay, Eugene G

    2007-05-01

    Pacific sockeye salmon (Oncorhynchus nerka) can travel several hundred kilometers to reach native spawning grounds and fulfill semelparous reproduction. The dramatic changes in lipid reserves during upstream migration can greatly affect internal toxicokinetics of persistent organic pollutants (POPs) such as PCBs, PCDDs, and PCDFs. We measured lipid content changes and contaminant concentrations in tissues (liver, muscle, roe/gonads) and biomarker responses (ethoxyresorufin O-deethylase or EROD activity and CYP1A levels) in two Pacific sockeye salmon stocks sampled at several locations along their spawning migration in the Fraser River, British Columbia. Muscle lipid contents declined significantly with increasing upstream migration distance and corresponded to elevated lipid normalized concentrations of PCBs and PCDD/Fs in spawning sockeye. Post-migration magnification factors (MFs) in spawning sockeye ranged between 3 and 12 and were comparable to model-predicted MFs. sigmaPCBs(150-500 ng x g(-1) lipid), sigmaPCDD/Fs (1-1000 pg x g(-1) lipid) and 2,3,7,8-TCDD toxic equivalent or TEQ levels (0.1-15 pg x g(-1) lipid) in spawning sockeye were relatively low and did not affect hepatic EROD activity/CYP1A induction. Despite a 3-fold magnification, TEQ levels in eggs of spawning Fraser River sockeye did not exceed 0.3 pg x g(-1) wet wt, a threshold level associated with 30% egg mortality in salmonids. PCBs in Fraser River sockeye are comparable to previous levels in Pacific sockeye. In contrast to Pacific sockeye from more remote coastal locations, PCDDs and PCDFs in Fraser River sockeye were generally minor components (<25%) of TEQ levels, compared to dioxin like PCB contributions (>75%). The data suggest that (i) the Fraser River is not a major contamination source of PCBs or PCDD/Fs and (ii) marine contaminant distribution, food-chain dynamics, and ocean-migration pathway are likely important factors controlling levels and patterns of POPs in returning Pacific

  10. 4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

    PubMed

    Fernandes, Karla S; Sandrim, Valéria C

    2012-05-01

    The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

  11. Kinetic analysis of the interaction between poly(amidoamine) dendrimers and model lipid membranes.

    PubMed

    Tiriveedhi, Venkataswarup; Kitchens, Kelly M; Nevels, Kerrick J; Ghandehari, Hamidreza; Butko, Peter

    2011-01-01

    We used fluorescence spectroscopy and surface tensiometry to study the interaction between low-generation (G1 and G4) poly(amidoamine) (PAMAM) dendrimers, potential vehicles for intracellular drug delivery, and model lipid bilayers. Membrane association of fluorescently labeled dendrimers, measured by fluorescence anisotropy, increased with increasing size of the dendrimer and with increasing negative charge density in the membrane, indicating the electrostatic nature of the interaction. When the membrane was doped with pyrene-labeled phosphatidyl glycerol (pyrene-PG), pyrene excimer fluorescence demonstrated a dendrimer-induced selective aggregation of negatively charged lipids when the membrane was in the liquid crystalline state. A nonlinear Stern-Volmer quenching of dendrimer fluorescence with cobalt bromide suggested a dendrimer-induced aggregation of lipid vesicles, which increased with the dendrimer's generation number. Surface tensiometry measurements showed that dendrimers penetrated into the lipid monolayer only at subphysiologic surface pressures (<30mN/m). We conclude that the low-generation PAMAM dendrimers associate with lipid membranes predominantly electrostatically, without significantly compromising the bilayer integrity. They bind stronger to membranes with higher fluidity and lower surface pressure, which are characteristic of rapidly dividing cells. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. 26 CFR 1.167(g)-1 - Basis for depreciation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Basis for depreciation. 1.167(g)-1 Section 1.167(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(g)-1 Basis...

  13. 26 CFR 1.167(g)-1 - Basis for depreciation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Basis for depreciation. 1.167(g)-1 Section 1.167(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(g)-1 Basis...

  14. 26 CFR 1.167(g)-1 - Basis for depreciation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Basis for depreciation. 1.167(g)-1 Section 1.167(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(g)-1 Basis...

  15. 26 CFR 1.167(g)-1 - Basis for depreciation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Basis for depreciation. 1.167(g)-1 Section 1.167(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(g)-1 Basis...

  16. 26 CFR 1.167(g)-1 - Basis for depreciation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Basis for depreciation. 1.167(g)-1 Section 1.167(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(g)-1 Basis...

  17. Nuclease digestion and mass spectrometric characterization of oligodeoxyribonucleotides containing 1,2-GpG, 1,2-ApG, and 1,3-GpXpG cisplatin intrastrand cross-links.

    PubMed

    Williams, Renee T; Nalbandian, Jenifer N; Tu, Audrey; Wang, Yinsheng

    2013-05-01

    The primary mode of action for cis-diamminedichloroplatinum (II), referred to as cisplatin, toward the treatment of solid malignancies is through formation of cross-links with DNA at purine sites, especially guanines. We prepared oligodeoxyribonucleotides (ODNs) containing a 1,2-GpG, 1,2-ApG, or 1,3-GpXpG cisplatin intrastrand cross-link and the corresponding ODNs modified with (15)N2-labeled cisplatin, and characterized these ODNs with electrospray ionization mass spectrometry (ESI-MS) and tandem MS (MS/MS). We also employed LC-MS/MS to characterize the digestion products of these ODNs after treatment with a cocktail of 4 enzymes (nuclease P1, phosphodiesterases I and II, and alkaline phosphatase). 1,2-GpG was released from the ODNs as a dinucleoside monophosphate or a dinucleotide. Analyses of the digestion products of ODNs containing a 1,2-GpG cross-link on the 5' or 3' terminus revealed that the dinucleotide carries a terminal 5' phosphate. On the other hand, digestion of the 1,3-GpXpG intrastrand cross-link yielded 3 dinucleoside products with 0, 1, or 2 phosphate groups. The availability of the ODNs carrying the stable isotope-labeled lesions, MS/MS analyses of the cisplatin-modified ODNs, and the characterization of the enzymatic digestion products of these ODNs set the stage for the future LC-MS/MS quantification of the 1,2-GpG, 1,2-ApG, and 1,3-GpXpG lesions in cellular DNA. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Nuclease Digestion and Mass Spectrometric Characterization of Oligodeoxyribonucleotides Containing 1,2-GpG, 1,2-ApG, and 1,3-GpXpG Cisplatin Intrastrand Cross-links

    PubMed Central

    Williams, Renee T.; Nalbandian, Jenifer; Tu, Audrey; Wang, Yinsheng

    2013-01-01

    Background The primary mode of action for cis-diamminedichloroplatinum (II), referred to as cisplatin, towards the treatment of solid malignancies is through formation of cross-links with DNA at purine sites, especially guanines. Methods We prepared oligodeoxyribonucleotides (ODNs) containing a 1,2-GpG, 1,2-ApG, or 1,3-GpXpG cisplatin intrastrand cross-link and the corresponding ODNs modified with 15N2-labeled cisplatin, and characterized these ODNs with electrospray ionization mass spectrometry (ESI-MS) and tandem MS (MS/MS). We also employed LC-MS/MS to characterize the digestion products of these ODNs after treatment with a cocktail of 4 enzymes (nuclease P1, phosphodiesterases I and II, and alkaline phosphatase). Results 1,2-GpG was released from the ODNs as a dinucleoside monophosphate or a dinucleotide. Analyses of the digestion products of ODNs containing a 1,2-GpG cross-link on the 5′ or 3′ terminus revealed that the dinucleotide carries a terminal 5′ phosphate. On the other hand, digestion of the 1,3-GpXpG intrastrand cross-link yielded 3 dinucleoside products with 0, 1, or 2 phosphate groups. Results The availability of the ODNs carrying the stable isotope-labeled lesions, MS/MS analyses of the cisplatin-modified ODNs, and the characterization of the enzymatic digestion products of these ODNs set the stage for the future LC-MS/MS quantification of the 1,2-GpG, 1,2-ApG, and 1,3-GpXpG lesions in cellular DNA. PMID:23266768

  19. 26 CFR 1.56(g)-1 - Adjusted current earnings.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 1 2014-04-01 2013-04-01 true Adjusted current earnings. 1.56(g)-1 Section 1.56(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Regulations Applicable to Taxable Years Beginning in 1969 and Ending in 1970 § 1.56(g)-1 Adjusted current...

  20. 26 CFR 1.56(g)-1 - Adjusted current earnings.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 1 2012-04-01 2012-04-01 false Adjusted current earnings. 1.56(g)-1 Section 1.56(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Regulations Applicable to Taxable Years Beginning in 1969 and Ending in 1970 § 1.56(g)-1 Adjusted current...

  1. 26 CFR 1.56(g)-1 - Adjusted current earnings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 1 2011-04-01 2009-04-01 true Adjusted current earnings. 1.56(g)-1 Section 1.56(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Regulations Applicable to Taxable Years Beginning in 1969 and Ending in 1970 § 1.56(g)-1 Adjusted current...

  2. 26 CFR 1.56(g)-1 - Adjusted current earnings.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 1 2013-04-01 2013-04-01 false Adjusted current earnings. 1.56(g)-1 Section 1.56(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Regulations Applicable to Taxable Years Beginning in 1969 and Ending in 1970 § 1.56(g)-1 Adjusted current...

  3. Lipid biosensor interactions with wild type and matrix deletion HIV-1 Gag proteins.

    PubMed

    Barklis, Eric; Staubus, August O; Mack, Andrew; Harper, Logan; Barklis, Robin Lid; Alfadhli, Ayna

    2018-05-01

    The matrix (MA) domain of the HIV-1 precursor Gag protein (PrGag) has been shown interact with the HIV-1 envelope (Env) protein, and to direct PrGag proteins to plasma membrane (PM) assembly sites by virtue of its affinity to phosphatidylinositol-4,5-bisphosphate (PI[4,5]P2). Unexpectedly, HIV-1 viruses with large MA deletions (ΔMA) have been shown to be conditionally infectious as long as they are matched with Env truncation mutant proteins or alternative viral glycoproteins. To characterize the interactions of wild type (WT) and ΔMA Gag proteins with PI(4,5)P2 and other acidic phospholipids, we have employed a set of lipid biosensors as probes. Our investigations showed marked differences in WT and ΔMA Gag colocalization with biosensors, effects on biosensor release, and association of biosensors with virus-like particles. These results demonstrate an alternative approach to the analysis of viral protein-lipid associations, and provide new data as to the lipid compositions of HIV-1 assembly sites. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome.

    PubMed

    Lin, Sun; Huiya, Zhang; Bo, Liu; Wei, Wei; Yongmei, Guan

    2009-12-01

    Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the combination genotype of 4G/4G and -844 A/A were 2.49 (95% confidence interval (CI), 1.4-4.44), 2.1 (95% CI, 1.43-3.08), and 2.9 (95% CI, 1.41-5.98), respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.

  5. 26 CFR 1.514(g)-1 - Business lease indebtedness.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Business lease indebtedness. 1.514(g)-1 Section 1.514(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(g)-1...

  6. 26 CFR 1.514(g)-1 - Business lease indebtedness.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Business lease indebtedness. 1.514(g)-1 Section 1.514(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(g)-1...

  7. 26 CFR 1.514(g)-1 - Business lease indebtedness.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Business lease indebtedness. 1.514(g)-1 Section 1.514(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(g)-1...

