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Sample records for liver-specific lipid droplet-associated

  1. Proteomic profiling of lipid droplet-associated proteins in primary adipocytes of normal and obese mouse

    Institute of Scientific and Technical Information of China (English)

    Yubo Ding; Yibo Wu; Rong Zeng; Kan Liao

    2012-01-01

    Lipid droplets in adipocytes serve as the principal longterm energy storage depot of animals.There is increasing recognition that lipid droplets are not merely a static neutral lipid storage site,but in fact dynamic and multifunctional organelles.Structurally,lipid droplet consists of a neutral lipid core surrounded by a phospholipid monolayer and proteins embedded in or bound to the phospholipid layer.Proteins on the surface of lipid droplets are crucial to droplet structure and dynamics.To understand the lipid droplet-associated proteome of primary adipocyte with a large central lipid droplet,lipid droplets of white adipose tissue from C57BL/6 mice were isolated.And the proteins were extracted and analyzed by liquid chromatography coupled with tandem mass spectrometry.A total of 193 proteins including 73 previously unreported proteins were identified.Furthermore,the isotope-coded affinity tags (ICAT) was used to compare the difference of lipid droplet-associated proteomes between the normal lean and the high-fat diet-induced obese C57BL/6 mice.Of 23proteins quantified by ICAT analysis,3 proteins were upregulated and 4 proteins were down-regulated in the lipid droplets of adipose tissue from the obese mice.Importantly,two structural proteins of lipid droplets,perilipin A and vimentin,were greatly reduced in the lipid droplets of the adipose tissue from the obese mice,implicating reduced protein machinery for lipid droplet stability.

  2. Identification of a new class of lipid droplet-associated proteins in plants.

    Science.gov (United States)

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

    2013-08-01

    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.

  3. [Lipid droplet-associated proteins. Importance in steatosis, steatohepatitis and hepatocarcinogenesis].

    Science.gov (United States)

    Straub, B K

    2015-11-01

    Hepatocellular steatosis constitutes the most frequent liver disease in western countries and may progress to steatohepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The lipid droplet (LD)-associated proteins perilipin, adipophilin, TIP47 ("tail interacting protein of 47 kDa"), S3-12 and myocardial LD protein (MLDP), so-called perilipins 1-5 (PAT family) govern formation, maintenance and degradation of LDs. A lack of perilipin in mice inhibits obesity and a lack of adipophilin or TIP47 inhibit the development of fatty liver disease. In long-term cell culture models as well as in liver biopsies of patients with different acute and chronic liver diseases, LD-associated proteins are sequentially recruited to LDs and regulated via peroxisome proliferator-activated receptor (PPAR) α and PPARγ as well as posttranscriptionally via alternative splicing, LD fusion and lipolysis. Whereas TIP47 and MLDP coat small newly formed LDs in acute microvesicular steatosis, adipophilin constitutes a robust general marker for LDs in many different cell types. Perilipin is important for the long-term storage of lipids in macrovesicular steatosis and controls lipolysis via hormone-dependent phosphorylation. During malignant transformation, increased formation of small LDs and overexpression of adipophilin, TIP47 and MLDP are detected, possibly as the expression of an altered tumor metabolism analogous to a Warburg effect. Adipophilin correlates positively with the proliferation rate of HCC cells. Cultured cells with downregulation of TIP47 or adipophilin via small interfering RNA (siRNA) or small hairpin RNA (shRNA) show less but larger LDs with reduced neutral fat content.

  4. Dynamic changes in lipid droplet-associated proteins in the "browning" of white adipose tissues.

    Science.gov (United States)

    Barneda, David; Frontini, Andrea; Cinti, Saverio; Christian, Mark

    2013-05-01

    The morphological and functional differences between lipid droplets (LDs) in brown (BAT) and white (WAT) adipose tissues will largely be determined by their associated proteins. Analysing mRNA expression in mice fat depots we have found that most LD protein genes are expressed at higher levels in BAT, with the greatest differences observed for Cidea and Plin5. Prolonged cold exposure, which induces the appearance of brown-like adipocytes in mice WAT depots, was accompanied with the potentiation of the lipolytic machinery, with changes in ATGL, CGI-58 and G0S2 gene expression. However the major change detected in WAT was the enhancement of Cidea mRNA. Together with the increase in Cidec, it indicates that LD enlargement through LD-LD transference of fat is an important process during WAT browning. To study the dynamics of this phenotypic change, we have applied 4D confocal microscopy in differentiated 3T3-L1 cells under sustained β-adrenergic stimulation. Under these conditions the cells experienced a LD remodelling cycle, with progressive reduction on the LD size by lipolysis, followed by the formation of new LDs, which were subjected to an enlargement process, likely to be CIDE-triggered, until the cell returned to the basal state. This transformation would be triggered by the activation of a thermogenic futile cycle of lipolysis/lipogenesis and could facilitate the molecular mechanism for the unilocular to multilocular transformation during WAT browning. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  5. Lipid droplet-associated proteins (LDAPs) are required for the dynamic regulation of neutral lipid compartmentation in plant cells

    Science.gov (United States)

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols (TAGs) in seeds, their biogenesis and function in non-seed tissues is poorly understood. Recently, we identified a class of plant-sp...

  6. Neutralized nanoparticle composed of SS-cleavable and pH-activated lipid-like material as a long-lasting and liver-specific gene delivery system.

    Science.gov (United States)

    Ukawa, Masami; Akita, Hidetaka; Hayashi, Yasuhiro; Ishiba, Ryohei; Tange, Kota; Arai, Masaya; Kubo, Kazuhiro; Higuchi, Yuriko; Shimizu, Kazunori; Konishi, Satoshi; Hashida, Mitsuru; Harashima, Hideyoshi

    2014-08-01

    Charge-neutralized lipid envelope-type nanoparticles formed with SS-cleavable and pH-activated lipid-like materials (ssPalm) accumulate rapidly in the liver without forming aggregates in the blood circulation, and result in a liver-specific gene expression for a long duration (>2 weeks) with neither immunological responses nor hepatotoxicity after intraveneous administration, when it carries pDNA free from CpG-motifs.

  7. Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

    Energy Technology Data Exchange (ETDEWEB)

    Vrablik, Tracy L. [Washington State Univ., Pullman, WA (United States); Petyuk, Vladislav A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Larson, Emily M. [Washington State Univ., Pullman, WA (United States); Smith, Richard D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Watts, Jennifer [Washington State Univ., Pullman, WA (United States)

    2015-06-27

    Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols was rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a relative decrease of MDT-28 abundance in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans.

  8. Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein.

    Science.gov (United States)

    Vrablik, Tracy L; Petyuk, Vladislav A; Larson, Emily M; Smith, Richard D; Watts, Jennifer L

    2015-10-01

    Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified Caenorhabditis elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary Escherichia coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.

  9. Liver-specific activities of FGF19 require Klotho beta.

    Science.gov (United States)

    Lin, Benjamin C; Wang, Manping; Blackmore, Craig; Desnoyers, Luc R

    2007-09-14

    Hepatocyte function is regulated by members of the fibroblast growth factor (FGF) family of proteins, but little is known about the specific molecular mechanisms of this endocrine pathway. FGF19 regulates bile acid homeostasis and gall bladder filling; FGF19 binds only to FGF receptor 4 (FGFR4), but its liver-specific activity cannot be explained solely by the distribution of this receptor. Although it has been suggested that Klotho beta (KLB) may have a role in mediating FGF19 activity, we have provided for the first time definitive evidence that KLB is required for FGF19 binding to FGFR4, intracellular signaling, and downstream modulation of gene expression. We have shown that FGFR4 is widely distributed in mouse, whereas KLB distribution is more restricted. Liver was the only organ in which both genes were abundantly expressed. We show that in mice, FGF19 injection triggers liver-specific induction of c-Fos and repression of CYP7A1. The tissue-specific activity of FGF19 supports the unique intersection of KLB and FGFR4 distribution in liver. These studies define KLB as a novel FGFR4 coreceptor required for FGF19 liver specific functions.

  10. INTRATHYMIC INOCULATION OF LIVER SPECIFIC ANTIGEN ALLEVIATES LIVER TRANSPLANT REJECTION

    Institute of Scientific and Technical Information of China (English)

    贾长库; 郑树森; 朱有法

    2004-01-01

    Objective To study the effects of liver specific antigen (LSA) on liver allotransplantation rejection. Methods Orthotopic liver transplantation was performed in this study. Group Ⅰ: syngeneic control (Wistar-to-Wistar); Group Ⅱ: acute rejection (SD-to-Wistar). Group Ⅲ: thymic inoculation of SD rat LSA day 7 before transplantation. The observation of general condition and survival time, rejection grades and the NF-κB activity of splenocytes were used to analyze severity of acute rejection and immune state of animals in different groups. Results The general condition of group Ⅰ was fair post transplantation with no sign of rejection. All recipients of group Ⅱ died within days 9 to 13 post transplantation with median survival time of 10.7 ±1.37 days. As for group Ⅲ, 5 out of 6 recipients survived for a long period with remarkably better general condition than that of group Ⅱ. Its rejection grades were significantly lower than group Ⅱ (P< 0.05).NF-κB activity was only detected in group Ⅰ between days 5 and 7 after transplantation, whereas high activity of NF-κB was detected at all points in group Ⅱ and low NF-κB activity was detected in group Ⅲ which was significantly lower than that of group Ⅱ (P < 0.05). Conclusions LSA is an important transplantation antigen directly involved in the immunorejection of liver transplantation. Intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation,grafts survive for a period of time thereby, allowing a novel way to liver transplantation immunotolerance.

  11. Lack of significant metabolic abnormalities in mice with liver-specific disruption of 11β-hydroxysteroid dehydrogenase type 1.

    LENUS (Irish Health Repository)

    Lavery, Gareth G

    2012-07-01

    Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA

  12. Expression of liver-specific functions in rat hepatocytes following sublethal and lethal acetaminophen poisoning

    DEFF Research Database (Denmark)

    Tygstrup, N; Jensen, S A; Krog, B

    1996-01-01

    AIM: In order to study the short-term effect of moderate and severe reduction of liver function by acetaminophen poisoning of different severity on gene expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg body weight acetaminophen intragastrically. The lower dose...

  13. Mice lacking lipid droplet-associated hydrolase, a gene linked to human prostate cancer, have normal cholesterol ester metabolism

    DEFF Research Database (Denmark)

    Kory, Nora; Grond, Susanne; Kamat, Siddhesh S

    2017-01-01

    , such as triacylglycerols and sterol esters, as precursors for membrane components and as reservoirs of metabolic energy. LDAH is reported to hydrolyze cholesterol esters and to be important in macrophage cholesterol ester metabolism. Here, we confirm that LDAH is localized to LDs in several model systems. We generated...... a murine model in which Ldah is disrupted but found no evidence for a major function of LDAH in cholesterol ester or triacylglycerol metabolism in vivo, nor a role in energy or glucose metabolism. Our data suggest that LDAH is not a major cholesterol ester hydrolase, and an alternative metabolic function...

  14. Lipases and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer.

    Science.gov (United States)

    Silvério, Renata; Lira, Fábio S; Oyama, Lila M; Oller do Nascimento, Cláudia M; Otoch, José P; Alcântara, Paulo S M; Batista, Miguel L; Seelaender, Marília

    2017-08-22

    Cancer cachexia is a multifactorial metabolic syndrome characterized by marked loss of adipose tissue and skeletal muscle. Fat loss from adipose tissue in cancer cachexia is partly the result of increased lipolysis. Despite the growing amount of studies focused on elucidating the mechanisms through which lipolysis-related proteins regulate the lipolytic process, there are scarce data concerning that profile in the adipose tissue of cancer cachectic patients. Considering its fundamental importance, it was our main purpose to characterize the expression of the lipolysis-related proteins in the white adipose tissue of cachectic cancer patients. Patients from the University Hospital were divided into three groups: control, cancer cachexia (CC), and weight-stable cancer patients (WSC). To gain greater insight into adipose tissue wasting during cancer cachexia progression, we have also analyzed an experimental model of cachexia (Walker 256 carcinosarcoma). Animals were divided into: control, intermediate cachexia (IC) and terminal cachexia (TC). Subcutaneous white adipose tissue of patients and epidydimal white adipose tissue of animals were investigated regarding molecular aspects by determining the protein content and gene expression of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), perilipin 1, leptin, adiponectin, visfatin, and tumour necrosis factor alpha (TNF-alpha). We found augmented lipolysis in CC associated with increased HSL expression, as well as upregulation of ATGL expression and reduction in perilipin 1 content. In IC, there was an imbalance in the secretion of pro- and anti-inflammatory factors. The alterations at the end-stage of cachexia were even more profound, and there was a reduction in the expression of almost all proteins analyzed in the animals. Our findings show that cachexia induces important morphological, molecular, and humoral alterations in the white adipose tissue, which are specific to the stage of the syndrome.

  15. Asialoglycoprotein receptor (ASGPR): a peculiar target of liver-specific autoimmunity

    OpenAIRE

    Roggenbuck, Dirk; Mytilinaiou, Maria G.; Lapin, Sergey V.; Reinhold, Dirk; Conrad, Karsten

    2012-01-01

    Asialoglycoprotein receptor (ASGPR) autoantibodies have been considered specific markers of autoimmune hepatitis (AIH). The exact mechanisms responsible for the development of these autoantibodies and leading to autoimmunity to this peculiar liver receptor remain elusive. Furthermore, loss of T cell tolerance to ASGPR has been demonstrated in patients with AIH, but it is poorly understood whether such liver-specific T cell responses bear a pathogenic potential and/or participate in the precip...

  16. ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Neri, E.; Boraschi, P.; Bartolozzi, C. [University of Pisa, Department of Diagnostic and Interventional Radiology, Pisa (Italy); Bali, M.A.; Matos, C. [Hopital Erasme, MRI Clinics, Department of Radiology, Bruxelles (Belgium); Ba-Ssalamah, A. [The General Hospital of the Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Brancatelli, G. [University of Palermo, Department of Radiology, Palermo (Italy); Alves, F.C. [University Hospital of Coimbra, Medical Imaging Department and Faculty of Medicine, Coimbra (Portugal); Grazioli, L. [Spedali Civili di Brescia, Department of Radiology, Brescia (Italy); Helmberger, T. [Academic Teaching Hospital of the Technical University, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich (Germany); Lee, J.M. [Seoul National University College of Medicine, Division of Abdominal Imaging, Department of Radiology, Seoul (Korea, Republic of); Manfredi, R. [University of Verona, Department of Radiology, Verona (Italy); Marti-Bonmati, L. [Hospital Universitario y Politecnico La Fe, Area Clinica de Imagen Medica, Valencia (Spain); Merkle, E.M. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland); Op De Beeck, B. [Antwerp University Hospital, Department of Radiology, Edegem (Belgium); Schima, W. [KH Goettlicher Heiland, Krankenhaus der Barmherzigen Schwestern and Sankt Josef-Krankenhaus, Department of Diagnostic and Interventional Radiology, Vienna (Austria); Skehan, S. [St Vincent' s University Hospital, Department of Radiology, Dublin (Ireland); Vilgrain, V. [Assistance Publique-Hopitaux de Paris, APHP, Hopital Beaujon, Radiology Department, Clichy, Paris (France); Zech, C. [Universitaetsspital Basel, Abteilungsleiter Interventionelle Radiologie, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland)

    2016-04-15

    To develop a consensus and provide updated recommendations on liver MR imaging and the clinical use of liver-specific contrast agents. The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a multinational European panel of experts, selected on the basis of a literature review and their leadership in the field of liver MR imaging. A modified Delphi process was adopted to draft a list of statements. Descriptive and Cronbach's statistics were used to rate levels of agreement and internal reliability of the consensus. Three Delphi rounds were conducted and 76 statements composed on MR technique (n = 17), clinical application of liver-specific contrast agents in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84 (SD ±0.17). Full consensus was reached in 22 % of all statements in all working groups, with no full consensus reached on diffuse and vascular diseases. The consensus provided updated recommendations on the methodology, and clinical indications, of MRI with liver specific contrast agents in the study of liver diseases. (orig.)

  17. Liver-specific gene expression in mesenchymal stem cells is induced by liver cells

    Institute of Scientific and Technical Information of China (English)

    Claudia Lange; Philipp Bassler; Michael V. Lioznov; Helge Bruns; Dietrich Kluth; Axel R. Zander; Henning C. Fiegel

    2005-01-01

    AIM: The origin of putative liver cells from distinct bone marrow stem cells, e.g. hematopoietic stem cells or multipotent adult progenitor cells was found in recent in vitro studies. Cell culture experiments revealed a key role of growth factors for the induction of liver-specific genes in stem cell cultures. We investigated the potential of rat mesenchymal stem cells (MSC) from bone marrow to differentiate into hepatocytic cells in vitro. Furthermore,we assessed the influence of cocultured liver cells on induction of liver-specific gene expression.METHODS: Mesenchymal stem cells were marked with green fluorescent protein (GFP) by retroviral gene transduction. Clonal marked MSC were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with SCF, HGF,EGF, and FGF-4 alone, or in presence of freshly isolated rat liver cells. Cells in cocultures were harvested and GFP+ or GFP- cells were separated using fluorescence activated cell sorting. RT-PCR analysis for the stem cell marker Thy1 and the hepatocytic markers CK-18, albumin, CK-19,and AFP was performed in the different cell populations.RESULTS: Under the specified culture conditions, rat MSC cocultured with liver cells expressed albumin-, CK-18,CK-19, and AFP-RNA over 3 weeks, whereas MSC cultured alone did not show liver specific gene expression.CONCLUSION: The results indicate that (1) rat MSC from bone marrow can differentiate towards hepatocytic lineage in vitro, and (2) that the microenvironment plays a decisive role for the induction of hepatic differentiation of rMSC.

  18. Suspected Greater Celandine hepatotoxicity: liver-specific causality evaluation of published case reports from Europe.

    Science.gov (United States)

    Teschke, Rolf; Glass, Xaver; Schulze, Johannes; Eickhoff, Axel

    2012-03-01

    In 21 published case reports, the use of the herb Greater Celandine (GC) (Chelidonium majus L.) has been causally related to liver injury, but a variety of confounding variables were evident that might have offset causality. This study reanalyses causality levels in these cases with a liver-specific causality evaluation method. All 21 cases were submitted to the liver-specific, standardized, structured, quantitative and updated scale of the Council for International Organizations of Medical Sciences. This scale considers, among other items, latency period, course of alanine aminotransferase after treatment discontinuation, risk factors, comedication and alternative causes. Using this method for assessment, causality for GC was highly probable in two and probable in six cases, with lower causality grading in the remaining 13 cases. In these patients, causality for GC was possible in 10 cases and excluded in three cases. On the basis of the eight cases with highly probable and probable causality gradings, GC hepatotoxicity represents an idiosyncratic reaction of the metabolic type, whereas immunologic or obligatory hepatotoxic features are lacking. In some cases, alternative diagnoses and poor data quality were confounding variables that reduced causality levels. Confounding variables reduced causality levels for GC in reported cases of liver injury, but there is still striking evidence for herb-induced liver injury by GC with high causality gradings. GC hepatotoxicity is caused by an idiosyncratic reaction of the metabolic form, but there is uncertainty with respect to its culprit(s).

  19. Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity.

    Science.gov (United States)

    Xian, Li; Hou, Siyuan; Huang, Zan; Tang, An; Shi, Peiliang; Wang, Qinghua; Song, Anying; Jiang, Shujun; Lin, Zhaoyu; Guo, Shiying; Gao, Xiang

    2015-04-01

    Protein phosphatase 2A (PP2A) is a key negative regulator of phosphatidylinositol 3-kinase/Akt pathway. Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and dyslipidemia. Here we studied the role of liver PP2Ac in glucose metabolism and evaluated whether PP2Ac is a suitable therapeutic target for treating insulin resistance syndrome. Liver-specific Ppp2cα knockout mice (Ppp2cα(loxp/loxp): Alb) exhibited improved glucose homeostasis compared with littermate controls in both normal and high-fat diet conditions, despite no significant changes in body weight and liver weight under chow diet. Ppp2cα(loxp/loxp): Alb mice showed enhanced glycogen deposition, serum triglyceride, cholesterol, low density lipoprotein and high density lipoprotein, activated insulin signaling, decreased expressions of gluconeogenic genes G6P and PEPCK, and lower liver triglyceride. Liver-specific Ppp2cα knockout mice showed enhanced glucose homeostasis and increased insulin sensitivity by activation of insulin signaling through Akt. These findings suggest that inhibition of hepatic Ppp2cα may be a useful strategy for the treatment of insulin resistance syndrome.

  20. Fatty Liver and Insulin Resistance in the Liver-Specific Knockout Mice of Mitogen Inducible Gene-6

    Science.gov (United States)

    Park, Byung Kil; Kim, Hee-Youn; Lee, Jun Choul; Kim, Koon Soon; Jeong, Won Hoon; Kim, Ki Young

    2016-01-01

    Mitogen inducible gene-6 (Mig-6) is a feedback inhibitor of epidermal growth factor receptor (EGFR) signaling pathway. The liver-specific knockout mice of the Mig-6 gene (Mig-6d/d) showed hepatomegaly and increased hypercholesterolemia. In this study, the biomarkers of insulin resistance and the effects of high-fat diets in the wild (Mig-6f/f) and Mig-6d/d mice were analyzed. The fasting plasma concentrations of glucose, triglyceride, cholesterols, free fatty acids, and HOMA-IR were measured and the glucose tolerance and insulin resistance tests were performed in the 25-week-old Mig-6f/f and the Mig-6d/d mice. The protein levels of active insulin receptor, glucose 6-phosphatase, and phosphoenolpyruvate carboxykinase were analyzed in the liver and fat. The fasting plasma cholesterol and glucose concentration were higher in the Mig-6d/d mice than the Mig-6f/f mice with increased fat deposition in the liver. But the Mig-6d/d mice had the improved glucose intolerance and insulin resistance without increased amount of phosphoinsulin receptor after insulin infusion in the liver. The hepatic concentration of phosphoenolpyruvate carboxykinase was increased in fasting Mig-6d/d mice. The feeding of high-fat diet accelerated the plasma lipids profiles and HOMA-IR in the Mig-6d/d mice but had no differential effects in oral glucose tolerance test and insulin tolerance test in both genotypes. These results suggest that the activated EGFR signaling might increase the fasting plasma glucose concentration through inducing the hepatic steatosis and the improved whole-body insulin resistance in the KO mice be caused by decreased adipogenesis in fat tissues. PMID:28053990

  1. Liver-specific expressions of HBx and src in the p53 mutant trigger hepatocarcinogenesis in zebrafish.

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    Jeng-Wei Lu

    Full Text Available Hepatocarcinogenesis is a multistep process that starts from fatty liver and transitions to fibrosis and, finally, into cancer. Many etiological factors, including hepatitis B virus X antigen (HBx and p53 mutations, have been implicated in hepatocarcinogenesis. However, potential synergistic effects between these two factors and the underlying mechanisms by which they promote hepatocarcinogenesis are still unclear. In this report, we show that the synergistic action of HBx and p53 mutation triggers progressive hepatocellular carcinoma (HCC formation via src activation in zebrafish. Liver-specific expression of HBx in wild-type zebrafish caused steatosis, fibrosis and glycogen accumulation. However, the induction of tumorigenesis by HBx was only observed in p53 mutant fish and occurred in association with the up-regulation and activation of the src tyrosine kinase pathway. Furthermore, the overexpression of src in p53 mutant zebrafish also caused hyperplasia, HCC, and sarcomatoid HCC, which were accompanied by increased levels of the signaling proteins p-erk, p-akt, myc, jnk1 and vegf. Increased expression levels of lipogenic factors and the genes involved in lipid metabolism and glycogen storage were detected during the early stages of hepatocarcinogenesis in the HBx and src transgenic zebrafish. The up-regulation of genes involved in cell cycle regulation, tumor progression and other molecular hallmarks of human liver cancer were found at later stages in both HBx and src transgenic, p53 mutant zebrafish. Together, our study demonstrates that HBx and src overexpression induced hepatocarcinogenesis in p53 mutant zebrafish. This phenomenon mimics human HCC formation and provides potential in vivo platforms for drug screening for therapies for human liver cancer.

  2. Asialoglycoprotein receptor (ASGPR): a peculiar target of liver-specific autoimmunity.

    Science.gov (United States)

    Roggenbuck, Dirk; Mytilinaiou, Maria G; Lapin, Sergey V; Reinhold, Dirk; Conrad, Karsten

    2012-12-01

    Asialoglycoprotein receptor (ASGPR) autoantibodies have been considered specific markers of autoimmune hepatitis (AIH). The exact mechanisms responsible for the development of these autoantibodies and leading to autoimmunity to this peculiar liver receptor remain elusive. Furthermore, loss of T cell tolerance to ASGPR has been demonstrated in patients with AIH, but it is poorly understood whether such liver-specific T cell responses bear a pathogenic potential and/or participate in the precipitation of AIH. Newly developed enzyme-linked immunosorbent assays have led to the investigation of the sensitivity and specificity of anti-ASGPR antibodies for AIH. The present review provides an overview of the diagnostic and clinical relevance of anti-ASGPR antibodies. A thorough investigation of the autoreactivity against ASGPR may assist efforts to understand liver autoimmunity in susceptible individuals.

  3. Liver-specific deletion of the signal transducer and activator of transcription 5 gene aggravates fatty liver in response to a high-fat diet in mice.

    Science.gov (United States)

    Baik, Myunggi; Nam, Yoon Seok; Piao, Min Yu; Kang, Hyeok Joong; Park, Seung Ju; Lee, Jae-Hyuk

    2016-03-01

    Growth hormone (GH) signal is mediated by signal transducer and activator of transcription 5 (STAT5), which controls hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is clinically associated with a deficiency in GH. This study was performed to understand the role of local STAT5 signaling on hepatic lipid and glucose metabolism utilizing liver-specific STAT5 gene deletion (STAT5 LKO) mice under both normal diet and high-fat diet (HFD) feeding conditions. STAT5 LKO induced hepatic steatosis under HFD feeding, while this change was not observed in mice on normal diet. STAT5 LKO caused hyperglycemia, hyperinsulinemia, hyperleptinemia and elevated free fatty acid and cholesterol concentrations under HFD feeding but induced only hyperglycemia on normal diet. At the molecular level, STAT5 LKO up-regulated the expression of genes involved in lipid uptake (CD36), very low-density lipoprotein receptor (VLDLR), lipogenic stearoyl-CoA desaturase and adipogenic peroxisome proliferator-activated receptor gamma, in both diet groups. In response to HFD feeding, further increases in CD36 and VLDLR expression were found in STAT5 LKO mice. In conclusion, our study suggests that low STAT5 signaling on normal diet predisposes STAT5 LKO mice to early development of fatty liver by hyperglycemia and activation of lipid uptake and adipogenesis. A deficiency in STAT5 signaling under HFD feeding deregulates hepatic and body glucose and lipid metabolism, leading to the development of hepatic steatosis. Our study indicates that low STAT5 signaling, due to low GH secretion, may increase a chance for NAFLD development in elderly people.

  4. Liver-specific expression of a phosphoenolpyruvate carboxykinase-neo gene in genetically modified chickens.

    Science.gov (United States)

    Cook, R F; Cook, S J; Savon, S; McGrane, M; Hartitz, M; Hanson, R W; Hodgson, C P

    1993-03-01

    In order to investigate the potential of the avian liver for the expression of recombinant proteins in vivo, replication-competent retroviral vectors were used to introduce a recombinant rat phosphoenolpyruvate carboxykinase promoter-driven neomycin resistance gene (PEPCKneo) into early Line 11 Leghorn embryos. After hatching, these birds possessed apparently intact PEPCKneo sequences in most tissues examined, however, the neo protein was expressed preferentially in the liver (up to .45% of total cellular protein). Therefore, the tissue specificity of the PEPCK promoter from the rat was retained in the chicken, although hormone responsiveness was not observed. Retroviral vectors used to transmit the genes were more stable during passage in either fibroblast cells or in the animal if the inserted genes were oriented in the same (sense) direction as the viral genome. After Geneticin drug selection in cultured cells, PEPCKneo mRNA was the predominant recombinant species observed on Northern blots, whereas embryos expressed mostly the RNA species originating in the retroviral long terminal repeats. The results demonstrate the potential usefulness of liver-specific gene expression in chickens, as well as the transcriptional effects observed when a foreign promoter is introduced into the replication-competent vector.

  5. Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth

    Directory of Open Access Journals (Sweden)

    Jeroen Declercq

    2015-01-01

    Full Text Available Proprotein convertases are subtilisin-like serine endoproteases that cleave and hence activate a variety of proproteins, including growth factors, receptors, metalloproteases, and extracellular matrix proteins. Therefore, it has been suggested that inhibition of the ubiquitously expressed proprotein convertase FURIN might be a good therapeutic strategy for several tumor types. Whether this is also the case for hepatocellular carcinoma (HCC is currently not clear. In a mouse model for HCC expression of Furin was not altered in the tumors, while those of PC7, PC5/6, and PACE4 significantly decreased, at least at some time points. To investigate the impact of Furin inhibition on the development and progression of HCC in this model, Furin was genetically ablated in the liver. Furin inactivation resulted in an increased tumor mass after 5 weeks. This was not caused by decreased apoptosis, since no differences in the apoptosis index could be observed. However, it could at least partially be explained by increased hepatocyte proliferation at 5 weeks. The tumors of the Furin knockout mice were histologically similar to those in wild type mice. In conclusion, liver-specific Furin inhibition in HCC enhances the tumor formation and will not be a good therapeutic strategy for this tumor type.

  6. Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes.

    Science.gov (United States)

    Sun, Zhiqi; Gong, Jingyi; Wu, Han; Xu, Wenyi; Wu, Lizhen; Xu, Dijin; Gao, Jinlan; Wu, Jia-Wei; Yang, Hongyuan; Yang, Maojun; Li, Peng

    2013-01-01

    Mature white adipocytes contain a characteristic unilocular lipid droplet. However, the molecular mechanisms underlying unilocular lipid droplet formation are poorly understood. We previously showed that Fsp27, an adipocyte-specific lipid droplet-associated protein, promotes lipid droplet growth by initiating lipid exchange and transfer. Here, we identify Perilipin1 (Plin1), another adipocyte-specific lipid droplet-associated protein, as an Fsp27 activator. Plin1 interacts with the CIDE-N domain of Fsp27 and markedly increases Fsp27-mediated lipid exchange, lipid transfer and lipid droplet growth. Functional cooperation between Plin1 and Fsp27 is required for efficient lipid droplet growth in adipocytes, as depletion of either protein impairs lipid droplet growth. The CIDE-N domain of Fsp27 forms homodimers and disruption of CIDE-N homodimerization abolishes Fsp27-mediated lipid exchange and transfer. Interestingly, Plin1 can restore the activity of CIDE-N homodimerization-defective mutants of Fsp27. We thus uncover a novel mechanism underlying lipid droplet growth and unilocular lipid droplet formation that involves the cooperative action of Fsp27 and Plin1 in adipocytes.

  7. Liver Steatosis and Increased ChREBP Expression in Mice Carrying a Liver Specific SIRT1 Null Mutation under a Normal Feeding Condition

    Directory of Open Access Journals (Sweden)

    Rui-Hong Wang, Cuiling Li, Chu-Xia Deng

    2010-01-01

    Full Text Available SIRT1, a homolog of yeast Sir2, is a type III NAD+ dependent histone and protein deacetylase. Previous studies of mice carrying liver specific deletion of exon 4 of the Sirt1 gene revealed opposite responses of mutant mice to a high-fat diet in terms of fatty liver formation, which obscures the function of SRIT1 in liver development and lipid metabolism. To investigate this, we deleted exons 5 and 6 of Sirt1 in the liver by using a Cre-loxP approach. Western blot using an antibody to N-terminal SIRT1 does not detect a truncated protein in the liver of the mutant mice (Sirt1flox5-6/flox5-6;Alb-Cre, suggesting a null mutation for SIRT1 is generated in the liver. Unlike the previously reported phenotypes, the Sirt1flox5-6/flox5-6;Alb-Cre mice develop fatty liver under a normal feeding condition. The disease starts at two months of age and incidence increases as the animals become older, affecting 78% of them when they are over one year of age. We showed that the steatosis is accompanied by altered expression of a number of genes, including increased expression of ChREBP, which acts as one of the central determinants of lipid synthesis in the liver. This data uncovers an important role of SIRT1 in regulating lipid metabolism in the liver, and the SIRT1 mutant mice may serve as an animal model for studying human fatty liver disease and facilitate the development of effective therapeutic approach for the disease.

  8. The human liver-specific proteome defined by transcriptomics and antibody-based profiling.

    Science.gov (United States)

    Kampf, Caroline; Mardinoglu, Adil; Fagerberg, Linn; Hallström, Björn M; Edlund, Karolina; Lundberg, Emma; Pontén, Fredrik; Nielsen, Jens; Uhlen, Mathias

    2014-07-01

    Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.-Kampf, C., Mardinoglu, A., Fagerberg, L., Hallström, B. M., Edlund, K., Lundberg, E., Pontén, F., Nielsen, J., Uhlen, M. The human liver-specific proteome defined by transcriptomics and antibody-based profiling. © FASEB.

  9. Reconstruction and analysis of human liver-specific metabolic network based on CNHLPP data.

    Science.gov (United States)

    Zhao, Jing; Geng, Chao; Tao, Lin; Zhang, Duanfeng; Jiang, Ying; Tang, Kailin; Zhu, Ruixin; Yu, Hong; Zhang, Weidong; He, Fuchu; Li, Yixue; Cao, Zhiwei

    2010-04-05

    Liver is the largest internal organ in the body that takes central roles in metabolic homeostasis, detoxification of various substances, as well as in the synthesis and storage of nutrients. To fulfill these complex tasks, thousands of biochemical reactions are going on in liver to cope with a wide range of foods and environmental variations, which are densely interconnected into an intricate metabolic network. Here, the first human liver-specific metabolic network was reconstructed according to proteomics data from Chinese Human Liver Proteome Project (CNHLPP), and then investigated in the context of the genome-scale metabolic network of Homo sapiens. Topological analysis shows that this organ-specific metabolic network exhibits similar features as organism-specific networks, such as power-law degree distribution, small-world property, and bow-tie structure. Furthermore, the structure of liver network exhibits a modular organization where the modules are formed around precursors from primary metabolism or hub metabolites from derivative metabolism, respectively. Most of the modules are dominated by one major category of metabolisms, while enzymes within same modules have a tendency of being expressed concertedly at protein level. Network decomposition and comparison suggest that the liver network overlays a predominant area in the global metabolic network of H. sapiens genome; meanwhile the human network may develop extra modules to gain more specialized functionality out of liver. The results of this study would permit a high-level interpretation of the metabolite information flow in human liver and provide a basis for modeling the physiological and pathological metabolic states of liver.

  10. Intrathymic inoculation of donor liver specific antigen alleviates rejection of liver allotransplantation

    Institute of Scientific and Technical Information of China (English)

    贾长库; 郑树森; 章爱斌

    2003-01-01

    Use and effects of liver specific antigen in orthotopie liver transplantations were researched in this study. Group I : syngeneie control (Wistar-to-Wistar) ; Group Ⅱ: acute rejection (SD-to-Wistar) ; Group Ⅲ:Thymie inoculation of SD rat LSA day 7 before transplantation. The observation of common situation and sur-vival time, rejection grades, NF-kB activity of splenoeytes and IL-2mRNA expression of grafted liver wereused to analyze acute rejection severity and immune state of animals in different groups. The common situation of group I was very well after transplantation and no signs of rejection were found. Recipients of group Ⅱ lostbody weight progressively. All dead within day 9 to day 13 posttransplantation; median survival time was 10.7±0.51 days. It was an optimal acute rejection control. As for group Ⅲ,5 out of 6 recipients survived for along time and common situation was remarkably better than that of group Ⅱ. Its rejection grades were signifi-cantly lower than that of group Ⅱ( P < 0.05) . NF-kB activity was only detected in group I at day 5 and day 7 after transplantation, whereas high activity of NF-kB was detected at all time points in group Ⅱ and the low NF-kB activity detected in group Ⅲ was significantly lower than that of group Ⅱ ( P < 0.05) . No IL-2mRNA ex-pres sion was detected at any time point in group Ⅰ, whereas high level expression was detected at all time pointsin group Ⅱ and the low level expression only detected at day 3 in group Ⅲ was significantly lower than that ofgroup Ⅱ (P < 0.05). Conclusion: LSA is an important transplantation antigen which is involved directly in the immunorejeetion of liver transplantation. We report here for the first time that intrathymie inoculation of LSA can alleviate the rejection of liver allotransplantation; and that grafts can survive for a long time thereby,thus leading to a novel way to achieve liver transplantation immunotoleranee.

  11. Establishment of reference interval for liver specific biochemical parameters in apparently healthy north Indian population.

    Science.gov (United States)

    Yadav, Dharamveer; Mishra, Sandhya; Gupta, Monika; John, P J; Sharma, Praveen

    2013-01-01

    Reference intervals (RI) are the most common decision support tool used for interpretation of numerical laboratory reports. The quality of the RI can play as large a role in result interpretation as the quality of the result itself. As such there is hardly any study examining RI for liver specific biochemical parameters in Indian population especially north Indians having drastically different food habits as compared to rest of the India. So there is a need to establish the RI for north Indian population. Present study was conducted on 2,021 apparently healthy individuals of north Indian origin ranging in age from 15-60 years, were selected randomly using defined criteria. Lipemic, hemolysed, icteric and stored samples were also excluded adopting preanalytical criteria for rejection of sample. Non parametric methodology for determination of RI was adopted as most of the biochemical parameters included revealed non Gaussian distribution. Data were analyzed for middle 95 percentile (2.5th-97.5th percentile), median and 95 % confidence interval using SPSS software package version 10.0. The upper and the lower limit of RI (reported Vs observed) for bilirubin (0-1.2 Vs 0.30-1.30 mg/dL), serum glutamate oxaloacetate transferase (SGOT) (0-41 Vs 13-52.80 IU/L), serum glutamate pyruvate transferase (SGPT) (0-50 Vs 10-68 IU/L) showed wide variation as compared to reported standard RI however Gamma glutamyl transferase (GGT) (0-50 Vs 5.00-50.60 IU/L) remained within the reported standard RI. Further gender wise evaluation revealed higher cutoff in males (AST 14-55, ALT 11-70.35, GGT 6.76-51.09 in IU/L, bilirubin (0.40-1.34 mg/dL) as compared to females (SGOT 13-50.43, SGPT 9-63.43, GGT 3.92-48.70 in IU/L, Bilirubin 0.30-1.20 mg/dL) for both enzymatic and non enzymatic biochemical parameters. The variations may be attributed to dietary pattern smoking and alcoholism.

  12. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Jacobsen, Kari Stougaard; Mirza, Aashiq Hussain

    2014-01-01

    Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role...... with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBe...... in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children...