  8. Compartmentalization of endocannabinoids into lipid rafts in a microglial cell line devoid of caveorrlin-1

    PubMed Central

    Rimmerman, Neta; Bradshaw, Heather B; Kozela, Ewa; Levy, Rivka; Juknat, Ana; Vogel, Zvi

    2012-01-01

    BACKGROUND AND PURPOSE N-acyl ethanolamines (NAEs) and 2-arachidonoyl glycerol (2-AG) are endogenous cannabinoids and along with related lipids are synthesized on demand from membrane phospholipids. Here, we have studied the compartmentalization of NAEs and 2-AG into lipid raft fractions isolated from the caveolin-1-lacking microglial cell line BV-2, following vehicle or cannabidiol (CBD) treatment. Results were compared with those from the caveolin-1-positive F-11 cell line. EXPERIMENTAL APPROACH BV-2 cells were incubated with CBD or vehicle. Cells were fractionated using a detergent-free continuous OptiPrep density gradient. Lipids in fractions were quantified using HPLC/MS/MS. Proteins were measured using Western blot. KEY RESULTS BV-2 cells were devoid of caveolin-1. Lipid rafts were isolated from BV-2 cells as confirmed by co-localization with flotillin-1 and sphingomyelin. Small amounts of cannabinoid CB1 receptors were found in lipid raft fractions. After incubation with CBD, levels and distribution in lipid rafts of 2-AG, N-arachidonoyl ethanolamine (AEA), and N-oleoyl ethanolamine (OEA) were not changed. Conversely, the levels of the saturated N-stearoyl ethanolamine (SEA) and N-palmitoyl ethanolamine (PEA) were elevated in lipid raft fractions. In whole cells with growth medium, CBD treatment increased AEA and OEA time-dependently, while levels of 2-AG, PEA and SEA did not change. CONCLUSIONS AND IMPLICATIONS Whereas levels of 2-AG were not affected by CBD treatment, the distribution and levels of NAEs showed significant changes. Among the NAEs, the degree of acyl chain saturation predicted the compartmentalization after CBD treatment suggesting a shift in cell signalling activity. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10

  9. Cytokinetically quiescent (G0/G1) human multiple myeloma cells are susceptible to simultaneous inhibition of Chk1 and MEK1/2

    PubMed Central

    Pei, Xin-Yan; Dai, Yun; Youssefian, Leena E.; Chen, Shuang; Bodie, Wesley W.; Takabatake, Yukie; Felthousen, Jessica; Almenara, Jorge A.; Kramer, Lora B.; Dent, Paul

    2011-01-01

    Effects of Chk1 and MEK1/2 inhibition were investigated in cytokinetically quiescent multiple myeloma (MM) and primary CD138+ cells. Coexposure to the Chk1 and MEK1/2 inhibitors AZD7762 and selumetinib (AZD6244) robustly induced apoptosis in various MM cells and CD138+ primary samples, but spared normal CD138− and CD34+ cells. Furthermore, Chk1/MEK1/2 inhibitor treatment of asynchronized cells induced G0/G1 arrest and increased apoptosis in all cell-cycle phases, including G0/G1. To determine whether this regimen is active against quiescent G0/G1 MM cells, cells were cultured in low-serum medium to enrich the G0/G1 population. G0/G1–enriched cells exhibited diminished sensitivity to conventional agents (eg, Taxol and VP-16) but significantly increased susceptibility to Chk1 ± MEK1/2 inhibitors or Chk1 shRNA knock-down. These events were associated with increased γH2A.X expression/foci formation and Bim up-regulation, whereas Bim shRNA knock-down markedly attenuated lethality. Immunofluorescent analysis of G0/G1–enriched or primary MM cells demonstrated colocalization of activated caspase-3 and the quiescent (G0) marker statin, a nuclear envelope protein. Finally, Chk1/MEK1/2 inhibition increased cell death in the Hoechst-positive (Hst+), low pyronin Y (PY)–staining (2N Hst+/PY−) G0 population and in sorted small side-population (SSP) MM cells. These findings provide evidence that cytokinetically quiescent MM cells are highly susceptible to simultaneous Chk1 and MEK1/2 inhibition. PMID:21911831

  10. Cytokinetically quiescent (G0/G1) human multiple myeloma cells are susceptible to simultaneous inhibition of Chk1 and MEK1/2.

    PubMed

    Pei, Xin-Yan; Dai, Yun; Youssefian, Leena E; Chen, Shuang; Bodie, Wesley W; Takabatake, Yukie; Felthousen, Jessica; Almenara, Jorge A; Kramer, Lora B; Dent, Paul; Grant, Steven

    2011-11-10

    Effects of Chk1 and MEK1/2 inhibition were investigated in cytokinetically quiescent multiple myeloma (MM) and primary CD138(+) cells. Coexposure to the Chk1 and MEK1/2 inhibitors AZD7762 and selumetinib (AZD6244) robustly induced apoptosis in various MM cells and CD138(+) primary samples, but spared normal CD138(-) and CD34(+) cells. Furthermore, Chk1/MEK1/2 inhibitor treatment of asynchronized cells induced G(0)/G(1) arrest and increased apoptosis in all cell-cycle phases, including G(0)/G(1). To determine whether this regimen is active against quiescent G(0)/G(1) MM cells, cells were cultured in low-serum medium to enrich the G(0)/G(1) population. G(0)/G(1)-enriched cells exhibited diminished sensitivity to conventional agents (eg, Taxol and VP-16) but significantly increased susceptibility to Chk1 ± MEK1/2 inhibitors or Chk1 shRNA knock-down. These events were associated with increased γH2A.X expression/foci formation and Bim up-regulation, whereas Bim shRNA knock-down markedly attenuated lethality. Immunofluorescent analysis of G(0)/G(1)-enriched or primary MM cells demonstrated colocalization of activated caspase-3 and the quiescent (G(0)) marker statin, a nuclear envelope protein. Finally, Chk1/MEK1/2 inhibition increased cell death in the Hoechst-positive (Hst(+)), low pyronin Y (PY)-staining (2N Hst(+)/PY(-)) G(0) population and in sorted small side-population (SSP) MM cells. These findings provide evidence that cytokinetically quiescent MM cells are highly susceptible to simultaneous Chk1 and MEK1/2 inhibition.

  11. Novel gemini cationic lipids with carbamate groups for gene delivery

    PubMed Central

    Zhao, Yi-Nan; Qureshi, Farooq; Zhang, Shu-Biao; Cui, Shao-Hui; Wang, Bing; Chen, Hui-Ying; Lv, Hong-Tao; Zhang, Shu-Fen; Huang, Leaf

    2014-01-01

    To obtain efficient non-viral vectors, a series of Gemini cationic lipids with carbamate linkers between headgroups and hydrophobic tails were synthesized. They have the hydrocarbon chains of 12, 14, 16 and 18 carbon atoms as tails, designated as G12, G14, G16 and G18, respectively. These Gemini cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. The DNA-bonding ability of these Gemini cationic liposomes was much better than their mono-head counterparts (designated as M12, M14, M16 and M18, respectively). In the same series of liposomes, bonding ability declined with an increase in tail length. They were tested for their gene-transferring capabilities in Hep-2 and A549 cells. They showed higher transfection efficiency than their mono-head counterparts and were comparable or superior in transfection efficiency and cytotoxicity to the commercial liposomes, DOTAP and Lipofectamine 2000. Our results convincingly demonstrate that the gene-transferring capabilities of these cationic lipids depended on hydrocarbon chain length. Gene transfection efficiency was maximal at a chain length of 14, as G14 can silence about 80 % of luciferase in A549 cells. Cell uptake results indicate that Gemini lipid delivery systems could be internalised by cells very efficiently. Thus, the Gemini cationic lipids could be used as synthetic non-viral gene delivery carriers for further study. PMID:25045521

  12. Lipids of Pseudomonas aeruginosa Cells Grown on Hydrocarbons and on Trypticase Soy Broth1

    PubMed Central

    Edmonds, Paul; Cooney, J. J.

    1969-01-01

    Lipids were extracted from cells of Pseudomonas aeruginosa grown on a pure hydrocarbon (tridecane), mixed hydrocarbons (JP-4 jet fuel), and on Trypticase Soy Broth. Total lipids produced from each substrate represented from 7.1 to 8.2% of cellular dry weight, of which 5.0 to 6.4% were obtained before cellular hydrolysis (free lipids) and 1.7 to 2.0% were extracted after cellular hydrolysis (bound lipids). Free lipids from cells grown on each medium were separated into four fractions by thin-layer chromatography. All fractions were present in cells from each type of medium, and the “neutral fraction” constituted the largest fraction. The fatty acid composition of free lipids was determined by gas-liquid chromatography. Cells grown on each medium contained saturated and unsaturated C14 to C20 fatty acids. Trace amounts of C13 fatty acids were found in tridecane-grown cells. Saturated C16 and C18 were the major acids present in all cells. Quantitative differences were found in fatty acids produced on the three media, but specific correlations between substrate carbon sources and fatty acid content of cells were not evident. Tridecane-grown cells contained only traces of C13 acid and small amounts of C15 and C17 acids, suggesting that the organism's fatty acids were derived from de novo synthesis rather than by direct incorporation of the hydrocarbon. PMID:4976464

  13. Sex differences in lipid profiles and treatment utilization among young adults with acute myocardial infarction: Results from the VIRGO study.

    PubMed

    Lu, Yuan; Zhou, Shengfan; Dreyer, Rachel P; Caulfield, Michael; Spatz, Erica S; Geda, Mary; Lorenze, Nancy P; Herbert, Peter; D'Onofrio, Gail; Jackson, Elizabeth A; Lichtman, Judith H; Bueno, Héctor; Spertus, John A; Krumholz, Harlan M

    2017-01-01

    Young women with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. An adverse lipid profile is an important risk factor for cardiovascular outcomes after AMI, but little is known about whether young women with AMI have a higher-risk lipid pattern than men. We characterized sex differences in lipid profiles and treatment utilization among young adults with AMI. A total of 2,219 adults with AMI (1,494 women) aged 18-55 years were enrolled from 103 hospitals in the United States (2008-2012). Serum lipids and lipoprotein subclasses were measured 1 month after discharge. More than 90% of adults were discharged on a statin, but less than half received a high-intensity dose and 12% stopped taking treatments by 1 month. For both men and women, the median of low-density lipoprotein (LDL) cholesterol was reduced to <100 mg/dL 1 month after discharge for AMI, but high-density lipoprotein (HDL) cholesterol remained <40 mg/dL. Multivariate regression analyses showed that young women had favorable lipoprotein profiles compared with men: women had higher HDL cholesterol and HDL large particle, but lower total cholesterol-to-HDL cholesterol ratio and LDL small particle. Young women with AMI had slightly favorable lipid and lipoprotein profiles compared with men, suggesting that difference in lipid and lipoprotein may not be a major contributor to sex differences in outcomes after AMI. In both men and women, statin remained inadequately used, and low HDL cholesterol level was a major lipid abnormality. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Effect of dietary lipid levels on body compositions, digestive ability and antioxidant parameters of common carp

    NASA Astrophysics Data System (ADS)

    Sun, Jinhui; Fan, Ze; Chen, Chunxiu; Li, Jinghui; Cheng, Zhenyan; Li, Yang; Qiao, Xiuting

    2017-11-01

    This study was designed to evaluate the effect of dietary lipid level on body composition, and digestive ability of common carp with initial average weight (36.12 ± 1.18)g. Five experimental diets with increasing lipid levels of 2.1%, 4.0%, 5.8%, 7.6%, 9.4% were fed to triplicate groups of fish for 9 weeks. The results showed that lipid content of whole body and muscle increased in parallel with the increase of dietary lipid levels. Protein content of muscle decreased with the increase of dietary lipid levels, and the lowest muscle protein content was observed in fish fed 9.4% lipid diet. Lipaseactivity was significantly affected by dietary lipid levels in hepatopancreas andintestine (P <0.05). Lipase activity in fish fed at 5.8% lipid level group was significantly higher than others inhepatopancreas (P <0.05). There were no significant differences in amylase and proteaseactivities (P > 0.05). The results suggested that the most excellentdigestive ability and antioxidant parameters were obtained at 7.6% lipid level group.

  15. Plasminogen Activator Inhibitor-1 (PAI-1) gene 4G/5G alleles frequency distribution in the Lebanese population.

    PubMed

    Shammaa, Dina M R; Sabbagh, Amira S; Taher, Ali T; Zaatari, Ghazi S; Mahfouz, Rami A R

    2008-09-01

    Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

  16. Salivary IgG subclasses in individuals with and without homozygous IGHG gene deletions.

    PubMed Central

    Engström, P E; Norhagen, G; Osipova, L; Helal, A; Wiebe, V; Brusco, A; Carbonara, A O; Lefranc, G; Lefranc, M P

    1996-01-01

    In this study, the levels of salivary IgG1, IgG2, IgG3 and IgG4 from individuals with and without homozygous immunoglobulin heavy chain constant gene deletions were quantified by enzyme-linked immunosorbent assay (ELISA). To analyse the restriction of salivary IgG subclasses, we used unstimulated whole saliva and sera collected at the same time from individuals with homozygous gene deletions, two with G1 deletion, one with G4 deletion, six with both G2 and G4 deletions and from eight individuals without IGHG gene deletions and expressing all four IgG subclasses. The median values of salivary IgG from individuals with homozygous G1, or G4, or both G2 and G4 deletions, and from individuals expressing all four subclasses were 24.2 mg/l and 23.4 mg/l, respectively. The median values of serum IgG were 13.7 g/l and 15.9 g/l, respectively. Our results show that the salivary and serum IgG levels were both within the normal range in individuals with homozygous gene deletions of either G1, or G4, or both G2 and G4. PMID:8943711

  17. Plasminogen activator inhibitor 1 4G/5G and -844G/A variants in idiopathic recurrent pregnancy loss.

    PubMed

    Magdoud, Kalthoum; Herbepin, Viviana G; Touraine, Renaud; Almawi, Wassim Y; Mahjoub, Touhami

    2013-09-01

    Plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis, and the common promoter region variants -675G/A (4G/5G) and -844G/A are associated with increased thrombotic risk. Despite evidence linking altered fibrinolysis with adverse pregnancy events, including idiopathic recurrent pregnancy loss (RPL), the contribution of PAI-1 variants to RPL risk remains controversial. We investigated the association between the PAI-1 -844G/A and 4G/5G (-675G/A) variants with altered risk of RPL. This was a case-control study involving 304 women with confirmed RPL and 371 age- and ethnically matched control women. PAI-1 genotyping was performed by PCR single-specific primer -675 (G/A) and real-time PCR (-844G/A) analysis. Minor allele frequency (MAF) of 4G/5G (P < 0.001), but not -844G/A (P = 0.507), was higher in RPL cases. PAI-1 4G/5G single-nucleotide polymorphism (SNP) was significantly associated with RPL under additive, dominant, and recessive genetic models; no association of -844G/A with RPL was seen irrespective of the genetic model tested. Taking common -844G/5G haplotype as reference (OR = 1.00), multivariate analysis confirmed the association of 4G-containing -844A/4G (P < 0.001) and -844G/4G (P = 0.011) haplotypes with increased RPL risk. 4G/5G, but not -844G/A, PAI-1 variant is associated with an increased risk of RPL. © 2013 John Wiley & Sons Ltd.

  18. Lipid emulsions – Guidelines on Parenteral Nutrition, Chapter 6

    PubMed Central

    Adolph, M.; Heller, A. R.; Koch, T.; Koletzko, B.; Kreymann, K. G.; Krohn, K.; Pscheidl, E.; Senkal, M.

    2009-01-01

    The infusion of lipid emulsions allows a high energy supply, facilitates the prevention of high glucose infusion rates and is indispensable for the supply with essential fatty acids. The administration of lipid emulsions is recommended within ≤7 days after starting PN (parenteral nutrition) to avoid deficiency of essential fatty acids. Low-fat PN with a high glucose intake increases the risk of hyperglycaemia. In parenterally fed patients with a tendency to hyperglycaemia, an increase in the lipid-glucose ratio should be considered. In critically ill patients the glucose infusion should not exceed 50% of energy intake. The use of lipid emulsions with a low phospholipid/triglyceride ratio is recommended and should be provided with the usual PN to prevent depletion of essential fatty acids, lower the risk of hyperglycaemia, and prevent hepatic steatosis. Biologically active vitamin E (α-tocopherol) should continuously be administered along with lipid emulsions to reduce lipid peroxidation. Parenteral lipids should provide about 25–40% of the parenteral non-protein energy supply. In certain situations (i.e. critically ill, respiratory insufficiency) a lipid intake of up to 50 or 60% of non-protein energy may be reasonable. The recommended daily dose for parenteral lipids in adults is 0.7–1.3 g triglycerides/kg body weight. Serum triglyceride concentrations should be monitored regularly with dosage reduction at levels >400 mg/dl (>4.6 mmol/l) and interruption of lipid infusion at levels >1000 mg/dl (>11.4 mmol/l). There is little evidence at this time that the choice of different available lipid emulsions affects clinical endpoints. PMID:20049078

  19. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis.

    PubMed

    Eickmeier, Olaf; Fussbroich, Daniela; Mueller, Klaus; Serve, Friederike; Smaczny, Christina; Zielen, Stefan; Schubert, Ralf

    2017-01-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients

  20. Melatonin enhances lipid production in Monoraphidium sp. QLY-1 under nitrogen deficiency conditions via a multi-level mechanism.

    PubMed

    Zhao, Yongteng; Li, Dafei; Xu, Jun-Wei; Zhao, Peng; Li, Tao; Ma, Huixian; Yu, Xuya

    2018-07-01

    In this study, melatonin (MT) promoted lipid accumulation in Monoraphidium sp. QLY-1 under nitrogen deficiency conditions. The lipid accumulation increased 1.22- and 1.36-fold compared with a nitrogen-starved medium and a normal BG-11 medium, respectively. The maximum lipid content was 51.38%. The reactive oxygen species (ROS) level in the presence of melatonin was lower than that in the control group, likely because of the high antioxidant activities. The application of melatonin upregulated the gibberellin acid (GA) production and rbcL and accD expression levels but downregulated the abscisic acid (ABA) content and pepc expression levels. These findings demonstrated that exogenous melatonin could further improve the lipid production in Monoraphidium sp. QLY-1 by regulating antioxidant systems, signalling molecules, and lipid biosynthesis-related gene expression under nitrogen deficiency conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy.

    PubMed

    Jaffrès, Paul-Alain; Gajate, Consuelo; Bouchet, Ana Maria; Couthon-Gourvès, Hélène; Chantôme, Aurélie; Potier-Cartereau, Marie; Besson, Pierre; Bougnoux, Philippe; Mollinedo, Faustino; Vandier, Christophe

    2016-09-01

    Synthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and/or inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages.

    PubMed

    Tüzün, Sefa; Yücel, Ahmet Fikret; Pergel, Ahmet; Kemik, Ahu Sarbay; Kemik, Ozgür

    2012-09-01

    High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects. HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001). Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05). These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer.

  3. Simultaneous enzymatic hydrolysis and anaerobic biodegradation of lipid-rich wastewater from poultry industry

    NASA Astrophysics Data System (ADS)

    Dors, Gisanara; Mendes, Adriano A.; Pereira, Ernandes B.; de Castro, Heizir F.; Furigo, Agenor

    2013-03-01

    Simultaneous enzymatic hydrolysis and anaerobic biodegradation of lipid-rich wastewater from poultry industry with porcine pancreatic lipase at different concentrations (from 1.0 to 3.0 g L-1) were performed. The efficiency of the enzymatic pretreatment was measured by the Chemical Oxygen Demand (COD) removal and formation of methane. All samples pretreated with lipase showed a positive effect on the COD removal and formation of methane. After 30 days of anaerobic biodegradation the methane production varied from 569 ± 95 to 1,101 ± 10 mL for crude wastewater and pretreated at 3.0 g L-1 enzyme, respectively. COD removal of wastewater supplemented at different enzyme concentrations was found to be threefold higher than crude wastewater. The use of lipases seems to be a promising alternative for treating lipid-rich wastewaters such as those from the poultry industry.

  4. August Median Streamflow on Ungaged Streams in Eastern Aroostook County, Maine

    USGS Publications Warehouse

    Lombard, Pamela J.; Tasker, Gary D.; Nielsen, Martha G.

    2003-01-01

    Methods for estimating August median streamflow were developed for ungaged, unregulated streams in the eastern part of Aroostook County, Maine, with drainage areas from 0.38 to 43 square miles and mean basin elevations from 437 to 1,024 feet. Few long-term, continuous-record streamflow-gaging stations with small drainage areas were available from which to develop the equations; therefore, 24 partial-record gaging stations were established in this investigation. A mathematical technique for estimating a standard low-flow statistic, August median streamflow, at partial-record stations was applied by relating base-flow measurements at these stations to concurrent daily flows at nearby long-term, continuous-record streamflow- gaging stations (index stations). Generalized least-squares regression analysis (GLS) was used to relate estimates of August median streamflow at gaging stations to basin characteristics at these same stations to develop equations that can be applied to estimate August median streamflow on ungaged streams. GLS accounts for varying periods of record at the gaging stations and the cross correlation of concurrent streamflows among gaging stations. Twenty-three partial-record stations and one continuous-record station were used for the final regression equations. The basin characteristics of drainage area and mean basin elevation are used in the calculated regression equation for ungaged streams to estimate August median flow. The equation has an average standard error of prediction from -38 to 62 percent. A one-variable equation uses only drainage area to estimate August median streamflow when less accuracy is acceptable. This equation has an average standard error of prediction from -40 to 67 percent. Model error is larger than sampling error for both equations, indicating that additional basin characteristics could be important to improved estimates of low-flow statistics. Weighted estimates of August median streamflow, which can be used when

  5. Enhanced lipid production by Rhodosporidium toruloides using different fed-batch feeding strategies with lignocellulosic hydrolysate as the sole carbon source

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

    Fei, Qiang; O'Brien, Marykate; Nelson, Robert

    Industrial biotechnology that is able to provide environmentally friendly bio-based products has attracted more attention in replacing petroleum-based industries. Currently, most of the carbon sources used for fermentation-based bioprocesses are obtained from agricultural commodities that are used as foodstuff for human beings. Lignocellulose-derived sugars as the non-food, green, and sustainable alternative carbon sources have great potential to avoid this dilemma for producing the renewable, bio-based hydrocarbon fuel precursors, such as microbial lipid. Efficient bioconversion of lignocellulose-based sugars into lipids is one of the critical parameters for industrial application. Therefore, the fed-batch cultivation, which is a common method used in industrialmore » applications, was investigated to achieve a high cell density culture along with high lipid yield and productivity. In this study, several fed-batch strategies were explored to improve lipid production using lignocellulosic hydrolysates derived from corn stover. Compared to the batch culture giving a lipid yield of 0.19 g/g, the dissolved-oxygen-stat feeding mode increased the lipid yield to 0.23 g/g and the lipid productivity to 0.33 g/L/h. The pulse feeding mode further improved lipid productivity to 0.35 g/L/h and the yield to 0.24 g/g. However, the highest lipid yield (0.29 g/g) and productivity (0.4 g/L/h) were achieved using an automated online sugar control feeding mode, which gave a dry cell weight of 54 g/L and lipid content of 59 % (w/w). The major fatty acids of the lipid derived from lignocellulosic hydrolysates were predominately palmitic acid and oleic acid, which are similar to those of conventional oilseed plants. Our results suggest that the fed-batch feeding strategy can strongly influence the lipid production. Lastly, the online sugar control feeding mode was the most appealing strategy for high cell density, lipid yield, and lipid productivity using lignocellulosic hydrolysates

  6. Enhanced lipid production by Rhodosporidium toruloides using different fed-batch feeding strategies with lignocellulosic hydrolysate as the sole carbon source

    DOE PAGES

    Fei, Qiang; O'Brien, Marykate; Nelson, Robert; ...

    2016-06-23

    Industrial biotechnology that is able to provide environmentally friendly bio-based products has attracted more attention in replacing petroleum-based industries. Currently, most of the carbon sources used for fermentation-based bioprocesses are obtained from agricultural commodities that are used as foodstuff for human beings. Lignocellulose-derived sugars as the non-food, green, and sustainable alternative carbon sources have great potential to avoid this dilemma for producing the renewable, bio-based hydrocarbon fuel precursors, such as microbial lipid. Efficient bioconversion of lignocellulose-based sugars into lipids is one of the critical parameters for industrial application. Therefore, the fed-batch cultivation, which is a common method used in industrialmore » applications, was investigated to achieve a high cell density culture along with high lipid yield and productivity. In this study, several fed-batch strategies were explored to improve lipid production using lignocellulosic hydrolysates derived from corn stover. Compared to the batch culture giving a lipid yield of 0.19 g/g, the dissolved-oxygen-stat feeding mode increased the lipid yield to 0.23 g/g and the lipid productivity to 0.33 g/L/h. The pulse feeding mode further improved lipid productivity to 0.35 g/L/h and the yield to 0.24 g/g. However, the highest lipid yield (0.29 g/g) and productivity (0.4 g/L/h) were achieved using an automated online sugar control feeding mode, which gave a dry cell weight of 54 g/L and lipid content of 59 % (w/w). The major fatty acids of the lipid derived from lignocellulosic hydrolysates were predominately palmitic acid and oleic acid, which are similar to those of conventional oilseed plants. Our results suggest that the fed-batch feeding strategy can strongly influence the lipid production. Lastly, the online sugar control feeding mode was the most appealing strategy for high cell density, lipid yield, and lipid productivity using lignocellulosic hydrolysates

  7. Highly sensitive C-reactive protein, body mass index, and serum lipids in HIV-infected persons receiving antiretroviral therapy: a longitudinal study.