  13. Lipid droplet mobilization: The different ways to loosen the purse strings.

    Science.gov (United States)

    D'Andrea, Sabine

    2016-01-01

    Cytosolic lipid droplets are dynamic lipid-storage organelles that play a crucial role as reservoirs of metabolic energy and membrane precursors. These organelles are present in virtually all cell types, from unicellular to pluricellular organisms. Despite similar structural organization, lipid droplets are heterogeneous in morphology, distribution and composition. The protein repertoire associated to lipid droplet controls the organelle dynamics. Distinct structural lipid droplet proteins are associated to specific lipolytic pathways. The role of these structural lipid droplet-associated proteins in the control of lipid droplet degradation and lipid store mobilization is discussed. The control of the strictly-regulated lipolysis in lipid-storing tissues is compared between mammals and plants. Differences in the cellular regulation of lipolysis between lipid-storing tissues and other cell types are also discussed.

  14. Establishment of liver specific glucokinase gene knockout mice:a new animal model for screening anti-diabetic drugs

    Institute of Scientific and Technical Information of China (English)

    Ya-li ZHANG; Xiao-hong TAN; Mei-fang XIAO; Hui LI; Yi-qing Mao; Xiao YANG; Huan-ran TAN

    2004-01-01

    AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knockout mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.

  15. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

    Directory of Open Access Journals (Sweden)

    Thilde Nordmann Winther

    2014-01-01

    Full Text Available Background and Aim. Hepatitis B e antigen positive (HBeAg-positive children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children with chronic hepatitis B (CHB and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children. Results. Thirteen microRNAs showed aberrant plasma expressions in HBeAg-positive children and targeted liver-specific genes. In particular, three microRNAs were upregulated and one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy control children, which showed equal levels. Conclusion. The identified microRNAs might impact the progression of CHB in children. Functional studies are warranted, however, to elucidate the microRNAs’ role in the immunopathogenesis of childhood CHB.

  16. Biliary cystadenoma with bile duct communication depicted on liver-specific contrast agent-enhanced MRI in a child

    Energy Technology Data Exchange (ETDEWEB)

    Marrone, Gianluca; Carollo, Vincenzo; Luca, Angelo [Mediterranean Institute of Transplantation and High Specialization Therapy (ISMETT), Diagnostic and Interventional Radiology, Palermo (Italy); Maggiore, Giuseppe [University Hospital S. Chiara, Gastroenterology and Hepatology, Department of Paediatrics, Pisa (Italy); Sonzogni, Aurelio [Riuniti Hospital, Pathology Department, Bergamo (Italy)

    2011-01-15

    Biliary cystadenoma is a benign, but potentially malignant, cystic neoplasm of the biliary ducts occurring most commonly in middle-aged females and very rarely in children. We present a 9-year-old boy with biliary cystadenoma, diagnosed by MRI using a new liver-specific contrast agent (gadoxetic acid) that is eliminated by the biliary system. The images clearly demonstrate the communication between the multiloculated cystic mass and the biliary tree, suggesting the possibility of biliary cystadenoma. Due to the malignant potential of a cystadenoma, the lesion was resected. The resection was complete and the postoperative course was uneventful. (orig.)

  17. Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase

    Directory of Open Access Journals (Sweden)

    Justin R. Prigge

    2017-06-01

    Full Text Available Energetic nutrients are oxidized to sustain high intracellular NADPH/NADP+ ratios. NADPH-dependent reduction of thioredoxin-1 (Trx1 disulfide and glutathione disulfide by thioredoxin reductase-1 (TrxR1 and glutathione reductase (Gsr, respectively, fuels antioxidant systems and deoxyribonucleotide synthesis. Mouse livers lacking both TrxR1 and Gsr sustain these essential activities using an NADPH-independent methionine-consuming pathway; however, it remains unclear how this reducing power is distributed. Here, we show that liver-specific co-disruption of the genes encoding Trx1, TrxR1, and Gsr (triple-null causes dramatic hepatocyte hyperproliferation. Thus, even in the absence of Trx1, methionine-fueled glutathione production supports hepatocyte S phase deoxyribonucleotide production. Also, Trx1 in the absence of TrxR1 provides a survival advantage to cells under hyperglycemic stress, suggesting that glutathione, likely via glutaredoxins, can reduce Trx1 disulfide in vivo. In triple-null livers like in many cancers, deoxyribonucleotide synthesis places a critical yet relatively low-volume demand on these reductase systems, thereby favoring high hepatocyte turnover over sustained hepatocyte integrity.

  18. Development of hepatocellular adenomas and carcinomas in mice with liver-specific G6Pase-α deficiency

    Directory of Open Access Journals (Sweden)

    Roberta Resaz

    2014-09-01

    Full Text Available Glycogen storage disease type 1a (GSD-1a is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α, and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs. A globally G6Pase-α-deficient (G6pc−/− mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liver-specific G6Pase-α-deficient (LS‑G6pc−/− mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LS‑G6pc−/− mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS‑G6pc−/− mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10–20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC. In conclusion, LS‑G6pc−/− mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.

  19. Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

    Science.gov (United States)

    Cowger, Taku A; Tang, Wei; Zhen, Zipeng; Hu, Kai; Rink, David E; Todd, Trever J; Wang, Geoffrey D; Zhang, Weizhong; Chen, Hongmin; Xie, Jin

    2015-01-01

    Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.

  20. Galactosylated poly(ε-caprolactone) membrane promoted liver-specific functions of HepG2 cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan, E-mail: zhang_yan@ecust.edu.cn [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhang, Yi [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Chen, Min; Zhou, Yan [The State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, 200237 (China); Lang, Meidong, E-mail: mdlang@ecust.edu.cn [The Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2014-08-01

    The lack of pendant functional groups on the PCL backbone has been a great challenge for surface bioactivation of poly(ε-caprolactone) (PCL). In the present study, covalently galactosylated PCL (GPCL) was developed through coupling between the amino-functionalized PCL (NPCL) and the lactobionic acid (LA) and its potential application in maintenance of physiological functions of HepG2 cells was further evaluated. The structure and properties of GPCL were explored by {sup 1}H NMR, FT-IR, GPC and DSC. Moreover, the incorporation of galactose ligands onto GPCL membranes not only promoted higher wettability, but also radically changed surface morphology in comparison with PCL and NPCL according to the contact angle measurement and atomic force microscopy. When HepG2 cells were seeded onto these membranes, the cells on GPCL membranes showed more pronounced cell adhesion and tended to form aggregates during the initial adhesion stage and then progressively grew into multi-layer structures compared to those without galactose ligands by the observation with fluorescence microscope and scanning electron microscopy. Furthermore, live–dead assay and functional tests demonstrated that HepG2 cells on GPCL membranes had superior viability and maintained better liver-specific functions. Collectively, GPCL has great potential for hepatic tissue engineering scaffolds. - Graphical abstract: The specific recognition between the galactose ligands on the galactosylated poly(ε-caprolactone) membrane and the ASGPR on the HepG2 cell surface. The galactosylated poly(ε-caprolactone) membranes improved the cell-matrix interaction. The galactosylated functionalized PCL scaffold is a potential candidate for liver tissue engineering. - Highlights: • The specific recognition between the galactose ligands on the galactosylated poly(ε-caprolactone) membrane and the ASGPR on the HepG2 cell surface. • The galactosylated poly(ε-caprolactone) membranes improved the cell-matrix interaction.

  1. Characterization of liver-specific structure and function during hepatocyte spheroid self-assembly: Implications for a bioartificial liver device

    Science.gov (United States)

    Friend, Julie Renee

    A hollow fiber bioreactor containing collagen-entrapped hepatocytes has been developed as a bioartificial liver device. For clinical application, further scale-up of the device is desirable. This may be achieved through the use of hepatocyte spheroids, which are compacted aggregates that exhibit prolonged viability, higher liver-specific function and a more tissue-like ultrastructure compared to hepatocytes cultured as monolayers. In order to gain a better understanding of structural changes in spheroids over the course of their self-assembly, confocal microscopy was used to optically section spheroids and monitor changes in situ. Channels within spheroids hypothesized to be bile canaliculi were first evaluated by monitoring the diffusion of a fluorescent tracer, FITC-dextran, into spheroids. Three-dimensional reconstruction of spheroids showed that a continuous network of channels was forming within spheroids. Functionality of these channels as bile canaliculi was demonstrated by monitoring secretion of a fluorescently tagged bile acid, FITC-glycocholate, by hepatocytes in spheroids. Secretion of FITC-glycocholate could be seen in both rat and porcine hepatocyte spheroids. To elucidate changes in metabolism occurring during spheroid self-assembly, metabolic flux analysis was applied to hepatocyte spinner cultures. Glucose, lactate, amino acid, albumin and urea concentration in culture medium were measured and used to estimate intracellular fluxes within hepatocytes. Metabolism before and after spheroid formation was compared. Overall, little difference was seen in metabolism before and after spheroid self-assembly. As the BAL approaches clinical trials, methods of bioreactor storage for shipping and inventory purposed need to be developed. Storage conditions were tested in various hepatocyte culture systems. A protocol for storing reactors for 24 hours without significant loss in function was developed. Further optimization will be necessary for storage for longer

  2. Rab32 is important for autophagy and lipid storage in Drosophila.

    Directory of Open Access Journals (Sweden)

    Chao Wang

    Full Text Available Lipids are essential components of all organisms. Within cells, lipids are mainly stored in a specific type of organelle, called the lipid droplet. The molecular mechanisms governing the dynamics of lipid droplets have been little explored. The protein composition of lipid droplets has been analyzed in numerous proteomic studies, and a large number of lipid droplet-associated proteins have been identified, including Rab small GTPases. Rab proteins are known to participate in many intracellular membranous events; however, their exact role in lipid droplets is largely unexplored. Here we systematically investigate the roles of Drosophila Rab family proteins in lipid storage in the larval adipose tissue, fat body. Rab32 and several other Rabs were found to affect the size of lipid droplets as well as lipid levels. Further studies showed that Rab32 and Rab32 GEF/Claret may be involved in autophagy, consequently affecting lipid storage. Loss-of-function mutants of several components in the autophagy pathway result in similar effects on lipid storage. These results highlight the potential functions of Rabs in regulating lipid metabolism.

  3. Lipid Profile

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Lipid Profile Share this page: Was this page helpful? Also ... as: Lipid Panel; Coronary Risk Panel Formal name: Lipid Profile Related tests: Cholesterol ; HDL Cholesterol ; LDL Cholesterol ; Triglycerides ; ...

  4. Differential Expression of Genes Associated with the Progression of Renal Disease in the Kidneys of Liver-Specific Glucokinase Gene Knockout Mice

    Directory of Open Access Journals (Sweden)

    Gang Niu

    2013-03-01

    Full Text Available Liver glucokinase (GCK deficient mice possess mild renal complications associated with diabetes. To investigate the progression of kidney disease and identify candidate genes involved in the pathogenesis of renal damage, we examined changes in tissue structure and gene expression in the kidneys of liver-specific GCK knockout (gckw/− mice and age-matched normal wild-type control (gckw/w mice as they aged. Suppression subtractive hybridization (SSH was used to identify candidate genes that showed a pattern of differential expression between kidneys of gckw/− and gckw/w mice at 60 weeks of age. Differential expression of the candidate genes was examined by real-time qPCR in liver-specific gckw/− and gckw/w mice at 16, 26, 40, 60, and 85 weeks of age. Among the candidate genes, only glutathione peroxidase-3 (GPX3 was confirmed to show differential expression by qPCR in the 60-week old mice, however two others genes, MALAT1 and KEG, showed significant changes at other ages. This study shows that liver-specific glucokinase deficient mice display changes in kidney morphology by 40 weeks of age, and that renal complication may be correlated with a reduction in GPX3 levels. Since decreased GPX3 mRNA expression was observed at 26 weeks, which is younger than the age when pathological changes can be seen in kidney biopsies, GPX3 may serve as an early marker for kidney damage.

  5. Characterization of hepatic lesions (≤30 mm) with liver-specific contrast agents: A comparison between ultrasound and magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masanori, E-mail: machat1215@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Maruyama, Hitoshi, E-mail: maru-cib@umin.ac.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Shimada, Taro, E-mail: bobtaro51@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Kamezaki, Hidehiro, E-mail: ugn29814@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Sekimoto, Tadashi, E-mail: tad_sekimoto@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Kanai, Fumihiko, E-mail: kanaif@faculty.chiba-u.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Yokosuka, Osamu, E-mail: yokosukao@faculty.chiba-u.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan)

    2013-01-15

    Purpose: Imaging-based differentiation of hepatic lesions (≤30 mm) between well-differentiated hepatocellular carcinomas (w-HCC) and regenerative nodules (RN) presents difficulties. The aim was to compare the diagnostic abilities to differentiate w-HCC from RN using contrast-enhanced ultrasound and magnetic resonance imaging (MRI) both with liver-specific contrast agents. Materials and methods: This prospective study included 67 pathologically proven hepatic lesions (17.5 ± 5.4 mm, 54 w-HCCs, 13 RNs) in 56 patients with chronic hepatitis/cirrhosis (male 40, female 16; 29–79y). Hepatic-arterial/liver-specific phase enhancements were assessed quantitatively by ultrasound with perflubutane microbubble agent and MRI with gadolinium-ethoxybenzyl-diethylenetriamine with respect to the histological findings. Results: Sensitivity, specificity and accuracy of hepatic-arterial phase hyper-enhancement for w-HCC were 59.3%, 100% and 67.2% by ultrasound and 46.3%, 100% and 56.7% by MRI without significant difference. Meanwhile, those of liver-specific-phase hypo-enhancement for w-HCC were 44.4%, 100% and 55.2% by ultrasound and 87.0% (p < 0.0001), 46.2% (p = 0.0052) and 79.1% (p = 0.0032) by MRI. Diagnostic accuracies for w-HCC by area under the receiver operating characteristic curves were higher in the hepatic-arterial phase in ultrasound (0.8316) than MRI (0.6659, p = 0.0101) and similar in the liver-specific phase in ultrasound (0.7225) and MRI (0.7347, p = 0.8814). Conclusions: Hypervascularity is a significant feature which distinguishes w-HCC from RN, and ultrasound exerts a beneficial impact better than MRI for such characterization. However, both imaging have comparable abilities in the characterization of non-hypervascular lesions, compensating mutually for the poor sensitivity of ultrasound and the poor specificity of MRI in the liver-specific phase.

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

    Science.gov (United States)

    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.

  7. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism.

    Science.gov (United States)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill; Ruckerbauer, David E; Hannibal-Bach, Hans Kristian; Zanghellini, Jürgen; Jensen, Ole N; Ejsing, Christer S

    2015-03-19

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level.

  8. Inhibition of hepatitis B virus replication by helper dependent adenoviral vectors expressing artificial anti-HBV pri-miRs from a liver-specific promoter.

    Science.gov (United States)

    Mowa, Mohube Betty; Crowther, Carol; Ely, Abdullah; Arbuthnot, Patrick

    2014-01-01

    Research on applying RNA interference (RNAi) to counter HBV replication has led to identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-term inhibition of HBV replication in vivo by using helper dependent adenoviral vectors (HD Ads) expressing anti-HBV sequences from a constitutively active cytomegalovirus (CMV) promoter. To develop the use of liver-specific transcription regulatory elements we investigated the utility of the murine transthyretin (MTTR) promoter for expression of anti-HBV primary microRNAs (pri-miRs). HD Ads containing MTTR promoter effected superior expression of anti-HBV pri-miRs in mice compared to HD Ads containing the CMV promoter. MTTR-containing HD Ads resulted in HBV replication knockdown of up to 94% in mice. HD Ads expressing trimeric anti-HBV pri-miRs silenced HBV replication for 5 weeks. We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility.

  9. Porcine Adipose-Derived Mesenchymal Stem Cells Retain Their Stem Cell Characteristics and Cell Activities While Enhancing the Expression of Liver-Specific Genes after Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Chenxia Hu

    2016-01-01

    Full Text Available Acute liver failure (ALF is a kind of complicated syndrome. Furthermore, adipose-derived mesenchymal stem cells (ADMSCs can serve as a useful cell resource for autotransplantation due to their abundance and micro-invasive accessability. However, it is unknown how ALF will influence the characteristics of ADMSCs and whether ADMSCs from patients suffering from end-stage liver diseases are potential candidates for autotransplantation. This study was designed to compare various properties of ALF-derived ADMSCs with normal ADMSCs in pig models, with regard to their cellular morphology, cell proliferative ability, cell apoptosis, expression of surface antigens, mitochondrial and lysosomal activities, multilineage potency, and expression of liver-specific genes. Our results showed that ALF does not influence the stem cell characteristics and cell activities of ADMSCs. Intriguingly, the expression levels of several liver-specific genes in ALF-derived ADMSCs are higher than in normal ADMSCs. In conclusion, our findings indicate that the stem cell characteristics and cell activities of ADMSCs were not altered by ALF and these cells can serve as a new source for regenerative medicine.

  10. Fabrication of 3D-culture platform with sandwich architecture for preserving liver-specific functions of hepatocytes using 3D bioprinter.

    Science.gov (United States)

    Arai, Kenichi; Yoshida, Toshiko; Okabe, Motonori; Goto, Mitsuaki; Mir, Tanveer Ahmad; Soko, Chika; Tsukamoto, Yoshinari; Akaike, Toshihiro; Nikaido, Toshio; Zhou, Kaixuan; Nakamura, Makoto

    2017-06-01

    The development of new three-dimensional (3D) cell culture system that maintains the physiologically relevant signals of hepatocytes is essential in drug discovery and tissue engineering research. Conventional two-dimensional (2D) culture yields cell growth, proliferation, and differentiation. However, gene expression and signaling profiles can be different from in vivo environment. Here, we report the fabrication of a 3D culture system using an artificial scaffold and our custom-made inkjet 3D bioprinter as a new strategy for studying liver-specific functions of hepatocytes. We built a 3D culture platform for hepatocytes-attachment and formation of cell monolayer by interacting the galactose chain of galactosylated alginate gel (GA-gel) with asialoglycoprotein receptor (ASGPR) of hepatocytes. The 3D geometrical arrangement of cells was controlled by using 3D bioprinter, and cell polarity was controlled with the galactosylated hydrogels. The fabricated GA-gel was able to successfully promote adhesion of hepatocytes. To observe liver-specific functions and to mimic hepatic cord, an additional parallel layer of hepatocytes was generated using two gel sheets. These results indicated that GA-gel biomimetic matrices can be used as a 3D culture system that could be effective for the engineering of liver tissues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1583-1592, 2017. © 2017 Wiley Periodicals, Inc.

  11. Plasma levels of liver-specific miR-122 is massively increased in a porcine cardiogenic shock model and attenuated by hypothermia.

    Science.gov (United States)

    Andersson, Patrik; Gidlöf, Olof; Braun, Oscar O; Götberg, Matthias; van der Pals, Jesper; Olde, Björn; Erlinge, David

    2012-02-01

    Tissue-specific circulating micro-RNAs (miRNAs) are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model, we investigated the release pattern of cardiac-specific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. Pigs were anesthetized, and cardiogenic shock was induced by inflation of a percutaneous coronary intervention balloon in the proximal left anterior descending artery for 40 min followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33°C, n = 6) or normothermia (38°C, n = 6). Circulating miRNAs were extracted from plasma and measured with quantitative real-time polymerase chain reaction (PCR). Tissue specificity was assessed by miRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific, whereas miR-208b was expressed exclusively in the heart. In the control group, ischemic cardiogenic shock induced a 460,000-fold and a 63,000-fold increase in plasma levels of miR-122 (P cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.

  12. Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter

    Directory of Open Access Journals (Sweden)

    Mohube Betty Mowa

    2014-01-01

    Full Text Available Research on applying RNA interference (RNAi to counter HBV replication has led to identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-term inhibition of HBV replication in vivo by using helper dependent adenoviral vectors (HD Ads expressing anti-HBV sequences from a constitutively active cytomegalovirus (CMV promoter. To develop the use of liver-specific transcription regulatory elements we investigated the utility of the murine transthyretin (MTTR promoter for expression of anti-HBV primary microRNAs (pri-miRs. HD Ads containing MTTR promoter effected superior expression of anti-HBV pri-miRs in mice compared to HD Ads containing the CMV promoter. MTTR-containing HD Ads resulted in HBV replication knockdown of up to 94% in mice. HD Ads expressing trimeric anti-HBV pri-miRs silenced HBV replication for 5 weeks. We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility.

  13. HCV非结构蛋白NS5A基因的斑马鱼肝脏表达模型%A zebrafish model for liver-specific expression of HCV NS5A gene

    Institute of Scientific and Technical Information of China (English)

    赵晔; 胡占英; 佟军威; 赵立勋; 蒋建东; 张靖溥

    2011-01-01

    Objective To establish a zebrafish model for liver-specific expression of HCV non-structural protein NS5A, and to explore the effects of HCV NS5A on liver pathological marker genes in vivo.Methods Liver-specific gene expression regulating element zebrafish fatty acid binding protein enhancer (eFABP) sequence and HCV NS5A was cloned. By ligating the eFABP, CMV promoter, NS5A, the IRES of encephalomyocarditis virus (EMCV) and DsRed in turn, a liver-specific gene expression vector pFC-5AiR was constructed. Reporter gene DsRed was detected in Huh7 cells transfected with pFC-5AiR. The linearized vector was subsequently microinjected into zebrafish embryos. Liver-specific expression of pFC-5AiR was detected by observation under fluorescence microscopy and whole mount in situ hybridization methods. Moreover, the transcriptional and translational levels of NS5A were investigated by RT-PCR and western blot. Finally, expression level of some liver pathology associated genes was investigated by RT-PCR.Results Cell transfection results showed that red fluorescent protein gene DsRed in pFC-5AiR is able to be expressed in Huh7 cells. After microinjection of the vector into zebrafish embryos, red fluorescence was observed to be located in the zebrafish liver under fluorescent microscopy. RT-PCR and western blot results indicated that NS5A is able to be expressed in zebrafish. In situ hybridization results further confirmed that the expression of NS5A in zebrafish liver. In addition, some pathological marker genes, such as Adiponectin, Argsyn, LDLR, TGF-β and HMGR etc., were up-regulated in response to HCV NS5A expression, suggesting that NS5A may be involved in liver lipid metabolism disorder and fibrosis.Conclusion A zebrafish model for HCV NS5A expression in liver has been successfully established. Preliminary investigation shows that HCV NS5A expression in vivo is associated with aberrant genes expression involved in liver pathological process. This model can be used to study

  14. The Evaluation of Liver Function Using Liver-Specific MR Contrast Agents%MR特异性对比剂肝功能评价研究

    Institute of Scientific and Technical Information of China (English)

    冯汝静; 黄仲奎

    2013-01-01

    Objective To evaluate the application value of liver-specific contrast agents in evaluating liver function. Methods Thirty six patients with liver dysfunction underwent MRI enhanced examination using liver specific contrast a-gent,including Gd BOPTA in 28 cases and Gd EOB DTPA in 12 cases, as well as MR conventional raulti phase enhanced scan. The liver function were evaluated with the biliary display in the hepatobiliary excretion phase. Results According to the visibility score of biliary in the hepatobiliary excretion phase images, 33 patients' liver function can be classified as grade A (grade > 16 points) in 17 cases,grade B (6 to 15 points) in 10 cases,grade C (6 to 15 points)in 6 cases. The consistency of image grading and clinical Child-pugh grading for liver function were good in the 33 patients (K = 0. 570, P = 0. 000). Especially, excellent consistency was presented in 10 cases using Gd EOB DTPA agent (K = 0. 804, P = 0.000). Conclusion The liver function could be evaluated by the liver-specific contrast agent enhanced MR images.%目的 探讨MRI特异性对比剂对肝功能评价的应用价值.方法 选择2011年至2012年行肝脏MRI检查的33例肝功能障碍患者资料.行肝脏常规MRI平扫、肝脏MRI特异性对比剂[钆贝葡胺(Gd-BOPTA)26例,钆塞酸二钠(Gd-EOB-DTPA) 10例]增强,对肝胆排泄期的各级胆管显示情况进行5级评分,再根据各级胆管显示总评分进行肝功能MRI分级.结果 33例患者的肝功能MR分级与临床Child-Pugh分级一致性良好(K=0.570,P=o.ooo),其中10例Gd-EOB-DTPA增强肝功能MR分级与临床Child-Pugh分级吻合程度极佳(K=0.804,P=0.000).结论 观察肝脏MRI特异性对比剂增强肝胆排泄期的胆管显示情况,可以评价整个肝脏肝功能情况.

  15. Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

    Science.gov (United States)

    Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2013-12-01

    Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

  16. Lipid somersaults

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Menon, Anant K.

    2016-01-01

    Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support divers...

  17. Adipophilin distribution and colocalization with lipid droplets in skeletal muscle.

    LENUS (Irish Health Repository)

    Shaw, Christopher S

    2009-05-01

    Intramyocellular lipids (IMCL) are stored as discrete lipid droplets which are associated with a number of proteins. The lipid droplet-associated protein adipophilin (the human orthologue of adipose differentiation-related protein) is ubiquitously expressed and is one of the predominant lipid droplet-proteins in skeletal muscle. The aim of this study was to investigate the subcellular distribution of adipophilin in human muscle fibres and to measure the colocalization of adipophilin with IMCL. Muscle biopsies from six lean male cyclists (BMI 23.4 +\\/- 0.4, aged 31 +\\/- 2 years, W (max) 346 +\\/- 8) were stained for myosin heavy chain type 1, IMCL, adipophilin and mitochondria using immunofluorescence and viewed with widefield and confocal fluorescence microscopy. The present study shows that like IMCL, the adipophilin content is ~twofold greater in type I skeletal muscle fibres and is situated in the areas between the mitochondrial network. Colocalization analysis demonstrated that 61 +\\/- 2% of IMCL contain adipophilin. Although the majority of adipophilin is contained within IMCL, 36 +\\/- 4% of adipophilin is not associated with IMCL. In conclusion, this study indicates that the IMCL pool is heterogeneous, as the majority but not all IMCL contain adipophilin.

  18. Isolation of modulators of the liver-specific organic anion-transporting polypeptides (OATPs) 1B1 and 1B3 from Rollinia emarginata Schlecht (Annonaceae).

    Science.gov (United States)

    Roth, Megan; Araya, Juan J; Timmermann, Barbara N; Hagenbuch, Bruno

    2011-11-01

    Organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) are liver-specific transporters that mediate the uptake of a broad range of drugs into hepatocytes, including statins, antibiotics, and many anticancer drugs. Compounds that alter transport by one or both of these OATPs could potentially be used to target drugs to hepatocytes or improve the bioavailability of drugs that are cleared by the liver. In this study, we applied a bioassay-guided isolation approach to identify such compounds from the organic extract of Rollinia emarginata Schlecht (Annonaceae). Fractions of the plant extract were screened for effects on OATP1B1- and OATP1B3-mediated transport of the model substrates estradiol-17β-glucuronide and estrone-3-sulfate. We isolated three compounds, ursolic acid, oleanolic acid, and 8-trans-p-coumaroyloxy-α-terpineol, which inhibited estradiol-17β-glucuronide uptake by OATP1B1 but not OATP1B3. In addition, a rare compound, quercetin 3-O-α-l-arabinopyranosyl(1→2) α-L-rhamnopyranoside, was identified that had distinct effects on each OATP. OATP1B1 was strongly inhibited, as was OATP1B3-mediated transport of estradiol-17β-glucuronide. However, OATP1B3-mediated uptake of estrone-3-sulfate was stimulated 4- to 5-fold. Kinetic analysis of this stimulation revealed that the apparent affinity for estrone-3-sulfate was increased (decreased K(m)), whereas the maximal rate of transport (V(max)) was significantly reduced. These results demonstrate a mechanism through which the hepatic uptake of drug OATP substrates could be stimulated.

  19. Microsomal Triglyceride Transfer Protein (MTP Associates with Cytosolic Lipid Droplets in 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Joseph D Love

    Full Text Available Lipid droplets are intracellular energy storage organelles composed of a hydrophobic core of neutral lipid, surrounded by a monolayer of phospholipid and a diverse array of proteins. The function of the vast majority of these proteins with regard to the formation and/or turnover of lipid droplets is unknown. Our laboratory was the first to report that microsomal triglyceride transfer protein (MTP, a lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins, was expressed in adipose tissue of humans and mice. In addition, our studies suggested that MTP was associated with lipid droplets in both brown and white fat. Our observations led us to hypothesize that MTP plays a key role in lipid droplet formation and/or turnover. The objective of these studies was to gain insight into the function of MTP in adipocytes. Using molecular, biochemical, and morphologic approaches we have shown: 1 MTP protein levels increase nearly five-fold as 3T3-L1 cells differentiate into adipocytes. 2 As 3T3-L1 cells undergo differentiation, MTP moves from the juxtanuclear region of the cell to the surface of lipid droplets. MTP and perilipin 2, a major lipid droplet surface protein, are found on the same droplets; however, MTP does not co-localize with perilipin 2. 3 Inhibition of MTP activity has no effect on the movement of triglyceride out of the cell either as a lipid complex or via lipolysis. 4 MTP is found associated with lipid droplets within hepatocytes from human fatty livers, suggesting that association of MTP with lipid droplets is not restricted to adipocytes. In summary, our data demonstrate that MTP is a lipid droplet-associated protein. Its location on the surface of the droplet in adipocytes and hepatocytes, coupled with its known function as a lipid transfer protein and its increased expression during adipocyte differentiation suggest a role in lipid droplet biology.

  20. Development of a convenient in vivo hepatotoxin assay using a transgenic zebrafish line with liver-specific DsRed expression.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Zhang

    Full Text Available Previously we have developed a transgenic zebrafish line (LiPan with liver-specific red fluorescent protein (DsRed expression under the fabp10a promoter. Since red fluorescence in the liver greatly facilitates the observation of liver in live LiPan fry, we envision that the LiPan zebrafish may provide a useful tool in analyses of hepatotoxicity based on changes of liver red fluorescence intensity and size. In this study, we first tested four well-established hepatotoxins (acetaminophen, aspirin, isoniazid and phenylbutazone in LiPan fry and demonstrated that these hepatotoxins could significantly reduce both liver red fluorescence and liver size in a dosage-dependent manner, thus the two measurable parameters could be used as indicators of hepatotoxicity. We then tested the LiPan fry with nine other chemicals including environmental toxicants and human drugs. Three (mefenamic acid, lindane, and arsenate behave like hepatotoxins in reduction of liver red fluorescence, while three others (17β-estradiol, TCDD [2,3,7,8-tetrachlorodibenzo-p-dioxin] and NDMA [N-nitrosodimethylamine] caused increase of liver red fluorescence and the liver size. Ethanol and two other chemicals, amoxicillin (antibiotics and chlorphenamine (pain killer did not resulted in significant changes of liver red fluorescence and liver size. By quantitative RT-PCR analysis, we found that the changes of red fluorescence intensity caused by different chemicals correlated to the changes of endogenous fabp10a RNA expression, indicating that the measured hepatotoxicity was related to fatty acid transportation and metabolism. Finally we tested a mixture of four hepatotoxins and observed a significant reduction of red fluorescence in the liver at concentrations below the lowest effective concentrations of individual hepatotoxins, suggesting that the transgenic zebrafish assay is capable of reporting compound hepatotoxicity effect from chemical mixtures. Thus, the LiPan transgenic fry

  1. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kuklin, Alexander [ORNL; Mynatt, Randall [ORNL; Klebig, Mitch [ORNL; Kiefer, Laura [Glaxo Wellcome, Research Triangle Park, NC; Wilkison, William O [Glaxo Wellcome, Research Triangle Park, NC; Woychik, Richard P [Jackson Laboratory, The, Bar Harbor, ME; Michaud III, Edward J [ORNL

    2004-01-01

    of liver tumors compared to non-transgenic control mice. Conclusions: The data demonstrate that liver-specific expression of the agouti gene is not sufficient to induce obesity or diabetes, but, in the absence of these factors, agouti continues to promote hepatocellular carcinogenesis.

  2. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Directory of Open Access Journals (Sweden)

    Kiefer Laura L

    2004-06-01

    with an increased number of liver tumors compared to non-transgenic control mice. Conclusions The data demonstrate that liver-specific expression of the agouti gene is not sufficient to induce obesity or diabetes, but, in the absence of these factors, agouti continues to promote hepatocellular carcinogenesis.

  3. The Lipid Droplet Protein Hypoxia-inducible Gene 2 Promotes Hepatic Triglyceride Deposition by Inhibiting Lipolysis*

    Science.gov (United States)

    DiStefano, Marina T.; Danai, Laura V.; Roth Flach, Rachel J.; Chawla, Anil; Pedersen, David J.; Guilherme, Adilson; Czech, Michael P.

    2015-01-01

    The liver is a major site of glucose, fatty acid, and triglyceride (TG) synthesis and serves as a major regulator of whole body nutrient homeostasis. Chronic exposure of humans or rodents to high-calorie diets promotes non-alcoholic fatty liver disease, characterized by neutral lipid accumulation in lipid droplets (LD) of hepatocytes. Here we show that the LD protein hypoxia-inducible gene 2 (Hig2/Hilpda) functions to enhance lipid accumulation in hepatocytes by attenuating TG hydrolysis. Hig2 expression increased in livers of mice on a high-fat diet and during fasting, two states associated with enhanced hepatic TG content. Hig2 expressed in primary mouse hepatocytes localized to LDs and promoted LD TG deposition in the presence of oleate. Conversely, tamoxifen-inducible Hig2 deletion reduced both TG content and LD size in primary hepatocytes from mice harboring floxed alleles of Hig2 and a cre/ERT2 transgene controlled by the ubiquitin C promoter. Hepatic TG was also decreased by liver-specific deletion of Hig2 in mice with floxed Hig2 expressing cre controlled by the albumin promoter. Importantly, we demonstrate that Hig2-deficient hepatocytes exhibit increased TG lipolysis, TG turnover, and fatty acid oxidation as compared with controls. Interestingly, mice with liver-specific Hig2 deletion also display improved glucose tolerance. Taken together, these data indicate that Hig2 plays a major role in promoting lipid sequestration within LDs in mouse hepatocytes through a mechanism that impairs TG degradation. PMID:25922078

  4. Lipid signaling in plants

    NARCIS (Netherlands)

    Munnik, T.

    2010-01-01

    This book highlights the current status of plant lipid signaling. Written by leading researchers in the field, the chapters include detailed information on the measurement, regulation and function of phospholipases, lipid kinases, lipid phosphatases, inositolpolyphosphates, polyphosphoinositides, ph

  5. Lipid Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They ...

  6. Plant lipid signaling protocols

    NARCIS (Netherlands)

    Munnik, T.; Heilmann, I.

    2013-01-01

    Eukaryotic cells are surrounded by membranes consisting of various lipids, including sterols, sphingolipids, glycolipids, and phospholipids. Besides structural functions, membranes also contain lipids with regulatory and signaling roles. Such lipids include polyphosphoinositides, the low-abundant

  7. Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA.

    Science.gov (United States)

    Liu, Kun; Zhou, Shengli; Kim, Ji-Young; Tillison, Kristin; Majors, David; Rearick, David; Lee, Jun Ho; Fernandez-Boyanapalli, Ruby F; Barricklow, Katherine; Houston, M Sue; Smas, Cynthia M

    2009-12-01

    The adipocyte-specific protein FSP27, also known as CIDEC, is one of three cell death-inducing DFF45-like effector (CIDE) proteins. The first known function for CIDEs was promotion of apoptosis upon ectopic expression in mammalian cells. Recent studies in endogenous settings demonstrated key roles for CIDEs in energy metabolism. FSP27 is a lipid droplet-associated protein whose heterologous expression enhances formation of enlarged lipid droplets and is required for unilocular lipid droplets typical of white adipocytes in vivo. Here, we delineate relationships between apoptotic function and lipid droplet localization of FSP27. We demonstrate that ectopic expression of FSP27 induces enlarged lipid droplets in multiple human cell lines, which is indicative that its mechanism involves ubiquitously present, rather than adipocyte-specific, cellular machinery. Furthermore, promotion of lipid droplet formation in HeLa cells via culture in exogenous oleic acid offsets FSP27-mediated apoptosis. Using transient cotransfections and analysis of lipid droplets in HeLa cells stably expressing FSP27, we show that FSP27 does not protect lipid droplets from action of ATGL lipase. Domain mapping with eGFP-FSP27 deletion constructs indicates that lipid droplet localization of FSP27 requires amino acids 174-192 of its CIDE C domain. The apoptotic mechanism of FSP27, which we show involves caspase-9 and mitochondrial cytochrome c, also requires this 19-amino acid region. Interaction assays determine the FSP27 CIDE C domain complexes with CIDEA, and Western blot reveals that FSP27 protein levels are reduced by coexpression of CIDEA. Overall, our findings demonstrate the function of the FSP27 CIDE C domain and/or regions thereof for apoptosis, lipid droplet localization, and CIDEA interaction.

  8. Correlation between hepatocarcinogenic effect of estragole and its influence on glucocorticoid induction of liver-specific enzymes and activities of FOXA and HNF4 transcription factors in mouse and rat liver.

    Science.gov (United States)

    Kaledin, V I; Pakharukova, M Yu; Pivovarova, E N; Kropachev, K Yu; Baginskaya, N V; Vasilieva, E D; Ilnitskaya, S I; Nikitenko, E V; Kobzev, V F; Merkulova, T I

    2009-04-01

    It is known that the carcinogenic effect of estragole, a component of essential oils of many spicy plants, is characterized by species, tissue, and sex specificity. It causes mainly liver tumors in female mice but is not carcinogenic for male mice and for rats. In this work, the estragole hepatocarcinogenicity was shown for female mice of previously not studied ICR line. The strict correlation between estragole hepatocarcinogenicity and its ability to decrease the level of glucocorticoid induction of liver-specific enzymes tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO) was found. Inhibition of TAT and TO inducibility by estragole takes place only in female mice but not in male mice and in rats. Studying the estragole effect on DNA-binding activity of transcription factors, present mainly in liver and regulating expression of genes encoding liver-specific proteins, has shown that estragole decreases FOXA and HNF4 activities but not activities of C/EBP and HNF1, and this happens only in female mice, for which this substance is hepatocarcinogen, but not in male mice and in rats. Pentachlorophenol, preventing hepatocarcinogenic effect of estragole, abolishes inhibitory influence of the latter on the TAT and TO glucocorticoid induction and restores DNA-binding activity of FOXA and HNF4. Thus, a correlation was revealed between the estragole hepatocarcinogenic effect and decrease in DNA-binding activity of transcription factors FOXA and HNF4, which might be indicative of the role of these factors in tumor suppression mechanisms in liver.

  9. Doxorubicin Lipid Complex Injection

    Science.gov (United States)

    Doxorubicin lipid complex is used to treat ovarian cancer that has not improved or that has worsened after treatment with other medications. Doxorubicin lipid complex is also used to treat Kaposi's ...

  10. Irinotecan Lipid Complex Injection

    Science.gov (United States)

    Irinotecan lipid complex is used in combination with other medications to treat pancreatic cancer that has spread to other ... worsened after treatment with other chemotherapy medications. Irinotecan lipid complex is in a class of antineoplastic medications ...

  11. Daunorubicin Lipid Complex Injection

    Science.gov (United States)

    Daunorubicin lipid complex is used to treat advanced Kaposi's sarcoma (a type of cancer that causes abnormal tissue to ... body) related to acquired immunodeficiency syndrome (AIDS). Daunorubicin lipid complex is in a class of medications called ...