    PubMed

    Boger, Michael S; Shintani, Ayumi; Redhage, Leigh Anne; Mitchell, Valerie; Haas, David W; Morrow, Jason D; Hulgan, Todd

    2009-12-01

    Antiretroviral therapy (ART) affects cardiovascular disease (CVD) risk. In the general population, highly sensitive creactive protein (hsCRP) is an established predictor of future coronary events. Little is known about its utility in chronic inflammatory conditions such as HIV infection. We assessed relationships between hsCRP and metabolic parameters over time in HIV-infected patients on ART. Data are from a prospective cohort of HIV-infected adults enrolled June 2005 to July 2007. Participants were receiving ART, had HIV-1 RNA,10,000 copies per milliliter, and no diabetes or CVD. Nonlinear mixed-effect regression models assessed relationships between body mass index (BMI), lipids, and hsCRP over time adjusting for covariates. Ninety-four individuals had data from $1 study visit. Median age was 44 years, 27% were female, 57% white, and 54% were on protease inhibitors. Median CD4+ T cells, HIV-1 RNA, and hsCRP were 502 cells per cubic millimeter, 50 copies per milliliter, and 2.94 mg/dL, respectively. Median Framingham score was 3. Multivariate analysis identified associations between increased hsCRP and greater BMI (P = 0.001), higher non-high-density lipoprotein cholesterol (P = 0.013) and triglycerides (P = 0.017), and lower high-density lipoprotein cholesterol (P = 0.015). Among HIV-infected adults with low estimated CVD risk and virologic suppression on ART, hsCRP was elevated and independently associated with BMI and lipid changes. Future studies should assess associations between hsCRP and clinical outcomes.

  8. Galaxy and Mass Assembly (GAMA): the GAMA galaxy group catalogue (G3Cv1)

    NASA Astrophysics Data System (ADS)

    Robotham, A. S. G.; Norberg, P.; Driver, S. P.; Baldry, I. K.; Bamford, S. P.; Hopkins, A. M.; Liske, J.; Loveday, J.; Merson, A.; Peacock, J. A.; Brough, S.; Cameron, E.; Conselice, C. J.; Croom, S. M.; Frenk, C. S.; Gunawardhana, M.; Hill, D. T.; Jones, D. H.; Kelvin, L. S.; Kuijken, K.; Nichol, R. C.; Parkinson, H. R.; Pimbblet, K. A.; Phillipps, S.; Popescu, C. C.; Prescott, M.; Sharp, R. G.; Sutherland, W. J.; Taylor, E. N.; Thomas, D.; Tuffs, R. J.; van Kampen, E.; Wijesinghe, D.

    2011-10-01

    Using the complete Galaxy and Mass Assembly I (GAMA-I) survey covering ˜142 deg2 to rAB= 19.4, of which ˜47 deg2 is to rAB= 19.8, we create the GAMA-I galaxy group catalogue (G3Cv1), generated using a friends-of-friends (FoF) based grouping algorithm. Our algorithm has been tested extensively on one family of mock GAMA lightcones, constructed from Λ cold dark matter N-body simulations populated with semi-analytic galaxies. Recovered group properties are robust to the effects of interlopers and are median unbiased in the most important respects. G3Cv1 contains 14 388 galaxy groups (with multiplicity ≥2), including 44 186 galaxies out of a possible 110 192 galaxies, implying ˜40 per cent of all galaxies are assigned to a group. The similarities of the mock group catalogues and G3Cv1 are multiple: global characteristics are in general well recovered. However, we do find a noticeable deficit in the number of high multiplicity groups in GAMA compared to the mocks. Additionally, despite exceptionally good local spatial completeness, G3Cv1 contains significantly fewer compact groups with five or more members, this effect becoming most evident for high multiplicity systems. These two differences are most likely due to limitations in the physics included of the current GAMA lightcone mock. Further studies using a variety of galaxy formation models are required to confirm their exact origin. The G3Cv1 catalogue will be made publicly available as and when the relevant GAMA redshifts are made available at .

  9. Localization and reactivity of a hydrophobic solute in lecithin and caseinate stabilized solid lipid nanoparticles and nanoemulsions.

    PubMed

    Yucel, Umut; Elias, Ryan J; Coupland, John N

    2013-03-15

    The distribution and reactivity of the lipophilic spin probe 4-phenyl-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl nitroxide (PTMIO) in tetradecane (C14)- and eicosane (C20)-in-water emulsions and solid lipid nanoparticles (SLN) respectively, were investigated by electron paramagnetic resonance (EPR) spectroscopy. The lipid phase (10 wt% C14 or C20) was emulsified into either caseinate solutions (1 wt%) or lecithin+bile salt dispersions (2.4 wt%+0.6 wt%) at 70-75 °C. In C14 emulsions stabilized with lecithin+bile salt, three populations of PTMIO were observed: a population in the lipid phase (~60%, a(N)~13.9 G), an aqueous phase population (~20%, a(N)~15.4 G) with high mobility, and an immobilized surface layer population (~20%, a(N)~14.2 G) with low mobility. However, in C14 emulsions stabilized by caseinate, only two distinct populations of PTMIO were seen: a lipid phase population (~70%, a(N)~13.8 G) and an aqueous phase population (~30%, a(N)~15.5 G) with high mobility. In C20 SLN stabilized with either lecithin+bile salt or caseinate, PTMIO was excluded from the lipid phase. In lecithin+bile salt-stabilized C20 SLN, the majority of the probe (~77%) was in the interfacial layer. For both surfactant systems the rate of PTMIO reduction by aqueous iron/ascorbate was greater for C20 SLN than C14 emulsions. Lecithin affects the properties of emulsions and SLN as delivery systems by providing a distinct environment for small molecules. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-08-01

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

  11. Effect of liquid-to-solid lipid ratio on characterizations of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for transdermal administration.

    PubMed

    Song, Aihua; Zhang, Xiaoshu; Li, Yanting; Mao, Xinjuan; Han, Fei

    2016-08-01

    The aim of this study is to evaluate the effect of liquid-to-solid lipid ratio on properties of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and to clarify the superiority of NLCs over SLNs for transdermal administration. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, differential scanning calorimetry, X-ray diffractometry, in vitro percutaneous permeation profile, and stability of SLNs and NLCs were compared. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, and in vitro percutaneous permeation amount of the developed NLCs were all <200 nm, < -20 mV, >78%, >35, and >240 μg/cm(2), respectively, however, for SLNs were 280 nm, -29.11 mV, 63.2%, 32.54, and 225.9 μg/cm(2), respectively. After 3 months storage at 4 °C and 25 °C, almost no significant differences between the evaluated parameters of NLCs were observed. However, for SLNs, particle size was increased to higher than 300 nm (4 °C and 25 °C), drug encapsulation efficiency was decreased to 51.2 (25 °C), in vitro occlusion factor was also decreased to lower than 25 (4 °C and 25 °C), and the cumulative amount was decreased to 148.9 μg/cm(2) (25 °C) and 184.4 μg/cm(2) (4 °C), respectively. And DSC and XRD studies indicated that not only the crystalline peaks of the encapsulated flurbiprofen disappeared but also obvious difference between samples and bulk Compritol® ATO 888 was seen. It could be concluded that liquid-to-solid lipid ratio has significant impact on the properties of SLNs and NLCs, and NLCs showed better stability than SLNs. Therefore, NLCs might be a better option than SLNs for transdermal administration.

  12. Salivary lipids: A review.

    PubMed

    Matczuk, Jan; Żendzian-Piotrowska, Małgorzata; Maciejczyk, Mateusz; Kurek, Krzysztof

    2017-09-01

    Saliva is produced by both large and small salivary glands and may be considered one of the most important factors influencing the behavior of oral cavity homeostasis. Secretion of saliva plays an important role in numerous significant biological processes. Saliva facilitates chewing and bolus formation as well as performs protective functions and determines the buffering and antibacterial prosperities of the oral environment. Salivary lipids appear to be a very important component of saliva, as their qualitative and quantitative composition can be changed in various pathological states and human diseases. It has been shown that disturbances in salivary lipid homeostasis are involved in periodontal diseases as well as various systemic disorders (e.g. cystic fibrosis, diabetes and Sjögren's syndrome). However, little is known about the role and composition of salivary lipids and their interaction with other important ingredients of human saliva, including proteins, glycoproteins and salivary mucins. The purpose of this review paper is to present the latest knowledge on salivary lipids in healthy conditions and in oral and systemic diseases.

  13. Landscaping of highway medians and roadway safety at unsignalized intersections.

    PubMed

    Chen, Hongyun; Fabregas, Aldo; Lin, Pei-Sung

    2016-05-01

    Well-planted and maintained landscaping can help reduce driving stress, provide better visual quality, and decrease over speeding, thus improving roadway safety. Florida Department of Transportation (FDOT) Standard Index (SI-546) is one of the more demanding standards in the U.S. for landscaping design criteria at highway medians near intersections. The purposes of this study were to (1) empirically evaluate the safety results of SI-546 at unsignalized intersections and (2) quantify the impacts of geometrics, traffic, and landscaping design features on total crashes and injury plus fatal crashes. The studied unsignalized intersections were divided into (1) those without median trees near intersections, (2) those with median trees near intersections that were compliant with SI-546, and (3) those with median trees near intersections that were non-compliant with SI-546. A total of 72 intersections were selected, for which five-year crash data from 2006-2010 were collected. The sites that were compliant with SI-546 showed the best safety performance in terms of the lowest crash counts and crash rates. Four crash predictive models-two for total crashes and two for injury crashes-were developed. The results indicated that improperly planted and maintained median trees near highway intersections can increase the total number of crashes and injury plus fatal crashes at a 90% confidence level; no significant difference could be found in crash rates between sites that were compliant with SI-546 and sites without trees. All other conditions remaining the same, an intersection with trees that was not compliant with SI-546 had 63% more crashes and almost doubled injury plus fatal crashes than those at intersections without trees. The study indicates that appropriate landscaping in highway medians near intersections can be an engineering technology that not only improves roadway environmental quality but also maintains intersection safety. Copyright © 2016. Published by

  14. Biomass and lipid production of Chlorella protothecoides under heterotrophic cultivation on a mixed waste substrate of brewer fermentation and crude glycerol.

    PubMed

    Feng, Xiaoyu; Walker, Terry H; Bridges, William C; Thornton, Charles; Gopalakrishnan, Karthik

    2014-08-01

    Biomass and lipid accumulation of heterotrophic microalgae Chlorella protothecoides by supplying mixed waste substrate of brewer fermentation and crude glycerol were investigated. The biomass concentrations of the old and the new C. protothecoides strains on day 6 reached 14.07 and 12.73 g/L, respectively, which were comparable to those in basal medium with supplement of glucose and yeast extract (BM-GY) (14.47 g/L for old strains and 11.43 g/L for new strains) (P>0.05). Approximately 81.5% of total organic carbon and 65.1% of total nitrogen in the mixed waste were effectively removed. The accumulated lipid productivities of the old and the new C. protothecoides strains in BM-GY were 2.07 and 1.61 g/L/day, respectively, whereas in the mixed waste, lipid productivities could reach 2.12 and 1.81 g/L/day, respectively. Our result highlights a new approach of mixing carbon-rich and nitrogen-rich wastes as economical and practical alternative substrates for biofuel production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effects of recombinant human leptin administration on hepatic lipid metabolism in yellow catfish Pelteobagrus fulvidraco: in vivo and in vitro studies.

    PubMed

    Song, Yu-Feng; Wu, Kun; Tan, Xiao-Ying; Zhang, Li-Han; Zhuo, Mei-Qin; Pan, Ya-Xiong; Chen, Qi-Liang

    2015-02-01

    The present study was conducted to investigate the effects and mechanism of leptin influencing lipid metabolism in yellow catfish Pelteobagrus fulvidraco. To this end, hepatic lipid (in vivo experiment) and intracellular triglyceride (TG) (in vitro experiment) content, the activities and/or expression level of several enzymes (CPT-1, 6PGD, G6PD, FAS, ME and ICDH) as well as the mRNA expression of transcription factors (PPARα, PPARγ and SREBP-1) involved in lipid metabolism were determined. Using the primary hepatocytes of yellow catfish, specific inhibitors AG490 (JAK-STAT inhibitor) and wortmannin (IRS-PI3K inhibitor) were used to explore the signaling pathways of leptin effects on lipid metabolism. Intraperitoneal injection of recombinant human leptin (rt-hLEP) significantly reduced hepatic lipid content, activities of lipogenic enzymes (6PGD, G6PD, ME, ICDH and FAS) as well as mRNA levels of 6PGD, G6PD, FAS, PPARγ and SREBP-1 genes, but up-regulated activity and mRNA level of CPT-1 and PPARα. Using primary hepatocytes, rt-hLEP incubation also reduced intracellular TG content, mRNA levels of G6PD and PPARγ genes, but enhanced mRNA levels of PPARα, CPT-1 and SREBP-1. Leptin-induced effects could partially be reversed by specific inhibitors AG490, suggesting that JAK-STAT signaling pathways played important roles in the process of leptin-induced changes in lipid metabolism. Wortmannin significantly suppressed the decrease of TG content induced by leptin, reflecting that IRS-PI3K was involved in the leptin-mediate changes as well. To our knowledge, the present study provides, for the first time, evidence that rt-hLEP can increase lipolysis and reduce lipogenesis at the both enzymatic and molecular levels in fish with the combination of in vivo with in vitro studies, which serves to increase our understanding into the roles and mechanisms of leptin regulating lipid metabolism in fish. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Inhibition of lipolysis in the novel transgenic quail model overexpressing G0/G1 switch gene 2 in the adipose tissue during feed restriction.

    PubMed

    Shin, Sangsu; Choi, Young Min; Han, Jae Yong; Lee, Kichoon

    2014-01-01

    In addition to the issue of obesity in humans, the production of low-fat meat from domestic animals is important in the agricultural industry to satisfy consumer demand. Understanding the regulation of lipolysis in adipose tissue could advance our knowledge to potentially solve both issues. Although the G0/G1 switch gene 2 (G0S2) was recently identified as an inhibitor of adipose triglyceride lipase (ATGL) in vitro, its role in vivo has not been fully clarified. This study was conducted to investigate the role of G0S2 gene in vivo by using two independent transgenic quail lines during different energy conditions. Unexpectedly, G0S2 overexpression had a negligible effect on plasma NEFA concentration, fat cell size and fat pad weight under ad libitum feeding condition when adipose lipolytic activity is minimal. A two-week feed restriction in non-transgenic quail expectedly caused increased plasma NEFA concentration and dramatically reduced fat cell size and fat pad weight. Contrary, G0S2 overexpression under a feed restriction resulted in a significantly less elevation of plasma NEFA concentration and smaller reductions in fat pad weights and fat cell size compared to non-transgenic quail, demonstrating inhibition of lipolysis and resistance to loss of fat by G0S2. Excessive G0S2 inhibits lipolysis in vivo during active lipolytic conditions, such as food restriction and fasting, suggesting G0S2 as a potential target for treatment of obesity. In addition, transgenic quail are novel models for studying lipid metabolism and mechanisms of obesity.

  17. High-fat diet reduces local myostatin-1 paralog expression and alters skeletal muscle lipid content in rainbow trout, Oncorhynchus mykiss

    PubMed Central

    Galt, Nicholas J.; Froehlich, Jacob Michael; Meyer, Ben M.; Barrows, Frederic T.; Biga, Peggy R.

    2014-01-01

    Muscle growth is an energetically demanding process that is reliant on intramuscular fatty acid depots in most fishes. The complex mechanisms regulating this growth and lipid metabolism are of great interest for human health and aquaculture applications. It is well established that the skeletal muscle chalone, myostatin, plays a role in lipid metabolism and adipogenesis in mammals; however, this function has not been fully assessed in fishes. We therefore examined the interaction between dietary lipid levels and myostatin expression in rainbow trout (Oncorhynchus mykiss). Five-weeks of high-fat (HFD; 25% lipid) dietary intake increased white muscle lipid content, and decreased circulating glucose levels and hepatosomatic index when compared to low-fat diet (LFD; 10% lipid) intake. In addition HFD intake reduced myostatin-1a and -1b expression in white muscle and myostatin-1b expression in brain tissue. Characterization of the myostatin-1a, -1b, and -2a promoters revealed putative binding sites for a subset of transcription factors associated with lipid metabolism. Taken together, these data suggest that HFD may regulate myostatin expression through cis-regulatory elements sensitive to increased lipid intake. Further, these findings provide a framework for future investigations of mechanisms describing the relationships between myostatin and lipid metabolism in fish. PMID:24264425

  18. Distal median nerve dysfunction

    MedlinePlus

    ... Distal median nerve dysfunction is a form of peripheral neuropathy that affects the movement of or sensation in ... and the A.D.A.M. Editorial team. Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more Health ...

  19. Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling.

    PubMed

    Shi, Haojun; Fang, Winston; Liu, Minda; Fu, Deliang

    2017-10-01

    Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. © 2017 UICC.

  20. Hydrogen isotopic messages in sulfate reducer lipids: a recorder of metabolic state?

    NASA Astrophysics Data System (ADS)

    Bradley, A. S.; Leavitt, W.; Zhou, A.; Cobban, A.; Suess, M.

    2017-12-01

    A significant range in microbial lipid 2H/1H ratios is observed in modern marine sediments. The magnitude of hydrogen isotope fractionation between microbial lipids and growth water (2ɛlipid-H2O) is hypothesized to relate to the central carbon and energy metabolism. These observations raise the possibility for culture independent identification of the dominant metabolic pathways operating in a given environment [Zhang et al. 2009]. One such metabolism we aim to track is microbial sulfate reduction. To-date, sulfate reducing bacteria have been observed to produce lipids that are depleted in fatty acid H-isotope composition, relative to growth water (2ɛlipid-H2O -50 to -175 ‰) [Campbell et al. 2009; Dawson et al. 2015; Osburn et al.], with recent work demonstrating a systematic relationship between lipid/water fractionation and growth rate when the electron-bifurcating NAD(P)(H) transhydrogenase (ebTH) activity was disrupted and the available electron requires the ebTH [Leavitt et al. 2016. Front Microbio]. Recent work in aerobic methylotrophs [Bradley et al. 2014. AGU] implicates non-bifurcating NAD(P)(H) transhydrogenase activity is a critical control on 2ɛlipid-H2O. This suggests a specific mechanism to control the range in fractionation is the ratio of intracellular NADPH/NADH/NADP/NAD in aerobes and perhaps the same in anaerobes with some consideration for FADH/FAD. Fundamentally this implies 2ɛlipid-H2O records intracellular redox state. In our sulfate reducer model system Desulfovibrio alaskensis strain G20 a key component of energy metabolism is the activity of ebTH. Nonetheless, this strain contains two independent copies of the genes, only one of which generates a distinctive isotopic phenotype [Leavitt et al. 2016. Front Microbio]. In this study we extend the recent work in G20 to continuous culture experiments comparing WT to nfnAB-2 transposon interruptions, where both organisms are cultivated continuously, at the rate of the slower growing mutant

  1. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

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

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates thatmore » Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.« less

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

    PubMed

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

    2016-05-01

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

  3. Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages

    PubMed Central

    Tüzün, Sefa; Yücel, Ahmet Fikret; Pergel, Ahmet; Kemik, Ahu Sarbay; Kemik, Özgür

    2012-01-01

    Objective: High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Material and Methods: Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects. Results: HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001). Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05). Conclusion: These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer. PMID:25207013

  4. Lack of association of ghrelin precursor gene variants and percentage body fat or serum lipid profiles.

    PubMed

    Martin, Glynn R; Loredo, J C; Sun, Guang

    2008-04-01

    Ghrelin has been recognized for its involvement in food intake, control of energy homeostasis, and lipid metabolism. However, the roles of genetic variations in the ghrelin precursor gene (GHRL) on body compositions and serum lipids are not clear in humans. Our study investigated five single-nucleotide polymorphisms (SNPs) within GHRL to determine their relationship with body fat percentage (BF), trunk fat percentage (TF), lower body (legs) fat percentage (LF), and serum lipids in 1,464 subjects, which were recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides were determined. Five SNPs are rs35684 (A/G: a transition substitution in exon 1), rs4684677 (A/T: a missense mutation), rs2075356 (C/T: intron), rs26802 (G/T: intron), and rs26311 (A/G: near the 3' untranslated region) of GHRL were genotyped using TaqMan validated or functionally tested SNP genotyping assays. Our study found no significant evidence of an allele or genotype association between any of the variant sites and body compositions or serum lipids. Furthermore, haplotype frequencies were not found to be significantly different between lean and obese subjects. In summary, the results of our study do not support a significant role for genetic variations in GHRL in the differences of body fat and serum lipid profiles in the NL population.

  5. The phosphorylation-dependent regulation of nuclear SREBP1 during mitosis links lipid metabolism and cell growth

    PubMed Central

    Bengoechea-Alonso, Maria Teresa; Ericsson, Johan

    2016-01-01

    ABSTRACT The SREBP transcription factors are major regulators of lipid metabolism. Disturbances in lipid metabolism are at the core of several health issues facing modern society, including cardiovascular disease, obesity and diabetes. In addition, the role of lipid metabolism in cancer cell growth is receiving increased attention. Transcriptionally active SREBP molecules are unstable and rapidly degraded in a phosphorylation-dependent manner by Fbw7, a ubiquitin ligase that targets several cell cycle regulatory proteins for degradation. We have previously demonstrated that active SREBP1 is stabilized during mitosis. We have now delineated the mechanisms involved in the stabilization of SREBP1 in mitotic cells. This process is initiated by the phosphorylation of a specific serine residue in nuclear SREBP1 by the mitotic kinase Cdk1. The phosphorylation of this residue creates a docking site for a separate mitotic kinase, Plk1. Plk1 interacts with nuclear SREBP1 in mitotic cells and phosphorylates a number of residues in the C-terminal domain of the protein, including a threonine residue in close proximity of the Fbw7 docking site in SREBP1. The phosphorylation of these residues by Plk1 blocks the interaction between SREBP1 and Fbw7 and attenuates the Fbw7-dependent degradation of nuclear SREBP1 during cell division. Inactivation of SREBP1 results in a mitotic defect, suggesting that SREBP1 could regulate cell division. We propose that the mitotic phosphorylation and stabilization of nuclear SREBP1 during cell division provides a link between lipid metabolism and cell proliferation. Thus, the current study provides additional support for the emerging hypothesis that SREBP-dependent lipid metabolism may be important for cell growth. PMID:27579997

  6. Light Remodels Lipid Biosynthesis in Nannochloropsis gaditana by Modulating Carbon Partitioning between Organelles1[OPEN

    PubMed Central

    Vitulo, Nicola; Diretto, Gianfranco; Block, Maryse; Jouhet, Juliette; Meneghesso, Andrea; Valle, Giorgio; Giuliano, Giovanni; Maréchal, Eric

    2016-01-01

    The seawater microalga Nannochloropsis gaditana is capable of accumulating a large fraction of reduced carbon as lipids. To clarify the molecular bases of this metabolic feature, we investigated light-driven lipid biosynthesis in Nannochloropsis gaditana cultures combining the analysis of photosynthetic functionality with transcriptomic, lipidomic and metabolomic approaches. Light-dependent alterations are observed in amino acid, isoprenoid, nucleic acid, and vitamin biosynthesis, suggesting a deep remodeling in the microalgal metabolism triggered by photoadaptation. In particular, high light intensity is shown to affect lipid biosynthesis, inducing the accumulation of diacylglyceryl-N,N,N-trimethylhomo-Ser and triacylglycerols, together with the up-regulation of genes involved in their biosynthesis. Chloroplast polar lipids are instead decreased. This situation correlates with the induction of genes coding for a putative cytosolic fatty acid synthase of type 1 (FAS1) and polyketide synthase (PKS) and the down-regulation of the chloroplast fatty acid synthase of type 2 (FAS2). Lipid accumulation is accompanied by the regulation of triose phosphate/inorganic phosphate transport across the chloroplast membranes, tuning the carbon metabolic allocation between cell compartments, favoring the cytoplasm, mitochondrion, and endoplasmic reticulum at the expense of the chloroplast. These results highlight the high flexibility of lipid biosynthesis in N. gaditana and lay the foundations for a hypothetical mechanism of regulation of primary carbon partitioning by controlling metabolite allocation at the subcellular level. PMID:27325666

  7. A comparative study: the impact of different lipid extraction methods on current microalgal lipid research

    PubMed Central

    2014-01-01

    Microalgae cells have the potential to rapidly accumulate lipids, such as triacylglycerides that contain fatty acids important for high value fatty acids (e.g., EPA and DHA) and/or biodiesel production. However, lipid extraction methods for microalgae cells are not well established, and there is currently no standard extraction method for the determination of the fatty acid content of microalgae. This has caused a few problems in microlagal biofuel research due to the bias derived from different extraction methods. Therefore, this study used several extraction methods for fatty acid analysis on marine microalga Tetraselmis sp. M8, aiming to assess the potential impact of different extractions on current microalgal lipid research. These methods included classical Bligh & Dyer lipid extraction, two other chemical extractions using different solvents and sonication, direct saponification and supercritical CO2 extraction. Soxhlet-based extraction was used to weigh out the importance of solvent polarity in the algal oil extraction. Coupled with GC/MS, a Thermogravimetric Analyser was used to improve the quantification of microalgal lipid extractions. Among these extractions, significant differences were observed in both, extract yield and fatty acid composition. The supercritical extraction technique stood out most for effective extraction of microalgal lipids, especially for long chain unsaturated fatty acids. The results highlight the necessity for comparative analyses of microalgae fatty acids and careful choice and validation of analytical methodology in microalgal lipid research. PMID:24456581

  8. Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles

    DOE PAGES

    Henderson, Ian M.; Collins, Aaron M.; Quintana, Hope A.; ...