  12. Vincristine Lipid Complex Injection

    Science.gov (United States)

    Vincristine lipid complex is used to treat a certain type of acute lymphoblastic leukemia (ALL; a type of cancer ... least two different treatments with other medications. Vincristine lipid complex is in a class of medications called ...

  13. Parenteral Nutrition and Lipids.

    Science.gov (United States)

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

    2017-04-14

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

  14. Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-1,4,7-trisacetic Acid (DO3A) Conjugate of Tranexamates: A Quest for a Liver-specific Magnetic Resonance Imaging Contrast Agent

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Kisoo; Jeong, Hyunjeong; Kim, Heekyung; Choi, Garam; Chang, Yongmin; Kim, Taejeong [Kyungpook National Univ., Daegu (Korea, Republic of); Suh, Kyungjin [Dongguk Univ., Kyungju (Korea, Republic of)

    2014-01-15

    The work is directed toward the synthesis of a series of DO3A conjugates of tranexamates (1c-e) and their Gd complexes (2c-e) for use as a liver-specific MRI CA. All these complexes show thermodynamic and kinetic stabilities comparable to those of structurally related clinical agents such as Dotarem. Their R{sub 1} relaxivities also compare well with those of commercial agent, ranging 3.68-4.84 mM{sup -1}s{sup -1}. In vivo MR images of mice with 2a-e reveal that only 2a exhibits liver-specificity. Although 2b and 2c show strong enhancement in liver, yet no bile-excretion is observed to be termed as a liver-specific agent. The rest behaves much like ordinary ECF CAs like Dotarem. The new series possess no toxicity to be employed in vivo.

  15. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus

    2014-01-01

    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation......, and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  16. Nutrients and neurodevelopment: lipids.

    Science.gov (United States)

    González, Horacio F; Visentin, Silvana

    2016-10-01

    Nutrients, lipids in particular, make up the central nervous system structure and play major functional roles: they stimulate development, migration, and nerve cell differentiation. They are part of gray matter, white matter, nerve nuclei, and synaptogenesis. Breast milk contains lipids which are crucial for infant brain development. The lipid profile of breast milk was used as a guideline for the development of breast milk substitutes. However, to date, no substitute has matched it. Complementary feeding should include docosahexaenoic acid, arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and complex lipids found in milk fat. The lipid composition of breast milk depends on maternal intake and nutritional status during pregnancy and breast-feeding. It has a great impact on development. Our goal is to review scientific literature regarding the role of lipids on infant brain development and the importance of breast milk lipid composition, maternal diet, and complementary feeding.

  17. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...... of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations...

  18. Polyene-lipids: a new tool to image lipids

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim

    2005-01-01

    conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated...... the superiority of polyene-lipids to both NBD- and BODIPY-tagged lipids. Cells readily take up various polyene-lipid precursors and generate the expected end products with no apparent disturbance by the tag. Applying two-photon excitation microscopy, we imaged the distribution of polyene-lipids in living...

  19. The IgG antibody reactivity of sera from patients with active chronic hepatitis to a crude liver antigen and liver specific protein (LSP): analysis by ELISA and immunoblotting.

    Science.gov (United States)

    Sundin, U; Heigl, Z; Sundqvist, K G

    1988-11-01

    The antibody reactivity to liver specific protein (LSP) and a crude liver antigen of sera from patients with chronic active hepatitis (CAH) were studied along with other related diseases and healthy individuals. CAH sera containing liver reacting antibodies were selected using an ELISA with a crude liver preparation as antigen and subsequently the specificity was analysed by immunoblotting of SDS-PAGE-separated LSP. The incidence of IgG antibodies to the crude liver antigen and LSP in sera from 15 patients with CAH was 94% and 55% respectively. In the healthy control group (n = 30) the corresponding figures were 3% and 17%. Sera from patients with other autoimmune conditions with considerable reactivity in the crude liver ELISA test were those with antibodies against extractable nuclear antigens (ENA) and thyroid gland antigens, while the anti-nuclear antibody (ANA) group as a whole did not differ from the control group. In immunoblotting of SDS-PAGE-separated crude liver and LSP antigens, the IgG binding pattern of ELISA IgG positive CAH sera and sera from patients with thyroid disease was distinct, with bands corresponding to antigens of molecular weights of 38, 45 and 50 kD which were not observed in ELISA negative CAH sera or in sera from patients with other diseases and among healthy controls.

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

    Science.gov (United States)

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

    2015-02-01

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

  1. Small Intestine but Not Liver Lysophosphatidylcholine Acyltransferase 3 (Lpcat3) Deficiency Has a Dominant Effect on Plasma Lipid Metabolism.

    Science.gov (United States)

    Kabir, Inamul; Li, Zhiqiang; Bui, Hai H; Kuo, Ming-Shang; Gao, Guangping; Jiang, Xian-Cheng

    2016-04-01

    Lysophosphatidylcholine acyltransferase 3 (Lpcat3) is involved in phosphatidylcholine remodeling in the small intestine and liver. We investigated lipid metabolism in inducible intestine-specific and liver-specificLpcat3gene knock-out mice. We producedLpcat3-Flox/villin-Cre-ER(T2)mice, which were treated with tamoxifen (at days 1, 3, 5, and 7), to deleteLpcat3specifically in the small intestine. At day 9 after the treatment, we found that Lpcat3 deficiency in enterocytes significantly reduced polyunsaturated phosphatidylcholines in the enterocyte plasma membrane and reduced Niemann-Pick C1-like 1 (NPC1L1), CD36, ATP-binding cassette transporter 1 (ABCA1), and ABCG8 levels on the membrane, thus significantly reducing lipid absorption, cholesterol secretion through apoB-dependent and apoB-independent pathways, and plasma triglyceride, cholesterol, and phospholipid levels, as well as body weight. Moreover, Lpcat3 deficiency does not cause significant lipid accumulation in the small intestine. We also utilized adenovirus-associated virus-Cre to depleteLpcat3in the liver. We found that liver deficiency only reduces plasma triglyceride levels but not other lipid levels. Furthermore, there is no significant lipid accumulation in the liver. Importantly, small intestine Lpcat3 deficiency has a much bigger effect on plasma lipid levels than that of liver deficiency. Thus, inhibition of small intestine Lpcat3 might constitute a novel approach for treating hyperlipidemia.

  2. Lipid bilayers and interfaces

    NARCIS (Netherlands)

    Kik, R.A.

    2007-01-01

    In biological systems lipid bilayers are subject to many different interactions with other entities. These can range from proteins that are attached to the hydrophilic region of the bilayer or transmembrane proteins that interact with the hydrophobic region of the lipid bilayer. Interaction between

  3. Lipids and lipid binding proteins: a perfect match.

    Science.gov (United States)

    Glatz, Jan F C

    2015-02-01

    Lipids serve a great variety of functions, ranging from structural components of biological membranes to signaling molecules affecting various cellular functions. Several of these functions are related to the unique physico-chemical properties shared by all lipid species, i.e., their hydrophobicity. The latter, however, is accompanied by a poor solubility in an aqueous environment and thus a severe limitation in the transport of lipids in aqueous compartments such as blood plasma and the cellular soluble cytoplasm. Specific proteins which can reversibly and non-covalently associate with lipids, designated as lipid binding proteins or lipid chaperones, greatly enhance the aqueous solubility of lipids and facilitate their transport between tissues and within tissue cells. Importantly, transport of lipids across biological membranes also is facilitated by specific (membrane-associated) lipid binding proteins. Together, these lipid binding proteins determine the bio-availability of their ligands, and thereby markedly influence the subsequent processing, utilization, or signaling effect of lipids. The bio-availability of specific lipid species thus is governed by the presence of specific lipid binding proteins, the affinity of these proteins for distinct lipid species, and the presence of competing ligands (including pharmaceutical compounds). Recent studies suggest that post-translational modifications of lipid binding proteins may have great impact on lipid-protein interactions. As a result, several levels of regulation exist that together determine the bio-availability of lipid species. This short review discusses the significance of lipid binding proteins and their potential application as targets for therapeutic intervention.

  4. Big, Fat World of Lipids

    Science.gov (United States)

    ... Science Home Page The Big, Fat World of Lipids By Emily Carlson Posted August 9, 2012 Cholesterol ... ways to diagnose and treat lipid-related conditions. Lipid Encyclopedia Just as genomics and proteomics spurred advances ...

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

    Science.gov (United States)

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

    2014-08-01

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

  6. Regulation of lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Peng LI

    2011-01-01

    @@ Lipids including cholesterol, phospholipids, fatty acids and triacylglycerols are important cellular constituents involved in membrane structure, energy homeostasis and many biological processes such as signal transduction, organelle development and cell differentiation.Recently, the area of lipid metabolism has drawn a great deal of attention due to its emerging role in the development of metabolic disorders such as obesity, diabetes, atherosclerosis and liver steatosis.We decided to organize a special issue of Frontiers in Biology focusing on our current understanding of lipid metabolism.

  7. Lake Superior lipids

    Science.gov (United States)

    Fish chemistry data (d13C, d15N, C:N, lipid content) published in Rapid Commun. Mass Spectrom. 2015, 29, 2069??2077 DOI: 10.1002/rcm.7367This dataset is associated with the following publication:Hoffman , J., M. Sierszen , and A. Cotter. Fish tissue lipid-C:N relationships for correcting ä13C values and estimating lipid content in aquatic food web studies. Rapid Communications in Mass Spectrometry. Wiley InterScience, Silver Spring, MD, USA, 29(21): 2069–2077, (2015).

  8. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.

    2007-01-01

    We developed new perspectives to identify important questions and to propose approaches for future research on marine food web lipids. They were related to (i) structure and function of lipids, (ii) lipid changes during critical life phases, (iii) trophic marker lipids, and (iv) potential impact...... of climate change. The first addresses the role of lipids in membranes, storage lipids, and buoyancy with the following key question: How are the properties of membranes and deposits affected by the various types of lipids? The second deals with the importance of various types of lipids during reproduction......, development, and resting phases and addresses the role of the different storage lipids during growth and dormancy. The third relates to trophic marker lipids, which are an important tool to follow lipid and energy transfer through the food web. The central question is how can fatty acids be used to identify...

  9. 443 Review Lipids

    African Journals Online (AJOL)

    Marinda

    2009-07-20

    Jul 20, 2009 ... Keywords: lipid emulsion therapy; local anaesthetic toxicity; local anaesthetic cardiotoxicity; .... of particular importance in generating sufficient ATP from fats because ..... Propofol is poorly water soluble and is dissolved in the.

  10. Metabolism. Part III: Lipids.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  11. Lipid-modifying therapy

    African Journals Online (AJOL)

    2009-03-20

    Mar 20, 2009 ... risk reduction for most patients, while patients with severe ... He runs the Diabetic, Endocrine and Lipid clinics at R K Khan Hospital. Treatment .... retinopathy requiring laser therapy). ... Despite knowledge of the risk factors for.

  12. Dynamic Transbilayer Lipid Asymmetry

    OpenAIRE

    van Meer, Gerrit

    2011-01-01

    Flippases move lipids from the outer leaflet of the membrane to the inner leaflet; floppases export them in the opposite direction. This creates an asymmetry critical for membrane function and facilitates vesicle budding.

  13. Lipids of mitochondria.

    Science.gov (United States)

    Horvath, Susanne E; Daum, Günther

    2013-10-01

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

  14. Omental Lipid-Coated Mesh

    Science.gov (United States)

    2011-06-16

    civilian medicine. REFERENCES: 1. Takada T, Kamei Y, Iwata T, et al. Effect of Omental Lipid Fraction on Enhancement of Skin Flap Survival. Annals of...Characterization of Feline Omentum Lipids. Lipids, 1987; 22:229-235. 7. Nottebaert M, Lane J, Juhn A, et al. Omental Angiogenic Lipid Fraction and

  15. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.

    2007-01-01

    We developed new perspectives to identify important questions and to propose approaches for future research on marine food web lipids. They were related to (i) structure and function of lipids, (ii) lipid changes during critical life phases, (iii) trophic marker lipids, and (iv) potential impact ...

  16. Expression of the serum liver specific antibodies with HBV and HCV infected%乙型肝炎和丙型肝炎患者血清抗肝特异性抗体测定

    Institute of Scientific and Technical Information of China (English)

    赵明才; 陈琼; 罗光成; 王梓; 王强; 陈悦

    2012-01-01

    目的:分析乙型肝炎病毒(hepantitis B virus,HBV)和丙型肝炎病毒(hepantitis C virus,HCV)感染患者血清中肝特异性抗体水平,探讨其与肝细胞损伤的关系.方法:收集2011年1月至2011年10月川北医学院附属医院HBV和HCV感染患者和健康体检者血清,检测患者丙氨酸氨基转移酶(alannine aminotransferase,ALT)和总胆红素水平;通过酶联免疫吸附法检测抗肝细胞膜特异性脂蛋白(liver specific lipoprotein,LSP)和抗去唾液酸糖蛋白受体(asialoglycoprotin receptor,ASGPR)的血清水平;以ALT> 40分为肝功能异常组与正常组.使用SPSS13.0统计软件分析结果,P<0.05认为有统计学意义.结果:HBV(H)与健康对照组比较anti-LSP、anti-ASGPR具有统计学差异,HBV组患者anti-ASGPR水平与ALT具有相关性.HCV(H)与健康对照组比较anti-LSP具有统计学差异,HCV组患者anti-LSP与anti-ASGPR具有相关性.HBV患者anti-LSP、anti-ASGPR表达水平较HCV患者高.结论:HBV、HCV感染后,anti-LSP和anti-ASGPR表达高于健康对照组,ALT水平升高时抗肝特异性抗体表达明显增高,表明其可能作为监测肝细胞损伤的特异性免疫学指标.

  17. Fsp27 Inhibits Lipolysis by Excluding HSL from Lipid Droplet Surface%Fsp27通过抑制HSL的脂滴定位调控脂肪水解

    Institute of Scientific and Technical Information of China (English)

    李聪; 周林康; 李蓬

    2014-01-01

    Fsp27是CIDE蛋白家族的一员,其特异性地在脂肪组织中表达并定位于脂滴表面,促进脂滴融合增大和脂肪积累.Fsp27敲除小鼠表现出胰岛素敏感性增强,有较高的能量消耗,并且可以抵抗高脂食物引起的肥胖,但Fsp27是否直接参与脂肪水解的调控过程并不清楚.本研究发现,在3T3-L1脂肪细胞中基因沉默Fsp27导致脂肪水解速率上升,并且这种上升是由激素敏感型脂肪酶(HSL)所介导.进一步在3T3-L1前脂肪细胞中过表达Fsp27以及HSL,对其定位的观察结果显示,Fsp27可以显著地抑制HSL在脂滴表面的定位.本研究表明,在脂肪组织中,Fsp27能够直接影响HSL在脂滴表面的定位,进而抑制脂肪水解速率,导致脂类积累.%Fat-specific protein 27 (Fsp27),a member of the CIDE family proteins,has been shown to be a lipid droplet-associated protein that promotes lipid storage in adipose tissue.Fsp27 knock-out mice have increased energy expenditure and are resistant to diet-induced obesity.Fsp27-induced lipid storage is mediated either by enhancing lipid droplet fusion or inhibiting lipolysis.However,the mechanism by which Fsp27 controls lipolysis remains unclear.Here,we observed that increased lipolysis in Fsp27 knockdown adipocytes was significantly abrogated when HSL was knocked down.In addition,we found that when co-expressed with Fsp27,HSL was excluded from lipid droplet surface.Furthermore,HSL exclusion was dependent on the C-terminal region of Fsp27.Our data indicate that Fsp27 regulates lipolysis by inhibiting the lipid droplet association of HSL,providing a novel mechanism for the regulation of lipid storage in adipose tissue and the development of obesity.

  18. Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver.

    Science.gov (United States)

    Zhu, Yun-Xia; Zhang, Ming-Liang; Zhong, Yuan; Wang, Chen; Jia, Wei-Ping

    2016-01-01

    Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγ or PPARα agonist, pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis.

  19. Deep Sequencing of the Fruit Transcriptome and Lipid Accumulation in a Non-Seed Tissue of Chinese Tallow, a Potential Biofuel Crop.

    Science.gov (United States)

    Divi, Uday K; Zhou, Xue-Rong; Wang, Penghao; Butlin, Jamie; Zhang, Dong-Mei; Liu, Qing; Vanhercke, Thomas; Petrie, James R; Talbot, Mark; White, Rosemary G; Taylor, Jennifer M; Larkin, Philip; Singh, Surinder P

    2016-01-01

    Chinese tallow (Triadica sebifera) is a valuable oilseed-producing tree that can grow in a variety of conditions without competing for food production, and is a promising biofuel feedstock candidate. The fruits are unique in that they contain both saturated and unsaturated fat present in the tallow and seed layer, respectively. The tallow layer is poorly studied and is considered only as an external fatty deposition secreted from the seed. In this study we show that tallow is in fact a non-seed cellular tissue capable of triglyceride synthesis. Knowledge of lipid synthesis and storage mechanisms in tissues other than seed is limited but essential to generate oil-rich biomass crops. Here, we describe the annotated transcriptome assembly generated from the fruit coat, tallow and seed tissues of Chinese tallow. The final assembly was functionally annotated, allowing for the identification of candidate genes and reconstruction of lipid pathways. A tallow tissue-specific paralog for the transcription factor gene WRINKLED1 (WRI1) and lipid droplet-associated protein genes, distinct from those expressed in seed tissue, were found to be active in tallow, underpinning the mode of oil synthesis and packaging in this tissue. Our data have established an excellent knowledge base that can provide genetic and biochemical insights for engineering non-seed tissues to accumulate large amounts of oil. In addition to the large data set of annotated transcripts, the study also provides gene-based simple sequence repeat and single nucleotide polymorphism markers.

  20. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  1. LIPID PEROXIDATION IN PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    T.Sharmila Krishna

    2015-03-01

    Full Text Available Hypertension in pregnancy is a leading cause of both maternal and fetal mortality and morbidity. Preeclampsia is characterised by hypertension and proteinuria. Lipid peroxidation is an important factor in the pathophysiology of Preeclampsia. The present study was undertaken to determine Serum Malondialdehyde (MDA levels , a product of lipid peroxidation , in clinically diagnosed Preeclamptic women(n=30 and the values were compared with that of Normotensive pregnant women (n=30 aged between 18-30yrs. All of them were in their third trimester and were primigravida. Serum MDA was estimated by TBARS (thiobarbituric acid reactive substances method. We observed that Serum MDA levels were significantly increased in Preeclamptic women (p <0.000 as compared to that of Normotensive pregnant women . Increased levels of lipid peroxiation product - MDA may contribute to the pathophysiology of Preeclampsia.

  2. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  3. Bioorthogonal chemical reporters for analyzing protein lipidation and lipid trafficking.

    Science.gov (United States)

    Hang, Howard C; Wilson, John P; Charron, Guillaume

    2011-09-20

    Protein lipidation and lipid trafficking control many key biological functions in all kingdoms of life. The discovery of diverse lipid species and their covalent attachment to many proteins has revealed a complex and regulated network of membranes and lipidated proteins that are central to fundamental aspects of physiology and human disease. Given the complexity of lipid trafficking and the protein targeting mechanisms involved with membrane lipids, precise and sensitive methods are needed to monitor and identify these hydrophobic molecules in bacteria, yeast, and higher eukaryotes. Although many analytical methods have been developed for characterizing membrane lipids and covalently modified proteins, traditional reagents and approaches have limited sensitivity, do not faithfully report on the lipids of interest, or are not readily accessible. The invention of bioorthogonal ligation reactions, such as the Staudinger ligation and azide-alkyne cycloadditions, has provided new tools to address these limitations, and their use has begun to yield fresh insight into the biology of protein lipidation and lipid trafficking. In this Account, we discuss how these new bioorthogonal ligation reactions and lipid chemical reporters afford new opportunities for exploring the biology of lipid-modified proteins and lipid trafficking. Lipid chemical reporters from our laboratory and several other research groups have enabled improved detection and large-scale proteomic analysis of fatty-acylated and prenylated proteins. For example, fatty acid and isoprenoid chemical reporters in conjunction with bioorthogonal ligation methods have circumvented the limited sensitivity and hazards of radioactive analogues, allowing rapid and robust fluorescent detection of lipidated proteins in all organisms tested. These chemical tools have revealed alterations in protein lipidation in different cellular states and are beginning to provide unique insights in mechanisms of regulation. Notably, the

  4. How proteins move lipids and lipids move proteins

    NARCIS (Netherlands)

    Sprong, H.|info:eu-repo/dai/nl/222364815; van der Sluijs, P.; van Meer, G.|info:eu-repo/dai/nl/068570368

    2001-01-01

    Cells determine the bilayer characteristics of different membranes by tightly controlling their lipid composition. Local changes in the physical properties of bilayers, in turn, allow membrane deformation, and facilitate vesicle budding and fusion. Moreover, specific lipids at specific locations

  5. Lipid Therapy for Intoxications

    NARCIS (Netherlands)

    Robben, Joris Henricus; Dijkman, Marieke Annet

    2017-01-01

    This review discusses the use of intravenous lipid emulsion (ILE) in the treatment of intoxications with lipophilic agents in veterinary medicine. Despite growing scientific evidence that ILE has merit in the treatment of certain poisonings, there is still uncertainty on the optimal composition of t

  6. Lipids in cheese

    Science.gov (United States)

    Lipids are present in cheese at levels above 20 percent and are analyzed by several techniques. Scanning electron microscopy and confocal laser scanning microscopy are used to examine the microstructure, gas chromatography is employed to look at fatty acid composition, and differential scanning cal...

  7. Lipid Therapy for Intoxications

    NARCIS (Netherlands)

    Robben, Joris Henricus; Dijkman, Marieke Annet

    2017-01-01

    This review discusses the use of intravenous lipid emulsion (ILE) in the treatment of intoxications with lipophilic agents in veterinary medicine. Despite growing scientific evidence that ILE has merit in the treatment of certain poisonings, there is still uncertainty on the optimal composition of t

  8. Amphotericin B Lipid Complex Injection

    Science.gov (United States)

    Amphotericin B lipid complex injection is used to treat serious, possibly life-threatening fungal infections in people who did not respond ... to tolerate conventional amphotericin B therapy. Amphotericin B lipid complex injection is in a class of medications ...

  9. Lipid nanotube or nanowire sensor

    Science.gov (United States)

    Noy, Aleksandr; Bakajin, Olgica; Letant, Sonia; Stadermann, Michael; Artyukhin, Alexander B.

    2009-06-09

    A sensor apparatus comprising a nanotube or nanowire, a lipid bilayer around the nanotube or nanowire, and a sensing element connected to the lipid bilayer. Also a biosensor apparatus comprising a gate electrode; a source electrode; a drain electrode; a nanotube or nanowire operatively connected to the gate electrode, the source electrode, and the drain electrode; a lipid bilayer around the nanotube or nanowire, and a sensing element connected to the lipid bilayer.

  10. Lanolin-derived lipid mixtures mimic closely the lipid composition and organization of vernix caseosa lipids.

    Science.gov (United States)

    Rissmann, Robert; Oudshoorn, Marion H M; Kocks, Elise; Hennink, Wim E; Ponec, Maria; Bouwstra, Joke A

    2008-10-01

    The aim of the present study was to use semi-synthetic lipid mixtures to mimic the complex lipid composition, organization and thermotropic behaviour of vernix caseosa (VC) lipids. As VC shows multiple protecting and barrier supporting properties before and after birth, it is suggested that a VC substitute could be an innovative barrier cream for barrier deficient skin. Lanolin was selected as the source of the branched chain sterol esters and wax esters--the main lipid classes of VC. Different lipid fractions were isolated from lanolin and subsequently mixed with squalene, triglycerides, cholesterol, ceramides and fatty acids to generate semi-synthetic lipid mixtures that mimic the lipid composition of VC, as established by high-performance thin-layer chromatography. Differential scanning calorimetry and Fourier transform infrared spectroscopy investigations revealed that triglycerides play an important role in the (lateral) lipid organization and thermotropic behaviour of the synthetic lipid mixtures. Excellent resemblance of VC lipids was obtained when adding unsaturated triglycerides. Moreover, these lipid mixtures showed similar long range ordering as VC. The optimal lipid mixture was evaluated on tape-stripped hairless mouse skin in vivo. The rate of barrier recovery was increased and comparable to VC lipid treatment.

  11. Lipid characterization of human saliva.

    Science.gov (United States)

    Defagó, Maria Daniela; Valentich, Mirta Ana; Actis, Adriana Beatriz

    2011-12-01

    Salivary lipids have been scarcely studied, and the reported results present disparities. This literature review is presented based on the importance of saliva as a diagnostic and/or prognostic medium for various diseases, its lipid content, and on its potential use for the analysis of nutritional markers that contribute to the study of diseases related to lipid consumption and metabolism.

  12. Lipid domains in bicelles containing unsaturated lipids and cholesterol.

    Science.gov (United States)

    Cho, Hyo Soon; Dominick, Johnna L; Spence, Megan M

    2010-07-22

    We have created a stable bicelle system capable of forming micrometer-scale lipid domains that orient in a magnetic field, suitable for structural biology determination in solid-state NMR. The bicelles consisted of a mixture of cholesterol, saturated lipid (DMPC), and unsaturated lipid (POPC), a mixture commonly used to create domains in model membranes, along with a short chain lipid (DHPC) that allows formation of the bicelle phase. While maintaining a constant molar ratio of long to short chain lipids, q = ([POPC]+[DMPC])/[DHPC] = 3, we varied the concentrations of the unsaturated lipid, POPC, and cholesterol to observe the effects of the components on bicelle stability. Using (31)P solid-state NMR, we observed that unsaturated lipids (POPC) greatly destabilized the alignment of the membranes in the magnetic field, while cholesterol stabilized their alignment. By combining cholesterol and unsaturated lipids in the bicelles, we created membranes aligning uniformly in the magnetic field, despite very high concentrations of unsaturated lipids. These bicelles, with high concentrations of both cholesterol and unsaturated lipid, showed similar phase behavior to bicelles commonly used in structural biology, but aligned over a wider temperature range (291-314 K). Domains were observed by measuring time-dependent diffusion constants reflecting restricted diffusion of the lipids within micrometer-scale regions of the bicelles. Micron-scale domains have never been observed in POPC/DMPC/cholesterol vesicles, implying that bilayers in bicelles show different phase behavior than their counterparts in vesicles, and that bilayers in bicelles favor domain formation.

  13. Stability of lipid excipients in solid lipid nanoparticles.

    Science.gov (United States)

    Radomska-Soukharev, Anna

    2007-07-10

    The paper is devoted to the investigation of chemical stability of lipids used as excipients in the production of Solid Lipid Nanoparticles (SLN). Different lipids and amounts of surfactants were considered. Most of the formulations were produced using identical binary surfactant mixtures and concentrations to analyze the effect of the chemical nature of the lipids on their stability in SLN. In some formulations, surfactants were exchanged or their concentration was increased to assess the contribution of surfactants on stability of lipids particles. Solid Lipid Nanoparticles were characterized by photon correlation spectroscopy, laser diffractometry, zeta potential determination and differential scanning calorimetry. Potential effects of lipid crystallinity and modifications were assessed. A gas chromatography (GC) analysis in combination with a method for lipid extraction from aqueous SLN dispersions was used to investigate the chemical stability of the lipid excipients forming the particle matrix. All formulations were produced by the hot homogenization technique. The production process of SLN itself did not affect the chemical stability of lipid excipient forming the particle matrix. The formulations where lipids consisted of trigylicerides showed a negligible decomposition of the structure during incubation at 25 degrees C. Dynasan 118 showed the highest chemical stability (loss<4%) within two years.

  14. Dysregulated lipid metabolism in cancer

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.

  15. Identification of novel GH-regulated pathway of lipid metabolism in adipose tissue: a gene expression study in hypopituitary men.

    Science.gov (United States)

    Zhao, Jing Ting; Cowley, Mark J; Lee, Paul; Birzniece, Vita; Kaplan, Warren; Ho, Ken K Y

    2011-07-01

    Adipose tissue is a major target of GH action. GH stimulates lipolysis and reduces fat mass. The molecular mechanism underlying cellular and metabolic effects of GH in adipose tissue is not well understood. The aim of this study is to identify GH-responsive genes that regulate lipid metabolism in adipose tissue. Eight men with GH deficiency underwent measurement of plasma free fatty acid (FFA), whole-body lipid oxidation, and fat biopsies before and after 1 month of GH treatment (0.5 mg/d). Gene expression profiling was performed using Agilent 44K G4112F arrays using a two-color design. Differentially expressed genes were identified using an empirical Bayes, moderated t test, with a false discovery rate under 5%. Target genes were validated by quantitative RT-PCR. GH increased circulating IGF-I and FFA and stimulated fat oxidation. A total of 246 genes were differentially expressed, of which 135 were up-regulated and 111 down-regulated. GH enhanced adipose tissue expression of IGF-I and SOCS3. GH increased expression of patatin-like phospholipase domain containing 3 (PNPLA3), a novel triglyceride (TG) hydrolase, but not hormone-sensitive lipase (HSL), a classical TG hydrolase. GH repressed cell death-inducing DFFA-like effector A (CIDEA), a novel lipid droplets-associated protein, promoting TG storage. GH differentially regulated genes promoting diacylglycerol synthesis. GH suppressed hydroxysteroid (11β) dehydrogenase 1, which activates local cortisol production and genes encoding components of extracellular matrix and TGF-β signaling pathway. GH stimulates the TG/FFA cycle by regulating the expression of novel genes that enhance TG hydrolysis, reduce TG storage, and promote diacylglycerol synthesis. GH represses adipocyte growth, differentiation and inflammation.

  16. Lipids and immune function.

    Science.gov (United States)

    Vitale, J J; Broitman, S A

    1981-09-01

    There is in vitro and in vivo evidence to suggest that dietary lipids play a role in modulating immune function. A review of the current literature on the interrelationships among dietary lipids, blood cholesterol levels, immunosuppression, and tumorigenesis makes for a very strong argument that (a) immunosuppression may be causally related to lymphoproliferative disorders, as well as to tumorigenesis and (b) diets high in polyunsaturated fat, relative to diets high in saturated fat, are more immunosuppressive and are better promotors of tumorigenesis. The effects of dietary fat on immune function seem to be mediated though its component parts, the unsaturated fatty acids, specially linoleic, linolenic, and arachidonic. It is not clear how these components affect immune function. Several studies suggest that one effect is mediated by altering the lipid component of the cell membrane and thus its fluidity; the more fluid the membrane, the less responsive it is. Thus, fluidity of both immune cells and those to be destroyed or protected may be affected. The effects of saturated as well as unsaturated fatty acids may be mediated by modulating serum lipoprotein levels, prostaglandin metabolism, and cholesterol concentrations and metabolism.

  17. Tear Film Lipids

    Science.gov (United States)

    Butovich, Igor A.

    2013-01-01

    Human meibomian gland secretions (MGS, or meibum) are formed from a complex mixture of lipids of different classes such as wax esters, cholesteryl esters, (O-acyl)-ω-hydroxy fatty acids (OAHFA) and their esters, acylglycerols, diacylated diols, free fatty acids, cholesterol, and a smaller amount of other polar and nonpolar lipids, whose chemical nature and the very presence in MGS have been a matter of intense debates. The purpose of this review is to discuss recent results that were obtained using different experimental techniques, estimate limitations of their usability, and discuss their biochemical, biophysical, and physiological implications. To create a lipid map of MGS and tears, the results obtained in the author’s laboratory were integrated with available information on chemical composition of MGS and tears. The most informative approaches that are available today to researchers, such as HPLC-MS, GC-MS, and proton NMR, are discussed in details. A map of the meibomian lipidome (as it is seen in reverse phase liquid chromatography/mass spectrometry experiments) is presented. Directions of future efforts in the area are outlined. PMID:23769846

  18. CIDE proteins and lipid metabolism.

    Science.gov (United States)

    Xu, Li; Zhou, Linkang; Li, Peng

    2012-05-01

    Lipid homeostasis is maintained through the coordination of lipid metabolism in various tissues, including adipose tissue and the liver. The disruption of lipid homeostasis often results in the development of metabolic disorders such as obesity, diabetes mellitus, liver steatosis, and cardiovascular diseases. Cell death-inducing DNA fragmentation factor 45-like effector family proteins, including Cidea, Cideb, and Fsp27 (Cidec), are emerging as important regulators of various lipid metabolic pathways and play pivotal roles in the development of metabolic disorders. This review summarizes the latest cell death-inducing DNA fragmentation factor 45-like effector protein discoveries related to the control of lipid metabolism, with emphasis on the role of these proteins in lipid droplet growth in adipocytes and in the regulation of very low-density lipoprotein lipidation and maturation in hepatocytes.

  19. Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae

    Directory of Open Access Journals (Sweden)

    Zhenting Zhou

    2017-01-01

    Full Text Available Alcoholic liver disease (ALD is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP zebrafish larvae (4 dpf. The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1. In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism.

  20. Strategies towards Improved Feed Efficiency in Pigs Comprise Molecular Shifts in Hepatic Lipid and Carbohydrate Metabolism

    Directory of Open Access Journals (Sweden)

    Henry Reyer

    2017-08-01

    Full Text Available Due to the central role of liver tissue in partitioning and metabolizing of nutrients, molecular liver-specific alterations are of considerable interest to characterize an efficient conversion and usage of feed in livestock. To deduce tissue-specific and systemic effects on nutrient metabolism and feed efficiency (FE twenty-four animals with extreme phenotypes regarding residual feed intake (RFI were analyzed. Transcriptome and fatty acid profiles of liver tissue were complemented with measurements on blood parameters and thyroid hormone levels. Based on 803 differentially-abundant probe sets between low- and high-FE animals, canonical pathways like integrin signaling and lipid and carbohydrate metabolism, were shown to be affected. Molecular alterations of lipid metabolism show a pattern of a reduced hepatic usage of fatty acids in high-FE animals. Complementary analyses at the systemic level exclusively pointed to increased circulating triglycerides which were, however, accompanied by considerably lower concentrations of saturated and polyunsaturated fatty acids in the liver of high-FE pigs. These results are in accordance with altered muscle-to-fat ratios usually ascribed to FE animals. It is concluded that strategies to improve FE might favor a metabolic shift from energy storage towards energy utilization and mobilization.

  1. Lipid nanocarriers: influence of lipids on product development and pharmacokinetics.

    Science.gov (United States)

    Pathak, Kamla; Keshri, Lav; Shah, Mayank

    2011-01-01

    Lipid nanocarriers are on the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery. Owing to their size-dependent properties, lipid nanoparticles offer the possibility for development of new therapeutics and an alternative system to other colloidal counterparts for drug administration. An important point to be considered in the selection of a lipid for the carrier system is its effect on the properties of the nanocarrier and also its intended use, as different types of lipids differ in their nature. Researchers around the globe have tapped the potential of solid lipid nanoparticles (SLNs) in developing formulation(s) that can be administered by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since the start of this millennium, a new generation of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes, has evolved that have the potential to overcome the limitations of SLNs. The current review article presents broad considerations on the influence of various types of lipids on the diverse characteristics of nanocarriers, encompassing their physicochemical, formulation, pharmacokinetic, and cytotoxic aspects.

  2. Lipides polaires marins

    OpenAIRE

    Fanni Jacques; Linder Michel; Parmentier Michel

    2004-01-01

    Les lipides polaires marins, notamment les phospholipides (PL), retiennent depuis quelques années l’attention des chercheurs et des industriels en raison de leur composition, particulièrement riche en acides gras polyinsaturés à longue chaîne (AGPI-LC). Ils combinent ainsi les propriétés reconnues des AGPI-LC à l’intérêt métabolique et structural des phospholipides. Les sources sont nombreuses et d’accès très diversifié. Le défi industriel provient de leurs caractéristiques amphiphiles et aro...

  3. RF Microalgal lipid content characterization

    Science.gov (United States)

    Ahmad, Mahmoud Al; Al-Zuhair, Sulaiman; Taher, Hanifa; Hilal-Alnaqbi, Ali

    2014-05-01

    Most conventional techniques for the determination of microalgae lipid content are time consuming and in most cases are indirect and require excessive sample preparations. This work presents a new technique that utilizes radio frequency (RF) for rapid lipid quantification, without the need for sample preparation. Tests showed that a shift in the resonance frequency of a RF open-ended coaxial resonator and a gradual increase in its resonance magnitude may occur as the lipids content of microalgae cells increases. These response parameters can be then calibrated against actual cellular lipid contents and used for rapid determination of the cellular lipids. The average duration of lipid quantification using the proposed technique was of about 1 minute, which is significantly less than all other conventional techniques, and was achieved without the need for any time consuming treatment steps.

  4. Chlorosome lipids from Chlorobium tepidum

    DEFF Research Database (Denmark)

    Sørensen, Peder Grove; Cox, Raymond Pickett; Miller, Mette

    2008-01-01

    We have extracted polar lipids and waxes from isolated chlorosomes from the green sulfur bacterium Chlorobium tepidum and determined the fatty acid composition of each lipid class. Polar lipids amounted to 4.8 mol per 100 mol bacteriochlorophyll in the chlorosomes, while non-polar lipids (waxes......) were present at a ratio of 5.9 mol per 100 mol bacteriochlorophyll. Glycolipids constitute 60 % of the polar lipids while phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and an aminoglycosphingolipid make up respectively 15, 3, 8 and 12 %. A novel glycolipid was identified...... as a rhamnose derivative of monogalactosyldiacylglycerol, while the other major glycolipid was monogalactosyldiacylglycerol. Tetradecanoic acid was the major fatty acid in the aminoglycosphingolipid, while the other polar lipids contained predominantly hexandecanoic acid. The chlorosome waxes are esters...

  5. Texture of lipid bilayer domains

    DEFF Research Database (Denmark)

    Jensen, Uffe Bernchou; Brewer, Jonathan R.; Midtiby, Henrik Skov

    2009-01-01

    chains. By imaging the intensity variations as a function of the polarization angle, we map the lateral variations of the lipid tilt within domains. Results reveal that gel domains are composed of subdomains with different lipid tilt directions. We have applied a Fourier decomposition method......We investigate the texture of gel (g) domains in binary lipid membranes composed of the phospholipids DPPC and DOPC. Lateral organization of lipid bilayer membranes is a topic of fundamental and biological importance. Whereas questions related to size and composition of fluid membrane domain...... are well studied, the possibility of texture in gel domains has so far not been examined. When using polarized light for two-photon excitation of the fluorescent lipid probe Laurdan, the emission intensity is highly sensitive to the angle between the polarization and the tilt orientation of lipid acyl...