    2015-12-13

    In this study, we develop a quantitative dye dequenching technique for the measurement of polymersome fusion, using it to characterize the salt mediated, mechanically-induced fusion of polymersomes with polymer, lipid, and so-called stealth lipid vesicles. While dye dequenching has been used to quantitatively explore liposome fusion in the past, this is the first use of dye dequenching to measure polymersome fusion of which we are aware. In addition to providing quantitative results, dye dequenching is ideal for detecting fusion in instances where DLS results would be ambiguous, such as low yield levels and size ranges outside the capabilities of DLS.more » The dye chosen for this study was a cyanine derivative, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), which proved to provide excellent data on the extent of polymersome fusion. Using this technique, we have shown the limited fusion capabilities of polymersome/liposome heterofusion, notably DOPC vesicles fusing with polymersomes at half the efficiency of polymersome homofusion and DPPC vesicles showing virtually no fusion. In addition to these key heterofusion experiments, we determined the broad applicability of dye dequenching in measuring kinetic rates of polymersome fusion; and showed that even at elevated temperatures or over multiple weeks' time, no polymersome fusion occurred without agitation. Stealth liposomes formed from DPPC and PEO-functionalized lipid, however, fused with polymersomes and stealth liposomes with relatively high efficiency, lending support to our hypothesis that the response of the PEO corona to salt is a key factor in the fusion process. This last finding suggests that although the conjugation of PEO to lipids increases vesicle biocompatibility and enables their longer circulation times, it also renders the vesicles subject to destabilization under high salt and shear (e.g. in the circulatory system) that may lead to, in this case, fusion.« less

  9. Blueberries reduce lipid peroxidation and boost antioxidant enzymes in apoe knockout mice

    USDA-ARS?s Scientific Manuscript database

    ApoE knockout (ApoE-/-) mice fed AIN-93G diet (CD) formulated to contain 1 % freeze-dried whole wild blueberries (CD1 percent BB) were found to have significantly less atherosclerotic lesions in aorta. Biomarkers of lipid peroxidation, including F2-isoprostanes, hydroxyoctadecadienoic acids (HODEs) ...

  10. Contributions of the three CYP1 monooxygenases to pro-inflammatory and inflammation-resolution lipid mediator pathways.

    PubMed

    Divanovic, Senad; Dalli, Jesmond; Jorge-Nebert, Lucia F; Flick, Leah M; Gálvez-Peralta, Marina; Boespflug, Nicholas D; Stankiewicz, Traci E; Fitzgerald, Jonathan M; Somarathna, Maheshika; Karp, Christopher L; Serhan, Charles N; Nebert, Daniel W

    2013-09-15

    All three cytochrome P450 1 (CYP1) monooxygenases are believed to participate in lipid mediator biosynthesis and/or their local inactivation; however, distinct metabolic steps are unknown. We used multiple-reaction monitoring and liquid chromatography-UV coupled with tandem mass spectrometry-based lipid-mediator metabololipidomics to identify and quantify three lipid-mediator metabolomes in basal peritoneal and zymosan-stimulated inflammatory exudates, comparing Cyp1a1/1a2/1b1(⁻/⁻) C57BL/6J-background triple-knockout mice with C57BL/6J wild-type mice. Significant differences between untreated triple-knockout and wild-type mice were not found for peritoneal cell number or type or for basal CYP1 activities involving 11 identified metabolic steps. Following zymosan-initiated inflammation, 18 lipid mediators were identified, including members of the eicosanoids and specialized proresolving mediators (i.e., resolvins and protectins). Compared with wild-type mice, Cyp1 triple-knockout mice exhibited increased neutrophil recruitment in zymosan-treated peritoneal exudates. Zymosan stimulation was associated with eight statistically significantly altered metabolic steps: increased arachidonic acid-derived leukotriene B₄ (LTB₄) and decreased 5S-hydroxyeicosatetraenoic acid; decreased docosahexaenoic acid-derived neuroprotectin D1/protectin D1, 17S-hydroxydocosahexaenoic acid, and 14S-hydroxydocosahexaenoic acid; and decreased eicosapentaenoic acid-derived 18R-hydroxyeicosapentaenoic acid (HEPE), 15S-HEPE, and 12S-HEPE. In neutrophils analyzed ex vivo, elevated LTB₄ levels were shown to parallel increased neutrophil numbers, and 20-hydroxy-LTB₄ formation was found to be deficient in Cyp1 triple-knockout mice. Together, these results demonstrate novel contributions of CYP1 enzymes to the local metabolite profile of lipid mediators that regulate neutrophilic inflammation.

  11. Development of γ-Oryzanol Rich Extract from Leum Pua Glutinous Rice Bran Loaded Nanostructured Lipid Carriers for Topical Delivery.

    PubMed

    Pornputtapitak, Warangkana; Pantakitcharoenkul, Jaturavit; Panpakdee, Ratchada; Teeranachaideekul, Veerawat; Sinchaipanid, Nuttanan

    2018-02-01

    Leum Pua is native Thai glutinous rice that contains antioxidants higher than white rice and other colored rice. One of the major antioxidants in rice brans is γ-oryzanol (GO). In this study, Leum Pua glutinous rice bran was extracted by different solvents. Oleic acid (~40 g/100 g extract), linoleic acid (~30 g/100 g extract), and palmitic acid (~20 g/100 g extract) were found to be major lipid components in the extracts. Methanol extract showed less variety of lipid components compared to the others. However, hexane extract showed the highest percent of γ-oryzanol compared to other solvents. Therefore, the hexane extract was selected to prepare nanostructured lipid carriers (NLC). The prepared NLC had small particles in the size range of 142.9 ± 0.4 nm for extract-loaded NLC and 137.1 ± 0.5 nm for GO-loaded NLC with narrow size distribution (PI < 0.1) in both formulations. The release profile of extract-loaded NLC formulation was slightly higher than GO-loaded NLC formulation. However, they did not follow the Higuchi model because of small amounts of γ-oryzanol loaded in NLC particles.

  12. August median streamflow on ungaged streams in Eastern Coastal Maine

    USGS Publications Warehouse

    Lombard, Pamela J.

    2004-01-01

    sampling error for both equations, indicating that additional or improved estimates of basin characteristics could be important to improved estimates of low-flow statistics. Weighted estimates of August median streamflow at partial- record or continuous-record gaging stations range from 0.003 to 31.0 cubic feet per second or from 0.1 to 0.6 cubic feet per second per square mile. Estimates of August median streamflow on ungaged streams in eastern coastal Maine, within the range of acceptable explanatory variables, range from 0.003 to 45 cubic feet per second or 0.1 to 0.6 cubic feet per second per square mile. Estimates of August median streamflow per square mile of drainage area generally increase as drainage area and fraction of basin underlain by a sand and gravel aquifer increase.

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

    PubMed

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

    2012-12-15

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

  14. SUMO1 depletion prevents lipid droplet accumulation and HCV replication.

    PubMed

    Akil, Abdellah; Wedeh, Ghaith; Zahid Mustafa, Mohammad; Gassama-Diagne, Ama

    2016-01-01

    Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a strain, which produces infectious particles and recapitulates all the steps of the HCV life cycle. We observed that SUMO1 is upregulated in Huh7.5 infected cells. Reciprocally, SUMO1 was found to regulate the expression of viral core protein. Moreover, knockdown of SUMO1 using specific siRNA influenced the accumulation of lipid droplets and reduced HCV replication as measured by qRT-PCR. Thus, we identify SUMO1 as a key host factor required for HCV replication. To our knowledge, this is the first report showing that SUMO1 regulates lipid droplets in the context of viral infection. Our report provides a meaningful insight into how HCV replicates and interacts with host proteins and is of significant importance for the field of HCV and RNA viruses.

  15. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

    PubMed

    Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

    2018-02-01

    Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. [Overweight, obesity and lipids abnormalities in adolescents with type 1 diabetes].

    PubMed

    Wysocka-Mincewicz, Marta; Kołodziejczyk, Honorata; Wierzbicka, Elżbieta; Szalecki, Mieczysław

    2016-02-18

    Overweight children are growing problem as in the pediatric, as well in the diabetic population. The aim of the study was to research the percentage of overweight and obesity in a group of adolescents with type 1 diabetes, and to analyzethe lipid parameters, as well risk factors of these abnormalities. The study group consist of 60 type 1 diabetic adolescents (including 32 girls, 53.3%), aged above 12 years (mean age for girls 14.6+/-0,3years, boys 15.6+/-0.4 years) with diabetes duration (girls 5.7+-0.6 years, boys 4.4+/-0.8 years). Statistical analysis was performed using Statistica v 9.0 and SPSS v20. The study revealed that boys with type 1 diabetes are significantly higher than healthy population, with weight, waist circumference and BMI comparable to the healthy counterparts. However, diabetic girls are more likely to be overweight and have bigger waist circumference, and higher BMI than the healthy population. Overweight were 12 adolescents (20%) using BMI ≥1SD criterion, and 10 (16%) using waist circumference as obesity parameter. Logistic regression revealed that the most important factors for obesity and abdominal obesity are female gender (OR=2.43 and OR=4.56for obesity and abdominal, respectively), diabetes duration above 5 years (respectively OR=1.96 and OR=3.27) and poor metabolic control (respectively OR=1.74 and OR=2.89). The most important risk factor for obesity in adolescents with type 1 diabetes is female gender. Lipids profile is closely dependent on metabolic control and mass excess. Diabetes duration, metabolic control and lipids profile are significant risk factors for overweight and abdominal obesity. © Polish Society for Pediatric Endocrinology and Diabetology.

  17. Functionalized lipids and surfactants for specific applications.

    PubMed

    Kepczynski, Mariusz; Róg, Tomasz

    2016-10-01

    Synthetic lipids and surfactants that do not exist in biological systems have been used for the last few decades in both basic and applied science. The most notable applications for synthetic lipids and surfactants are drug delivery, gene transfection, as reporting molecules, and as support for structural lipid biology. In this review, we describe the potential of the synergistic combination of computational and experimental methodologies to study the behavior of synthetic lipids and surfactants embedded in lipid membranes and liposomes. We focused on select cases in which molecular dynamics simulations were used to complement experimental studies aiming to understand the structure and properties of new compounds at the atomistic level. We also describe cases in which molecular dynamics simulations were used to design new synthetic lipids and surfactants, as well as emerging fields for the application of these compounds. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Determination of the median lethal dose of botulinum serotype E in channel catfish fingerlings

    USDA-ARS?s Scientific Manuscript database

    The median lethal dose of botulinum serotype E in 5.3-g channel catfish Ictalurus punctatus fingerlings was determined. Five tanks (five fish/tank) were assigned to each of the following treatment groups: 70, 50, 35, 25, or 15 pg of purified botulinum serotype E. Fish were injected intracoelomically...

  19. Betaine and arginine supplementation of low protein diets improves plasma lipids but does not affect hepatic fatty acid composition and related gene expression profiling in pigs.