  6. Lipids and membrane lateral organization

    Directory of Open Access Journals (Sweden)

    Sandro eSonnino

    2010-11-01

    Full Text Available Shortly after the elucidation of the very basic structure and properties of cellular membranes, it became evident that cellular membranes are highly organized structures with multiple and multi-dimensional levels of order. Very early observations suggested that the lipid components of biological membranes might be active players in the creations of these levels of order. In the late 80’s, several different and diverse experimental pieces of evidence coalesced together giving rise to the lipid raft hypothesis. Lipid rafts became enormously (and, in the opinion of these authors, sometimes acritically popular, surprisingly not just within the lipidologist community (who is supposed to be naturally sensitive to the fascination of lipid rafts. Today, a PubMed search using the key word lipid rafts returned a list of 3767 papers, including 690 reviews (as a term of comparison, searching over the same time span for a very hot lipid-related key word, ceramide returned 6187 hits with 799 reviews, and a tremendous number of different cellular functions have been described as lipid raft-dependent. However, a clear consensus definition of lipid raft has been proposed only in recent times, and the basic properties, the ruling forces, and even the existence of lipid rafts in living cells have been recently matter of intense debate. The scenario that is gradually emerging from the controversies elicited by the lipid raft hypothesis emphasize multiple roles for membrane lipids in determining membrane order, that encompasses their tendency to phase separation but are clearly not limited to this. In this review, we would like to re-focus the attention of the readers on the importance of lipids in organizing the fine structure of cellular membranes.

  7. Absorption Of Dietary Lipid Components

    OpenAIRE

    Abdulkadir Hurşit

    2015-01-01

    Although the digestion and absorption of lipids that are necessary for the survival of living organisms are well known in general terms, nevertheless how different lipids to be digested, how it is distributed into the bloodstream, and how to be used by the cells, are unknown issues by most non specialist people. In recent years, knowledge of lipid digestion and absorption has expanded considerably. More insight has been gained in the mechanism of action of H + pump as a transport system in fa...

  8. Increased hepatic fatty acids uptake and oxidation by LRPPRC-driven oxidative phosphorylation reduces blood lipid levels

    Directory of Open Access Journals (Sweden)

    Ping Zhou

    2016-07-01

    Full Text Available Hyperlipidemia is one of the major risk factors of atherosclerosis and other cardiovascular diseases. This study aimed to investigate the impact of leucine rich pentatricopeptide repeat containing protein (LRPPRC-driven hepatic oxidative phoshorylation on blood lipid levels. The hepatic LRPPRC level was modulated by liver-specific transgenic or adeno-associated virus 8 carried shRNA targeting Lrpprc (aav-shLrpprc. Mice were fed with a high fat diet to induce obesity. Gene expression was analyzed by quantitative real-time PCR and / or western blot. The hepatic ATP level, hepatic and serum lipids contents, and mitochondria oxidative phosphorylation complex activities were measured using specific assay kits. The uptake and oxidation of fatty acid by hepatocytes were assessed using 14C-palmitate. LRPPRC regulated the expression of genes encoded by mitochondrial genome but not those by nuclear genome involved in mitochondria biogenesis, oxidative phosphorylation, and lipid metabolism. Increased oxidative phosphorylation in liver mediated by LRPPRC resulted in the increase of hepatic ATP level. Lrpprc promoted palmitate uptake and oxidation by hypatocytes. The hepatic and serum triglyceride and total cholesterol levels were inversely associated with the hepatic LRPPRC level. These data demonstrated that LRPPRC-driven hepatic oxidative phosphorylation could promote fatty acids uptake and oxidation by hepatocytes and reduce both hepatic and circulating triglyceride and cholesterol levels.

  9. Lipid hydroperoxides in plants.

    Science.gov (United States)

    Griffiths, G; Leverentz, M; Silkowski, H; Gill, N; Sánchez-Serrano, J J

    2000-12-01

    Hydroperoxides are the primary oxygenated products of polyunsaturated fatty acids and were determined spectrophotometrically based on their reaction with an excess of Fe2+ at low pH in the presence of the dye Xylenol Orange. Triphenylphosphine-mediated hydroxide formation was used to authenticate the signal generated by the hydroperoxides. The method readily detected lipid peroxidation in a range of plant tissues including Phaseolus hypocotyls (26 +/- 5 nmol.g of fresh weight(-1); mean +/- S.D.), Alstroemeria floral tissues (sepals, 66+/-13 nmol.g of fresh weight(-1); petals, 49+/-6 nmol.g of fresh weight(-1)), potato leaves (334+/-75 nmol.g of fresh weight(-1)), broccoli florets (568+/-68 nmol.g of fresh weight(-1)) and Chlamydomonas cells (602+/-40 nmol.g of wet weight(-1)). Relative to the total fatty acid content of the tissues, the percentage hydroperoxide content was within the range of 0.6-1.7% for all tissue types (photosynthetic and non-photosynthetic) and represents the basal oxidation level of membrane fatty acids in plant cells. Leaves of transgenic potato with the fatty acid hydroperoxide lyase enzyme expressed in the antisense orientation were elevated by 38%, indicating a role for this enzyme in the maintenance of cellular levels of lipid hydroperoxides.

  10. Update of the LIPID MAPS comprehensive classification system for lipids

    NARCIS (Netherlands)

    Fahy, E.; Subramaniam, S.; Murphy, R.C.; Nishijima, M.; Raetz, C.R.H.; Shimizu, T.; Spener, F.; van Meer, G.; Wakelam, M.J.O.; Dennis, E.A.

    2009-01-01

    In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a “Comprehensive Classification System for Lipids” based on well-defined chemical and biochemical principles and using an ontology that is extensibl

  11. Study of antioxidant enzymes, lipid peroxidation, lipid profile and ...

    African Journals Online (AJOL)

    McRoy

    Background: The oxidative stress and inflammation are cooperative events involved in atherosclerosis ... reactive protein (hs-CRP) and lipid status parameters in the patients with coronary artery .... Data were analyzed with t-test and expressed as mean ± SD. ... biomolecules including; lipids, proteins and DNA. Antioxidative ...

  12. Update of the LIPID MAPS comprehensive classification system for lipids

    NARCIS (Netherlands)

    Fahy, E.; Subramaniam, S.; Murphy, R.C.; Nishijima, M.; Raetz, C.R.H.; Shimizu, T.; Spener, F.; van Meer, G.|info:eu-repo/dai/nl/068570368; Wakelam, M.J.O.; Dennis, E.A.

    2009-01-01

    In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a “Comprehensive Classification System for Lipids” based on well-defined chemical and biochemical principles and using an ontology that is

  13. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticle

  14. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC)

  15. Molecular Dynamics of Lipid Bilayers

    Science.gov (United States)

    1989-08-09

    The aim of this work is to study, by molecular dynamics simulations, the properties of lipid bilayers. We have applied the vectorizable, order-N...fast angle-dependent force/potential algorithms to treat angle bending and torsion. Keywords: Molecular dynamics , Lipid bilayers.

  16. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events.......Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  17. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events.......Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  18. Lipid droplets, lipophagy, and beyond.

    Science.gov (United States)

    Wang, Chao-Wen

    2016-08-01

    Lipids are essential components for life. Their various structural and physical properties influence diverse cellular processes and, thereby, human health. Lipids are not genetically encoded but are synthesized and modified by complex metabolic pathways, supplying energy, membranes, signaling molecules, and hormones to affect growth, physiology, and response to environmental insults. Lipid homeostasis is crucial, such that excess fatty acids (FAs) can be harmful to cells. To prevent such lipotoxicity, cells convert excess FAs into neutral lipids for storage in organelles called lipid droplets (LDs). These organelles do not simply manage lipid storage and metabolism but also are involved in protein quality management, pathogenesis, immune responses, and, potentially, neurodegeneration. In recent years, a major trend in LD biology has centered around the physiology of lipid mobilization via lipophagy of fat stored within LDs. This review summarizes key findings in LD biology and lipophagy, offering novel insights into this rapidly growing field. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

  19. Roles of Lipids in Photosynthesis.

    Science.gov (United States)

    Kobayashi, Koichi; Endo, Kaichiro; Wada, Hajime

    2016-01-01

    Thylakoid membranes in cyanobacterial cells and chloroplasts of algae and higher plants are the sites of oxygenic photosynthesis. The lipid composition of the thylakoid membrane is unique and highly conserved among oxygenic photosynthetic organisms. Major lipids in thylakoid membranes are glycolipids, monogalactosyldiacylglycerol, digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol, and the phospholipid, phosphatidylglycerol. The identification of almost all genes involved in the biosynthesis of each lipid class over the past decade has allowed the generation and isolation of mutants of various photosynthetic organisms incapable of synthesizing specific lipids. Numerous studies using such mutants have revealed that these lipids play important roles not only in the formation of the lipid bilayers of thylakoid membranes but also in the folding and assembly of the protein subunits in photosynthetic complexes. In addition to the studies with the mutants, recent X-ray crystallography studies of photosynthetic complexes in thylakoid membranes have also provided critical information on the association of lipids with photosynthetic complexes and their activities. In this chapter, we summarize our current understanding about the structural and functional involvement of thylakoid lipids in oxygenic photosynthesis.

  20. The Flexibility of Ectopic Lipids

    Directory of Open Access Journals (Sweden)

    Hannah Loher

    2016-09-01

    Full Text Available In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL, skeletal (intramyocellular lipids; IMCL or cardiac muscle cells (intracardiomyocellular lipids; ICCL. Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass, insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  1. Neuroimaging of Lipid Storage Disorders

    Science.gov (United States)

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  2. The Flexibility of Ectopic Lipids.

    Science.gov (United States)

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-09-14

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. ¹H-magnetic resonance spectroscopy (¹H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  3. Lipides polaires marins

    Directory of Open Access Journals (Sweden)

    Fanni Jacques

    2004-03-01

    Full Text Available Les lipides polaires marins, notamment les phospholipides (PL, retiennent depuis quelques années l’attention des chercheurs et des industriels en raison de leur composition, particulièrement riche en acides gras polyinsaturés à longue chaîne (AGPI-LC. Ils combinent ainsi les propriétés reconnues des AGPI-LC à l’intérêt métabolique et structural des phospholipides. Les sources sont nombreuses et d’accès très diversifié. Le défi industriel provient de leurs caractéristiques amphiphiles et aromatiques particulièrement marquées qui rend leur extraction très difficile.

  4. Lipid functionalized biopolymers: A review.

    Science.gov (United States)

    Qurat-Ul-Ain; Zia, Khalid Mahmood; Zia, Fatima; Ali, Muhammad; Rehman, Saima; Zuber, Mohammad

    2016-12-01

    Lipids are the main source of energy and widely used for various applications. In this review, the modification of lipids by using them in combination with other biomaterials like natural and synthetic polymers is elaborated. These new blends have characteristic features of both polymers and are characterized by different techniques (NMR, DSC, TGA, IR and Raman spectroscopy etc.) to understand their structure, properties and functional behavior. Lipids are hydrophobic, have anti-oxidant and anti-bacterial properties and thus impart hydrophobicity and flexibility to the polymers. While the polymers, on the other hand, make the lipids tougher. Properties of few polymers such as starch, polyethylene protein and chitosan that have brittleness, low combustion rate and hydrophobicity, are improved by incorporation of lipids ultimately increased their flexibility, combustion rate and hydrophobicity respectively. This review article is also focused on emerging fields for the applications of these composite materials. The most notable application of composite materials are in the field of paint industry.

  5. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  6. Lipid traffic: the ABC of transbilayer movement

    NARCIS (Netherlands)

    Raggers, R.J.; Pomorski, T.; Holthuis, J.C.M.; Kälin, N.; van Meer, G.

    2000-01-01

    Membrane lipids do not spontaneously exchange between the two leaflets of lipid bilayers because the polar headgroups cannot cross the hydrophobic membrane interior. Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one

  7. SOLID LIPID NANOPARTICLES AND NANO LIPID CARRIERS: AS NOVEL SOLID LIPID BASED DRUG CARRIER

    Directory of Open Access Journals (Sweden)

    Girish B. Singhal

    2011-02-01

    Full Text Available Interest in lipid based drug delivery has developed over the past decade fuelled by a better understanding of the multiple roles lipids may play in enhancing oral bioavailability. Moreover, the emergence of novel excipients with acceptable regulatory and safety profiles coupled with advances in formulation technologies have greatly improved the potential for successful lipid based formulations. Solid lipid nanoparticles (SLN introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro- and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN/ nanostructured lipid carrier (NLC, drug incorporation method and types, stability. The potential of SLN/NLC to be exploited for the different administration routes is also highlighted.

  8. Lipid composition of human meibum

    Directory of Open Access Journals (Sweden)

    R. Schnetler

    2013-12-01

    Full Text Available The structure and function of meibomian gland lipids in the tear film are highly complex. Evidence shows that the precorneal tear film consists of discrete layers: the inner mucin layer, the middle aqueous layer and the outer lipid layer. In this review we focus on the outer, biphasic lipid layer of the tear film which consists of a ‘thick’ outer, non-polar layer  and a ‘thin’ inner, polar layer. We discuss the main composition of the polar and non-polar lipids within meibum (wax esters, cholesteryl esters, mono-, di- and tri-acylglycerols, ceramides, phospholipids  et cetera. We address the composition of meibomian lipids in subjects suffering from various ocular diseases in comparison with the composition in healthy individuals. Further analysis is needed to determine whether a correlation exists between the etiology of various ocular diseases and the fluctuation on the lipids as well as to establish whether or not tear lipid analysis can be used as a diagnostic tool.

  9. Lipid peroxidation and water penetration in lipid bilayers

    DEFF Research Database (Denmark)

    Conte, Elena; Megli, Francesco Maria; Khandelia, Himanshu

    2012-01-01

    Lipid peroxidation plays a key role in the alteration of cell membrane's properties. Here we used as model systems multilamellar vesicles (MLVs) made of the first two products in the oxidative cascade of linoleoyl lecithin, namely 1-palmitoyl-2-(13-hydroperoxy-9,11-octadecanedienoyl)-lecithin (Hp......PLPC) and 1-palmitoyl-2-(13-hydroxy-9,11-octadecanedienoyl)-lecithin (OHPLPC), exhibiting a hydroperoxide or a hydroxy group at position 13, respectively. The two oxidized lipids were used either pure or in a 1:1 molar ratio mixture with untreated 1-palmitoyl-2-linoleoyl-lecithin (PLPC). The model membranes...... were doped with spin-labeled lipids to study bilayer alterations by electron paramagnetic resonance (EPR) spectroscopy. Two different spin-labeled lipids were used, bearing the doxyl ring at position (n) 5 or 16: γ-palmitoyl-β-(n-doxylstearoyl)-lecithin (n-DSPPC) and n-doxylstearic acid (n-DSA). Small...

  10. Dietary lipids and cancer.

    Science.gov (United States)

    Granados, S; Quiles, J L; Gil, A; Ramírez-Tortosa, M C

    2006-05-01

    Cancer is one of the main causes of death in Western countries. Among the factors that contribute to the appearance of this disease, diet has a fundamental role, and specifically fats are the main component related to the increase in the incidence of cancerous diseases, particularly breast, colon-rectal, and prostate cancer. From dietary lipids, much attention has been given to the beneficial effects of fish oil, rich in polyunsaturated fatty acids n-3 serie, as well as of olive oil, rich in monounsaturated fatty acids--primarily oleic acid. On the contrary, a negative effect has been reported for polyunsaturated fatty acids n-6 serie and for saturated fatty acids. Nutrition constitutes an important aspect of the life of cancer patients. Currently, nutritional formulas are being designed with supplements of polyunsaturated n-3 fatty acids and other components such as arginine, RNA, lysine, etc., with the aim of ameliorating the effects of this pathology. The results demonstrate the lower morbility and therefore improved quality of life, a decline in mortality, and a reduction in related costs.

  11. Hybrid lipid-based nanostructures

    Science.gov (United States)

    Dayani, Yasaman

    Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and

  12. Analysis of Lipid Experiments (ALEX)

    DEFF Research Database (Denmark)

    Husen, Peter; Tarasov, Kirill; Katafiasz, Maciej

    2013-01-01

    Global lipidomics analysis across large sample sizes produces high-content datasets that require dedicated software tools supporting lipid identification and quantification, efficient data management and lipidome visualization. Here we present a novel software-based platform for streamlined data ...

  13. SOLID LIPID NANOPARTICLES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Mudavath Hanumanaik*, Sandeep Kumar Patel and K. Ramya Sree

    2013-03-01

    Full Text Available ABSTRACT: Solid lipid nanoparticles (SLN are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Due to their unique size dependent properties, lipid nanoparticles offer possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could use for drug targeting. Hence solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their aims, production procedures, advantages, limitations and their possible remedies. Appropriate analytical techniques for the characterization of SLN like Photon Correlation Spectroscopy (PCS, Scanning Electron Microscopy (SEM, and Differential Scanning Calorimetry are highlighted. Aspects of SLN route of administration and the in vivo fate of the carriers are also discussed.

  14. Electronic polymers in lipid membranes.

    Science.gov (United States)

    Johansson, Patrik K; Jullesson, David; Elfwing, Anders; Liin, Sara I; Musumeci, Chiara; Zeglio, Erica; Elinder, Fredrik; Solin, Niclas; Inganäs, Olle

    2015-06-10

    Electrical interfaces between biological cells and man-made electrical devices exist in many forms, but it remains a challenge to bridge the different mechanical and chemical environments of electronic conductors (metals, semiconductors) and biosystems. Here we demonstrate soft electrical interfaces, by integrating the metallic polymer PEDOT-S into lipid membranes. By preparing complexes between alkyl-ammonium salts and PEDOT-S we were able to integrate PEDOT-S into both liposomes and in lipid bilayers on solid surfaces. This is a step towards efficient electronic conduction within lipid membranes. We also demonstrate that the PEDOT-S@alkyl-ammonium:lipid hybrid structures created in this work affect ion channels in the membrane of Xenopus oocytes, which shows the possibility to access and control cell membrane structures with conductive polyelectrolytes.

  15. Lipid dynamics at dendritic spines.

    Science.gov (United States)

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  16. Mealworms: Alternate Source of Lipids

    OpenAIRE

    2014-01-01

    The aim of present study was to determine the physicochemical properties of the oil obtained from Tenebrio molitor larvae (mealworms) and explore its potential as edible oil. Five batches of Tenebrio molitor larvae were investigated for their lipid content and physiochemical properties. Three batches were reared in lab (3 different productions) and two were purchased from a local supplier. The lipids were extracted using a cold extraction technique employing 2:1 ratio chloroform/methanol as s...

  17. NMR spectroscopy for evaluation of lipid oxidation

    Science.gov (United States)

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

  18. Phase structure of liposome in lipid mixtures.

    Science.gov (United States)

    Zhang, Tianxi; Li, Yuzhuo; Mueller, Anja

    2011-11-01

    Gas microbubbles present in ultrasound imaging contrast agents are stabilized by lipid aggregates that typically contain a mixture of lipids. In this study, the phase structure of the lipid mixtures that contained two or three lipids was investigated using three different methods: dynamic light scattering, (1)H NMR, and microfluidity measurements with fluorescence probes. Three lipids that are commonly present in imaging agents (DPPC, DPPE-PEG, and DPPA) were used. Two types of systems, two-lipid model systems and simulated imaging systems were investigated. The results show that liposomes were the dominant aggregates in all the samples studied. The polar PEG side chains from the PEGylated lipid lead to the formation of micelles and micellar aggregates in small sizes. In the ternary lipid systems, almost all the lipids were present in bilayers with micelles absent and free lipids at very low concentration. These results suggest that liposomes, not micelles, contribute to the stabilization of microbubbles in an ultrasound imaging contrast agent.

  19. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids.

    Science.gov (United States)

    Fu, Xianghui; Dong, Bingning; Tian, Yan; Lefebvre, Philippe; Meng, Zhipeng; Wang, Xichun; Pattou, François; Han, Weidong; Wang, Xiaoqiong; Lou, Fang; Jove, Richard; Staels, Bart; Moore, David D; Huang, Wendong

    2015-06-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D.

  20. Lipid nanoparticle interactions and assemblies

    Science.gov (United States)

    Preiss, Matthew Ryan

    Novel liposome-nanoparticle assemblies (LNAs) provide a biologically inspired route for designing multifunctional bionanotheranostics. LNAs combine the benefits of lipids and liposomes to encapsulate, transport, and protect hydrophilic and hydrophobic therapeutics with functional nanoparticles. Functional nanoparticles endow LNAs with additional capabilities, including the ability to target diseases, triggered drug release, controlled therapeutic output, and diagnostic capabilities to produce a drug delivery system that can effectively and efficiently deliver therapeutics while reducing side effects. Not only could LNAs make existing drugs better, they could also provide an avenue to allow once promising non-approved drugs (rejected due to harmful side effects, inadequate pharmacokinetics, and poor efficacy) to be safely used through targeted and controlled delivery directly to the diseased site. LNAs have the potential to be stimuli responsive, delivering drugs on command by external (ultrasound, RF heating, etc.) or internal (pH, blood sugar, heart rate, etc.) stimuli. Individually, lipids and nanoparticles have been clinically approved for therapy, such as Doxil (a liposomal doxorubicin for cancer treatment), and diagnosis, such as Feridex (an iron oxide nanoparticle an MRI contrast enhancement agent for liver tumors). In order to engineer these multifunctional LNAs for theranostic applications, the interactions between nanoparticles and lipids must be better understood. This research sought to explore the formation, design, structures, characteristics, and functions of LNAs. To achieve this goal, different types of LNAs were formed, specifically magnetoliposomes, bilayer decorated LNAs (DLNAs), and lipid-coated magnetic nanoparticles (LMNPs). A fluorescent probe was embedded in the lipid bilayer of magnetoliposomes allowing the local temperature and membrane fluidity to be observed. When subjected to an electromagnetic field that heated the encapsulated iron

  1. Solid lipid nanoparticles and nanostructured lipid carriers--innovative generations of solid lipid carriers.

    Science.gov (United States)

    Shidhaye, S S; Vaidya, Reshma; Sutar, Sagar; Patwardhan, Arati; Kadam, V J

    2008-10-01

    The first generation of solid lipid carrier systems in nanometer range, Solid Lipid Nanoparticles (SLN), was introduced as an alternative to liposomes. SLN are aqueous colloidal dispersions, the matrix of which comprises of solid biodegradable lipids. SLN are manufactured by techniques like high pressure homogenization, solvent diffusion method etc. They exhibit major advantages such as modulated release, improved bioavailability, protection of chemically labile molecules like retinol, peptides from degradation, cost effective excipients, improved drug incorporation and wide application spectrum. However there are certain limitations associated with SLN, like limited drug loading capacity and drug expulsion during storage, which can be minimized by the next generation of solid lipids, Nanostructured lipid carriers (NLC). NLC are lipid particles with a controlled nanostructure that improves drug loading and firmly incorporates the drug during storage. Owing to their properties and advantages, SLN and NLC may find extensive application in topical drug delivery, oral and parenteral administration of cosmetic and pharmaceutical actives. Cosmeceuticals is emerging as the biggest application target of these carriers. Carrier systems like SLN and NLC were developed with a perspective to meet industrial needs like scale up, qualification and validation, simple technology, low cost etc. This paper reviews present status of SLN and NLC as carrier systems with special emphasis on their application in Cosmeceuticals; it also gives an overview about various manufacturing techniques of SLN and NLC.

  2. Mass Spectrometry Methodology in Lipid Analysis

    OpenAIRE

    Lin Li; Juanjuan Han; Zhenpeng Wang; Jian'an Liu; Jinchao Wei; Shaoxiang Xiong; Zhenwen Zhao

    2014-01-01

    Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics tech...

  3. Lipid bilayers on nano-templates

    Science.gov (United States)

    Noy, Aleksandr; Artyukhin, Alexander B.; Bakajin, Olgica; Stoeve, Pieter

    2009-08-04

    A lipid bilayer on a nano-template comprising a nanotube or nanowire and a lipid bilayer around the nanotube or nanowire. One embodiment provides a method of fabricating a lipid bilayer on a nano-template comprising the steps of providing a nanotube or nanowire and forming a lipid bilayer around the polymer cushion. One embodiment provides a protein pore in the lipid bilayer. In one embodiment the protein pore is sensitive to specific agents

  4. [Lipids, depression and suicide].

    Science.gov (United States)

    Colin, A; Reggers, J; Castronovo, V; Ansseau, M

    2003-01-01

    Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3

  5. Hybrid Lipid as Biological Surfactants

    Science.gov (United States)

    Brewster, Robert; Pincus, Phil; Safran, Sam

    2009-03-01

    Systems capable of forming finite-sized, equilibrium domains are of biological interest in the context of membrane rafts where it has been observed that certain cellular functions are mediated by small (nanometric to tens of nanometers) domains with specific lipid composition that differs from the average composition of the membrane. These small domains are composed mainly of lipids with completely saturated hydrocarbon tails that show good orientational order in the membrane. The surrounding phase consists mostly of lipids with at least one unsaturated bond in the hydrocarbon tails which forces a ``kink'' in the chain and inhibits ordering. In vitro, this phase separation can be replicated; however, the finite domains coarsen into macroscopic domains with time. We have extended a model for the interactions of lipids in the membrane, akin to that developed in the group of Schick (Elliott et al., PRL 2006 and Garbes Putzel and Schick, Biophys. J. 2008), which depends entirely on the local ordering of hydrocarbon tails. We generalize this model to an additional species and identify a biologically relevant component, a lipid with one fully saturated hydrocarbon chain and one chain with at least one unsaturated bond, that may serve as a line-active component, capable of reducing the line tension between domains to zero, thus stabilizing finite sized domains in equilibrium.

  6. Immunological Regulation by Bioactive Lipids.

    Science.gov (United States)

    Taketomi, Yoshitaka; Murakami, Makoto

    2017-01-01

     Mast cells originate from hematopoietic stem cells and undergo terminal maturation in the extravascular tissues, in which they are ultimately resident. Mast maturation, phenotype, and function are dictated by the local microenvironment, which has a significant influence on the ability of mast cells to recognize and respond to stimuli. Activation of mast cells can lead to the release of three distinct classes of mediators, including preformed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo-synthesized bioactive lipid mediators. It is currently recognized that bioactive lipids such as arachidonic acid metabolites (prostaglandins and leukotrienes) released from mast cells modulate innate and adaptive immune responses both directly and indirectly through communication with other microenvironmental immune cells or stroma cells. Moreover, mast cells express a variety of lipid receptors and, if activated by bioactive lipids such as arachidonic acid, ω3 fatty acids, lysophospholipids, and their metabolites, can alter the release and production of other mediators including histamine, cytokines, and chemokines, and thereby alter homeostatic or pathophysiological responses. This review focuses on newly identified functional aspects of bioactive lipids with regard to their immune regulation and functional outcomes in both homeostasis and allergic disease.

  7. Direct observation of lipid domains in free standing bilayers: from simple to complex lipid mixtures

    DEFF Research Database (Denmark)

    Bagatolli, Luis A

    2003-01-01

    The direct observation of temperature-dependent lipid phase equilibria, using two-photon excitation fluorescence microscopy on giant unilamellar vesicles (GUVs) composed of different lipid mixtures, provides novel information about the physical characteristics of lipid domain coexistence. Physica...

  8. Lipids, lipid droplets and lipoproteins in their cellular context; an ultrastructural approach

    NARCIS (Netherlands)

    Mesman, R.J.

    2013-01-01

    Lipids are essential for cellular life, functioning either organized as bilayer membranes to compartmentalize cellular processes, as signaling molecules or as metabolic energy storage. Our current knowledge on lipid organization and cellular lipid homeostasis is mainly based on biochemical data.

  9. Mass Spectrometry Methodology in Lipid Analysis

    Directory of Open Access Journals (Sweden)

    Lin Li

    2014-06-01

    Full Text Available Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.

  10. Identification of Lipid Binding Modulators Using the Protein-Lipid Overlay Assay.

    Science.gov (United States)

    Tang, Tuo-Xian; Xiong, Wen; Finkielstein, Carla V; Capelluto, Daniel G S

    2017-01-01

    The protein-lipid overlay assay is an inexpensive, easy-to-implement, and high-throughput methodology that employs nitrocellulose membranes to immobilize lipids in order to rapid screen and identify protein-lipid interactions. In this chapter, we show how this methodology can identify potential modulators of protein-lipid interactions by screening water-soluble lipid competitors or even the introduction of pH changes during the binding assay to identify pH-dependent lipid binding events.

  11. Blood lipids and prostate cancer

    DEFF Research Database (Denmark)

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P

    2016-01-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL...... into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL......, comparing high- (≥7 Gleason score) versus low-grade (cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0...

  12. Fuel from microalgae lipid products

    Energy Technology Data Exchange (ETDEWEB)

    Hill, A.M.; Feinberg, D.A.

    1984-04-01

    The large-scale production of microalgae is a promising method of producing a renewable feedstock for a wide variety of fuel products currently refined from crude petroleum. These microalgae-derived products include lipid extraction products (triglycerides, fatty acids, and hydrocarbons) and catalytic conversion products (paraffins and olefins). Microalgal biomass productivity and lipid composition of current experimental systems are estimated at 66.0 metric tons per hectare year and 30% lipid content. Similar yields in a large-scale facility indicate that production costs are approximately six times higher than the average domestic price for crude, well-head petroleum. Based on achievable targets for productivity and production costs, the potential for microalgae as a fuel feedstock is presented in context with selected process refining routes and is compared with conventional and alternative feedstocks (e.g., oilseeds) with which microalgae must compete. 24 references, 9 figures, 4 tables.

  13. Yeast lipid metabolism at a glance.

    Science.gov (United States)

    Klug, Lisa; Daum, Günther

    2014-05-01

    During the last decades, lipids have gained much attention due to their involvement in health and disease. Lipids are required for the formation of membranes and contribute to many different processes such as cell signaling, energy supply, and cell death. Various organelles such as the endoplasmic reticulum, mitochondria, peroxisomes, and lipid droplets are involved in lipid metabolism. The yeast Saccharomyces cerevisiae has become a reliable model organism to study biochemistry, molecular biology, and cell biology of lipids. The availability of mutants bearing defects in lipid metabolic pathways and the ease of manipulation by culture conditions facilitated these investigations. Here, we summarize the current knowledge about lipid metabolism in yeast. We grouped this large topic into three sections dealing with (1) fatty acids; (2) membrane lipids; and (3) storage lipids. Fatty acids serve as building blocks for the synthesis of membrane lipids (phospholipids, sphingolipids) and storage lipids (triacylglycerols, steryl esters). Phospholipids, sterols, and sphingolipids are essential components of cellular membranes. Recent investigations addressing lipid synthesis, degradation, and storage as well as regulatory aspects are presented. The role of enzymes governing important steps of the different lipid metabolic pathways is described. Finally, the link between lipid metabolic and dynamic processes is discussed.

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

    Science.gov (United States)

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

    2013-01-01

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

  15. Distribution of neutral lipids in the lipid droplet core

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    Cholesteryl esters (CEs) are a form of cholesterol (CHOL) storage in the living cells, as opposed to free CHOL. CEs are major constituents of low density lipoprotein particles. Therefore, CEs are implicated in provoking atherosclerosis. Arranged into cytoplasmic lipid droplets (LDs), CEs are stored...

  16. Cholesterol lipids and cholesterol-containing lipid rafts in bacteria.

    Science.gov (United States)

    Huang, Zhen; London, Erwin

    2016-09-01

    Sterols are important components of eukaryotic membranes, but rare in bacteria. Some bacteria obtain sterols from their host or environment. In some cases, these sterols form membrane domains analogous the lipid rafts proposed to exist in eukaryotic membranes. This review describes the properties and roles of sterols in Borrelia and Helicobacter.

  17. Nanoparticle-lipid bilayer interactions studied with lipid bilayer arrays

    Science.gov (United States)

    Lu, Bin; Smith, Tyler; Schmidt, Jacob J.

    2015-04-01

    The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which can provide insight into the nature of the particle-membrane interaction through variation of membrane and solution properties not possible with cell-based assays. However, the scope of these studies can be limited because of the low throughput characteristic of lipid bilayer platforms. We have recently described an easy to use, parallel lipid bilayer platform which we have used to electrically investigate the activity of 60 nm diameter amine and carboxyl modified polystyrene nanoparticles (NH2-NP and COOH-NP) with over 1000 lipid bilayers while varying lipid composition, bilayer charge, ionic strength, pH, voltage, serum, particle concentration, and particle charge. Our results confirm recent studies finding activity of NH2-NP but not COOH-NP. Detailed analysis shows that NH2-NP formed pores 0.3-2.3 nm in radius, dependent on bilayer and solution composition. These interactions appear to be electrostatic, as they are regulated by NH2-NP surface charge, solution ionic strength, and bilayer charge. The ability to rapidly measure a large number of nanoparticle and membrane parameters indicates strong potential of this bilayer array platform for additional nanoparticle bilayer studies.The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which

  18. You Sank My Lipid Rafts!

    Science.gov (United States)

    Campbell, Tessa N.

    2009-01-01

    The plasma membrane is the membrane that serves as a boundary between the interior of a cell and its extracellular environment. Lipid rafts are microdomains within a cellular membrane that possess decreased fluidity due to the presence of cholesterol, glycolipids, and phospholipids containing longer fatty acids. These domains are involved in many…

  19. Lipid membranes on nanostructured silicon.

    Energy Technology Data Exchange (ETDEWEB)

    Slade, Andrea Lynn; Lopez, Gabriel P. (University of New Mexico, Albuquerque, NM); Ista, Linnea K. (University of New Mexico, Albuquerque, NM); O' Brien, Michael J. (University of New Mexico, Albuquerque, NM); Sasaki, Darryl Yoshio; Bisong, Paul (University of New Mexico, Albuquerque, NM); Zeineldin, Reema R. (University of New Mexico, Albuquerque, NM); Last, Julie A.; Brueck, Stephen R. J. (University of New Mexico, Albuquerque, NM)

    2004-12-01

    A unique composite nanoscale architecture that combines the self-organization and molecular dynamics of lipid membranes with a corrugated nanotextured silicon wafer was prepared and characterized with fluorescence microscopy and scanning probe microscopy. The goal of this project was to understand how such structures can be assembled for supported membrane research and how the interfacial interactions between the solid substrate and the soft, self-assembled material create unique physical and mechanical behavior through the confinement of phases in the membrane. The nanometer scale structure of the silicon wafer was produced through interference lithography followed by anisotropic wet etching. For the present study, a line pattern with 100 nm line widths, 200 nm depth and a pitch of 360 nm pitch was fabricated. Lipid membranes were successfully adsorbed on the structured silicon surface via membrane fusion techniques. The surface topology of the bilayer-Si structure was imaged using in situ tapping mode atomic force microscopy (AFM). The membrane was observed to drape over the silicon structure producing an undulated topology with amplitude of 40 nm that matched the 360 nm pitch of the silicon structure. Fluorescence recovery after photobleaching (FRAP) experiments found that on the microscale those same structures exhibit anisotropic lipid mobility that was coincident with the silicon substructure. The results showed that while the lipid membrane maintains much of its self-assembled structure in the composite architecture, the silicon substructure indeed influences the dynamics of the molecular motion within the membrane.

  20. Lipids of the Golgi membrane

    NARCIS (Netherlands)

    van Meer, G.

    1998-01-01

    The thin membrane of the endoplasmic reticulum matures into the thick plasma membrane in the Golgi apparatus. Along the way, the concentrations of cholesterol and sphingolipids increase. Here, Gerrit van Meer discusses how this phenomenon may reflect an intricate lipid-protein sorting machinery. Syn

  1. The Membrane and Lipids as Integral Participants in Signal Transduction: Lipid Signal Transduction for the Non-Lipid Biochemist

    Science.gov (United States)

    Eyster, Kathleen M.

    2007-01-01

    Reviews of signal transduction have often focused on the cascades of protein kinases and protein phosphatases and their cytoplasmic substrates that become activated in response to extracellular signals. Lipids, lipid kinases, and lipid phosphatases have not received the same amount of attention as proteins in studies of signal transduction.…

  2. Digital Cushion Fatty Acid Composition and Lipid Metabolism Gene Network Expression in Holstein Dairy Cows Fed a High-Energy Diet.

    Directory of Open Access Journals (Sweden)

    Zeeshan Muhammad Iqbal

    Full Text Available The hoof digital cushion is a complex structure composed of adipose tissue beneath the distal phalanx, i.e. axial, middle and abaxial fat pad. The major role of these fat depots is dampening compression of the corium underneath the cushion. The study aimed to determine expression of target genes and fatty acid profiles in the hoof of non-pregnant dry Holstein cows fed low (CON or high-energy (OVE diets. The middle fat pad of the hoof digital cushion was collected soon after slaughter. Despite the lack of effect on expression of the transcription regulators SREBF1 and PPARG, the expression of the lipogenic enzymes ACACA, FASN, SCD, and DGAT2 was upregulated with OVE. Along with the upregulation of G6PD and IDH1, important for NADPH synthesis during lipogenesis, and the basal glucose transporter SLC2A1, these data indicated a pro-lipogenic response in the digital cushion with OVE. The expression of the lipid droplet-associated protein PLIN2 was upregulated while expression of lipolytic enzymes (ATGL, ABDH5, and LIPE only tended to be upregulated with OVE. Therefore, OVE induced lipogenesis, lipid droplet formation, and lipolysis, albeit to different extents. Although concentration of monounsaturated fatty acids (MUFA did not differ, among the polyunsaturated fatty acids (PUFA, the concentration of 20:5n3 was lower with OVE. Among the saturated fatty acids, 20:0 concentration was greater with OVE. Although data indicated that the hoof digital cushion metabolic transcriptome is responsive to higher-energy diets, this did not translate into marked differences in the fatty acid composition. The decrease in concentration of PUFA, which could contribute to synthesis of inflammatory molecules, in OVE-fed cows indicated that feeding higher-energy diets might be detrimental for the mediation of inflammation in digital cushion. This effect could be further exacerbated by physiologic and endocrine changes during the peripartal period that favor inflammation.

  3. Exogenous ether lipids predominantly target mitochondria.

    Directory of Open Access Journals (Sweden)

    Lars Kuerschner

    Full Text Available Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria in ether lipid metabolism and intracellular ether lipid trafficking.

  4. Substrate-supported lipid nanotube arrays.

    Energy Technology Data Exchange (ETDEWEB)

    Smirnov, A. I.; Poluektov, O. G.; Chemistry; North Carolina State

    2003-07-16

    This Communication describes the self-assembly of phospholipids into lipid nanotubes inside nanoporous anodic aluminum oxide substrate. Orientations of the lipid molecules in such lipid nanoscale structures were verified by high-resolution spin labeling EPR at 95 GHz. The static order parameter of lipids in such nanotube arrays was determined from low-temperature EPR spectra and was found to be exceptionally high, S{sub static} {approx} 0.9. We propose that substrate-supported lipid nanotube arrays have potential for building robust biochips and biosensors in which rigid nanoporous substrates protect the bilayer surface from contamination. The total bilayer surface in the lipid nanotube arrays is much greater than that in the planar substrate-supported membranes. The lipid nanotube arrays seem to be suitable for developing patterned lipid deposition and could be potentially used for patterning of membrane-associated molecules.

  5. Spontaneous Formation of Lipid Nanotubes and Lipid Nanofibers from Giant Charged Dendrimer Lipids

    Science.gov (United States)

    Zidovska, Alexandra; Ewert, Kai K.; Safinya, Cyrus R.; Quispe, Joel; Carragher, Bridgett; Potter, Clinton S.