    PubMed

    Madeira, Marta S; Rolo, Eva A; Lopes, Paula A; Ramos, Denis A; Alfaia, Cristina M; Pires, Virgínia Mr; Martins, Susana V; Pinto, Rui Ma; Prates, José Am

    2018-01-01

    The individual and combined effects of betaine and arginine supplemented to reduced protein diets were investigated on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid-sensitive factors in commercial pigs. Betaine has previously been shown to reduce carcass fat deposition and arginine improves meat quality of finishing pigs. Forty male crossbred pigs were randomly assigned to one of five diets (n = 8): 160 g kg -1 of crude protein (NPD), 130 g kg -1 of crude protein (RPD), RPD with 3.3 g kg -1 of betaine, RPD with 15 g kg -1 of arginine, and RPD with 3.3 g kg -1 of betaine and 15 g kg -1 of arginine. The restriction of dietary protein increased total lipids (P < 0.001), total cholesterol (P < 0.001), high-density lipoprotein-cholesterol (P < 0.001) and low-density lipoprotein cholesterol (P < 0.001). Betaine and arginine, individually or combined, reduced the majority of plasma lipids (P < 0.05) without affecting total fatty acids in the liver and the overall gene expression pattern. These findings suggest a positive effect of betaine and arginine, singly or combined, by reversing plasma lipids increase promoted by dietary protein restriction. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. Phase I development of a non-proprietary, four-cable, high tension median barrier.

    DOT National Transportation Integrated Search

    2011-12-28

    During the last decade, the use of cable median barriers has risen dramatically. Cable barriers are often utilized in depressed medians : with widths ranging from 30 to 50 ft (9.1 to 15.2 m) and with fill slopes as steep as 4H:1V. Although cable barr...

  1. Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination.

    PubMed

    Ko, Eun-Ju; Lee, Young-Tae; Lee, Youri; Kim, Ki-Hye; Kang, Sang-Moo

    2017-10-01

    Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating in vitro dendritic cells (DCs), in vivo innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs in vitro to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination.

  2. Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination

    PubMed Central

    Ko, Eun-Ju; Lee, Young-Tae; Lee, Youri; Kim, Ki-Hye

    2017-01-01

    Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating in vitro dendritic cells (DCs), in vivo innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs in vitro to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination. PMID:29093654

  3. Effect of Light Intensity for Optimum Biomass and Lipid Production from Scenedesmus dimorphus (Turpin) Kützing

    NASA Astrophysics Data System (ADS)

    Kurniawati, F. N.; Mahajoeno, E.; Sunarto; Sari, S. L. A.

    2017-07-01

    One source of alternative energy substitute for petroleum raw materials is renewable vegetable oils known as biodiesel. Biodiesel can be produced from microalgae, since it was more efficient and environmentally friendly. Scenedesmus dimorphus (Turpin) Kützing was developed as a source of biodiesel since it had potential of high lipid production. The aims of this research were to know the rate of growth of Scenedesmus dimorphus in different lighting and the optimimum light intensity for biomass and lipid production. This research used a completely randomized design consisting of 3 treatments with 3 replications. Treatments in this research were the light intensity, i.e. 7,500, 10,000, and 12,500 lux. Scenedesmus dimorphus was grew in Bold’s Basal Medium (BBM). Parameters observed in this research were the cell number, biomass and lipid production of S. dimorphus. Data were analyzed by ANOVA followed by DMRT 5%. The results showed that the optimum growth rate of S. dimorphus was in the intensity of 12,500 lux that was 100.80 x 106 cells.ml-1. The optimum production of biomass and lipids was in treatment 12,500 lux i.e; 1.1407 g.L-1 and 0.2520 g.L-1 (22.28% dry weight).

  4. Association of LIPC -250G>A polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    PubMed Central

    2010-01-01

    Background The association between -250G>A polymorphism in the promoter region of the hepatic lipase gene (LIPC) and plasma high-density lipoprotein cholesterol (HDL-C) concentration is contradictory in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association of LIPC -250G>A (rs2070895) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 778 subjects of Bai Ku Yao and 648 participants of Han Chinese aged 15-80 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LIPC -250G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequencies of GG, GA and AA genotypes were 50.0%, 43.3% and 6.7% in Bai Ku Yao, and 35.7%, 50.6% and 13.7% in Han (P < 0.01); respectively. The frequencies of G and A alleles were 71.7% and 28.3% in Bai Ku Yao, and 61.0% and 39.0% in Han (P < 0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao were lower in GG genotype than in GA or AA genotype (P < 0.05-0.01). The levels of TC, HDL-C, LDL-C and ApoB in Han were lower in GG genotype than in GA or AA genotype (P < 0.05-0.01). The levels of HDL-C and the ratio of ApoAI to ApoB in Bai Ku Yao, and the levels of HDL-C, LDL-C and ApoB in Han were correlated with genotype and/or allele (P < 0.05 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both ethnic groups. Conclusions The differences in the serum lipid profiles between the two ethnic groups might partly result from

  5. The H,G_1,G_2 photometric system with scarce observational data

    NASA Astrophysics Data System (ADS)

    Penttilä, A.; Granvik, M.; Muinonen, K.; Wilkman, O.

    2014-07-01

    The H,G_1,G_2 photometric system was officially adopted at the IAU General Assembly in Beijing, 2012. The system replaced the H,G system from 1985. The 'photometric system' is a parametrized model V(α; params) for the magnitude-phase relation of small Solar System bodies, and the main purpose is to predict the magnitude at backscattering, H := V(0°), i.e., the (absolute) magnitude of the object. The original H,G system was designed using the best available data in 1985, but since then new observations have been made showing certain features, especially near backscattering, to which the H,G function has troubles adjusting to. The H,G_1,G_2 system was developed especially to address these issues [1]. With a sufficient number of high-accuracy observations and with a wide phase-angle coverage, the H,G_1,G_2 system performs well. However, with scarce low-accuracy data the system has troubles producing a reliable fit, as would any other three-parameter nonlinear function. Therefore, simultaneously with the H,G_1,G_2 system, a two-parameter version of the model, the H,G_{12} system, was introduced [1]. The two-parameter version ties the parameters G_1,G_2 into a single parameter G_{12} by a linear relation, and still uses the H,G_1,G_2 system in the background. This version dramatically improves the possibility to receive a reliable phase-curve fit to scarce data. The amount of observed small bodies is increasing all the time, and so is the need to produce estimates for the absolute magnitude/diameter/albedo and other size/composition related parameters. The lack of small-phase-angle observations is especially topical for near-Earth objects (NEOs). With these, even the two- parameter version faces problems. The previous procedure with the H,G system in such circumstances has been that the G-parameter has been fixed to some constant value, thus only fitting a single-parameter function. In conclusion, there is a definitive need for a reliable procedure to produce

  6. Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress

    PubMed Central

    Young, Regina M.; Ackerman, Daniel; Quinn, Zachary L.; Mancuso, Anthony; Gruber, Michaela; Liu, Liping; Giannoukos, Dionysios N.; Bobrovnikova-Marjon, Ekaterina; Diehl, J. Alan; Keith, Brian; Simon, M. Celeste

    2013-01-01

    Solid tumors exhibit heterogeneous microenvironments, often characterized by limiting concentrations of oxygen (O2), glucose, and other nutrients. How oncogenic mutations alter stress response pathways, metabolism, and cell survival in the face of these challenges is incompletely understood. Here we report that constitutive mammalian target of rapamycin complex 1 (mTORC1) activity renders hypoxic cells dependent on exogenous desaturated lipids, as levels of de novo synthesized unsaturated fatty acids are reduced under low O2. Specifically, we demonstrate that hypoxic Tsc2−/− (tuberous sclerosis complex 2−/−) cells deprived of serum lipids exhibit a magnified unfolded protein response (UPR) but fail to appropriately expand their endoplasmic reticulum (ER), leading to inositol-requiring protein-1 (IRE1)-dependent cell death that can be reversed by the addition of unsaturated lipids. UPR activation and apoptosis were also detected in Tsc2-deficient kidney tumors. Importantly, we observed this phenotype in multiple human cancer cell lines and suggest that cells committed to unregulated growth within ischemic tumor microenvironments are unable to balance lipid and protein synthesis due to a critical limitation in desaturated lipids. PMID:23699409

  7. Cable median barrier failure analysis and prevention.

    DOT National Transportation Integrated Search

    2012-12-01

    Cross-median crashes have been identified as one of the highest injury or fatality risk crash types. Although crossmedian : crashes account for only 2% to 5% of all median crash events, they are disproportionately represented in the number : and freq...

  8. No effect of yeast-like fungi on lipid metabolism and vascular endothelial growth factor level in children and adolescents with type 1 diabetes mellitus.

    PubMed

    Zorena, Katarzyna; Kowalewska, Beata; Szmigiero-Kawko, Małgorzata; Wąż, Piotr; Myśliwiec, Małgorzata

    2016-12-12

    The objective of the research was to investigate vascular endothelial growth factor (VEGF) levels in the context of lipid metabolism and amount of yeast-like fungi colonizing the digestive tract in children and adolescents with type 1 diabetes mellitus (T1DM). The study included 45 children with T1DM and 27 age- and sex-matched healthy control subjects. In the study sample 33 T1DM patients were administered insulin pump therapy and 12 T1DM patients were administered multiple daily injections with insulin pen devices. All T1DM patients were free of micro- and macrovascular complications. In T1DM patients and healthy controls biochemical tests were performed and measurements of yeast-like fungi colonizing the alimentary tract were conducted. Moreover all study subjects had their serum VEGF levels measured with ELISA test. The subgroup of children and adolescents with T1DM and yeast-like fungus colony number 10^ 3 CFU/g was shown statistically significantly lower HbA1c levels, and lower but not statistically significantly total cholesterol, LDL cholesterol and VEGF levels versus T1DM patients with the amount of yeast-like fungi 10^ 6 CFU/g. Moreover higher HDL levels were observed in this subgroup versus T1DM patients with the amount of yeast-like fungi 10^ 6 CFU/g although the difference was not statistically significant. Our study has shown no influence of yeast-like fungi on lipid metabolism and VEGF level in children and adolescents with T1DM. Comprehensive treatment of T1DM patients and intensive insulin therapy with help of personal insulin pumps can reduce or prevent the development of long-term diabetic complications. Further studies in this field are needed.

  9. Functional reconstitution of rhodopsin into tubular lipid bilayers supported by nanoporous media.

    PubMed

    Soubias, Olivier; Polozov, Ivan V; Teague, Walter E; Yeliseev, Alexei A; Gawrisch, Klaus

    2006-12-26

    We report on a novel reconstitution method for G-protein-coupled receptors (GPCRs) that yields detergent-free, single, tubular membranes in porous anodic aluminum oxide (AAO) filters at concentrations sufficient for structural studies by solid-state NMR. The tubular membranes line the inner surface of pores that traverse the filters, permitting easy removal of detergents during sample preparation as well as delivery of ligands for functional studies. Reconstitution of bovine rhodopsin into AAO filters did not interfere with rhodopsin function. Photoactivation of rhodopsin in AAO pores, monitored by UV-vis spectrophotometry, was indistinguishable from rhodopsin in unsupported unilamellar liposomes. The rhodopsin in AAO pores is G-protein binding competent as shown by a [35S]GTPgammaS binding assay. The lipid-rhodopsin interaction was investigated by 2H NMR on sn-1- or sn-2-chain perdeuterated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phospholine as a matrix lipid. Rhodopsin incorporation increased mosaic spread of bilayer orientations and contributed to spectral density of motions with correlation times in the range of nano- to microseconds, detected as a significant reduction in spin-spin relaxation times. The change in lipid chain order parameters due to interaction with rhodopsin was insignificant.

  10. Phase II development of a non-proprietary, four-cable, high tension median barrier.

    DOT National Transportation Integrated Search

    2012-03-21

    During the last decade, the use of cable median barriers has risen dramatically. Cable barriers are often utilized in depressed medians : with widths ranging from 30 to 50 ft (9.1 to 15.2 m) and with fill slopes as steep as 4H:1V. A careful review of...