    2007-03-01

    Liposomes have attracted much scientific interest due to their applications in model cells studies and in drug encapsulation. We report on the discovery of new vesicle phases formed in mixtures of MVLBG2, DOPC and water. MVLBG2 is a newly synthesized highly charged (16+) lipid (K. Ewert et al., JACS, 2006) with giant dendrimer headgroup thus leading to a high spontaneous curvature of the molecule. In combination with zero-curvature DOPC, MVLBG2 exhibits a rich phase diagram showing novel vesicle morphologies such as bones, lipid nanotubes and nanofibers as revealed by differential contrast microscopy (DIC) and cryo-TEM. At the micron scale DIC reveals a new phase consisting of bone-like vesicles. This novel morphology persists down to the nanometer scale as shown by cryo-TEM. The nanotubes are of diameter 10-50 nm, length > 1μm and consist of a single lipid bilayer. A surprising new morphology arises resulting from a spontaneous topological transition from tubes to lipid nanorods. Funded by DOE DE-FG-02-06ER46314, NIH GM-59288, NSF DMR-0503347.

  6. Myoglobin-induced lipid oxidation : A review

    DEFF Research Database (Denmark)

    Baron, Caroline; Andersen, H.J.

    2002-01-01

    An overview of myoglobin-initiated lipid oxidation in simple model systems, muscle, and muscle-based foods is presented. The potential role of myoglobin spin and redox states in initiating lipid oxidation is reviewed. Proposed mechanisms for myoglobin- initiated lipid oxidation in muscle tissue (p...

  7. How Do Lipids Localize in Lewy Bodies?

    NARCIS (Netherlands)

    Chaudhary, Himanshu; Subramaniam, Vinod; Claessens, Mireille

    2014-01-01

    Lewy bodies are the pathological hallmark of Parkinson's disease (PD). While fibrillar α-synuclein (αS) is the main protein component of Lewy bodies, these structures also contain lipids. To elucidate the presence of lipids in Lewy bodies, we investigated the interaction of lipids with monomeric and

  8. Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence.

    Science.gov (United States)

    Narayanan, Sruthi; Prasad, P V Vara; Welti, Ruth

    2016-03-01

    Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-regulated or down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat.

  9. Polydopamine-Supported Lipid Bilayers

    Directory of Open Access Journals (Sweden)

    Souryvanh Nirasay

    2012-12-01

    Full Text Available We report the formation of lipid membranes supported by a soft polymeric cushion of polydopamine. First, 20 nm thick polydopamine films were formed on mica substrates. Atomic force microscopy imaging indicated that these films were also soft with a surface roughness of 2 nm under hydrated conditions. A zwitterionic phospholipid bilayer was then deposited on the polydopamine cushion by fusion of dimyristoylphosphatidylcholine (DMPC and dioleoylphosphatidylcholine (DOPC vesicles. Polydopamine films preserved the lateral mobility of the phospholipids as shown by fluorescence microscopy recovery after photobleaching (FRAP experiments. Diffusion coefficients of ~5.9 and 7.2 µm2 s−1 were respectively determined for DMPC and DOPC at room temperature, values which are characteristic of lipids in a free standing bilayer system.

  10. Polydopamine-Supported Lipid Bilayers

    Science.gov (United States)

    Nirasay, Souryvanh; Badia, Antonella; Leclair, Grégoire; Claverie, Jerome P.; Marcotte, Isabelle

    2012-01-01

    We report the formation of lipid membranes supported by a soft polymeric cushion of polydopamine. First, 20 nm thick polydopamine films were formed on mica substrates. Atomic force microscopy imaging indicated that these films were also soft with a surface roughness of 2 nm under hydrated conditions. A zwitterionic phospholipid bilayer was then deposited on the polydopamine cushion by fusion of dimyristoylphosphatidylcholine (DMPC) and dioleoylphosphatidylcholine (DOPC) vesicles. Polydopamine films preserved the lateral mobility of the phospholipids as shown by fluorescence microscopy recovery after photobleaching (FRAP) experiments. Diffusion coefficients of ~5.9 and 7.2 µm2 s−1 were respectively determined for DMPC and DOPC at room temperature, values which are characteristic of lipids in a free standing bilayer system.

  11. Effects of ovariectomy and resistance training on lipid content in skeletal muscle, liver, and heart; fat depots; and lipid profile

    National Research Council Canada - National Science Library

    Baldissera, Vilmar; de Andrade Perez, Sérgio Eduardo; Prestes, Jonato; Domingos, Mateus Moraes; Shiguemoto, Gilberto Eiji; Pereira, Guilherme Borges; Bernardes, Celene Fernandes; Duarte, Josiane Oliveira; Leite, Richard Diego

    2009-01-01

    The aim of the present study was to investigate the effects of resistance training on skeletal muscle lipid content, liver lipid content, heart lipid content, fat depots, and lipid profile in ovariectomized rats...

  12. Anesthetics interacting with lipid rafts.

    Science.gov (United States)

    Bandeiras, Cátia; Serro, Ana Paula; Luzyanin, Konstantin; Fernandes, Anabela; Saramago, Benilde

    2013-01-23

    The exact mechanism by which anesthetics induce cell membrane-mediated modifications is still an open question. Although the fluidization effect of the anesthetic molecules on the cellular membrane is widely recognized, it is not known if anesthetics show any preference for specific membrane domains, namely the lipid rafts. The importance of these membrane micro-domains derives from the fact that they have been associated with cell signaling pathways, as well as with specific drug interactions. The objective of this work is to contribute for the elucidation of this question through the comparison of the anesthetic interactions with membranes of various lipid compositions. Liposomes prepared with an equimolar mixture of POPC, sphingomyelin and cholesterol, were chosen as models for lipid rafts. The interactions of these liposomes with two local anesthetics, tetracaine and lidocaine, and one general anesthetic, propofol, were studied. The effect of cholesterol was investigated by comparing anesthetic interactions with POPC/SM liposomes and POPC/SM/CHOL liposomes. The following experimental techniques were used: quartz crystal microbalance with dissipation, differential scanning calorimetry and phosphorus nuclear magnetic resonance. Although the liposomes investigated by the different techniques are not in the same conditions, it is possible to assemble the information obtained from all experimental techniques employed to reach a general conclusion. Tetracaine interacts more with raftlike domains, lidocaine induces stronger modifications on POPC/SM liposomes and the results for propofol are not fully conclusive but it seems to be the least prone to lipid interactions. The results were compared with those obtained with DMPC-containing liposomes, reported in a previous work.

  13. Dynamics of multicomponent lipid membranes

    Science.gov (United States)

    Camley, Brian Andrew

    We present theoretical and computational descriptions of the dynamics of multicomponent lipid bilayer membranes. These systems are both model systems for "lipid rafts" in cell membranes and interesting physical examples of quasi-two-dimensional fluids. Our chief tool is a continuum simulation that uses a phase field to track the composition of the membrane, and solves the hydrodynamic equations exactly using the appropriate Green's function (Oseen tensor) for the membrane. We apply this simulation to describe the diffusion of domains in phase-separated membranes, the dynamics of domain flickering, and the process of phase separation in lipid membranes. We then derive an analytical theory to describe domain flickering that is consistent with our simulation results, and use this to analyze experimental measurements of membrane domains. Through this method, we measure the membrane viscosity solely from fluorescence microscopy measurements. We study phase separation in quasi-two-dimensional membranes in depth with both simulations and scaling theory, and classify the different scaling regimes and morphologies, which differ from pure two-dimensional fluids. Our results may explain previous inconsistent measurements of the dynamical scaling exponent for phase separation in membranes. We also extend our theory beyond the simplest model, including the possibility that the membrane will be viscoelastic, as well as considering the inertia of the membrane and the fluid surrounding the membrane.

  14. Stratum corneum barrier lipids in cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G;

    2000-01-01

    Specimens from primary cholesteatomas were examined under the electron microscope using a lipid-retaining method that is best suited for intracellular lipids and a method that is best for intercellular lipids. In the stratum granulosum of the squamous epithelium, a large number of Odland bodies...... emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes......, as seen in the formation and maintenance of the cutaneous permeability barrier. In this study we draw the attention to the facts that the cholesteatoma epithelium is capable of producing not only cholesterol, but also several lipids, and that the lipid molecules are organized in multilamellar structures...

  15. Stratum Corneum Barrier Lipids in Cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G

    2000-01-01

    emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes......Specimens from primary cholesteatomas were examined under the electron microscope using a lipid-retaining method that is best suited for intracellular lipids and a method that is best for intercellular lipids. In the stratum granulosum of the squamous epithelium, a large number of Odland bodies......, as seen in the formation and maintenance of the cutaneous permeability barrier. In this study we draw the attention to the facts that the cholesteatoma epithelium is capable of producing not only cholesterol, but also several lipids, and that the lipid molecules are organized in multilamellar structures...

  16. Introduction to fatty acids and lipids.

    Science.gov (United States)

    Burdge, Graham C; Calder, Philip C

    2015-01-01

    The purpose of this article is to describe the structure, function and metabolism of fatty acids and lipids that are of particular importance in the context of parenteral nutrition. Lipids are a heterogeneous group of molecules that share the common property of hydrophobicity. Lipids range in structure from simple short hydrocarbon chains to more complex molecules, including triacylglycerols, phospholipids and sterols and their esters. Lipids within each class may differ structurally. Fatty acids are common components of complex lipids, and these differ according to chain length and the presence, number and position of double bonds in the hydrocarbon chain. Structural variation among complex lipids and among fatty acids gives rise to functional differences that result in different impacts upon metabolism and upon cell and tissue responses. Fatty acids and complex lipids exhibit a variety of structural variations that influence their metabolism and their functional effects.

  17. Lipid metabolism in Drosophila: development and disease

    Institute of Scientific and Technical Information of China (English)

    Zhonghua Liu; Xun Huang

    2013-01-01

    Proteins,nucleic acids,and lipids are three major components of the cell.Despite a few basic metabolic pathways,we know very little about lipids,compared with the explosion of knowledge about proteins and nucleic acids.How many different forms of lipids are there? What are the in vivo functions of individual lipid? How does lipid metabolism contribute to normal development and human health? Many of these questions remain unanswered.For over a century,the fruit fly Drosophila melanogaster has been used as a model organism to study basic biological questions.In recent years,increasing evidences proved that Drosophila models are highly valuable for lipid metabolism and energy homeostasis researches.Some recent progresses of lipid metabolic regulation during Drosophila development and in Drosophila models of human diseases will be discussed in this review.

  18. Relationship and Nursing Countermeasures of Antinuclear Antibodies, Liver Specific Autoantibodies with Chronic Hepatitis B%抗核抗体、自身免疫性抗体与慢性乙肝的关系及护理对策分析

    Institute of Scientific and Technical Information of China (English)

    刘育琼; 魏桂菊; 何秋娴

    2015-01-01

    Objective:To study relationship and nursing countermeasures of antinuclear antibodies, liver specific autoantibodies with chronic hepatitis B.Method:From March 2013 to March 2014 in our hospital for treatment of 100 cases of patients with chronic hepatitis B (CHB) as the research object.Chose 92 cases in our hospital received physical examination of normal persons as control group, the related antibodies, CHB from positive and negative group of related indicators, nursing care of patients before and after treatment adherence of two groups were compared.Result:Chronic hepatitis B group’s ANA positive rate was 24.00% (24/100), was significantly higher than the control group’s 4.35% (4/92), the difference was statistically significant (P0.05).After nursing of treatment adherence for patients with chronic hepatitis B was significantly higher than before treatment, the difference was statistically significant (P0.05)。护理后慢性乙肝患者的治疗依从性显著高于护理前,差异有统计学意义(P<0.05)。结论:慢性乙肝患者血清中存在较多抗体,但ANA及肝病相关抗体测定对于预测患者预后和转归具有较大的意义,其可能是导致乙肝后肝硬化的一种病因。同时,为患者制定护理对策并施以护理能增加治疗依从性,值得临床重视。

  19. Lipid-lipid and lipid-drug interactions in biological membranes

    Science.gov (United States)

    Martynowycz, Michael W.

    Interactions between lipids and drug molecules in biological membranes help govern proper biological function in organisms. The mechanisms responsible for hydrophobic drug permeation remain elusive. Many small molecule drugs are hydrophobic. These drugs inhibit proteins in the cellular interior. The rise of antibiotic resistance in bacteria is thought to be caused by mutations in protein structure, changing drug kinetics to favor growth. However, small molecule drugs have been shown to have different mechanisms depending in the structure of the lipid membrane of the target cell. Biological membranes are investigated using Langmuir monolayers at the air-liquid interface. These offer the highest level of control in the mimetic system and allow them to be investigated using complementary techniques. Langmuir isotherms and insertion assays are used to determine the area occupied by each lipid in the membrane and the change in area caused by the introduction of a drug molecule, respectively. Specular X-ray reflectivity is used to determine the electron density of the monolayer, and grazing incidence X-ray diffraction is used to determine the in-plane order of the monolayer. These methods determine the affinity of the drug and the mechanism of action. Studies are presented on hydrophobic drugs with mammalian membrane mimics using warfarin along with modified analogues, called superwarfarins. Data shows that toxicity of these modified drugs are modulated by the membrane cholesterol content in cells; explaining several previously unexplained effects of the drugs. Membrane mimics of bacteria are investigated along with their interactions with a hydrophobic antibiotic, novobiocin. Data suggests that permeation of the drug is mediated by modifications to the membrane lipids, and completely ceases translocation under certain circumstances. Circumventing deficiencies in small, hydrophobic drugs is approached by using biologically mimetic oligomers. Peptoids, mimetic of host

  20. Isolation and analysis of membrane lipids and lipid rafts in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Brogden, Graham; Propsting, Marcus; Adamek, Mikolaj; Naim, Hassan Y; Steinhagen, Dieter

    2014-03-01

    Cell membranes act as an interface between the interior of the cell and the exterior environment and facilitate a range of essential functions including cell signalling, cell structure, nutrient uptake and protection. It is composed of a lipid bilayer with integrated proteins, and the inner leaflet of the lipid bilayer comprises of liquid ordered (Lo) and liquid disordered (Ld) domains. Lo microdomains, also named as lipid rafts are enriched in cholesterol, sphingomyelin and certain types of proteins, which facilitate cell signalling and nutrient uptake. Lipid rafts have been extensively researched in mammals and the presence of functional lipid rafts was recently demonstrated in goldfish, but there is currently very little knowledge about their composition and function in fish. Therefore a protocol was established for the analysis of lipid rafts and membranous lipids in common carp (Cyprinus carpio L.) tissues. Twelve lipids were identified and analysed in the Ld domain of the membrane with the most predominant lipids found in all tissues being; triglycerides, cholesterol, phosphoethanolamine and phosphatidylcholine. Four lipids were identified in lipid rafts in all tissues analysed, triglycerides (33-62%) always found in the highest concentration followed by cholesterol (24-32%), phosphatidylcholine and sphingomyelin. Isolation of lipid rafts was confirmed by identifying the presence of the lipid raft associated protein flotillin, present at higher concentrations in the detergent resistant fraction. The data provided here build a lipid library of important carp tissues as a baseline for further studies into virus entry, protein trafficking or environmental stress analysis.

  1. Effect of deferrioxamine and diethyldithiocarbamate on paracetamol-induced hepato- and nephrotoxicity. The role of lipid peroxidation.

    Science.gov (United States)

    Younes, M; Sause, C; Siegers, C P; Lemoine, R

    1988-08-01

    In mice subjected to glutathione depletion by pretreatment with phorone (diisopropylidene acetone, 200 mg/kg i.p. in 10 ml/kg olive oil) paracetamol (acetaminophen, 300 mg/kg p.o. in 10 ml/kg tylose 2 h later) led to a marked hepatotoxicity as evidenced by increased plasma activities of the liver-specific enzymes sorbitol dehydrogenase (SDH) and glutamate-pyruvate-transaminase (GPT) 3 and 24 h after treatment. Nephrotoxicity was also indicated at both timepoints by an increased creatinine concentration in plasma, while neither the urine volume nor its content in gamma-glutamyl transpeptitase over 20 h were affected. Hepato- and nephrotoxicity were also assessed histomorphologically. In vivo lipid peroxidation (LPO), as measured by ethane exhalation over 3 h, was clearly enhanced by paracetamol. Malondialdehyde content was increased and glutathione concentration diminished in the liver, but not in the kidney. Diethyldithiocarbamate (DTC, 200 mg/kg i.p.) or deferrioxamine (DFO, 500 mg/kg i.p.) both given 30 min before PA, inhibited in vivo LPO. However, only DTC was capable of antagonizing the hepato- and nephrotoxic effects of paracetamol, while DFO only delayed the onset of nephrotoxicity but left the hepatotoxicity unaffected. Both agents inhibited the rise in hepatic malondialdehyde-content, but only DTC prevented paracetamol-induced glutathione depletion. These results indicate that LPO is not mainly responsible for paracetamol toxicity towards liver or kidney.

  2. Antithrombotic lipids from Semen Persicae.

    Science.gov (United States)

    Yang, Nian-Yun; Liu, Li; Tao, Wei-Wei; Duan, Jin-Ao; Liu, Xun-Hong; Huang, Su-Ping

    2011-10-01

    Chemical investigation of Semen Persicae has led to the isolation of decane (1), triolein (2), nonacosanoic acid (3), oleic acid ethyl ester (4), palmitic acid (5), oleic acid (6) and 15,16-dihydroxy-9Z,12Z-octadecadienoic acid 2,3-dihydroxypropyl ester (7). Amongst these, compound 7 is a new lipid. Their structures were elucidated by chemical and extensive spectral analysis. Their anticoagulative activities were also evaluated in vitro, which showed that petroleum ether extract and compounds 5-6 could significantly prolong thrombin time while methanol extract could obviously inhibit platelet aggregation.

  3. Superdiffusion in supported lipid bilayers

    CERN Document Server

    Campagnola, Grace; Schroder, Bryce W; Peersen, Olve B; Krapf, Diego

    2015-01-01

    We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported lipid bilayers. The ensemble-averaged mean square displacement (MSD) exhibits superdiffusive behavior. However, the time-averaged MSD of individual trajectories is found to be linear with respect to lag time, as in Brownian diffusion. These observations are explained in terms of bulk excursions that introduce jumps with a heavy-tail distribution. Our experimental results are shown to agree with analytical models of bulk-mediated diffusion and with numerical simulations.

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

    Science.gov (United States)

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

    2011-04-27

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

  5. Lipid Disturbances in Psoriasis: An Update

    Directory of Open Access Journals (Sweden)

    Aldona Pietrzak

    2010-01-01

    Full Text Available Psoriasis is a common disease with the population prevalence ranging from 2% to 3%. Its prevalence in the population is affected by genetic, environmental, viral, infectious, immunological, biochemical, endocrinological, and psychological factors, as well as alcohol and drug abuse. In the recent years, psoriasis has been recognised as a systemic disease associated with numerous multiorgan abnormalities and complications. Dyslipidemia is one of comorbidities in psoriatic patients. Lipid metabolism studies in psoriasis have been started at the beginning of the 20th century and are concentrated on skin surface lipids, stratum corneum lipids and epidermal phospholipids, serum lipids, dermal low-density lipoproteins in the psoriatic skin, lipid metabolism, oxidative stress and correlations between inflammatory parameters, lipid parameters and clinical symptoms of the disease. On the basis of the literature data, psoriasis can be described as an immunometabolic disease.

  6. Circadian regulators of intestinal lipid absorption

    OpenAIRE

    Hussain, M. Mahmood; Pan, Xiaoyue

    2015-01-01

    Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circa...

  7. APP Function and Lipids: A Bidirectional Link.

    Science.gov (United States)

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

    2017-01-01

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

  8. Lipid bilayer composition influences small multidrug transporters

    Directory of Open Access Journals (Sweden)

    Curnow Paul

    2008-11-01

    Full Text Available Abstract Background Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins. Results Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr. Conclusion These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer.

  9. Lipid Nanoparticles for Ocular Gene Delivery

    Directory of Open Access Journals (Sweden)

    Yuhong Wang

    2015-06-01

    Full Text Available Lipids contain hydrocarbons and are the building blocks of cells. Lipids can naturally form themselves into nano-films and nano-structures, micelles, reverse micelles, and liposomes. Micelles or reverse micelles are monolayer structures, whereas liposomes are bilayer structures. Liposomes have been recognized as carriers for drug delivery. Solid lipid nanoparticles and lipoplex (liposome-polycation-DNA complex, also called lipid nanoparticles, are currently used to deliver drugs and genes to ocular tissues. A solid lipid nanoparticle (SLN is typically spherical, and possesses a solid lipid core matrix that can solubilize lipophilic molecules. The lipid nanoparticle, called the liposome protamine/DNA lipoplex (LPD, is electrostatically assembled from cationic liposomes and an anionic protamine-DNA complex. The LPD nanoparticles contain a highly condensed DNA core surrounded by lipid bilayers. SLNs are extensively used to deliver drugs to the cornea. LPD nanoparticles are used to target the retina. Age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy are the most common retinal diseases in humans. There have also been promising results achieved recently with LPD nanoparticles to deliver functional genes and micro RNA to treat retinal diseases. Here, we review recent advances in ocular drug and gene delivery employing lipid nanoparticles.

  10. DMSO Induces Dehydration near Lipid Membrane Surfaces

    Science.gov (United States)

    Cheng, Chi-Yuan; Song, Jinsuk; Pas, Jolien; Meijer, Lenny H.H.; Han, Songi

    2015-01-01

    Dimethyl sulfoxide (DMSO) has been broadly used in biology as a cosolvent, a cryoprotectant, and an enhancer of membrane permeability, leading to the general assumption that DMSO-induced structural changes in cell membranes and their hydration water play important functional roles. Although the effects of DMSO on the membrane structure and the headgroup dehydration have been extensively studied, the mechanism by which DMSO invokes its effect on lipid membranes and the direct role of water in this process are unresolved. By directly probing the translational water diffusivity near unconfined lipid vesicle surfaces, the lipid headgroup mobility, and the repeat distances in multilamellar vesicles, we found that DMSO exclusively weakens the surface water network near the lipid membrane at a bulk DMSO mole fraction (XDMSO) of DMSO was found to effectively destabilize the hydration water structure at the lipid membrane surface at XDMSO 0.1, DMSO enters the lipid interface and restricts the lipid headgroup motion. We postulate that DMSO acts as an efficient cryoprotectant even at low concentrations by exclusively disrupting the water network near the lipid membrane surface, weakening the cohesion between water and adhesion of water to the lipid headgroups, and so mitigating the stress induced by the volume change of water during freeze-thaw. PMID:26200868

  11. Lipid peroxides level in the Indonesian elderly

    Directory of Open Access Journals (Sweden)

    Purwantyastuti Purwantyastuti

    2005-06-01

    Full Text Available A cross-sectional study was done to see the possible association of plasma lipid peroxides in the elderly with age and other factors. Plasma lipid peroxides is a product of free radical reactions which according to the latest theory of aging is the cause of aging process. Lipid peroxides were also found high in coronary heart disease. Four hundred forty relatively healthy elderly, age 55-85 years, were randomly chosen from free living elderly under guidance of health care centers (PUSKESMAS in Jakarta. Anamnesis and physical examination were done in the morning in the health centers. Blood samples were taken in fasting conditions, plasma lipids and lipid peroxides were measured according to standard methods. There was an age difference of lipid peroxides level in the elderly, which increased with age up to 70 years old. Elderly 70 years old and over had low plasma lipid peroxides. The level was not related to high plasma lipids. Higher level was found when more chronic degenerative diseases were found. (Med J Indones 2005; 14: 71-7Keywords: lipid peroxides, aging

  12. Electrodiffusion of lipids on membrane surfaces

    Science.gov (United States)

    Zhou, Y. C.

    2012-05-01

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

  13. Lipid transport in cholecystokinin knockout mice.

    Science.gov (United States)

    King, Alexandra; Yang, Qing; Huesman, Sarah; Rider, Therese; Lo, Chunmin C

    2015-11-01

    Cholecystokinin (CCK) is released in response to lipid feeding and regulates pancreatic digestive enzymes vital to the absorption of nutrients. Our previous reports demonstrated that cholecystokinin knockout (CCK-KO) mice fed for 10 weeks of HFD had reduced body fat mass, but comparable glucose uptake by white adipose tissues and skeletal muscles. We hypothesized that CCK is involved in energy homeostasis and lipid transport from the small intestine to tissues in response to acute treatment with dietary lipids. CCK-KO mice with comparable fat absorption had increased energy expenditure and were resistant to HFD-induced obesity. Using intraduodenal infusion of butter fat and intravenous infusion using Liposyn III, we determined the mechanism of lipid transport from the small intestine to deposition in lymph and adipocytes in CCK-KO mice. CCK-KO mice had delayed secretion of Apo B48-chylomicrons, lipid transport to the lymphatic system, and triglyceride (TG)-derived fatty acid uptake by epididymal fat in response to acute treatment of intraduodenal lipids. In contrast, CCK-KO mice had comparable TG clearance and lipid uptake by white adipocytes in response to TGs in chylomicron-like emulsion. Thus, we concluded that CCK is important for lipid transport and energy expenditure to control body weight in response to dietary lipid feeding.

  14. Biologic Activity of Porphyromonas endodontalis complex lipids

    Science.gov (United States)

    Mirucki, Christopher S.; Abedi, Mehran; Jiang, Jin; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran E.; Clark, Robert B.; Nichols, Frank C.

    2014-01-01

    Introduction Periapical infections secondary to pulpal necrosis are associated with bacterial contamination of the pulp. Porphyromonas endodontalis, a Gram-negative organism, is considered to be a pulpal pathogen. P. gingivalis is phylogenetically related to P. endodontalis and synthesizes several classes of novel complex lipids that possess biological activity, including the capacity to promote osteoclastogenesis and osteoclast activation. The purpose of this study was to extract and characterize constituent lipids of P. endodontalis, and evaluate their capacity to promote pro-inflammatory secretory responses in the macrophage cell line, RAW 264.7, as well as their capacity to promote osteoclastogenesis and inhibit osteoblast activity. Methods Constituent lipids of both organisms were fractionated by HPLC and were structurally characterized using electrospray-mass spectrometry (ESI-MS) or ESI-MS/MS. The virulence potential of P. endodontalis lipids was then compared with known biologically active lipids isolated from P. gingivalis. Results P. endodontalis total lipids were shown to promote TNF-α secretion from RAW 264.7 cells and the serine lipid fraction appeared to account for the majority of this effect. P. endodontalis lipid preparations also increased osteoclast formation from RAW 264.7 cells but osteoblast differentiation in culture was inhibited and appeared to be dependent on TLR2 expression. Conclusions These effects underscore the importance of P. endodontalis lipids in promoting inflammatory and bone cell activation processes that could lead to periapical pathology. PMID:25146013

  15. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang

    2015-01-01

    Full Text Available Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

  16. Impact of lipid content and composition on lipid oxidation and protein carbonylation in experimental fermented sausages.

    Science.gov (United States)

    Fuentes, Verónica; Estévez, Mario; Ventanas, Jesús; Ventanas, Sonia

    2014-03-15

    This study aims to investigate the effect of lipid content (∼4%, ∼10% and ∼15%) and composition (different lipid sources; animal fat and sunflower oil) on the oxidative stability of proteins and lipids in experimental fermented sausages. Increasing the lipid content of sausages enhanced the susceptibility of lipids to oxidation whereas the effect on the formation of specific carbonyls from protein oxidation was not so evident. Sausages manufactured with different lipid sources affected the susceptibility of lipids and proteins to oxidation as a likely result of the modifications in the fatty acid profile, as well as to the presence of antioxidant compounds. While the fatty acid profile had a major effect on the occurrence and extent of lipid oxidation, the presence of compounds with potential antioxidant activity may be more influential on the extent of protein carbonylation.

  17. Clinical controversies in lipid management.

    Science.gov (United States)

    Tziomalos, K

    2015-06-01

    Even though it is firmly established that statins are the cornerstone of management of dyslipidemias, several controversies still exist in this area. In the present review, the most pertinent controversies in lipid management are discussed and the current evidence is summarized. Treatment with statins increases the risk for type 2 diabetes mellitus (T2DM) but this increase appears to be small and outweighed by the benefits of statins on cardiovascular disease prevention. Accordingly, statin treatment-associated T2DM should not affect management decisions. In patients who cannot achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with the maximum tolerated dose of a potent statin, adding ezetimibe appears to be the treatment of choice. Finally, patients who achieved LDL-C targets with a statin but have elevated triglyceride levels appear to have increased cardiovascular risk and adding fenofibrate appears to reduce this risk. Even though additional large randomized controlled trials are unlikely to be performed with the existing lipid-lowering agents, mechanistic, genetic and epidemiological studies, as well as careful analyses of the existing trials will provide further insights in these controversial issues and will allow the optimization of the management of dyslipidemia aiming at further reductions in cardiovascular morbidity.

  18. Electroporation of heterogeneous lipid membranes.

    Science.gov (United States)

    Reigada, Ramon

    2014-03-01

    Electroporation is the basis for the transfection of genetic material and for drug delivery to cells, including electrochemotherapy for cancer. By means of molecular dynamics many aspects of membrane electroporation have been unveiled at the molecular detail in simple, homogeneous, lipid bilayers. However, the correspondence of these findings \\with the process happening in cell membranes requires, at least, the consideration of laterally structured membranes. Here, I present a systematic molecular dynamics study of bilayers composed of different liquid-ordered and liquid-disordered lipid phases subjected to a transversal electric field. The simulations reveal two significant results. First, the electric field mainly affects the properties of the disordered phases, so that electroporation takes place in these membrane regions. Second, the smaller the disordered domains are, the faster they become electroporated. These findings may have a relevant significance in the experimental application of cell electroporation in vivo since it implies that electro-induced and pore-mediated transport processes occur in particularly small disordered domains of the plasma membrane, thus locally affecting only specific regions of the cell.

  19. Natural lipids in nanostructured lipid carriers and its cytotoxicity

    Science.gov (United States)

    Lima, Paula A.; Rampazo, Caroline A. D.; Costa, Amanda F.; Rodrigues, Tiago; Watashi, Carolina M.; Durán, Nelson

    2017-06-01

    Nanostructured lipid carriers (NLCs) are active carrier systems which modulate the sustained release of actives and protect unstable compounds against degradation. NLCs can also protect skin from sun light, due to its particulates nature, which gives them intrinsic scattering properties. In this work, we present the preparation of NLCs using natural lipids and its cytotoxicity profile. It was used a vegetal butter with melting point (m.p.) ~32-40°C, an animal wax (m.p. 35-40°C) and a vegetal oil (boiling point ~120-150°C). NLCs were prepared by hot high pressure homogenization method and particles were characterized by average size (Zave), polydispersity index (PDI) and zeta potential (PZ) (Fig.1). The thermal behavior of the NLCs was studied using Differential Scanning Calorimetry (DSC). All the formulations were followed up for 60 days in order to evaluate their stability. NLCs exhibited a Zave around 150-200 nm, PDI less than 0.2 and PZ varying from -25 to -40 mV. The m.p. for the lyophilized NLCs was about 40-56°C. Cytotoxicity of the formulations were evaluated for human keratinocytes (HaCaT) and melanocytes (Melan-A) in the exponential growth phase. Cell viability was used as indicator of cytotoxicity and determined after 4 days of culture by MTT assay. It was found that the NLC formulations were not toxic against HaCaT and Melan-A cells. Results showed that the NLCs produced are potential carriers for nanocosmetics and sunscreen products.

  20. Inclusion of the helper lipid dioleoyl-phosphatidylethanolamine in solid lipid nanoparticles inhibits their transfection efficiency

    NARCIS (Netherlands)

    de Jesus, Marcelo B.; Radaic, Allan; Hinrichs, Wouter L J; Ferreira, Carmen V; de Paula, Eneida; Hoekstra, Dirk; Zuhorn, Inge S

    2014-01-01

    Solid lipid nanoparticles (SLNs) are a promising system for the delivery of lipophilic and hydrophilic drugs. They consist of a solid lipid core that is stabilized by a layer of surfactants. By the incorporation of cationic lipids in the formulation, positively charged SLNs can be generated, that ar

  1. Lipids, lipid droplets and lipoproteins in their cellular context; an ultrastructural approach

    NARCIS (Netherlands)

    Mesman, R.J.

    2013-01-01

    Lipids are essential for cellular life, functioning either organized as bilayer membranes to compartmentalize cellular processes, as signaling molecules or as metabolic energy storage. Our current knowledge on lipid organization and cellular lipid homeostasis is mainly based on biochemical data. How

  2. Fluorescent lipid probes : some properties and applications (a review)

    NARCIS (Netherlands)

    Maier, O; Oberle, [No Value; Hoekstra, D

    2002-01-01

    Odd as it may seem, experimental challenges in lipid research are often hampered by the simplicity of the lipid structure. Since, as in protein research. mutants or overexpression of lipids are not realistic, a considerable amount of lipid research relies on the use Of tagged lipid analogues. Howeve

  3. Fluorescent lipid probes : some properties and applications (a review)

    NARCIS (Netherlands)

    Maier, O; Oberle, [No Value; Hoekstra, D

    Odd as it may seem, experimental challenges in lipid research are often hampered by the simplicity of the lipid structure. Since, as in protein research. mutants or overexpression of lipids are not realistic, a considerable amount of lipid research relies on the use Of tagged lipid analogues.

  4. [Nitric oxide and lipid peroxidation].

    Science.gov (United States)

    Cristol, J P; Maggi, M F; Guérin, M C; Torreilles, J; Descomps, B

    1995-01-01

    Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different

  5. Intravenous lipid emulsion in clinical toxicology

    Directory of Open Access Journals (Sweden)

    Oswald Sarah

    2010-10-01

    Full Text Available Abstract Intravenous lipid emulsion is an established, effective treatment for local anesthetic-induced cardiovascular collapse. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. Recent case reports of successful resuscitation suggest the efficacy of lipid emulsion infusion for treating non-local anesthetic overdoses across a wide spectrum of drugs: beta blockers, calcium channel blockers, parasiticides, herbicides and several varieties of psychotropic agents. Lipid emulsion therapy is gaining acceptance in emergency rooms and other critical care settings as a possible treatment for lipophilic drug toxicity. While protocols exist for administration of lipid emulsion in the setting of local anesthetic toxicity, no optimal regimen has been established for treatment of acute non-local anesthetic poisonings. Future studies will shape the evolving recommendations for lipid emulsion in the setting of non-local anesthetic drug overdose.

  6. Stratum Corneum Barrier Lipids in Cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G

    2000-01-01

    emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes...

  7. Lipids of the living coelacanth, Latimeria chalumnae.

    Science.gov (United States)

    Nevenzel, J C; Rodegker, W; Mead, J F; Gordon, M S

    1966-06-24

    The muscle of Latimeria chalumnae contains 30 to 71 percent (dry weight) of lipid deposited extracellularly. Wax esters constituted 90 percent or more of the lipids from muscle and fat storage tissues. These esters, by gaschromatographic analysis, consisted of C(30) to C(40) homologs with one or two double bonds.

  8. Amylose folding under the influence of lipids

    NARCIS (Netherlands)

    Lopez, Cesar A.; de Vries, Alex H.; Marrink, Siewert J.

    2012-01-01

    The molecular dynamics simulation technique was used to study the folding and complexation process of a short amylose fragment in the presence of lipids. In aqueous solution, the amylose chain remains as an extended left-handed helix. After the addition of lipids in the system, however, we observe s

  9. Transport and sorting of membrane lipids

    NARCIS (Netherlands)

    van Meer, G.|info:eu-repo/dai/nl/068570368

    1993-01-01

    The lipid composition of cellular membranes may seem unnecessarily complex. However, the lipid composition of each membrane is carefully regulated by local metabolism and specificity in transport, marking the functional significance for the cell. Recent research has revealed unexpected discoveries c

  10. Lateral pressure profiles in lipid monolayers

    NARCIS (Netherlands)

    Baoukina, Svetlana; Marrink, Siewert J.; Tieleman, D. Peter

    2010-01-01

    We have used molecular dynamics simulations with coarse-grained and atomistic models to study the lateral pressure profiles in lipid monolayers. We first consider simple oil/air and oil/water interfaces, and then proceed to lipid monolayers at air/water and oil/water interfaces. The results are qual

  11. A comprehensive classification system for lipids

    NARCIS (Netherlands)

    Fahy, E.; Subramaniam, S.; Brown, H.A.; Glass, C.K.; Merrill, A.H.; Murphy, R.C.; Raetz, C.R.H.; Russell, D.W.; Seyama, Y.; Shaw, W.; Shimizu, T.; Spener, F.; van Meer, G.; VanNieuwenhze, M.S.; White, S.H.; Witztum, J.; Dennis, E.A.

    2005-01-01

    Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, “lipidomics,” in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; conseque

  12. The physics of stratum corneum lipid membranes.

    Science.gov (United States)

    Das, Chinmay; Olmsted, Peter D

    2016-07-28

    The stratum corneum (SC), the outermost layer of skin, comprises rigid corneocytes (keratin-filled dead cells) in a specialized lipid matrix. The continuous lipid matrix provides the main barrier against uncontrolled water loss and invasion of external pathogens. Unlike all other biological lipid membranes (such as intracellular organelles and plasma membranes), molecules in the SC lipid matrix show small hydrophilic groups and large variability in the length of the alkyl tails and in the numbers and positions of groups that are capable of forming hydrogen bonds. Molecular simulations provide a route for systematically probing the effects of each of these differences separately. In this article, we present the results from atomistic molecular dynamics of selected lipid bilayers and multi-layers to probe the effect of these polydispersities. We address the nature of the tail packing in the gel-like phase, the hydrogen bond network among head groups, the bending moduli expected for leaflets comprising SC lipids and the conformation of very long ceramide lipids in multi-bilayer lipid assemblies.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

  13. Chemically Stable Lipids for Membrane Protein Crystallization

    Energy Technology Data Exchange (ETDEWEB)

    Ishchenko, Andrii; Peng, Lingling; Zinovev, Egor; Vlasov, Alexey; Lee, Sung Chang; Kuklin, Alexander; Mishin, Alexey; Borshchevskiy, Valentin; Zhang, Qinghai; Cherezov, Vadim (MIPT); (USC); (Scripps)

    2017-05-01

    The lipidic cubic phase (LCP) has been widely recognized as a promising membrane-mimicking matrix for biophysical studies of membrane proteins and their crystallization in a lipidic environment. Application of this material to a wide variety of membrane proteins, however, is hindered due to a limited number of available host lipids, mostly monoacylglycerols (MAGs). Here, we designed, synthesized, and characterized a series of chemically stable lipids resistant to hydrolysis, with properties complementary to the widely used MAGs. In order to assess their potential to serve as host lipids for crystallization, we characterized the phase properties and lattice parameters of mesophases made of two most promising lipids at a variety of different conditions by polarized light microscopy and small-angle X-ray scattering. Both lipids showed remarkable chemical stability and an extended LCP region in the phase diagram covering a wide range of temperatures down to 4 °C. One of these lipids has been used for crystallization and structure determination of a prototypical membrane protein bacteriorhodopsin at 4 and 20 °C.

  14. NMR spectroscopy for assessing lipid oxidation

    Science.gov (United States)

    Although lipid oxidation involves a variety of chemical reactions to produce numerous substances, most of traditional methods assessing lipid oxidation measure only one kind of oxidation product. For this reason, in general, one indicator of oxidation is not enough to accurately describe the oxidati...

  15. Obstructive sleep apnea and lipid abnormalities

    Directory of Open Access Journals (Sweden)

    Dimitar Karkinski

    2017-01-01

    CONCLUSION:OSA and obesity are potent risk factors for dyslipidemias. OSA could play a significant role in worsening of lipid metabolism in non-obese patients. But in obese patients, the extra weight makes the metabolic changes of lipid metabolism, and the role of OSA is not that very important like in non-obese patients.

  16. Do lipids influence the allergic sensitization process?

    Science.gov (United States)

    Bublin, Merima; Eiwegger, Thomas; Breiteneder, Heimo

    2014-09-01

    Allergic sensitization is a multifactorial process that is not only influenced by the allergen and its biological function per se but also by other small molecular compounds, such as lipids, that are directly bound as ligands by the allergen or are present in the allergen source. Several members of major allergen families bind lipid ligands through hydrophobic cavities or electrostatic or hydrophobic interactions. These allergens include certain seed storage proteins, Bet v 1-like and nonspecific lipid transfer proteins from pollens and fruits, certain inhalant allergens from house dust mites and cockroaches, and lipocalins. Lipids from the pollen coat and furry animals and the so-called pollen-associated lipid mediators are codelivered with the allergens and can modulate the immune responses of predisposed subjects by interacting with the innate immune system and invariant natural killer T cells. In addition, lipids originating from bacterial members of the pollen microbiome contribute to the outcome of the sensitization process. Dietary lipids act as adjuvants and might skew the immune response toward a TH2-dominated phenotype. In addition, the association with lipids protects food allergens from gastrointestinal degradation and facilitates their uptake by intestinal cells. These findings will have a major influence on how allergic sensitization will be viewed and studied in the future.

  17. Lipid polarity and sorting in epithelial cells

    NARCIS (Netherlands)

    van Meer, G.; Simons, K.

    1988-01-01

    Apical and basolateral membrane domains of epithelial cell plasma membranes possess unique lipid compositions. The tight junction, the structure separating the two domains, forms a diffusion barrier for membrane components and thereby prevents intermixing of the two sets of lipids. The barrier appar

  18. Computational Modeling of Lipid Metabolism in Yeast

    Directory of Open Access Journals (Sweden)

    Vera Schützhold

    2016-09-01

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

  19. Lipids in plant-microbe interactions.

    Science.gov (United States)

    Siebers, Meike; Brands, Mathias; Wewer, Vera; Duan, Yanjiao; Hölzl, Georg; Dörmann, Peter

    2016-09-01

    Bacteria and fungi can undergo symbiotic or pathogenic interactions with plants. Membrane lipids and lipid-derived molecules from the plant or the microbial organism play important roles during the infection process. For example, lipids (phospholipids, glycolipids, sphingolipids, sterol lipids) are involved in establishing the membrane interface between the two organisms. Furthermore, lipid-derived molecules are crucial for intracellular signaling in the plant cell, and lipids serve as signals during plant-microbial communication. These signal lipids include phosphatidic acid, diacylglycerol, lysophospholipids, and free fatty acids derived from phospholipase activity, apocarotenoids, and sphingolipid breakdown products such as ceramide, ceramide-phosphate, long chain base, and long chain base-phosphate. Fatty acids are the precursors for oxylipins, including jasmonic acid, and for azelaic acid, which together with glycerol-3-phosphate are crucial for the regulation of systemic acquired resistance. This article is part of a Special Issue titled "Plant Lipid Biology," guest editors Kent Chapman and Ivo Feussner. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Keratins and lipids in ethnic hair.

    Science.gov (United States)

    Cruz, C F; Fernandes, M M; Gomes, A C; Coderch, L; Martí, M; Méndez, S; Gales, L; Azoia, N G; Shimanovich, U; Cavaco-Paulo, A

    2013-06-01

    Human hair has an important and undeniable relevance in society due to its important role in visual appearance and social communication. Hair is mainly composed of structural proteins, mainly keratin and keratin associated proteins and lipids. Herein, we report a comprehensive study of the content and distribution of the lipids among ethnic hair, African, Asian and Caucasian hair. More interestingly, we also report the study of the interaction between those two main components of hair, specifically, the influence of the hair internal lipids in the structure of the hair keratin. This was achieved by the use of a complete set of analytical tools, such as thin layer chromatography-flame ionization detector, X-ray analysis, molecular dynamics simulation and confocal microscopy. The experimental results indicated different amounts of lipids on ethnic hair compositions and higher percentage of hair internal lipids in African hair. In this type of hair, the axial diffraction of keratin was not observed in X-ray analysis, but after hair lipids removal, the keratin returned to its typical packing arrangement. In molecular dynamic simulation, lipids were shown to intercalate dimers of keratin, changing its structure. From those results, we assume that keratin structure may be influenced by higher concentration of lipids in African hair. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  1. Penetration of lipid monolayers by psychoactive drugs

    NARCIS (Netherlands)

    Demel, R.A.; Deenen, L.L.M. van

    1966-01-01

    The ability of a number of psychoactive drugs to penetrate lipid monolayers of varying composition was examined, and the following observation were made: (1) The increase in surface pressure of a monomolecular film appeared to depend on the chemical nature of the lipid as well as on the initial film

  2. Functionality of lipids and lipid-protein interactions in cereal-derived food products

    Directory of Open Access Journals (Sweden)

    Marion Didier

    2003-01-01

    Full Text Available Lipids and especially cereal lipids play a significant role in the processing and quality of cereals and baked cereal foods (bread, biscuits and beverages (beer. Most of the physico-chemical mechanisms responsible for the lipid functionality has been investigated and recently the specific role of lipid-binding proteins, e.g. lipid transfer proteins and puroindolines, has been highlighted. The state of the researches performed in this field are briefly presented in this review and the data obtained until now show that new perspectives are opened in cereal breeding and processing for improving the quality of cereals and cereal products.

  3. Immunostimulatory lipid nanoparticles from herbal medicine.

    Science.gov (United States)

    Hasson, Tal H; Takaoka, Anna; de la Rica, Roberto; Matsui, Hiroshi; Smeureanu, Gabriela; Drain, Charles M; Kawamura, Akira

    2014-04-01

    Reproducibility is an important issue in biological characterization of drug candidates and natural products. It is not uncommon to encounter cases in which supposedly the same sample exhibits very different biological activities. During our characterization of macrophage-stimulatory lipids from herbal medicine, it was found that the potency of these lipids could vary substantially from experiment to experiment. Further analysis of this reproducibility issue led to the discovery of solvent-dependent nanoparticle formation by these lipids. While larger nanoparticles (approximately 100 nm) of these lipids showed modest macrophage-stimulatory activity, smaller nanoparticles (nanoparticle formation and macrophage-stimulatory activity of plant lipids. Although nanoparticles have been extensively studied in the context of vehicles for drug delivery, our finding indicates that drugs themselves can form nanoassemblies, and their biological properties may be altered by the way they assemble. © 2013 John Wiley & Sons A/S.

  4. Anaerobic lipid degradation through acidification and methanization.

    Science.gov (United States)

    Kim, Ijung; Kim, Sang-Hyoun; Shin, Hang-Sik; Jung, Jin-Young

    2010-01-01

    In biological wastewater treatment high lipid concentration is known to inhibit microorganisms and cause active biomass flotation. To reduce lipid inhibition, a two-phase anaerobic system, consisting of an anaerobic sequencing batch reactor (ASBR) and an upflow anaerobic sludge blanket (UASB) reactor, was applied to synthetic dairy wastewater. During 153 days of operation, the two-phase system showed stable performance in lipid degradation. In the ASBR, a 13% lipid removal efficiency and 10% double bond removal efficiency were maintained. In the UASB, the chemical oxygen demand (COD), lipid and volatile fatty acid (VFA) removal efficiencies were more than 80%, 70% and 95%, respectively, up to organic loading rate 6.5 g COD/L/day. There were no operational problems such as serious scum formation or sludge washout. Protein degradation occurred prior to degradation during acidogenesis.

  5. Insulin-induced lipid binding to hemoglobin

    Directory of Open Access Journals (Sweden)

    VESNA NIKETIC

    2003-01-01

    Full Text Available Under hypoglycemic conditions, concomitant hyperinsulinism causes an apparent modification of hemoglobin (Hb which is manifested by its aggregation (Niketi} et al., Clin. Chim. Acta 197 (1991 47. In the present work the causes and mechanisms underlying this Hb modification were studied. Hemoglobin isolated from normal erythrocytes incubated with insulin was analyzed by applying 31P-spectrometry and lipid extraction and analysis. To study the dynamics of the plasma membrane during hyperinsulinism, a fluorescent lipid-analog was applied. In the presence of insulin, phosphatidylserine (PS, phosphatidylethanolamine (PE and cholesterol were found to bind to Hb. Lipid binding resulted in Hb aggregation, a condition that can be reproduced when phospholipids are incubated with Hb in vitro. Using a fluorescent lipid-analog, it was also shown that exposing erythrocytes to supraphysiological concentrations of insulin in vitro resulted in the internalization of lipids. The results presented in this work may have relevance to cases of diabetes mellitus and hypoglycemia.

  6. [Germ cell membrane lipids in spermatogenesis].

    Science.gov (United States)

    Wang, Ting; Shi, Xiao; Quan, Song

    2016-05-01

    Spermatogenesis is a complex developmental process in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. During spermatogenesis, membrane remodeling takes place, and cell membrane permeability and liquidity undergo phase-specific changes, which are all associated with the alteration of membrane lipids. Lipids are important components of the germ cell membrane, whose volume and ratio fluctuate in different phases of spermatogenesis. Abnormal lipid metabolism can cause spermatogenic dysfunction and consequently male infertility. Germ cell membrane lipids are mainly composed of cholesterol, phospholipids and glycolipids, which play critical roles in cell adhesion and signal transduction during spermatogenesis. An insight into the correlation of membrane lipids with spermatogenesis helps us to better understand the mechanisms of spermatogenesis and provide new approaches to the diagnosis and treatment of male infertility.

  7. Lipid protrusions membrane softness, and enzymatic activity

    DEFF Research Database (Denmark)

    Jensen, Morten Østergaard; Høyrup, P.; Callisen, T.H.;

    2004-01-01

    The activity of phospholipase A(2) on lipid bilayers displays a characteristic lag burst behavior that has previously been shown to reflect the physical properties of the substrate. It has remained unclear which underlying molecular mechanism is responsible for this phenomenon. We propose here...... that protrusions of single lipid molecules out of the bilayer plane could provide such a mechanism. The proposal is supported by a combination of atomic-scale molecular dynamics simulations, theory, and experiments that have been performed in order to investigate the relationship between on the one side lipid...... protrusion modes and mechanical softness of phospholipid bilayers and on the other side the activity of enzymes acting on lipid bilayers composed of different unsaturated lipids. Specifically, our experiments show a correlation between the bilayer bending rigidity and the apparent Arrhenius activation energy...

  8. Model parameters for simulation of physiological lipids

    Science.gov (United States)

    McGlinchey, Nicholas

    2016-01-01

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

  9. Molecular restructuring of water and lipids upon the interaction of DNA with lipid monolayers.

    Science.gov (United States)

    Campen, R Kramer; Ngo, Thuy T M; Sovago, Maria; Ruysschaert, Jean-Marie; Bonn, Mischa

    2010-06-16

    Understanding the molecular mechanism of DNA/lipid interaction is critical in optimizing the use of lipid cofactors in gene therapy. Here, we address this question by employing label-free vibrational sum frequency (VSF) spectroscopy to study the interaction of DNA with lipid monolayers of the cationic lipids DPTAP(1,2-dipalmitoyl-3-trimethylammonium-propane) and diC14-amidine as well as the zwitterionic lipid DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) in the presence and absence of calcium. Our approach has the advantage both of allowing us to explicitly probe intermolecular interactions and of providing insight into the structure of water and lipids around DNA at the lipid interface. We find, by examination of the OD stretch of interfacial D(2)O, that water structure differs markedly between systems containing DNA adsorbed to cationic and those that contain DNA adsorbed to zwitterionic lipid monolayers (in the presence or absence of Ca(2+)). The spectral response of interfacial water in the cationic system is consistent with a highly structured, undercoordinated, structural 'type' of water. Further, by investigation of CH stretch modes of the diC14-amidine lipid tails, we demonstrate that the adsorption of DNA to this lipid leads to increased ordering of lipid tails.

  10. Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. Method of fabricating lipid bilayer membranes on solid supports

    Science.gov (United States)

    Cho, Nam-Joon (Inventor); Frank, Curtis W. (Inventor); Glenn, Jeffrey S. (Inventor); Cheong, Kwang Ho (Inventor)

    2012-01-01

    The present invention provides a method of producing a planar lipid bilayer on a solid support. With this method, a solution of lipid vesicles is first deposited on the solid support. Next, the lipid vesicles are destabilized by adding an amphipathic peptide solution to the lipid vesicle solution. This destabilization leads to production of a planar lipid bilayer on the solid support. The present invention also provides a supported planar lipid bilayer, where the planar lipid bilayer is made of naturally occurring lipids and the solid support is made of unmodified gold or titanium oxide. Preferably, the supported planar lipid bilayer is continuous. The planar lipid bilayer may be made of any naturally occurring lipid or mixture of lipids, including, but not limited to phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinsitol, cardiolipin, cholesterol, and sphingomyelin.

  13. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  14. Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Duelund, Lars; Pakkanen, Kirsi Inkeri

    2010-01-01

    Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO) than earlier anticipated, by sequestering...... aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model...

  15. Interfacial & colloidal aspects of lipid digestion.

    Science.gov (United States)

    Wilde, P J; Chu, B S

    2011-06-09

    Amongst the main issues challenging the food manufacturing sector, health and nutrition are becoming increasingly important. Global concerns such as obesity, the ageing population and food security will have to be addressed. Food security is not just about assuring food supply, but is also about optimising nutritional delivery from the food that is available [1]. Therefore one challenge is to optimise the health benefits from the lipids and lipid soluble nutrients. Colloid scientists have an affinity for lipids because they are water insoluble, however this presents a challenge to the digestive system, which has to convert them to structures that are less insoluble so they are available for uptake. Despite this, the human digestive system is remarkably effective at digesting and absorbing most lipids. This is primarily driven through maximising energy intake, as lipids possess the highest calorific value, which was a survival trait to survive times of famine, but is now an underlying cause of obesity in developed countries with high food availability. The critical region here is the lipid-water interface, where the key reactions take place to solubilise lipids and lipid soluble nutrients. Digestive lipases have to adsorb to the oil water interface in order to hydrolyse triacylglycerols into fatty acids and mono glycerides, which accumulate at the interface [2], and inhibit lipase activity. Pancreatic lipase, which is responsible for the majority of lipid hydrolysis, also requires the action of bile salts and colipase to function effectively. Bile salts both aid the adsorption of co-lipase and lipase, and help solubilise the lipolysis products which have accumulated at the interface, into mixed micelles composing bile salts and a range of other lipids, to facilitate transport to the gut mucosal surface prior to uptake and absorption. The process can be affected by the lipid type, as shorter chain, fatty acids are more easily absorbed, whereas the uptake of longer

  16. The lipid raft proteome of Borrelia burgdorferi.

    Science.gov (United States)

    Toledo, Alvaro; Pérez, Alberto; Coleman, James L; Benach, Jorge L

    2015-11-01

    Eukaryotic lipid rafts are membrane microdomains that have significant amounts of cholesterol and a selective set of proteins that have been associated with multiple biological functions. The Lyme disease agent, Borrelia burgdorferi, is one of an increasing number of bacterial pathogens that incorporates cholesterol onto its membrane, and form cholesterol glycolipid domains that possess all the hallmarks of eukaryotic lipid rafts. In this study, we isolated lipid rafts from cultured B. burgdorferi as a detergent resistant membrane (DRM) fraction on density gradients, and characterized those molecules that partitioned exclusively or are highly enriched in these domains. Cholesterol glycolipids, the previously known raft-associated lipoproteins OspA and OpsB, and cholera toxin partitioned into the lipid rafts fraction indicating compatibility with components of the DRM. The proteome of lipid rafts was analyzed by a combination of LC-MS/MS or MudPIT. Identified proteins were analyzed in silico for parameters that included localization, isoelectric point, molecular mass and biological function. The proteome provided a consistent pattern of lipoproteins, proteases and their substrates, sensing molecules and prokaryotic homologs of eukaryotic lipid rafts. This study provides the first analysis of a prokaryotic lipid raft and has relevance for the biology of Borrelia, other pathogenic bacteria, as well as for the evolution of these structures. All MS data have been deposited in the ProteomeXchange with identifier PXD002365 (http://proteomecentral.proteomexchange.org/dataset/PXD002365).

  17. Analysis of meibum and tear lipids.

    Science.gov (United States)

    Pucker, Andrew D; Nichols, Jason J

    2012-10-01

    The meibum is a lipid-rich secretion that is the primary component of the external layer of the tear film. The meibomian glands produce the meibum, and meibomian gland dysfunction can lead to degradation of the tear film. Such dysfunction can result in ocular irritation, inflammation, and clinical disease. Understanding this relationship is critical to preventing ocular disease; therefore, a search of peer-reviewed literature focusing on the collection, quantification, and analysis of normal and abnormal meibum and tear lipids was conducted. Numerous collection and quantification techniques are described, including their advantages and disadvantages. Studies indicate that the meibum and tear lipids consist of a large array of polar and nonpolar lipids; individual lipids or their classes can be correlated to pathology. Significant amounts of lipids are deposited on contact lenses, depending on the nature of their polymer chemistry. These findings taken together indicate that normal meibum and tear lipids are essential for normal ocular health. Additional studies are required to provide a better understanding of the meibum and tear film biomolecules so that more effective treatments for blepharitis, dry eye disease, and tear film-related contact lens complications can be devised.

  18. Temperature dependent heterogeneous rotational correlation in lipids

    Science.gov (United States)

    Dadashvand, Neda; Othon, Christina M.

    2016-12-01

    Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids. We explore heterogeneous relaxation in in a single constituent lipid monolayer of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine by measuring the rotational diffusion of a fluorescent probe (1-palmitoyl-2-[1]-sn-glycero-3-phosphocholine), which is embedded in the lipid monolayer at low labeling density. Dynamic distributions are measured using wide-field time-resolved fluorescence anisotropy. The observed relaxation exhibits a narrow, liquid-like distribution at high temperatures (τ ˜ 2.4 ns), consistent with previous experimental measures (Dadashvand et al 2014 Struct. Dyn. 1 054701, Loura and Ramalho 2007 Biochim. Biophys. Acta 1768 467-478). However, as the temperature is quenched, the distribution broadens, and we observe the appearance of a long relaxation population (τ ˜ 16.5 ns). This supports the heterogeneity observed for lipids at high packing densities, and demonstrates that the nanoscale diffusion and reorganization in lipid structures can be significantly complex, even in the simplest amorphous architectures. Dynamical heterogeneity of this form can have a significant impact on the organization, permeability and energetics of lipid membrane structures.

  19. LipidHome: a database of theoretical lipids optimized for high throughput mass spectrometry lipidomics.

    Directory of Open Access Journals (Sweden)

    Joseph M Foster

    Full Text Available Protein sequence databases are the pillar upon which modern proteomics is supported, representing a stable reference space of predicted and validated proteins. One example of such resources is UniProt, enriched with both expertly curated and automatic annotations. Taken largely for granted, similar mature resources such as UniProt are not available yet in some other "omics" fields, lipidomics being one of them. While having a seasoned community of wet lab scientists, lipidomics lies significantly behind proteomics in the adoption of data standards and other core bioinformatics concepts. This work aims to reduce the gap by developing an equivalent resource to UniProt called 'LipidHome', providing theoretically generated lipid molecules and useful metadata. Using the 'FASTLipid' Java library, a database was populated with theoretical lipids, generated from a set of community agreed upon chemical bounds. In parallel, a web application was developed to present the information and provide computational access via a web service. Designed specifically to accommodate high throughput mass spectrometry based approaches, lipids are organised into a hierarchy that reflects the variety in the structural resolution of lipid identifications. Additionally, cross-references to other lipid related resources and papers that cite specific lipids were used to annotate lipid records. The web application encompasses a browser for viewing lipid records and a 'tools' section where an MS1 search engine is currently implemented. LipidHome can be accessed at http://www.ebi.ac.uk/apweiler-srv/lipidhome.

  20. Lipid synthesis inhibitors: effect on epidermal lipid conformational changes and percutaneous permeation of levodopa.

    Science.gov (United States)

    Babita, Kumar; Rana, Vikas; Tiwary, Ashok K

    2005-10-24

    A combination of lipid synthesis inhibitors was used to enhance the in vitro and in vivo permeation of levodopa (LD) across rat epidermis, and their influence on epidermal lipids was investigated using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Rat epidermis was treated with ethanol and a combination of atorvastatin (750 microg/7 cm2), cerulenin (20 microg/7 cm2), and beta-chloroalanine (600 microg/7 cm2) for sustaining the reduced content of epidermal cholesterol, fatty acids (as triglycerides), and ceramide (as sphingosine), respectively, in viable rat skin. This treatment resulted in significant (P < .05) synthesis inhibition of skin lipids up to 48 hours and 6-fold enhancement in the in vitro permeation of LD. The effective plasma concentration of LD was achieved within 1 hour and maintained over 48 hours after topical application to rat epidermis treated with a combination of these lipid synthesis inhibitors. ATR-FTIR studies of inhibitor(s)-treated rat epidermis revealed a significant decrease (P < .05) in peak height and area for both asymmetric and symmetric C-H stretching absorbances, suggesting extraction of lipids. However, an insignificant (P < .05) shift in the frequency of these peaks suggested no fluidization of epidermal lipids by lipid synthesis inhibitors. A direct correlation was observed between epidermal lipid synthesis inhibition, decrease in peak height or area, and percutaneous permeation of LD. Skin lipid synthesis inhibition by a combination of lipid synthesis inhibitors seems to offer a feasible approach for enhancing the transcutaneous delivery of LD.

  1. The differential protein and lipid compositions of noncaveolar lipid microdomains and caveolae

    Institute of Scientific and Technical Information of China (English)

    Yao Yao; Shangyu Hong; Hu Zhou; Taichang Yuan; Rong Zeng; Kan Liao

    2009-01-01

    Morphologically, caveolae and lipid rafts are two different membrane structures. They are often reported to share similar lipid and protein compositions, and are considered to be two subtypes of membrane lipid microdomains. By modifying sucrose density gradient flotation centrifugation, which is used to isolate lipid microdomains, we were able to separate caveolae and noncaveolar lipid microdomains into two distinct fractions. The caveolar membranes are membrane vesicles of 100-nm diameter, enriched with caveolin-1 and flotillin-1. The noncaveolar lipid microdomains are amorphous membranes and most likely the coalescence of heterogeneous lipid rafts. They are depleted of caveolin-1 and are more enriched with cholesterol and sphingolipids than the caveolae. Many membrane proteins, such as insulin-like growth factor-1 receptor (membrane receptor), aquaporin-1 (membrane transporter), Thy-1 and N-cadherin (glycosylphosphatidylinositol-anchored membrane protein and membrane glycoprotein), are specifically associated with noncaveolar lipid microdomains, but not with caveolae. These results indicate that the lipid and protein compositions of caveolae differ from those of noncaveolar lipid microdomains. The difference in their protein compositions implies that these two membrane microdomains may have different cellular functions.

  2. DNA release from lipoplexes by anionic lipids: correlation with lipid mesomorphism, interfacial curvature, and membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Tarahovsky, Yury S.; Koynova, Rumiana; MacDonald, Robert C. (Northwestern)

    2010-01-18

    DNA release from lipoplexes is an essential step during lipofection and is probably a result of charge neutralization by cellular anionic lipids. As a model system to test this possibility, fluorescence resonance energy transfer between DNA and lipid covalently labeled with Cy3 and BODIPY, respectively, was used to monitor the release of DNA from lipid surfaces induced by anionic liposomes. The separation of DNA from lipid measured this way was considerably slower and less complete than that estimated with noncovalently labeled DNA, and depends on the lipid composition of both lipoplexes and anionic liposomes. This result was confirmed by centrifugal separation of released DNA and lipid. X-ray diffraction revealed a clear correlation of the DNA release capacity of the anionic lipids with the interfacial curvature of the mesomorphic structures developed when the anionic and cationic liposomes were mixed. DNA release also correlated with the rate of fusion of anionic liposomes with lipoplexes. It is concluded that the tendency to fuse and the phase preference of the mixed lipid membranes are key factors for the rate and extent of DNA release. The approach presented emphasizes the importance of the lipid composition of both lipoplexes and target membranes and suggests optimal transfection may be obtained by tailoring lipoplex composition to the lipid composition of target cells.

  3. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    DEFF Research Database (Denmark)

    Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco;

    2014-01-01

    Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary...... phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic...... and explain how cells switch neutral lipid metabolism from storage to consumption....

  4. Lipid - Motor Interactions: Soap Opera or Symphony?

    Science.gov (United States)

    Pathak, Divya; Mallik, Roop

    2017-02-01

    Intracellular transport of organelles can be driven by multiple motor proteins that bind to the lipid membrane of the organelle and work as a team. We review present knowledge on how lipids orchestrate the recruitment of motors to a membrane. Looking beyond recruitment, we also discuss how heterogeneity and local mechanical properties of the membrane may influence function of motor-teams. These issues gain importance because phagocytosed pathogens use lipid-centric strategies to manipulate motors and survive in host cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Lipides et comportement alimentaire chez les enfants

    Directory of Open Access Journals (Sweden)

    Nicklaus Sophie

    2016-05-01

    Full Text Available Cet article analyse la place des lipides dans l’alimentation des jeunes enfants. Premièrement, il montre d’une part la contribution importante que devraient avoir les lipides aux apports énergétiques totaux des enfants de moins de deux ans, en raison de leur intérêt fonctionnel dans le développement neuronal et de leur effet potentiellement protecteur d’une obésité ultérieure; d’autre part, il souligne la faible contribution des lipides aux apports énergétiques totaux chez les enfants français, d’après les estimations disponibles, avec une minorité d’enfants pour lesquels les apports en lipides sont satisfaisants. Deuxièmement, il rapporte les connaissances disponibles concernant le contrôle « sensoriel » de la consommation de lipides. Chez les nouveau-nés et les nourrissons, quelques travaux portent sur les préférences pour les lipides, et indiquent l’absence d’une préférence pour les lipides. Chez les enfants, une teneur augmentée en lipides a parfois (mais pas toujours un effet positif sur l’appréciation d’un aliment, avec souvent une teneur optimale; mais elle n’est pas associée à une consommation plus élevée de l’aliment. Des teneurs élevées en lipides ont deux effets sur les apprentissages alimentaires. Chez des enfants de moins de 3 ans, un triplement de la densité énergétique par l’ajout de lipides est associé à la mise en place d’un rassasiement conditionné pour l’aliment concerné; chez des enfants plus âgés, un doublement de la densité énergétique par l’ajout de lipides, est associé à une augmentation de l’appréciation des flaveurs associées aux versions les plus riches en lipides. Des pistes d’études complémentaires sont discutées.

  6. Binding of Serotonin to Lipid Membranes

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Wang, Chunhua; Cruys-Bagger, Nicolaj;

    2013-01-01

    dynamics (MD) simulations. 5-HT was found to interact strongly with lipid bilayers (partitioning coefficient ∼1200 in mole fraction units), and this is highly unusual for a hydrophilic solute like 5-HT which has a bulk, oil–water partitioning coefficient well below unity. It follows that membrane affinity...... and a prevailing residence between the phosphate and the carbonyl groups of the lipid. The unprotonated form of 5-HT shows the opposite orientation, with the primary amine pointing toward the membrane core. Partitioning of 5-HT was found to decrease lipid chain order. These distinctive interactions of 5-HT...

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

    Science.gov (United States)

    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

  8. Microdomains Associated to Lipid Rafts.

    Science.gov (United States)

    Pacheco, Jonathan; Ramírez-Jarquín, Josué O; Vaca, Luis

    2016-01-01

    Store Operated Ca(2+) Entry (SOCE), the main Ca(2+) influx mechanism in non-excitable cells, is implicated in the immune response and has been reported to be affected in several pathologies including cancer. The basic molecular constituents of SOCE are Orai, the pore forming unit, and STIM, a multidomain protein with at least two principal functions: one is to sense the Ca(2+) content inside the lumen of the endoplasmic reticulum(ER) and the second is to activate Orai channels upon depletion of the ER. The link between Ca(2+) depletion inside the ER and Ca(2+) influx from extracellular media is through a direct association of STIM and Orai, but for this to occur, both molecules have to interact and form clusters where ER and plasma membrane (PM) are intimately apposed. In recent years a great number of components have been identified as participants in SOCE regulation, including regions of plasma membrane enriched in cholesterol and sphingolipids, the so called lipid rafts, which recruit a complex platform of specialized microdomains, which cells use to regulate spatiotemporal Ca(2+) signals.

  9. Oxidized lipoprotein lipids and atherosclerosis.

    Science.gov (United States)

    Ahotupa, Markku

    2017-04-01

    Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This article gives an overview of the present knowledge of lipoprotein LOP transport and its association with the risk of atherosclerosis and cardiovascular diseases (CVD). Evidence of the significance of lipoprotein LOP transport comes mainly from studies of physiological oxidative stress and is supported by studies of the functionality apolipoprotein A-1 mimetic peptides. A large body of data has accumulated indicating that lipoprotein LOP transport is connected to the risk of atherosclerosis. While high levels of LOP carried by LDL are indicative of elevated risk, high LOP level in HDL appears to associate with protection. If confirmed, the proposed lipoprotein LOP transport function would affect conception of the etiology of atherosclerosis, but would not conflict current views of the pathophysiological mechanisms. It could open new perspectives, such as the dietary origin of LOP, and the protective function of HDL in clearance of LOP. Focusing on LOP could give additional tools especially for prevention and diagnosis, but would not radically change the management of atherosclerosis and CVD.

  10. Notch, lipids, and endothelial cells

    Science.gov (United States)

    Briot, Anaïs; Bouloumié, Anne; Iruela-Arispe, M. Luisa

    2017-01-01

    Purpose of review Notch signaling is an evolutionary conserved pathway critical for cardiovascular development and angiogenesis. More recently, the contribution of Notch signaling to the homeostasis of the adult vasculature has emerged as an important novel paradigm, but much remains to be understood. Recent findings Recent findings shed light on the impact of Notch in vascular and immune responses to microenvironmental signals as well as on the onset of atherosclerosis. In the past year, studies in human and mice explored the role of Notch in the maintenance of a nonactivated endothelium. Novel pieces of evidence suggest that this pathway is sensitive to environmental factors, including inflammatory mediators and diet-derived by-products. Summary An emerging theme is the ability of Notch to respond to changes in the microenvironment, including glucose and lipid metabolites. In turn, alterations in Notch enable an important link between metabolism and transcriptional changes, thus this receptor appears to function as a metabolic sensor with direct implications to gene expression. PMID:27454451

  11. Spastin binds to lipid droplets and affects lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Chrisovalantis Papadopoulos

    2015-04-01

    Full Text Available Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP. HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87. We now show that spastin-M1 can sort from the endoplasmic reticulum (ER to pre- and mature lipid droplets (LDs. A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP.

  12. Lipid partitioning in maize (Zea mays L.) endosperm highlights relationships among starch lipids, amylose, and vitreousness.

    Science.gov (United States)

    Gayral, Mathieu; Bakan, Bénédicte; Dalgalarrondo, Michele; Elmorjani, Khalil; Delluc, Caroline; Brunet, Sylvie; Linossier, Laurent; Morel, Marie-Hélène; Marion, Didier

    2015-04-08

    Content and composition of maize endosperm lipids and their partition in the floury and vitreous regions were determined for a set of inbred lines. Neutral lipids, i.e., triglycerides and free fatty acids, accounted for more than 80% of endosperm lipids and are almost 2 times higher in the floury than in the vitreous regions. The composition of endosperm lipids, including their fatty acid unsaturation levels, as well as their distribution may be related to metabolic specificities of the floury and vitreous regions in carbon and nitrogen storage and to the management of stress responses during endosperm cell development. Remarkably, the highest contents of starch lipids were observed systematically within the vitreous endosperm. These high amounts of starch lipids were mainly due to lysophosphatidylcholine and were tightly linked to the highest amylose content. Consequently, the formation of amylose-lysophosphatidylcholine complexes has to be considered as an outstanding mechanism affecting endosperm vitreousness.

  13. Investigation of Lipid Oxidation in High- and Low-Lipid-Containing Topical Skin Formulations

    DEFF Research Database (Denmark)

    Raagaard Thomsen, Birgitte; Frisenfeldt Horn, Anna; Hyldig, G.

    2017-01-01

    Abstract: Lipid oxidation can impact the odour of skin care products during storage. A study was conducted to identify and monitor representative markers for lipid oxidation in skin care products over time. Four lip care formulations and three skin care formulations with different lipid contents...... were stored at various cosmetic industry-relevant conditions for 84 days. The skin care products were analysed for lipid hydroperoxides and secondary volatile oxidation products. A trained sensory panel performed an odour difference (triangle) test and odour-profiled the products to detect and describe...... odour changes during storage. Several potential markers for lipid oxidation were identified. In skin care formulations, peroxide value (PV) analysis was a useful marker for lipid oxidation if the product was exposed to light during storage, but no clear changes were observed for PV in samples stored...

  14. Computer Simulations of Lipid Bilayers and Proteins

    DEFF Research Database (Denmark)

    Sonne, Jacob

    2006-01-01

    , Pressure profile calculations in lipid bilayers: A lipid bilayer is merely $\\sim$5~nm thick, but the lateral pressure (parallel to the bilayer plane) varies several hundred bar on this short distance (normal to the bilayer). These variations in the lateral pressure are commonly referred to as the pressure...... of neglecting pressure contributions from long range electrostatic interactions. The first issue is addressed by comparing two methods for calculating pressure profiles, and judged by the similar results obtained by these two methods the pressure profile appears to be well-defined for fluid phase lipid bilayers......The importance of computer simulations in lipid bilayer research has become more prominent for the last couple of decades and as computers get even faster, simulations will play an increasingly important part of understanding the processes that take place in and across cell membranes. This thesis...

  15. Atomistic Monte Carlo simulation of lipid membranes

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Sklenar, Heinz

    2014-01-01

    , as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential......Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction...... into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches...

  16. ER stress and hepatic lipid metabolism

    Directory of Open Access Journals (Sweden)

    Huiping eZhou

    2014-05-01

    Full Text Available The endoplasmic reticulum (ER is an important player in regulating protein synthesis and lipid metabolism. Perturbation of ER homeostasis, referred as ER stress, has been linked to numerous pathological conditions, such as inflammation, cardiovascular diseases and metabolic disorders. The liver plays a central role in regulating nutrient and lipid metabolism. Accumulating evidence implicates that ER stress disrupts lipid metabolism and induces hepatic lipotoxicity. Here, we review the major ER stress signaling pathways, how ER stress contributes to the dysregulation of hepatic lipid metabolism, and the potential causative mechanisms of ER stress in hepatic lipotoxicity. Understanding the role of ER stress in hepatic metabolism may lead to the identification of new therapeutic targets for metabolic diseases.

  17. Coalescence Kinetics of Lipid Based Bicelles

    Science.gov (United States)

    Hu, Andrew; Fan, Tai-Hsi; Katsaras, John; Xia, Yan; Li, Ming; Nieh, Mu-Ping

    2014-03-01

    Uniform nanodisc can be self-assembled from lipid mixtures of dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG), and dihexanoyl phosphatidylcholine (DHPC). This study focuses on the theoretical and experimental growth kinetics of phospholipid based nanodiscs. Motivation for this project comes from the nanodisc's small size and their potential use as a carrier for drug delivery. It was observed that at high total lipid concentration the nanodiscs are stable at approximately 10 nm. However, growth of these nanodiscs is observed at relatively low total lipid concentrations. Dynamic light scattering (DLS) is used to monitor the size and growth rate of these nanodiscs at different solution conditions. The growth at low concentrations is caused by to the transfer of charged lipid (DMPG) from the discs to the solution, reducing the Columbic interaction. The growth of nanodisc as a function of size and surface potential is modeled using the Smoluchowski transport equation with transport-limited boundary conditions.

  18. A STUDY OF LIPID PROFILE IN PREDIABETES

    Directory of Open Access Journals (Sweden)

    Manoj

    2016-06-01

    Full Text Available BACKGROUND Lipid abnormalities are common in diabetes mellitus and play an important role in acceleration of atherosclerosis leading to increased cardiovascular diseases. Due to increasing burden of diabetes, it is becoming important to identify dyslipidaemia in high-risk state for diabetes especially prediabetes so that early intervention can reduce cardiovascular risk. AIM To study lipid profile in prediabetes individuals. METHODS This study was a cross-sectional case control study which included 107 prediabetes and 101 healthy controls. Lipid profile of prediabetes and controls were measured and statistically analysed. RESULT Total cholesterol, LDL, triglycerides, VLDL, TG/HDL ratio, and LDL/HDL ratio were significantly high whereas HDL was significantly low in prediabetes subjects as compared to controls. CONCLUSION This study showed significant lipid abnormalities in prediabetes subjects. Because of these they are at high risk of developing atherosclerotic cardiovascular diseases. Therefore, proper screening and appropriate therapy of these conditions becomes important.

  19. Voltage-gated lipid ion channels

    DEFF Research Database (Denmark)

    Blicher, Andreas; Heimburg, Thomas Rainer

    2013-01-01

    Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current...... histograms in patch-experiments on lipid membranes. We derived a theoretical current-voltage relationship for pores in lipid membranes that describes the experimental data very well when assuming an asymmetric membrane. We determined the equilibrium constant between closed and open state and the open...... probability as a function of voltage. The voltage-dependence of the lipid pores is found comparable to that of protein channels. Lifetime distributions of open and closed events indicate that the channel open distribution does not follow exponential statistics but rather power law behavior for long open times...

  20. Lipid measures and cardiovascular disease prediction

    NARCIS (Netherlands)

    van Wijk, D.F.; Stroes, E.S.G.; Kastelein, J.J.P.

    2009-01-01

    Traditional lipid measures are the cornerstone of risk assessment and treatment goals in cardiovascular prevention. Whereas the association between total, LDL-, HDL-cholesterol and cardiovascular disease risk has been generally acknowledged, the rather poor capacity to distinguish between patients

  1. Lipid profile, hyperglycaemia, systemic inflammation and ...

    African Journals Online (AJOL)

    Lipid profile, hyperglycaemia, systemic inflammation and anthropometry as ... Methods: A random sample of 233 children, aged 6-18 years, was used for ... test for equality of variances, one-way analysis of variance and Pearson correlations.

  2. Atomistic Monte Carlo simulation of lipid membranes

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Sklenar, Heinz

    2014-01-01

    Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction......, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential...... of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol....

  3. Lipid peroxidation in experimental uveitis: sequential studies.

    Science.gov (United States)

    Goto, H; Wu, G S; Chen, F; Kristeva, M; Sevanian, A; Rao, N A

    1992-06-01

    Previously we have detected the occurrence of retinal lipid peroxidation initiated by phagocyte-derived oxygen radicals in experimental autoimmune uveitis (EAU). In the current studies, the confirmation of inflammation-mediated lipid peroxidation was proceeded further to include measurement of multiple parameters, including conjugated dienes, ketodienes, thiobarbituric acid reactive substances and fluorescent chromolipids. The assay for myeloperoxidase, a measure for the number of polymorphonuclear leukocytes in the inflammatory sites was also carried out. The levels of all these parameters were followed through the course of EAU development. The sequential evaluation of histologic changes using both light and electron microscopy was also carried out and the results were correlated with lipid peroxidation indices. These data suggest that the retinal lipid peroxidation plays a causative role in the subsequent retinal degeneration.