  11. Expression profiling suggests a regulatory role of gallbladder in lipid homeostasis

    PubMed Central

    Yuan, Zuo-Biao; Han, Tian-Quan; Jiang, Zhao-Yan; Fei, Jian; Zhang, Yi; Qin, Jian; Tian, Zhi-Jie; Shang, Jun; Jiang, Zhi-Hong; Cai, Xing-Xing; Jiang, Yu; Zhang, Sheng-Dao; Jin, Gang

    2005-01-01

    AIM: To examine expression profile of gallbladder using microarray and to investigate the role of gallbladder in lipid homeostasis. METHODS: 33P-labelled cDNA derived from total RNA of gallbladder tissue was hybridized to a cDNA array representing 17000 cDNA clusters. Genes with intensities ≥2 and variation <0.33 between two samples were considered as positive signals with subtraction of background chosen from an area where no cDNA was spotted. The average gray level of two gallbladders was adopted to analyze its bioinformatics. Identified target genes were confirmed by touch-down polymerase chain reaction and sequencing. RESULTS: A total of 11 047 genes expressed in normal gallbladder, which was more than that predicted by another author, and the first 10 genes highly expressed (high gray level in hybridization image), e.g., ARPC5 (2225.88±90.46), LOC55972 (2220.32±446.51) and SLC20A2 (1865.21±98.02), were related to the function of smooth muscle contraction and material transport. Meanwhile, 149 lipid-related genes were expressed in the gallbladder, 89 of which were first identified (with gray level in hybridization image), e.g., FASN (11.42±2.62), APOD (92.61±8.90) and CYP21A2 (246.11±42.36), and they were involved in each step of lipid metabolism pathway. In addition, 19 of those 149 genes were gallstone candidate susceptibility genes (with gray level in hybridization image), e.g., HMGCR (10.98±0.31), NPC1 (34.88±12.12) and NR1H4 (16.8±0.65), which were previously thought to be expressed in the liver and/or intestine tissue only. CONCLUSION: Gallbladder expresses 11 047 genes and takes part in lipid homeostasis. PMID:15810076

  12. Dimethyl carbonate-mediated lipid extraction and lipase-catalyzed in situ transesterification for simultaneous preparation of fatty acid methyl esters and glycerol carbonate from Chlorella sp. KR-1 biomass.

    PubMed

    Jo, Yoon Ju; Lee, Ok Kyung; Lee, Eun Yeol

    2014-04-01

    Fatty acid methyl esters (FAMEs) and glycerol carbonate were simultaneously prepared from Chlorella sp. KR-1 containing 40.9% (w/w) lipid using a reactive extraction method with dimethyl carbonate (DMC). DMC was used as lipid extraction agent, acyl acceptor for transesterification of the extracted triglycerides, substrate for glycerol carbonate synthesis from glycerol, and reaction medium for the solvent-free reaction system. For 1g of biomass, 367.31 mg of FAMEs and 16.73 mg of glycerol carbonate were obtained under the optimized conditions: DMC to biomass ratio of 10:1 (v/w), water content of 0.5% (v/v), and Novozyme 435 to biomass ratio of 20% (w/w) at 70°C for 24h. The amount of residual glycerol was only in the range of 1-2.5mg. Compared to conventional method, the cost of FAME production with the proposed technique could be reduced by combining lipid extraction with transesterification and omitting the extraction solvent recovery process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

    PubMed

    Wang, Shangqian; Cao, Qiang; Wang, Xiaoxiang; Li, Bingjie; Tang, Min; Yuan, Wanqing; Fang, Jianzheng; Qian, Jian; Qin, Chao; Zhang, Wei

    2013-01-01

    The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results. A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I(2) test. Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03-1.18, I(2) = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06-1.39, I(2) = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04-1.18, I(2) = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09-1.59, I(2) = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04-1.21, I(2) = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05-1.21, I(2) = 25.3%). The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.

  14. Microalgae to biofuels: life cycle impacts of methane production of anaerobically digested lipid extracted algae.

    PubMed

    Quinn, Jason C; Hanif, Asma; Sharvelle, Sybil; Bradley, Thomas H

    2014-11-01

    This study presents experimental measurements of the biochemical methane production for whole and lipid extracted Nannochloropsis salina. Results show whole microalgae produced 430 cm(3)-CH4 g-volatile solids(-1) (g-VS) (σ=60), 3 times more methane than was produced by the LEA, 140 cm(3)-CH4 g-VS(-1) (σ=30). Results illustrate current anaerobic modeling efforts in microalgae to biofuel assessments are not reflecting the impact of lipid removal. On a systems level, the overestimation of methane production is shown to positively skew the environmental impact of the microalgae to biofuels process. Discussion focuses on a comparison results to those of previous anaerobic digestion studies and quantifies the corresponding change in greenhouse gas emissions of the microalgae to biofuels process based on results from this study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Cardiovascular effects of anti-G suit inflation at 1 and 2 G.

    PubMed

    Montmerle, Stéphanie; Linnarsson, Dag

    2005-06-01

    We sought to determine to which pressure a full-coverage anti-G suit needs to be inflated in order to obtain the same stroke volume during a brief exposure to twice the normal gravity (2 G) as that at 1 G without anti-G suit inflation. Nine sitting subjects were studied at normal (1 G) and during 20 s of exposure to 2 G. They wore anti-G suits, which were inflated at both G-levels to the following target pressures: 0, 70, 140 and 210 mmHg. Stroke volume was computed from cardiac output, which was measured by rebreathing. Heart rate and mean arterial pressure at heart level were recorded. Inflation to 70 mmHg compensated for the decrease in stroke volume and cardiac output caused by hypergravity. Mean arterial pressure at heart level was comparable at 1 G and at 2 G and increased gradually and similarly with inflation (P<0.001) at both gravity levels. Thus, anti-G suits act by increasing both preload and afterload but the two effects counteract each other in terms of cardiac output, so that cardiac output at 2 G is maintained at its 1 G level. This effect is reached already at 70 mmHg of inflation. Greater inflation pressure further increases mean arterial pressure at heart level and compensates for the increased difference in hydrostatic pressure between heart and head in moderate hypergravity.

  16. Medical nutrition therapy is the essential cornerstone for effective treatment of "refractory" severe hypertriglyceridemia regardless of pharmaceutical treatment: Evidence from a Lipid Management Program.

    PubMed

    Rhodes, Katherine S; Weintraub, Martha; Marchlewicz, Elizabeth H; Rubenfire, Melvyn; Brook, Robert D

    2015-01-01

    Patients with refractory severe hypertriglyceridemia are at risk of pancreatitis and cardiovascular disease. The role of individualized nutrition therapy in these patients independent of pharmaceutical treatment has not been documented. To document the effect of nutrition intervention on severe hypertriglyceridemia regardless of medication status or prior nutrition counseling. Outcomes of new patients with triglycerides ≥ 500 mg/dL presenting to a Lipid Management Program over a 6-year period were tracked. Patients received comprehensive laboratory assessment, nutrition assessment, and initiation of an individualized diet intervention before seeing the lipidologist. Clinical and behavioral outcomes were recorded. In all, 168 patients (117 men; mean age, 49.03 ± 11.22 years; body mass index, 32.61 ± 5.85 kg/m(2); 110 (65.5%) on lipid-lowering medications) returned for assessment of nutrition intervention. Triglycerides were reduced from median (interquartile range) 961.5 (611.5-1785.3) to 493.0 (337-736.3) mg/dL (P < .0001 for log transformation of triglycerides). There was no difference in median percentage reduction in triglycerides after nutrition intervention between those not on lipid-lowering medication, on a fibric acid derivative, on other lipid-lowering medication, or on a combination of lipid-lowering medications (P = .376) in a median (interquartile range) of 5 (3-7) weeks. Effect was independent of prior nutrition counseling (P = .260). Reported percentage fat in the diet at second visit correlated with log-transformed triglycerides achieved, independent of initial triglycerides level (r = 0.290; P = .001). Individualized nutrition therapy results in changes in eating behavior and reductions in triglyceride levels in patients with refractory severe hypertriglyceridemia independent of lipid-lowering medication(s) and prior nutrition counseling. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  17. 26 CFR 1.414(g)-1 - Definition of plan administrator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of plan administrator. 1.414(g)-1 Section 1.414(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(g)-1...

  18. ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content

    PubMed Central

    Joseph, Roy; Poschmann, Jeremie; Sukarieh, Rami; Too, Peh Gek; Julien, Sofi G.; Xu, Feng; Teh, Ai Ling; Holbrook, Joanna D.; Ng, Kai Lyn; Chong, Yap Seng; Gluckman, Peter D.; Prabhakar, Shyam

    2015-01-01

    Individuals who are born small for gestational age (SGA) have a risk to develop various metabolic diseases during their life course. The biological memory of the prenatal state of growth restricted individuals may be reflected in epigenetic alterations in stem cell populations. Mesenchymal stem cells (MSCs) from the Wharton's jelly of umbilical cord tissue are multipotent, and we generated primary umbilical cord MSC isolates from SGA and normal neonates, which were subsequently differentiated into adipocytes. We established chromatin state maps for histone marks H3K27 acetylation and H3K27 trimethylation and tested whether enrichment of these marks was associated with gene expression changes. After validating gene expression levels for 10 significant chromatin immunoprecipitation sequencing candidate genes, we selected acyl-coenzyme A synthetase 1 (ACSL1) for further investigations due to its key roles in lipid metabolism. The ACSL1 gene was found to be highly associated with histone acetylation in adipocytes differentiated from MSCs with SGA background. In SGA-derived adipocytes, the ACSL1 expression level was also found to be associated with increased lipid loading as well as higher insulin sensitivity. ACSL1 depletion led to changes in expression of candidate genes such as proinflammatory chemokines and down-regulated both, the amount of cellular lipids and glucose uptake. Increased ACSL1, as well as modulated downstream candidate gene expression, may reflect the obese state, as detected in mice fed a high-fat diet. In summary, we believe that ACSL1 is a programmable mediator of insulin sensitivity and cellular lipid content and adipocytes differentiated from Wharton's jelly MSCs recapitulate important physiological characteristics of SGA individuals. PMID:25915184

  19. ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content.

    PubMed

    Joseph, Roy; Poschmann, Jeremie; Sukarieh, Rami; Too, Peh Gek; Julien, Sofi G; Xu, Feng; Teh, Ai Ling; Holbrook, Joanna D; Ng, Kai Lyn; Chong, Yap Seng; Gluckman, Peter D; Prabhakar, Shyam; Stünkel, Walter

    2015-06-01

    Individuals who are born small for gestational age (SGA) have a risk to develop various metabolic diseases during their life course. The biological memory of the prenatal state of growth restricted individuals may be reflected in epigenetic alterations in stem cell populations. Mesenchymal stem cells (MSCs) from the Wharton's jelly of umbilical cord tissue are multipotent, and we generated primary umbilical cord MSC isolates from SGA and normal neonates, which were subsequently differentiated into adipocytes. We established chromatin state maps for histone marks H3K27 acetylation and H3K27 trimethylation and tested whether enrichment of these marks was associated with gene expression changes. After validating gene expression levels for 10 significant chromatin immunoprecipitation sequencing candidate genes, we selected acyl-coenzyme A synthetase 1 (ACSL1) for further investigations due to its key roles in lipid metabolism. The ACSL1 gene was found to be highly associated with histone acetylation in adipocytes differentiated from MSCs with SGA background. In SGA-derived adipocytes, the ACSL1 expression level was also found to be associated with increased lipid loading as well as higher insulin sensitivity. ACSL1 depletion led to changes in expression of candidate genes such as proinflammatory chemokines and down-regulated both, the amount of cellular lipids and glucose uptake. Increased ACSL1, as well as modulated downstream candidate gene expression, may reflect the obese state, as detected in mice fed a high-fat diet. In summary, we believe that ACSL1 is a programmable mediator of insulin sensitivity and cellular lipid content and adipocytes differentiated from Wharton's jelly MSCs recapitulate important physiological characteristics of SGA individuals.

  20. Growth and lipid accumulation characteristics of Scenedesmus obliquus in semi-continuous cultivation outdoors for biodiesel feedstock production.

    PubMed

    Feng, Pingzhong; Yang, Kang; Xu, Zhongbin; Wang, Zhongming; Fan, Lu; Qin, Lei; Zhu, Shunni; Shang, Changhua; Chai, Peng; Yuan, Zhenhong; Hu, Lei

    2014-12-01

    In an effort to identify suitable microalgal species for biodiesel production, seven species were isolated from various habitats and their growth characteristics were compared. The results demonstrated that a green alga Scenedesmus obliquus could grow more rapidly and synthesize more lipids than other six microalgal strains. S. obliquus grew well both indoors and outdoors, and reached higher μmax indoors than that outdoors. However, the cells achieved higher dry weight (4.36 g L(-1)), lipid content (49.6%) and productivity (183 mg L(-1) day(-1)) outdoors than in indoor cultures. During the 61 days semi-continuous cultivation outdoors, high biomass productivities (450-550 mg L(-1) day(-1)) and μmax (1.05-1.44 day(-1)) were obtained. The cells could also achieve high lipid productivities (151-193 mg L(-1) day(-1)). These results indicated that S. obliquus was promising for lipids production in semi-continuous cultivation outdoors. Copyright © 2014 Elsevier Ltd. All rights reserved.