  4. The impact of lipid composition on the stability of the tear fluid lipid layer

    DEFF Research Database (Denmark)

    Kulovesi, P.; Telenius, J.; Koivuniemi, A.

    2012-01-01

    The tear fluid protects the corneal epithelium from drying and pathogens and it also provides nutrients to these cells. Tear fluid is composed of an aqueous layer as well as a lipid layer that resides at the air-tear interface. The function of the lipid layer is to lower the surface tension of th......-neutral lipid ratio. The results provide a plausible rationale for the development of dry eye syndrome in blepharitis patients....

  5. Improved characterization of EV preparations based on protein to lipid ratio and lipid properties.

    Directory of Open Access Journals (Sweden)

    Xabier Osteikoetxea

    Full Text Available In recent years the study of extracellular vesicles has gathered much scientific and clinical interest. As the field is expanding, it is becoming clear that better methods for characterization and quantification of extracellular vesicles as well as better standards to compare studies are warranted. The goal of the present work was to find improved parameters to characterize extracellular vesicle preparations. Here we introduce a simple 96 well plate-based total lipid assay for determination of lipid content and protein to lipid ratios of extracellular vesicle preparations from various myeloid and lymphoid cell lines as well as blood plasma. These preparations included apoptotic bodies, microvesicles/microparticles, and exosomes isolated by size-based fractionation. We also investigated lipid bilayer order of extracellular vesicle subpopulations using Di-4-ANEPPDHQ lipid probe, and lipid composition using affinity reagents to clustered cholesterol (monoclonal anti-cholesterol antibody and ganglioside GM1 (cholera toxin subunit B. We have consistently found different protein to lipid ratios characteristic for the investigated extracellular vesicle subpopulations which were substantially altered in the case of vesicular damage or protein contamination. Spectral ratiometric imaging and flow cytometric analysis also revealed marked differences between the various vesicle populations in their lipid order and their clustered membrane cholesterol and GM1 content. Our study introduces for the first time a simple and readily available lipid assay to complement the widely used protein assays in order to better characterize extracellular vesicle preparations. Besides differentiating extracellular vesicle subpopulations, the novel parameters introduced in this work (protein to lipid ratio, lipid bilayer order, and lipid composition, may prove useful for quality control of extracellular vesicle related basic and clinical studies.

  6. Lipid Neuroprotectants and Traumatic Glaucomatous Neurodegeneration

    Science.gov (United States)

    2016-05-01

    uniquely present in the normal aqueous humor act as regulators of intraocular pressure . Methods, topical application of lipids, IOP measurements by...Intraocular pressure (IOP) has been measured in DBA/2J and normotensive monkeys (major goals 1 and 2). These results are presented in Figure 1 below...without pain or obvious symptoms. Specific lipids naturally present in the clear fluid of the anterior chamber of the eye in healthy individuals but

  7. Exogenous ether lipids predominantly target mitochondria

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Richter, Doris; Hannibal-Bach, Hans Kristian

    2012-01-01

    Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high......, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria...

  8. Lipid storage myopathies with unusual clinical manifestations

    Directory of Open Access Journals (Sweden)

    Uppin Megha

    2008-01-01

    Full Text Available We describe the clinical presentation, course and pathologic findings found in three adult patients with lipid storage myopathy. Excessive lipid storage was found in Type 1 fibers of muscle. Clinical improvement on oral levo-carnitine therapy suggests the possibility of carnitine deficiency as the most likely etiology in two of the patients and one had mitochondrial myopathy confirmed on genetic analysis.

  9. Exercise Intensity Modulation of Hepatic Lipid Metabolism

    OpenAIRE

    Lira, Fábio S.; Carnevali, Luiz C; Zanchi, Nelo E.; Ronaldo VT. Santos; Jean Marc Lavoie; Marília Seelaender

    2012-01-01

    Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL), ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations...

  10. Lipid Microarray Biosensor for Biotoxin Detection.

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Anup K.; Throckmorton, Daniel J.; Moran-Mirabal, Jose C.; Edel, Joshua B.; Meyer, Grant D.; Craighead, Harold G.

    2006-05-01

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

  11. Development and evaluation of lipid nanoparticles for camptothecin de-livery: a comparison of solid lipid nanoparticles, nanostructured lipid car-riers, and lipid emulsion

    Institute of Scientific and Technical Information of China (English)

    Zih-rou HUANG; Shu-chiou HUA; Yueh-lung YANG; Jia-you FANG

    2008-01-01

    Aim:Camptothecin is an anticancer drug that acta against a broad spectrum of tumors. The clinical application of camptothecin is limited by its insolubility, instability, and toxicity problems. The aim of this study was to develop and characterize lipid nanoparticles with different lipid cores which can circumvent these problems. Methods: Lipid nanoparticles made of Precirol (solid lipid nanoparticles; SLN-P), Compritol (SLN-C), Precirol+squalene (nanostructured lipid carriers; NLC), and squalene (a lipid emulsion; LE) as the lipid core ma-terial were prepared. These systems were assessed and compared by evaluat-ing the mean diameter, surface charge, molecular environment, camptothecin release, and cell viability against a melanoma. The safety and storage stability of these systems were also preliminarily examined. Results: The particle size ranged from 190 to 310 nm, with the NLC and LE showing the smallest and largest sizes, respectively. The in vitro drug release occurred in a sustained manner in decreasing order as follows: LE>NLC>SLN-P>SLN-C. It was found that varying the type of inner phase had profound effects on cell viability. The SLN-P generally showed higher cytotoxicity than the free control. The treat-ment of melanomas with the camptothecin-loaded SLN-C and NLC yielded cytotoxicity comparable to that of the free form. The percentage of erythrocyte hemolysis by all nanoparticles was ≤5%, suggesting a good tolerance to lipid nanoparticles. Conclusion: The results collectively suggest that the SLN-P may have the potential to serve as a delivery system for parenteral camptothecin ad-ministration because of the sustained drug release, strong cytotoxicity, limited hemolysis, and good storage stability.

  12. Lipid Measures and Cardiovascular Disease Prediction

    OpenAIRE

    van Wijk, Diederik F.; Stroes, Erik S. G.; Kastelein, John J.P.

    2009-01-01

    Traditional lipid measures are the cornerstone of risk assessment and treatment goals in cardiovascular prevention. Whereas the association between total, LDL-, HDL-cholesterol and cardiovascular disease risk has been generally acknowledged, the rather poor capacity to distinguish between patients who will and those who will not develop cardiovascular disease has prompted the search for further refinement of these traditional measures. A thorough understanding of lipid metabolism is mandatory...

  13. Trypanosoma cruzi Infection and Host Lipid Metabolism

    OpenAIRE

    2014-01-01

    Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected worldwide. Several players in host lipid metabolism have been implicated in T. cruzi-host interactions in recent research, including macrophages, adipocytes, low density lipoprotein (LDL), low density lipoprotein receptor (LDLR), and high density lipoprotein (HDL). All of these factors are required to maintain host lipid homeostasis and are intricately connected via several me...

  14. Rapid modification of retroviruses using lipid conjugates

    Science.gov (United States)

    Mukherjee, Nimisha G.; Lyon, L. Andrew; LeDoux, Joseph M.

    2009-02-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  15. Ionic interaction of sulfatide with choline lipids.

    Science.gov (United States)

    Abramson, M B; Katzman, R

    1968-08-09

    Aqueous systems of sphingomyelin-sulfatide and lecithin-sulfatide were compared with aqueous systems of the individual lipids. The acid capacity of the mixed lipids increased, a result of the formation of an ionic bond between the sulfate of one molecule and the positive nitrogen of the other, making the phosphate available for direct titration. Cholesterol reduces this ionic interaction, probably because of the increased spacing of the ionized groups.

  16. Tuning molecular interactions in lipid-oligonucleotides assemblies via locked nucleic acid (LNA)-based lipids.

    Science.gov (United States)

    Patwa, Amit; Salgado, Gilmar; Dole, François; Navailles, Laurence; Barthélémy, Philippe

    2013-11-07

    Hybrid nucleotide-lipids containing locked nucleic acid (LNA) show enhanced hybridization properties with complementary single strand RNAs compared to DNA lipid analogues. The LNA adenosine lipid features unique binding properties with a high binding affinity for poly-uridine and the entropically driven formation of a stable complex (K(d) ≈ 43 nM). Enhanced hybridization properties of LNA-based lipids should be applicable for the development of oligonucleotide (ON) delivery systems or as small molecule binders to RNA for novel therapeutic strategies.

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

    Science.gov (United States)

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

    2014-02-01

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

  18. Cholecystokinin Elevates Mouse Plasma Lipids

    Science.gov (United States)

    Zhou, Lichun; Yang, Hong; Lin, Xinghua; Okoro, Emmanuel U.; Guo, Zhongmao

    2012-01-01

    Cholecystokinin (CCK) is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR−/−) mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL) with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo) B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR−/− mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine. PMID:23300532

  19. Cholecystokinin elevates mouse plasma lipids.

    Directory of Open Access Journals (Sweden)

    Lichun Zhou

    Full Text Available Cholecystokinin (CCK is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR(-/- mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR(-/- mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine.

  20. Engineering Rhodosporidium toruloides for increased lipid production.

    Science.gov (United States)

    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.

  1. Functional organization of the HIV lipid envelope

    Science.gov (United States)

    Huarte, Nerea; Carravilla, Pablo; Cruz, Antonio; Lorizate, Maier; Nieto-Garai, Jon A.; Kräusslich, Hans-Georg; Pérez-Gil, Jesús; Requejo-Isidro, Jose; Nieva, José L.

    2016-01-01

    The chemical composition of the human immunodeficiency virus type 1 (HIV-1) membrane is critical for fusion and entry into target cells, suggesting that preservation of a functional lipid bilayer organization may be required for efficient infection. HIV-1 acquires its envelope from the host cell plasma membrane at sites enriched in raft-type lipids. Furthermore, infectious particles display aminophospholipids on their surface, indicative of dissipation of the inter-leaflet lipid asymmetry metabolically generated at cellular membranes. By combining two-photon excited Laurdan fluorescence imaging and atomic force microscopy, we have obtained unprecedented insights into the phase state of membranes reconstituted from viral lipids (i.e., extracted from infectious HIV-1 particles), established the role played by the different specimens in the mixtures, and characterized the effects of membrane-active virucidal agents on membrane organization. In determining the molecular basis underlying lipid packing and lateral heterogeneity of the HIV-1 membrane, our results may help develop compounds with antiviral activity acting by perturbing the functional organization of the lipid envelope. PMID:27678107

  2. Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis

    Directory of Open Access Journals (Sweden)

    Arya Bagus Boedi Iswanto

    2017-04-01

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

  3. Persistence of virus lipid signatures upon silicification

    Science.gov (United States)

    Kyle, J.; Jahnke, L. L.; Stedman, K. M.

    2011-12-01

    To date there is no known evidence of viruses within the rock record. Their small size and absence of a metabolism has led to the hypothesis that they lack unique biological signatures, and the potential to become preserved. Biosignature research relevant to early Earth has focused on prokaryotic communities; however, the most abundant member of modern ecosystems, viruses, have been ignored. In order to establish a baseline for research on virus biosignatures, we have initiated laboratory research on known lipid-containing viruses. PRD1 is a lipid-containing virus that infects and replicates in Salmonella typhimurium LT2. PRD1 is a 65 nm spherical virus with an internal lipid membrane, which is a few nanometers thick. When the PRD1 virus stock was mixed with a 400 ppm SiO2 (final concentration) solution and incubated for six months. Fourier Transform Infrared Spectroscopy and lipid analysis using gas chromatography revealed that the virus lipids were still detectable despite complete removal of dissolved silica. Free fatty acids were also detected. Titers of infectious PRD1 viruses after six months in the presence of silica decreased 40 times more than without silica. Though virus biosignature research is in its incipient stages, the data suggest that virus lipid signatures are preserved under laboratory conditions and may offer the potential for contribution to the organic geochemical record.

  4. Mechanical Properties of Nanoscopic Lipid Domains.

    Science.gov (United States)

    Nickels, Jonathan D; Cheng, Xiaolin; Mostofian, Barmak; Stanley, Christopher; Lindner, Benjamin; Heberle, Frederick A; Perticaroli, Stefania; Feygenson, Mikhail; Egami, Takeshi; Standaert, Robert F; Smith, Jeremy C; Myles, Dean A A; Ohl, Michael; Katsaras, John

    2015-12-23

    The lipid raft hypothesis presents insights into how the cell membrane organizes proteins and lipids to accomplish its many vital functions. Yet basic questions remain about the physical mechanisms that lead to the formation, stability, and size of lipid rafts. As a result, much interest has been generated in the study of systems that contain similar lateral heterogeneities, or domains. In the current work we present an experimental approach that is capable of isolating the bending moduli of lipid domains. This is accomplished using neutron scattering and its unique sensitivity to the isotopes of hydrogen. Combining contrast matching approaches with inelastic neutron scattering, we isolate the bending modulus of ∼13 nm diameter domains residing in 60 nm unilamellar vesicles, whose lipid composition mimics the mammalian plasma membrane outer leaflet. Importantly, the bending modulus of the nanoscopic domains differs from the modulus of the continuous phase surrounding them. From additional structural measurements and all-atom simulations, we also determine that nanoscopic domains are in-register across the bilayer leaflets. Taken together, these results inform a number of theoretical models of domain/raft formation and highlight the fact that mismatches in bending modulus must be accounted for when explaining the emergence of lateral heterogeneities in lipid systems and biological membranes.

  5. Generic sorting of raft lipids into secretory vesicles in yeast

    DEFF Research Database (Denmark)

    Surma, Michal A; Klose, Christian; Klemm, Robin W;

    2011-01-01

    a complete lipid overview of the yeast late secretory pathway. We could show that vesicles captured with different baits carry the same cargo and have almost identical lipid compositions; being highly enriched in ergosterol and sphingolipids. This finding indicates that lipid raft sorting is a generic...... feature of vesicles carrying PM cargo and suggests a common lipid-based mechanism for their formation....

  6. The metabolic importance of unabsorbed dietary lipids in the colon

    NARCIS (Netherlands)

    Vonk, RJ; Kalivianakis, M; Minich, DM; Bijleveld, CMA; Verkade, HJ

    1997-01-01

    Digestion and absorption of lipids is a highly efficient process. From Western diets about 95% will be absorbed. This implies that together with lipids from endogenous sources 6-8 g of lipids will enter the colon daily. This input significantly increases during various lipid malabsorption syndromes.

  7. Fluorescopic evaluation of protein-lipid relations in cellular signalling.

    NARCIS (Netherlands)

    Pap, E.H.W.

    1994-01-01

    IntroductionCellular communication is partly mediated through the modulation of protein activity, structure and dynamics by lipids. In contrast to the biochemical aspects of lipid signalling, relatively little is known about the physical properties of the "signal" lipids (lipids involved in cellular

  8. 8.3.Protein,carbohydrate and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920049 Clinical studies on the relationshipbetween serum lipids and lipid peroxidation.GUO Hong (郭虹),et al.Cardiovasc instit &Fuwai Hosp,CAMS,Beijing.Chin Cir J 1991; 6(5):373-375.This paper presented the relationship amongserum lipid fractions,lipid peroxides (LPO) and

  9. Reactive Oxygen Species, Lipid Peroxidation and Antioxidative Defense Mechanism

    Directory of Open Access Journals (Sweden)

    Hossam S. EL-BELTAGI

    2013-05-01

    Full Text Available Lipid peroxidation can be defined as the oxidative deterioration of lipids containing any number of carbon-carbon double bonds. Lipid peroxidation is a well-established mechanism of cellular injury in both plants and animals, and is used as an indicator of oxidative stress in cells and tissues. Lipid peroxides are unstable and decompose to form a complex series of compounds including reactive carbonyl compounds. The oxidation of linoleates and cholesterol is discussed in some detail. Analytical methods for studying lipid peroxidation were mentioned. Various kinds of antioxidants with different functions inhibit lipid peroxidation and the deleterious effects caused by the lipid peroxidation products.

  10. Bilayer Deformation, Pores, and Micellation Induced by Oxidized Lipids.

    Science.gov (United States)

    Boonnoy, Phansiri; Jarerattanachat, Viwan; Karttunen, Mikko; Wong-Ekkabut, Jirasak

    2015-12-17

    The influence of different oxidized lipids on lipid bilayers was investigated with 16 individual 1 μs atomistic molecular dynamics (MD) simulations. Binary mixtures of lipid bilayers of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) and its peroxide and aldehyde products were performed at different concentrations. In addition, an asymmetrical short chain lipid, 1-palmitoyl-2-decanoyl-sn-glycero-3-phosphatidylcholine (PDPC), was used to compare the effects of polar/apolar groups in the lipid tail on lipid bilayer. Although water defects occurred with both aldehyde and peroxide lipids, full pore formation was observed only for aldehyde lipids. At medium concentrations the pores were stable. At higher concentrations, however, the pores became unstable and micellation occurred. Data analysis shows that aldehyde lipids' propensity for pore formation is due to their shorter and highly mobile tail. The highly polar peroxide lipids are stabilized by strong hydrogen bonds with interfacial water.

  11. Targeting bacteria via iminoboronate chemistry of amine-presenting lipids.

    Science.gov (United States)

    Bandyopadhyay, Anupam; McCarthy, Kelly A; Kelly, Michael A; Gao, Jianmin

    2015-03-12

    Synthetic molecules that target specific lipids serve as powerful tools for understanding membrane biology and may also enable new applications in biotechnology and medicine. For example, selective recognition of bacterial lipids may give rise to novel antibiotics, as well as diagnostic methods for bacterial infection. Currently known lipid-binding molecules primarily rely on noncovalent interactions to achieve lipid selectivity. Here we show that targeted recognition of lipids can be realized by selectively modifying the lipid of interest via covalent bond formation. Specifically, we report an unnatural amino acid that preferentially labels amine-presenting lipids via iminoboronate formation under physiological conditions. By targeting phosphatidylethanolamine and lysylphosphatidylglycerol, the two lipids enriched on bacterial cell surfaces, the iminoboronate chemistry allows potent labelling of Gram-positive bacteria even in the presence of 10% serum, while bypassing mammalian cells and Gram-negative bacteria. The covalent strategy for lipid recognition should be extendable to other important membrane lipids.

  12. Computational studies of plasma lipoprotein lipids.

    Science.gov (United States)

    Pan, Lurong; Segrest, Jere P

    2016-10-01

    Plasma lipoproteins are macromolecular assemblies of proteins and lipids found in the blood. The lipid components of lipoproteins are amphipathic lipids such as phospholipids (PLs), and unesterified cholesterols (UCs) and hydrophobic lipids such as cholesteryl esters (CEs) and triglycerides (TGs). Since lipoproteins are soft matter supramolecular assemblies easily deformable by thermal fluctuations and they also exist in varying densities and protein/lipid components, a detailed understanding of their structure/function is experimentally difficult. Molecular dynamics (MD) simulation has emerged as a particularly promising way to explore the structure and dynamics of lipoproteins. The purpose of this review is to survey the current status of computational studies of the lipid components of the lipoproteins. Computational studies aim to explore three levels of complexity for the 3-dimensional structural dynamics of lipoproteins at various metabolic stages: (i) lipoprotein particles consist of protein with minimal lipid; (ii) lipoprotein particles consist of PL-rich discoidal bilayer-like lipid particles; (iii) mature circulating lipoprotein particles consist of CE-rich or TG-rich spheroidal lipid-droplet-like particles. Due to energy barriers involved in conversion between these species, other biomolecules also participate in lipoprotein biological assembly. For example: (i) lipid-poor apolipoprotein A-I (apoA-I) interacts with ATP-binding cassette transporter A1 (ABCA1) to produce nascent discoidal high density lipoprotein (dHDL) particles; (ii) lecithin-cholesterol acyltransferase (LCAT) mediates the conversion of UC to CE in dHDL, driving spheroidal HDL (sHDL) formation; (iii) transfer proteins, cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP), transfer both CE and TG and PL, respectively, between lipoprotein particles. Computational studies have the potential to explore different lipoprotein particles at each metabolic stage in

  13. Studying lipid-protein interactions with electron paramagnetic resonance spectroscopy of spin-labeled lipids.

    Science.gov (United States)

    Páli, Tibor; Kóta, Zoltán

    2013-01-01

    Spin label electron paramagnetic resonance (EPR) of lipid-protein interactions reveals crucial features of the structure and assembly of integral membrane proteins. Spin label EPR spectroscopy is the technique of choice to characterize the protein-solvating lipid shell in its highly dynamic nature, because the EPR spectra of lipids that are spin labeled close to the terminal methyl end of their acyl chains display two spectral components, those corresponding to lipids directly contacting the protein and those corresponding to lipids in the bulk fluid bilayer regions of the membrane. In this chapter, typical spin label EPR procedures are presented that allow determination of the stoichiometry of interaction of spin-labeled lipids with the intra-membranous region of membrane proteins or polypeptides, as well as the association constant of the spin-labeled lipid with respect to the host lipid. The lipids giving rise to the so-called immobile spectral component in the EPR spectrum of such samples are identified as the motionally restricted first-shell lipids solvating membrane proteins in biomembranes. Stoichiometry and selectivity are directly related to the structure of the intra-membranous sections of membrane-associated proteins or polypeptides and can be used to study the state of assembly of such proteins in the membrane. Since these characteristics of lipid-protein interactions are discussed in detail in the literature [see Marsh (Eur Biophys J 39:513-525, 2010) for a most recent review], here we focus more on how to spin label model and biomembranes and how to measure and analyze the two-component EPR spectra of spin-labeled lipids in phospholipid bilayers that contain proteins or polypeptides. After a description of how to prepare spin-labeled model and native biological membranes, we present the reader with computational procedures for determining the molar fraction of motionally restricted lipids when both, one, or none of the pure isolated-mobile or

  14. Non-enzymatically derived minor lipids found in Escherichia coli lipid extracts.

    Science.gov (United States)

    Garrett, Teresa A; Raetz, Christian R H; Son, Jennifer D; Richardson, Travis D; Bartling, Craig; Guan, Ziqiang

    2011-11-01

    Electrospray ionization mass spectrometry is a powerful technique to analyze lipid extracts especially for the identification of new lipid metabolites. A hurdle to lipid identification is the presence of solvent contaminants that hinder the identification of low abundance species or covalently modify abundant lipid species. We have identified several non-enzymatically derived minor lipid species in lipid extracts of Escherichia coli; phosphatidylmethanol, ethyl and methyl carbamates of PE and N-succinyl PE were identified in lipid extracts of E. coli. Phosphatidylmethanol (PM) was identified by exact mass measurement and collision induced dissociation tandem mass spectrometry (MS/MS). Extraction in the presence of deuterated methanol leads to a 3 atomic mass unit shift in the [M-H](-) ions of PM indicating its formation during extraction. Ethyl and methyl carbamates of PE, also identified by exact mass measurement and MS/MS, are likely to be formed by phosgene, a breakdown product of chloroform. Addition of phosgene to extractions containing synthetic PE significantly increases the levels of PE-MC detected in the lipid extracts by ESI-MS. Extraction in the presence of methylene chloride significantly reduced the levels of these lipid species. N-succinyl PE is formed from reaction of succinyl-CoA with PE during extraction. Interestingly N-succinyl PE can be formed in an aqueous reaction mixture in the absence of added E. coli proteins. This work highlights the reactivity of the amine of PE and emphasizes that careful extraction controls are required to ensure that new minor lipid species identified using mass spectrometry are indeed endogenous lipid metabolites.

  15. Triglyceride blisters in lipid bilayers: implications for lipid droplet biogenesis and the mobile lipid signal in cancer cell membranes.

    Directory of Open Access Journals (Sweden)

    Himanshu Khandelia

    Full Text Available Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO than earlier anticipated, by sequestering triolein molecules to the bilayer center in the form of a disordered, isotropic, mobile neutral lipid aggregate, at least 17 nm in diameter, which forms spontaneously, and remains stable on at least the microsecond time scale. The results give credence to the hotly debated existence of mobile neutral lipid aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model, and possibly living membranes. The blisters will result in anomalous membrane probe partitioning, which should be accounted for in the interpretation of probe-related measurements.

  16. Lipid metabolism in experimental animals

    Directory of Open Access Journals (Sweden)

    Sánchez-Muñiz, Francisco J.

    1998-08-01

    Full Text Available Publications are scarce in the way in chich metabolic processes are affected by the ingestion of heated fats used to prepare food. Similarly studies measuring metabolic effects of the consumption on fried food are poorly known. The purpose of this presentation is to summarize information on frying fats and frying foods upon lipid metabolism in experimental animals. Food consumption is equivalent or even higher when oils or the fat content of frying foods are poorly alterated decreasing their acceptability when their alteration degree increase. After 4hr. experiment the digestibility and absorption coefficients of a single dosis of thermooxidized oils were significantly decreased in rats, however the digestive utilization of frying thermooxidized oils included in diets showed very little change in comparison with unused oils by feeding trials on rats. Feeding rats different frying fats induced a slight hypercholesterolemic effect being the magnitude of this effect related to the linoleic decrease in diet produced by frying. However HDL, the main rat-cholesterol carrier, also increased, thus the serum cholesterol/HDL-cholesterol ratio did not change. Results suggest that rats fed frying fats adapt their lipoprotein metabolism increasing the number of HDL particles. Deep fat frying deeply changed the fatty acid composition of foods, being possible to increase their n-9 or n-6 fatty acid and to decrease the saturated fatty acid contents by frying. When olive oil-and sunflower oil-fried sardines were used as the only protein and fat sources of rats-diets in order to prevent the dietary hypercholesterolemia it was provided that both fried-sardine diets showed a powerful check effect on the cholesterol raising effect induced by dietary cholesterol. The negative effect of feeding rats cholesterol plus bovine bile to induce hypercholesterolemia on some cell-damage markers such as lactate dehydrogenase, transaminases, alkaline phosphatase, was

  17. Archaeological bone lipids as palaeodietary markers.

    Science.gov (United States)

    Colonese, André C; Farrell, Thomas; Lucquin, Alexandre; Firth, Daniel; Charlton, Sophy; Robson, Harry K; Alexander, Michelle; Craig, Oliver E

    2015-04-15

    Stable isotope analysis of archaeological and fossil bone samples can provide important insights into past environments, ecologies and diets. Previous studies have focused on stable carbon and nitrogen isotopes in bone collagen, or carbon isotopes in bone mineral (bioapatite). Carbon isotope analysis of lipids from archaeological bone has received much less attention, partly due to the lack of suitable methodologies allowing sufficient recovery of compounds for structural and isotopic characterisation. Here we show that lipids can be easily and reliably recovered from archaeological bone using a modified protocol, and that these provide complementary dietary information to other bone components. Human and animal bones were obtained from a variety of archaeological contexts. Lipids were sequentially extracted using solvent extraction (dichloromethane/methanol), followed by acidified methanol extraction (methanol/H2SO4). The lipids were then analysed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Appreciable amounts of endogenous lipid were recovered from archaeological bone. Importantly, a comparison between compound-specific and bulk collagen isotopic data shows that archaeological bone lipids reflect dietary input and can be used to distinguish between marine and terrestrial consumers, as well as between C3 and C4 plant consumers. Furthermore, the presence of essential fatty acids directly incorporated from diet to bone may provide additional palaeodietary information. Our findings suggest that archaeological bone lipids are a hitherto untapped resource of dietary information that offer additional insights to those gained from other isotopic analyses of bone. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice.

    NARCIS (Netherlands)

    n den Hil, E.F. Hoek-va; Keijer, J.; Bunschoten, A.; Vervoort, J.J.; Stankova, B.; Bekkenkamp, M.; Herreman, L.; Venema, D.; Hollman, P.C.H.; Tvrzicka, E.; Rietjens, I.M.C.M.; Schothorst, E.M. van

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and (1)

  19. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice

    NARCIS (Netherlands)

    Hoek-van den Hil, E.F.; Keijer, J.; Bunschoten, A.; Vervoort, Jacques; Stankova, B.; Bekkenkamp-Grovestein, M.; Herreman, L.; Venema, D.P.; Hollman, P.C.H.; Tvrzicka, E.; Rietjens, I.; Schothorst, van E.M.

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H

  20. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice.

    NARCIS (Netherlands)

    n den Hil, E.F. Hoek-va; Keijer, J.; Bunschoten, A.; Vervoort, J.J.; Stankova, B.; Bekkenkamp, M.; Herreman, L.; Venema, D.; Hollman, P.C.H.; Tvrzicka, E.; Rietjens, I.M.C.M.; Schothorst, E.M. van

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and (1)

  1. Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy.

    Science.gov (United States)

    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.

  2. Interactions and Translational Dynamics of Phosphatidylinositol Bisphosphate (PIP2) Lipids in Asymmetric Lipid Bilayers.

    Science.gov (United States)

    Shi, Xiaojun; Kohram, Maryam; Zhuang, Xiaodong; Smith, Adam W

    2016-02-23

    Phosphatidylinositol phosphate (PIP) lipids are critical to many cell signaling pathways, in part by acting as molecular beacons that recruit peripheral membrane proteins to specific locations within the plasma membrane. Understanding the biophysics of PIP-protein interactions is critical to developing a chemically detailed model of cell communication. Resolving such interactions is challenging, even in model membrane systems, because of the difficulty in preparing PIP-containing membranes with high fluidity and integrity. Here we report on a simple, vesicle-based protocol for preparing asymmetric supported lipid bilayers in which fluorescent PIP lipid analogues are found only on the top leaflet of the supported membrane facing the bulk solution. With this asymmetric distribution of lipids between the leaflets, the fluorescent signal from the PIP lipid analogue reports directly on interactions between the peripheral molecules and the top leaflet of the membrane. Asymmetric PIP-containing bilayers are an ideal platform to investigate the interaction of PIP with peripheral membrane proteins using fluorescence-based imaging approaches. We demonstrate their usefulness here with a combined fluorescence correlation spectroscopy and single particle tracking study of the interaction between PIP2 lipids and a polycationic polymer, quaternized polyvinylpyridine (QPVP). With this approach we are able to quantify the microscopic features of the mobility coupling between PIP2 lipids and polybasic QPVP. With single particle tracking we observe individual PIP2 lipids switch from Brownian to intermittent motion as they become transiently trapped by QPVP.

  3. Cidea controls lipid droplet fusion and lipid storage in brown and white adipose tissue.

    Science.gov (United States)

    Wu, Lizhen; Zhou, Linkang; Chen, Cheng; Gong, Jingyi; Xu, Li; Ye, Jing; Li, De; Li, Peng

    2014-01-01

    Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes, fatty liver and cardiovascular diseases. The lipid droplet (LD) is an important subcellular organelle responsible for lipid storage. We previously observed that Fsp27, a member of the CIDE family proteins, is localized to LD-contact sites and promotes atypical LD fusion and growth. Cidea, a close homolog of Fsp27, is expressed at high levels in brown adipose tissue. However, the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown. Here, we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth. Next, we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype. In addition, Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold. Furthermore, we observed that the brown and white adipose tissues of Cidea/Fsp27 double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27 single deficient mice. Overall, these data reveal an important role of Cidea in controlling lipid droplet fusion, lipid storage in brown and white adipose tissue, and the development of obesity.

  4. A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress

    DEFF Research Database (Denmark)

    Surma, Michal A; Klose, Christian; Peng, Debby

    2013-01-01

    Biological membranes are complex, and the mechanisms underlying their homeostasis are incompletely understood. Here, we present a quantitative genetic interaction map (E-MAP) focused on various aspects of lipid biology, including lipid metabolism, sorting, and trafficking. This E-MAP contains ∼250......) desaturase Ole1p. Loss of Ubx2p affects the transcriptional control of OLE1, resulting in impaired FA desaturation and a severe shift toward more saturated membrane lipids. Both the induction of the unfolded protein response and aberrant nuclear membrane morphologies observed in cells lacking UBX2...... are suppressed by the supplementation of unsaturated FAs. Our results point toward the existence of dedicated bilayer stress responses for membrane homeostasis....

  5. Dry cured ham quality as related to lipid quality of raw material and lipid changes during processing: a review.

    OpenAIRE

    Gilles, Gandemer

    2009-01-01

    Lipids play a key role in sensory traits of dry cured hams. Both the quantity and the composition of lipids in raw material affect dry-cured hams quality. The lipid characteristics strongly depend on rearing systems developed in different area in Europe. During processing, lipids undergo lipolysis and oxidation. Phospholipids are the main substrates of both lipolysis and oxidation. Lipolysis forms free fatty acids rich in polyunsaturated fatty acids all along the process. Lipids are also subj...

  6. Direct visualization of lipid domains in human skin stratum corneum's lipid membranes

    DEFF Research Database (Denmark)

    Plasencia, I; Norlen, Lars; Bagatolli, Luis

    2007-01-01

    ; and iii), whether pH has a direct effect on the lipid matrix phase behavior. In this work the lateral structure of membranes composed of lipids extracted from human skin stratum corneum was studied in a broad temperature range (10 degrees C-90 degrees C) using different techniques such as differential......The main function of skin is to serve as a physical barrier between the body and the environment. This barrier capacity is in turn a function of the physical state and structural organization of the stratum corneum extracellular lipid matrix. This lipid matrix is essentially composed of very long...... scanning calorimetry, fluorescence spectroscopy, and two-photon excitation and laser scanning confocal fluorescence microscopy. Here we show that hydrated bilayers of human skin stratum corneum lipids express a giant sponge-like morphology with dimensions corresponding to the global three...

  7. Chain ordering of hybrid lipids can stabilize domains in saturated/hybrid/cholesterol lipid membranes

    Science.gov (United States)

    Yamamoto, T.; Brewster, R.; Safran, S. A.

    2010-07-01

    We use a liquid-crystal model to predict that hybrid lipids (lipids that have one saturated and one unsaturated tail) can stabilize line interfaces between domains in mixed membranes of saturated lipids, hybrid lipids, and cholesterol (SHC membranes). The model predicts the phase separation of SHC membranes with both parabolic and loop binodals depending on the cholesterol concentration, modeled via an effective pressure. In some cases, the hybrid lipids can reduce the line tension to zero in SHC membranes at temperatures that approach the critical temperature as the pressure is increased. The differences in the hybrid saturated tail conformational order in bulk and at the interface are responsible for the reduction of the line tension.

  8. Single-component solid lipid nanocarriers prepared with ultra-long chain amphiphilic lipids

    DEFF Research Database (Denmark)

    Wei, Wei; Lu, Xiaonan; Wang, Zegao

    2017-01-01

    HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect...... the smallest mean size (∼100nm with PdI of 0.26). In addition, they displayed high entrapment efficiency of fenofibrate (95%) and long term drug release. Nanocarriers prepared by emulsification-diffusion method entrapped fenofibrate into lipid bilayers. In contrast, Nanocarriers prepared by melting......-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system....

  9. Interaction of antimicrobial peptides with lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Hanulova, Maria

    2008-12-15

    This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar phases. POPE forms lamellar phases at low temperatures that upon heating transform into a highly curved inverse hexagonal phase. Insertion of the peptide induced inverse bicontinuous cubic phases which are an ideal compromise between the curvature stress and the packing frustration. Melittin usually induced a mixture of two cubic phases, Im3m and Pn3m, with a ratio of lattice parameters close to 1.279, related to the underlying minimal surfaces. They formed during the lamellar to hexagonal phase transition and persisted during cooling till the onset of the gel phase. The phases formed at different lipid-to-peptide ratios had very similar lattice parameters. Epitaxial relationships existed between coexisting cubic phases and hexagonal or lamellar phases due to confinement of all phases to an onion vesicle, a vesicle with several layers consisting of different lipid phases. Alamethicin induced the same cubic phases, although their formation and lattice parameters were dependent on the peptide concentration. The cubic phases formed during heating from the lamellar phase and their onset

  10. Orphan enzymes in ether lipid metabolism.

    Science.gov (United States)

    Watschinger, Katrin; Werner, Ernst R

    2013-01-01

    Ether lipids are an emerging class of lipids which have so far not been investigated and understood in every detail. They have important roles as membrane components of e.g. lens, brain and testis, and as mediators such as platelet-activating factor. The metabolic enzymes for biosynthesis and degradation have been investigated to some extent. As most involved enzymes are integral membrane proteins they are tricky to handle in biochemical protocols. The sequence of some ether lipid metabolising enzymes has only recently been reported and other sequences still remain obscure. Defined enzymes without assigned sequence are known as orphan enzymes. One of these enzymes with uncharacterised sequence is plasmanylethanolamine desaturase, a key enzyme for the biosynthesis of one of the most abundant phospholipids in our body, the plasmalogens. This review aims to briefly summarise known functions of ether lipids, give an overview on their metabolism including the most prominent members, platelet-activating factor and the plasmalogens. A special focus is set on the description of orphan enzymes in ether lipid metabolism and on the successful strategies how four previous orphans have recently been assigned a sequence. Only one of these four was characterised by classical protein purification and sequencing, whereas the other three required alternative strategies such as bioinformatic candidate gene selection and recombinant expression or development of an inhibitor and multidimensional metabolic profiling.

  11. Atomistic Monte Carlo simulation of lipid membranes.

    Science.gov (United States)

    Wüstner, Daniel; Sklenar, Heinz

    2014-01-24

    Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches. We use our recently devised chain breakage/closure (CBC) local move set in the bond-/torsion angle space with the constant-bond-length approximation (CBLA) for the phospholipid dipalmitoylphosphatidylcholine (DPPC). We demonstrate rapid conformational equilibration for a single DPPC molecule, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol.

  12. Biotechnology Applications of Tethered Lipid Bilayer Membranes

    Directory of Open Access Journals (Sweden)

    Joshua A. Jackman

    2012-12-01

    Full Text Available The importance of cell membranes in biological systems has prompted the development of model membrane platforms that recapitulate fundamental aspects of membrane biology, especially the lipid bilayer environment. Tethered lipid bilayers represent one of the most promising classes of model membranes and are based on the immobilization of a planar lipid bilayer on a solid support that enables characterization by a wide range of surface-sensitive analytical techniques. Moreover, as the result of molecular engineering inspired by biology, tethered bilayers are increasingly able to mimic fundamental properties of natural cell membranes, including fluidity, electrical sealing and hosting transmembrane proteins. At the same time, new methods have been employed to improve the durability of tethered bilayers, with shelf-lives now reaching the order of weeks and months. Taken together, the capabilities of tethered lipid bilayers have opened the door to biotechnology applications in healthcare, environmental monitoring and energy storage. In this review, several examples of such applications are presented. Beyond the particulars of each example, the focus of this review is on the emerging design and characterization strategies that made these applications possible. By drawing connections between these strategies and promising research results, future opportunities for tethered lipid bilayers within the biotechnology field are discussed.

  13. Intravenous Lipids for Preterm Infants: A Review

    Directory of Open Access Journals (Sweden)

    Ghassan S. A. Salama

    2015-01-01

    Full Text Available Extremely low birth weight infants (ELBW are born at a time when the fetus is undergoing rapid intrauterine brain and body growth. Continuation of this growth in the first several weeks postnatally during the time these infants are on ventilator support and receiving critical care is often a challenge. These infants are usually highly stressed and at risk for catabolism. Parenteral nutrition is needed in these infants because most cannot meet the majority of their nutritional needs using the enteral route. Despite adoption of a more aggressive approach with amino acid infusions, there still appears to be a reluctance to use early intravenous lipids. This is based on several dogmas that suggest that lipid infusions may be associated with the development or exacerbation of lung disease, displace bilirubin from albumin, exacerbate sepsis, and cause CNS injury and thrombocytopena. Several recent reviews have focused on intravenous nutrition for premature neonate, but very little exists that provides a comprehensive review of intravenous lipid for very low birth and other critically ill neonates. Here, we would like to provide a brief basic overview, of lipid biochemistry and metabolism of lipids, especially as they pertain to the preterm infant, discuss the origin of some of the current clinical practices, and provide a review of the literature, that can be used as a basis for revising clinical care, and provide some clarity in this controversial area, where clinical care is often based more on tradition and dogma than science.

  14. Lipid binding proteins from parasitic platyhelminthes.

    Science.gov (United States)

    Alvite, Gabriela; Esteves, Adriana

    2012-01-01

    TWO MAIN FAMILIES OF LIPID BINDING PROTEINS HAVE BEEN IDENTIFIED IN PARASITIC PLATYHELMINTHES: hydrophobic ligand binding proteins (HLBPs) and fatty acid binding proteins (FABPs). Members of the former family of proteins are specific to the Cestoda class, while FABPs are conserved across a wide range of animal species. Because Platyhelminthes are unable to synthesize their own lipids, these lipid-binding proteins are important molecules in these organisms. HLBPs are a high molecular mass complex of proteins and lipids. They are composed of subunits of low molecular mass proteins and a wide array of lipid molecules ranging from CoA esters to cholesterol. These proteins are excretory-secretory molecules and are key serological tools for diagnosis of diseases caused by cestodes. FABPs are mainly intracellular proteins of low molecular weight. They are also vaccine candidates. Despite that the knowledge of their function is scarce, the differences in their molecular organization, ligand preferences, intra/extracellular localization, evolution, and phylogenetic distribution, suggest that platyhelminths HLBPs and FABPs should play different functions. FABPs might be involved in the removal of fatty acids from the inner surface of the cell membrane and in their subsequent targeting to specific cellular destinations. In contrast, HLBPs might be involved in fatty acid uptake from the host environment.

  15. Status of Lipid Profile in Pregnancy

    Directory of Open Access Journals (Sweden)

    Deepak Parchwani

    2011-02-01

    Full Text Available Pregnancy greatly increases demand for metabolic fuels that are needed for growth and development of the fetus and its support structures. The total gestation related energy cost has been estimated at approximately 83000 kcal. The major change in energy expenditure and in the accumulation of fat occurs at different times during pregnancy. In the current study a serial study of serum lipids was performed in a group of women throughout gestation and six weeks post partum while they were having their usual diet and unrestricted daily activity. The control group consisted of non pregnant healthy women of child bearing age. Data was analyzed by SPSS software. All lipid fractions underwent a gradual and persistent rise throughout pregnancy with the exception of HDL-C i.e. a progressive rise was observed in serum total cholesterol, serum triglyceride, serum VLDL and LDL-C as pregnancy advances, while serum HDL-C showed a biphasic pattern, as initial rise and then decline in later third of pregnancy. However, during early pregnancy the values of all lipid fractions do not differ significantly from those for normal non pregnant controls. No significant difference was observed in vegetarian and non-vegetarian group in any of the lipid fractions in different trimester of pregnancy—so diet had no significant influence on lipid synthesis during pregnancy. [National J of Med Res 2011; 1(1.000: 10-12

  16. Integral hair lipid in human hair follicle.

    Science.gov (United States)

    Lee, Won-Soo

    2011-12-01

    Integral hair lipid (IHL) is bound to the keratinized cell surface to make an environmentally resistant lipid envelope. It is mainly positioned on the hair cuticle and inner root sheath. IHL in the hair follicle may regard as hair barrier to be similar to the epidermal lipid layer functioning as skin barrier. Major constituents of IHL are fatty acid, phytosphingosine, ceramide in decreasing order. Minor constituents of IHL are cholesterol, cholesterol sulfate and cholesterol oleate. Cuticle or cortical cell surface in hair are abundant in fatty acids unlike the keratinized area of epidermis or sebaceous gland, and about 30-40% of such fatty acids are composed of 18-methyl-eicosanoic acid which is known to be bound to proteins by ester or thioester bond. Various factors including moisture, solvent, oxidative damage during bleaching or permanent waving affect IHL. Photochemical changes also can occur in IHL as well as in hair protein and hair pigment. Lipid metabolism is thought to play an essential role in lipid envelope of hair, but also involvement in hair development and function. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Lipid Binding Proteins from Parasitic Platyhelmithes

    Directory of Open Access Journals (Sweden)

    Gabriela eAlvite

    2012-09-01

    Full Text Available Two main families of lipid binding proteins have been identified in parasitic Platyhelminthes: hydrophobic ligand binding proteins (HLBPs and fatty acid binding proteins (FABPs. Members of the former family of proteins are specific to the Cestoda class, while FABPs are conserved across a wide range of animal species. Because Platyhelminthes are unable to synthesise their own lipids, these lipid-binding proteins are important molecules in these organisms.HLBPs are a high molecular mass complex of proteins and lipids. They are composed of subunits of low molecular mass proteins and a wide array of lipid molecules ranging from CoA esters to cholesterol. These proteins are excretory-secretory molecules and are key serological tools for diagnosis of diseases caused by cestodes. FABPs are mainly intracellular proteins of low molecular weight. They are also vaccine candidates.Despite that the knowledge of their function is scarce, the differences in their molecular organisation, ligand preferences, intra/extracellular localisation, evolution, and phylogenetic distribution, suggest that platyhelminths HLBPs and FABPs should play different functions. FABPs might be involved in the removal of fatty acids from the inner surface of the cell membrane and in their subsequent targeting to specific cellular destinations. In contrast, HLBPs might be involved in fatty acid uptake from the host environment.

  18. Lipid-based antifungal agents: current status.

    Science.gov (United States)

    Arikan, S; Rex, J H

    2001-03-01

    Immunocompromised patients are well known to be predisposed to developing invasive fungal infections. These infections are usually difficult to diagnose and more importantly, the resulting mortality rate is high. The limited number of antifungal agents available and their high rate of toxicity are the major factors complicating the issue. However, the development of lipid-based formulations of existing antifungal agents has opened a new era in antifungal therapy. The best examples are the lipid-based amphotericin B preparations, amphotericin B lipid complex (ABLC; Abelcet), amphotericin B colloidal dispersion (ABCD; Amphotec or Amphocil), and liposomal amphotericin B (AmBisome). These formulations have shown that antifungal activity is maintained while toxicity is reduced. This progress is followed by the incorporation of nystatin into liposomes. Liposomal nystatin formulation is under development and studies of it have provided encouraging data. Finally, lipid-based formulations of hamycin, miconazole, and ketoconazole have been developed but remain experimental. Advances in technology of liposomes and other lipid formulations have provided promising new tools for management of fungal infections.

  19. Atomistic Monte Carlo Simulation of Lipid Membranes

    Directory of Open Access Journals (Sweden)

    Daniel Wüstner

    2014-01-01

    Full Text Available Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC simulation of lipid membranes. We provide an introduction into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches. We use our recently devised chain breakage/closure (CBC local move set in the bond-/torsion angle space with the constant-bond-length approximation (CBLA for the phospholipid dipalmitoylphosphatidylcholine (DPPC. We demonstrate rapid conformational equilibration for a single DPPC molecule, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol.

  20. Serum Lipid Profiles, Lipid Ratios and Chronic Kidney Disease in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Liying Zhang

    2014-07-01

    Full Text Available Aim: To examine the association of serum lipids, lipid ratios with Chronic Kidney Disease (CKD in a Chinese population. Methods: Data were drawn from a cross-sectional survey in China. CKD was defined as estimated glomerular filtration rate (eGFR < 60 mL/min/1.73m2 or albuminuria-to-creatinine ratio (ACR > 30 mg/g. Multivariable logistic regressions and multivariate regression models were used. Serum lipids and lipid ratios included total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, TG/HDL-C ratio, TC/HDL-C ratio and LDL-C/HDL-C ratio. Results: In men, only logarithm-transformed (log TG was associated with CKD. The odds ratio (every SD increment was 1.39 (95% CI 1.03–1.87, P = 0.03. In women, none of the serum lipids and lipid ratios was associated with CKD. Using multivariate regression models, it was shown that log TG and log TG/HDL-C were negatively correlated with eGFR (P < 0.05 in men and LDL-C and log LDL-C/HDL-C ratio were correlated with ACR in men. In female subjects, serum TC, log TG, log TG/HDL-C and log TC/HDL-C were negatively correlated with eGFR (P < 0.05. All of serum lipid profiles and lipid related ratio were not correlated with ACR in women. Conclusion: Serum TG is the only suitable predictor for CKD in men. However, in women, none of serum lipids and lipid ratio can be used as a predictor for CKD. Log TG and log TG/HDL-C are negatively correlated with eGFR in both genders.

  1. Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

    Directory of Open Access Journals (Sweden)

    Katie D. Hickey

    2011-01-01

    Full Text Available Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+ K+-ATPase or -amylase. Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+ K+-ATPase within the membranes.

  2. ER Stress and Lipid Metabolism in Adipocytes

    Directory of Open Access Journals (Sweden)

    Beth S. Zha

    2012-01-01

    Full Text Available The role of endoplasmic reticulum (ER stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

  3. Biosynthesis and function of plant lipids

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, W.W.; Mudd, J.B.; Gibbs, M. (eds.)

    1983-01-01

    The Sixth Annual Symposium in Botany and Plant Physiology was held January 13-15, 1983, at the University of California, Riverside. This volume comprises the papers that were presented. Subjects discussed at the symposium covered a wide range in the field of plant lipids. Biosynthesis of lipids occupied an important fraction of the presentations at the symposium. Subjects included detailed studies of the enzymes of fatty acid synthesis, several discussions of the incorporation of fatty acids into glycerolipids and the further modification of the fatty acids, and the synthesis of glycerolipids and desaturation of fatty acids in both maturing oilseeds and chloroplasts. The physicochemical studies of glycerolipids and sterols in artificial membranes have led to distinct conclusions about their behaviour which must be relevant in the biological membrane. Results on the functional consequences of modifying the galactolipid composition in the chloroplast were an encouraging sign of progress in the attempts to relate membrane lipid composition to physiological function.

  4. Assessing the nature of lipid raft membranes

    DEFF Research Database (Denmark)

    Niemelä, Perttu S; Ollila, Samuli; Hyvönen, Marja T

    2007-01-01

    to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content....... of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL). These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins....... However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom...

  5. Drug targeting using solid lipid nanoparticles.

    Science.gov (United States)

    Rostami, Elham; Kashanian, Soheila; Azandaryani, Abbas H; Faramarzi, Hossain; Dolatabadi, Jafar Ezzati Nazhad; Omidfar, Kobra

    2014-07-01

    The present review aims to show the features of solid lipid nanoparticles (SLNs) which are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Because of some unique features of SLNs such as their unique size dependent properties it offers possibility to develop new therapeutics. A common denominator of all these SLN-based platforms is to deliver drugs into specific tissues or cells in a pathological setting with minimal adverse effects on bystander cells. SLNs are capable to incorporate drugs into nanocarriers which lead to a new prototype in drug delivery which maybe used for drug targeting. Hence solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. This review presents a broad treatment of targeted solid lipid nanoparticles discussing their types such as antibody SLN, magnetic SLN, pH sensitive SLN and cationic SLN.

  6. Bioactive lipids in kidney physiology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Daria Sałata

    2014-01-01

    Full Text Available Lipids not only have structural functions, but also play an important role as signaling and regulatory molecules and participate in many cellular processes such as proliferation, differentiation, migration, and apoptosis. Bioactive lipids act both as extracellular mediators, which are associated with receptors on the surface of cells, and intracellular mediators triggering different signal pathways. They are present and active in physiological conditions, and are also involved in the pathogenesis of inflammation, asthma, cancer, diabetes, and hypertension. Bioactive lipids such as derivatives of arachidonic acid and sphingolipids have an important role in renal development, physiology and in many renal diseases. Some of them are potential indicators of kidney damage degree and/or function of the transplanted kidneys.

  7. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  8. Atomic force microscopy of model lipid membranes.

    Science.gov (United States)

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

    2013-02-01

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

  9. Genetic architecture of circulating lipid levels

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; Amin, Najaf; Isaacs, Aaron

    2011-01-01

    the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify...... levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from...... suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture...

  10. Characteristics of lipids and their feeding value in swine diets.

    Science.gov (United States)

    Kerr, Brian J; Kellner, Trey A; Shurson, Gerald C

    2015-01-01

    In livestock diets, energy is one of the most expensive nutritional components of feed formulation. Because lipids are a concentrated energy source, inclusion of lipids are known to affect growth rate and feed efficiency, but are also known to affect diet palatability, feed dustiness, and pellet quality. In reviewing the literature, the majority of research studies conducted on the subject of lipids have focused mainly on the effects of feeding presumably high quality lipids on growth performance, digestion, and metabolism in young animals. There is, however, the wide array of composition and quality differences among lipid sources available to the animal industry making it essential to understand differences in lipid composition and quality factors affecting their digestion and metabolism more fully. In addition there is often confusion in lipid nomenclature, measuring lipid content and composition, and evaluating quality factors necessary to understand the true feeding value to animals. Lastly, advances in understanding lipid digestion, post-absorption metabolism, and physiological processes (e.g., cell division and differentiation, immune function and inflammation); and in metabolic oxidative stress in the animal and lipid peroxidation, necessitates a more compressive assessment of factors affecting the value of lipid supplementation to livestock diets. The following review provides insight into lipid classification, digestion and absorption, lipid peroxidation indices, lipid quality and nutritional value, and antioxidants in growing pigs.

  11. Assessing the nature of lipid raft membranes.

    Directory of Open Access Journals (Sweden)

    Perttu S Niemelä

    2007-02-01

    Full Text Available The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL. These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins. However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM, and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult. The findings reveal aspects of the role of favored (specific lipid-lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of

  12. Treatment of cocaine overdose with lipid emulsion.

    Science.gov (United States)

    Jakkala-Saibaba, R; Morgan, P G; Morton, G L

    2011-12-01

    We describe the management and recovery of a 28-year-old man following a history of overdose by nasal inhalation of cocaine. The patient was presented in a comatose state suffering from seizures and marked cardiovascularly instability. Intravenous lipid emulsion was administered following initial resuscitation and tracheal intubation, as a means of treating persistent cardiac arrhythmias and profound hypotension. Following lipid emulsion therapy, the patient's life-threatening cardiovascular parameters rapidly improved and he recovered well without any side effects, thus being discharged within 2 days. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  13. Lipid peroxidation in adrenal and testicular microsomes.

    OpenAIRE

    1981-01-01

    Studies were carried out to determine the actions of and interactions between ascorbate, NADPH, Fe2+, and Fe3+ on lipid peroxidation in adrenal and testicular microsomes. Ascorbate-induced malonaldehyde production was maximal in adrenal and testicular microsomes at an ascorbate concentration of 1 X 10(-4)M. Fe2+, at levels between 10(-6) and 10(-3)M, produced concentration-dependent increases in lipid peroxidation in adrenal and testicular microsomes; Fe2+ had a far greater effect than Fe3+ i...

  14. [Lipids in the diet and atherosclerosis].

    Science.gov (United States)

    Fauré Nogueras, E

    1990-01-01

    Description of the main metabolic methods of different lipoproteins in relation to transportation of both exogenous lipids and endogenous lipids, with special reference to the regulation of synthesis and the destination of colesterol. An analysis was then made of the influence of dietetic colesterol on the different lipoproteins, and that of fatty acids. An evaluation was made of its possible influence on the pathogeny of the atheroma plate. Finally, an alternative unified diet was proposed as a main dietetic guide, both in prevention and therapy.

  15. Lipid analysis of a ground sloth coprolite

    Science.gov (United States)

    Gill, Fiona L.; Crump, Matthew P.; Schouten, Remmert; Bull, Ian D.

    2009-09-01

    Coprolites can provide detailed information about the nutritional habits and digestive processes of the animals that produced them and may also yield information about the palaeoenvironment in which the animal existed. To test the utility of the lipid biomarker approach to coprolite analysis, lipids were extracted from a coprolite of the Pleistocene ground sloth Nothrotheriops shastensis. Gas chromatography/mass spectrometry results revealed a dominant spiroketal sapogenin component identified, using nuclear magnetic resonance spectroscopy, as epismilagenin. The dominance of epismilagenin is probably due to ingestion of Yucca spp. and Agave spp., which is consistent with previous studies on the diet of this species.

  16. Consistent thermodynamic properties of lipids systems

    DEFF Research Database (Denmark)

    Cunico, Larissa; Ceriani, Roberta; Sarup, Bent

    Physical and thermodynamic properties of pure components and their mixtures are the basic requirement for process design, simulation, and optimization. In the case of lipids, our previous works[1-3] have indicated a lack of experimental data for pure components and also for their mixtures...... different pressures, with azeotrope behavior observed. Available thermodynamic consistency tests for TPx data were applied before performing parameter regressions for Wilson, NRTL, UNIQUAC and original UNIFAC models. The relevance of enlarging experimental databank of lipids systems data in order to improve...

  17. Lipid Mediators and Human Leukemic Blasts

    Directory of Open Access Journals (Sweden)

    Rémi Fiancette

    2011-01-01

    Full Text Available Some of the most potent inflammatory mediators share a lipid origin. They regulate a wide spectrum of cellular processes including cell proliferation and apoptosis. However, the precise roles and ways (if any in which these compounds impact the growth and apoptosis of leukemic blasts remain incompletely resolved. In spite of this, significant advances have been recently made. Here we briefly review the current knowledge about the production of lipid mediators (prostaglandins, leukotrienes, platelet-activating factor by leukemic blasts, the enzymatic activities (phospholipase A2, cyclooxygenases, lipoxygenases involved in their productions and their effects (through specific membrane bound receptors on the growth, and apoptosis of leukemic blasts.

  18. Lipid Oligonucleotide Conjugates as Responsive Material

    Science.gov (United States)

    2012-09-28

    U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS Amphiphiles, oligonucleotides, lipids...peer-reviewed journals: (c) Presentations 1. Philippe Barthélémy, « Hybrid Lipids for Biomedical Applications », Targeting and Triggering Basic Research ...Steadel C. ; Pierre, N. ; Barthélémy, P. : Oligonucléotides amphiphile : Journée Scientifique de l’IFR 66, Talence, le 2 décembre 2008, France 29. Taib

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

    Science.gov (United States)

    Montano, Gabriel

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

  20. Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid organization.

    Science.gov (United States)

    Mojumdar, E H; Gooris, G S; Bouwstra, J A

    2015-06-07

    The lipid matrix in the stratum corneum (SC), the upper layer of the skin, plays a critical role in the skin barrier. The matrix consists of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). In human SC, these lipids form two coexisting crystalline lamellar phases with periodicities of approximately 6 and 13 nm. In the studies reported here, we investigated the effect of CHOL on lipid organization in each of these lamellar phases separately. For this purpose, we used lipid model mixtures. Our studies revealed that CHOL is imperative for the formation of each of the lamellar phases. At low CHOL levels, the formation of the lamellar phases was dramatically changed: a minimum 0.2 CHOL level in the CER/CHOL/FFA (1 : 0.2 : 1) mixture is required for the formation of each of the lamellar phases. Furthermore, CHOL enhances the formation of the highly dense orthorhombic lateral packing. The gradual increment of CHOL increases the fraction of lipids forming the very dense orthorhombic lateral packing. Therefore, these studies demonstrate that CHOL is an indispensable component of the SC lipid matrix and is of fundamental importance for appropriate dense lipid organization and thus important for the skin barrier function.

  1. Extension of the GLYCAM06 Biomolecular Force Field to Lipids, Lipid Bilayers and Glycolipids.

    Science.gov (United States)

    Tessier, Matthew B; Demarco, Mari L; Yongye, Austin B; Woods, Robert J

    2008-01-01

    GLYCAM06 is a generalisable biomolecular force field that is extendible to diverse molecular classes in the spirit of a small-molecule force field. Here we report parameters for lipids, lipid bilayers and glycolipids for use with GLYCAM06. Only three lipid-specific atom types have been introduced, in keeping with the general philosophy of transferable parameter development. Bond stretching, angle bending, and torsional force constants were derived by fitting to quantum mechanical data for a collection of minimal molecular fragments and related small molecules. Partial atomic charges were computed by fitting to ensemble-averaged quantum-computed molecular electrostatic potentials.In addition to reproducing quantum mechanical internal rotational energies and experimental valence geometries for an array of small molecules, condensed-phase simulations employing the new parameters are shown to reproduce the bulk physical properties of a DMPC lipid bilayer. The new parameters allow for molecular dynamics simulations of complex systems containing lipids, lipid bilayers, glycolipids, and carbohydrates, using an internally consistent force field. By combining the AMBER parameters for proteins with the GLYCAM06 parameters, it is also possible to simulate protein-lipid complexes and proteins in biologically relevant membrane-like environments.

  2. Lipid rafts and Alzheimer’s disease: protein-lipid interactions and perturbation of signalling

    Directory of Open Access Journals (Sweden)

    David A. Hicks

    2012-06-01

    Full Text Available Lipid rafts are membrane domains, more ordered than the bulk membrane and enriched in cholesterol and sphingolipids. They represent a platform for protein-lipid and protein-protein interactions and for cellular signalling events. In addition to their normal functions, including membrane trafficking, ligand binding (including viruses, axonal development and maintenance of synaptic integrity, rafts have also been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD. Lipid rafts promote interaction of the amyloid precursor protein (APP with the secretase (BACE-1 responsible for generation of the amyloid β peptide, Aβ. Rafts also regulate cholinergic signalling as well as acetylcholinesterase and Aβ interaction. In addition, such major lipid raft components as cholesterol and GM1 ganglioside have been directly implicated in pathogenesis of the disease. Perturbation of lipid raft integrity can also affect various signalling pathways leading to cellular death and AD. In this review, we discuss modulation of APP cleavage by lipid rafts and their components, while also looking at more recent findings on the role of lipid rafts in signalling events.

  3. Lipid anti-lipid antibody responses correlate with disease activity in systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Vojislav Jovanović

    Full Text Available Systemic lupus erythematosus (SLE is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using a combination of immunological and biophysical techniques. Disease monitoring in the SLE cohort was undertaken with serial British Isles Lupus Assessment Group (BILAG scoring. Correlations between specific lipid/anti-lipid responses were investigated as disease activity developed from active flares to quiescent during a follow up period. We report a significant negative correlation between anti-lipid antibodies for 24S-hydroxycholesterol, cardiolipin and phosphatidylserine with SLE disease activity. Taken together, these data suggest that lipid autoantigens represent a new family of biomarkers that can be employed to monitor disease activity plus the efficacy of therapeutic intervention in SLE.

  4. Silica-lipid hybrid microcapsules: influence of lipid and emulsifier type on in vitro performance.

    Science.gov (United States)

    Lim, Li Hui; Tan, Angel; Simovic, Spomenka; Prestidge, Clive A

    2011-05-16

    This study reports on the physicochemical characterisation and in vitro investigations of macro-porous silica-lipid hybrid (SLH) microcapsules when formulated using various lipids: long-chain triglycerides (LCT), medium-chain triglycerides (MCT), medium-chain mono-, diglycerides (MCMDG); and emulsifiers: anionic lecithin and cationic oleylamine. For the lipophilic compound coumarin 102 (logP=4.09), a complete and immediate in vitro release was attained for the SLH microcapsules under simulated intestinal sink conditions. The in vitro digestion study of various types of SLH microcapsules demonstrates: (i) reduced variability and enhanced lipid digestibility for the MCMDG-based microcapsules (i.e. 90-100% lipolysis) in comparison with an equivalent lipid solution and emulsion (50-90% lipolysis); and (ii) more controllable digestion kinetics for the LCT-based microcapsules which produce a lipolysis rate higher than that of a lipid solution but lower than that of a lipid emulsion. The drug phase partition results show approximately 5- to 17-fold increase in the drug solubilisation degree resulting from the digestion of MCT and MCMDG-based microcapsules (116 μg/mL), and LCT-based microcapsules (416 μg/mL) in comparison with the blank micellar medium (24 μg/mL). In conclusion, the SLH microcapsules could be tailored to manipulate the digestion patterns of both medium- and long-chain lipids in order to maximise the drug solubilisation capacity. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. A comparative study: the impact of different lipid extraction methods on current microalgal lipid research.

    Science.gov (United States)

    Li, Yan; Ghasemi Naghdi, Forough; Garg, Sourabh; Adarme-Vega, Tania Catalina; Thurecht, Kristofer J; Ghafor, Wael Abdul; Tannock, Simon; Schenk, Peer M

    2014-01-24

    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.

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

    Directory of Open Access Journals (Sweden)

    Philip P. Cheney

    2017-03-01

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

  7. Lipid composition of metacestodes of Taenia taeniaeformis and lipid changes during growth.

    Science.gov (United States)

    Mills, G L; Taylor, D C; Williams, J F

    1981-09-01

    A lipid analysis was performed on developing metacestodes of Taenia taeniaeformis removed from the livers of rats at times varying from 3 to 35 weeks post infection. Lipid accounted for 7-21% of the dry weight of the parasites. The highest proportions were found at the earlier stages. The distribution was as follows; neutral lipid 27-45%; glycolipid 5-11%; and phospholipid 50-61%. The major neutral lipid was cholesterol, and minor neutral lipids were sterol esters, triglycerides, diglycerides and monoglycerides. Hydrocarbons were present throughout development, but in the highest amounts at the earlier stages. Five different glycolipids were found, all of which were identified as glycosphingolipids. An increase in the proportion of more complex glycolipids was noted as parasites grew older. Ten different phospholipids were identified, with the major components being phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Other phospholipids were: lysophosphatides, phosphatidylinositol, phosphatidic acid, diphosphatidylglycerol, sphingomyelin, and an unknown phospholipid component. Changes in the relative amounts of the two major phospholipids were found when the early and late stages were compared. Two lipids found throughout development were identified as glycosylated dolichol phosphates, and they comprised between 1 and 3% of the total phospholipid fraction. Nineteen fatty acids were detected, and the fatty acid distribution for each lipid class at each stage was determined. Seven major fatty acids were common to each. These were: hexadecanoic, octadecanoic, oleic, linoleic, arachidonic, docosanoic, and docosahexaenoic.

  8. An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER

    Science.gov (United States)

    Markgraf, Daniel F.; Klemm, Robin W.; Junker, Mirco; Hannibal-Bach, Hans K.; Ejsing, Christer S.; Rapoport, Tom A.

    2014-01-01

    Eukaryotic cells store neutral lipids, such as triacylglycerol (TAG), in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show in S. cerevisiae that LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein, Ice2p, facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG-degradation and -synthesis, promoting the rapid re-localization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER, and explain how cells switch neutral lipid metabolism from storage to consumption. PMID:24373967

  9. An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER.

    Science.gov (United States)

    Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco; Hannibal-Bach, Hans K; Ejsing, Christer S; Rapoport, Tom A

    2014-01-16

    Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.

  10. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    Directory of Open Access Journals (Sweden)

    Daniel F. Markgraf

    2014-01-01

    Full Text Available Eukaryotic cells store neutral lipids such as triacylglycerol (TAG in lipid droplets (LDs. Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER. We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG. During LD breakdown in early exponential phase, an ER membrane protein (Ice2p facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.

  11. An unusual lipid in the human pathogenic fungus Epidermophyton floccosum.

    Science.gov (United States)

    Yamada, T A; Nozawa, Y

    1979-09-28

    The dermatophyte Epidermophyton floccosum contains an unusual lipid characterized as 1(3),2-diacylglyceryl-3(1)-O-4'-(N,N,N-trimethyl)homoserine. Its concentration in E. floccosum is approx. 15% of the polar lipids. The role of this lipid in the biosynthesis of polar lipids and fatty acids is not yet known. However, it is interesting from a chemotaxonomic viewpoint that the lipids from two other genera of dermatophyte, Microsporum cookei and Trichophyton rubrum do not contain this novel lipid.

  12. The interaction between purple membrane and membrane lipid

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Bacteriorhodopsin in purple membrane was reconstituted into different lipid vesicles. The effect of three different lipids on the structure and function of bacteriorhodopsin in lipid vesicles was studied by the observation on freeze-fracture eletron microscopy, the rotational diffusion of bacteriorhodopsin in lipid vesicles, the measurement of absorption spectrum, and the absorbance change with time. For these prepared samples, the results showed that DMPC was the stable lipid environment of bacteriorhodopsin; egg-pc causeed the loss of retinal chromophore of bacteriorhodopsin and it was not reversible change, cholesterol could stabilize the bacteriorhodopsin in lipid environment,but it caused the aggregation of bacteriorhodopsin.

  13. Revisiting transbilayer distribution of lipids in the plasma membrane.

    Science.gov (United States)

    Murate, Motohide; Kobayashi, Toshihide

    2016-01-01

    Whereas asymmetric transbilayer lipid distribution in the plasma membrane is well recognized, methods to examine the precise localization of lipids are limited. In this review, we critically evaluate the methods that are applied to study transbilayer asymmetry of lipids, summarizing the factors that influence the measurement. Although none of the present methods is perfect, the current application of immunoelectron microscopy-based technique provides a new picture of lipid asymmetry. Next, we summarize the transbilayer distribution of individual lipid in both erythrocytes and nucleated cells. Finally we discuss the concept of the interbilayer communication of lipids.

  14. Lipid corralling and poloxamer squeeze-out in membranes

    DEFF Research Database (Denmark)

    Wu, G.H.; Majewski, J.; Ege, C.;

    2004-01-01

    Using x-ray scattering measurements we have quantitatively determined the effect of poloxamer 188 (P188), a polymer known to seal damaged membranes, on the structure of lipid monolayers. P188 selectively inserts into low lipid-density regions of the membrane and "corrals" lipid molecules to pack...... tightly, leading to unexpected Bragg peaks at low nominal lipid density and inducing lipid/poloxamer phase separation. At tighter lipid packing, the once inserted P188 is squeezed out, allowing the poloxamer to gracefully exit when the membrane integrity is restored....

  15. Extraction of microalgal lipids and the influence of polar lipids on biodiesel production by lipase-catalyzed transesterification.

    Science.gov (United States)

    Navarro López, Elvira; Robles Medina, Alfonso; González Moreno, Pedro Antonio; Esteban Cerdán, Luis; Molina Grima, Emilio

    2016-09-01

    In order to obtain microalgal saponifiable lipids (SLs) fractions containing different polar lipid (glycolipids and phospholipids) contents, SLs were extracted from wet Nannochloropsis gaditana microalgal biomass using seven extraction systems, and the polar lipid contents of some fractions were reduced by low temperature acetone crystallization. We observed that the polar lipid content in the extracted lipids depended on the polarity of the first solvent used in the extraction system. Lipid fractions with polar lipid contents between 75.1% and 15.3% were obtained. Some of these fractions were transformed into fatty acid methyl esters (FAMEs, biodiesel) by methanolysis, catalyzed by the lipases Novozym 435 and Rhizopus oryzae in tert-butanol medium. We observed that the reaction velocity was higher the lower the polar lipid content, and that the final FAME conversions achieved after using the same lipase batch to catalyze consecutive reactions decreased in relation to an increase in the polar lipid content.

  16. Inclusion of the helper lipid dioleoyl-phosphatidylethanolamine in solid lipid nanoparticles inhibits their transfection efficiency.

    Science.gov (United States)

    de Jesus, Marcelo B; Radaic, Allan; Hinrichs, Wouter L J; Ferreira, Carmen V; de Paula, Eneida; Hoekstra, Dick; Zuhorn, Inge S

    2014-02-01

    Solid lipid nanoparticles (SLNs) are a promising system for the delivery of lipophilic and hydrophilic drugs. They consist of a solid lipid core that is stabilized by a layer of surfactants. By the incorporation of cationic lipids in the formulation, positively charged SLNs can be generated, that are suitable carriers for nucleic acids (DNA, siRNA). Considering the beneficial effect of helper lipids on the transfection efficiency with cationic liposomes, the effect of the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) on transfection with cationic lipid-containing solid lipid nanoparticles was investigated in PC3 prostate cancer cells. The inclusion of DOPE in SLN formulations, instead of promoted, strongly inhibited SLN transfection efficiency, by frustrating the accommodation of DNA by the particles, as was revealed by biochemical analysis. SLNs devoid of DOPE maintained a homogenous size distribution of approximately 150 nm following lipoplex assembly and cellular delivery, and showed transfection efficiency comparable to that of Lipofectamine 2000' (LF2k). Moreover, the SLNs maintain their high transfection efficiency after lyophilization and long-term storage (1-2 years), an important asset for biomedical applications. There is even the possibility to lyophilize the SLN carrier together with its DNA cargo, which represents an interesting pharmaceutical advantage of the SLN formulations over LF2k. These results reflect marked differences between the physicochemical properties of cationic liposomes and SLNs, the latter requiring more critical lipid-depending properties for effective 'packaging' of DNA but displaying a higher storage stability than cationic lipid based carriers like LF2k.

  17. Complex roles of hybrid lipids in the composition, order, and size of lipid membrane domains.

    Science.gov (United States)

    Hassan-Zadeh, Ebrahim; Baykal-Caglar, Eda; Alwarawrah, Mohammad; Huang, Juyang

    2014-02-11

    Hybrid lipids (HL) are phospholipids with one saturated chain and one unsaturated chain. HL are hypothesized to act as linactants (i.e., 2D surfactants) in cell membranes, reducing line tension and creating nanoscopic lipid domains. Here we compare three hybrid lipids of different chain unsaturation (16:0-18:1PC (POPC), 16:0-18:2PC (PLPC), and 16:0-20:4PC (PAPC)) in their abilities to alter the composition, line tension, order, and compactness of lipid domains. We found that the liquid-ordered (Lo) and liquid-disordered (Ld) lipid domains in PAPC/di18:0PC(DSPC)/cholesterol and PLPC/DSPC/cholesterol mixtures are micrometer-sized, and only the POPC/DSPC/cholesterol system has nanoscopic domains. The results indicate that some HLs with polyunsaturated chains are not linactants, and the monounsaturated POPC displays both properties of weak linactants and "Ld-phase" lipids such as di18:1PC (DOPC). The obtained phase boundaries from giant unilamellar vesicles (GUV) show that both POPC and PLPC partition well in the Lo phases. Our MD simulations reveal that these hybrid lipids decrease the order and compactness of Lo domains. Thus, hybrid lipids distinguish themselves from other lipid groups in this combined "partitioning and loosening" ability, which could explain why the Lo domains of GUVs, which often do not contain HL, are more compact than the raft domains in cell membranes. Our line tension measurement and Monte Carlo simulation both show that even the monounsaturated POPC is a weak linactant with only modest ability to occupy domain boundaries and reduce line tension. A more important property of HLs is that they can reduce physical property differences of Lo and Ld bulk domains, which also reduces line tension at domain boundaries.

  18. Edelfosine and miltefosine effects on lipid raft properties: membrane biophysics in cell death by antitumor lipids.

    Science.gov (United States)

    Castro, Bruno M; Fedorov, Aleksander; Hornillos, Valentin; Delgado, Javier; Acuña, A Ulises; Mollinedo, Faustino; Prieto, Manuel

    2013-07-03

    Edelfosine (1-O-octadecyl-2-O-methyl-sn-glycero-phosphocholine) and miltefosine (hexadecylphosphocholine) are synthetic alkylphospholipids (ALPs) that are reported to selectively accumulate in tumor cell membranes, inducing Fas clustering and activation on lipid rafts, triggering apoptosis. However, the exact mechanism by which these lipids elicit these events is still not fully understood. Recent studies propose that their mode of action might be related with alterations of lipid rafts biophysical properties caused by these lipid drugs. To achieve a clear understanding of this mechanism, we studied the effects of pharmacologically relevant amounts of edelfosine and miltefosine in the properties of model and cellular membranes. The influence of these molecules on membrane order, lateral organization, and lipid rafts molar fraction and size were studied by steady-state and time-resolved fluorescence methods, Förster resonance energy transfer (FRET), confocal and fluorescence lifetime imaging microscopy (FLIM). We found that the global membrane and lipid rafts biophysical properties of both model and cellular membranes were not significantly affected by both the ALPs. Nonetheless, in model membranes, a mild increase in membrane fluidity induced by both alkyl lipids was detected, although this effect was more noticeable for edelfosine than miltefosine. This absence of drastic alterations shows for the first time that ALPs mode of action is unlikely to be directly linked to alterations of lipid rafts biophysical properties caused by these drugs. The biological implications of this result are discussed in the context of ALPs effects on lipid metabolism, mitochondria homeostasis modulation, and their relationship with tumor cell death.

  19. Long and Short Lipid Molecules Experience the Same Interleaflet Drag in Lipid Bilayers

    Science.gov (United States)

    Horner, Andreas; Akimov, Sergey A.; Pohl, Peter

    2015-01-01

    Membrane interleaflet viscosity ηe affects tether formation, phase separation into domains, cell shape changes, and budding. Contrary to the expected contribution to interleaflet coupling from interdigitation, the slide of lipid patches in opposing monolayers conferred the same value ηe ≈ 3×109 J s m−4 for the friction experienced by the ends of both short and long chain fluorescent lipid analogues. Consistent with the weak dependence of the translational diffusion coefficient on lipid length, the in-layer viscosity was, albeit length dependent, much smaller than ηe. PMID:23848924

  20. Effect of different lipids and surfactants on formulation of solid lipid nanoparticles incorporating tamoxifen citrate

    Directory of Open Access Journals (Sweden)

    S U Upadhyay

    2012-01-01

    Full Text Available Tamoxifen Citrate (TC is an estrogen receptor antagonist and drug of choice for hormone sensitive breast cancer. Solid Lipid Nanoparticles loaded with TC were prepared by High Shear Homogenization followed by Ultrasonication. The aim of the present work is to study the effect of four different Solid Lipids and three Surfactants on Formulation and Stability of SLN. They were characterized for Particle size, Polydispersity Index and Zeta Potential by Zetasizer Nano. SLN prepared by Solid Lipid Compritol 888 (Glyceryldibehenate and Tween 80 (1% showed desired Particle Size of 206.9 nm, PDI of 0.046 and Zeta Potential of 9.32 mV.

  1. Brominated lipids identify lipid binding sites on the surface of the reaction center from Rhodobacter sphaeroides.

    Science.gov (United States)

    Roszak, Aleksander W; Gardiner, Alastair T; Isaacs, Neil W; Cogdell, Richard J

    2007-03-20

    This study describes the use of brominated phospholipids to distinguish between lipid and detergent binding sites on the surface of a typical alpha-helical membrane protein. Reaction centers isolated from Rhodobacter sphaeroides were cocrystallized with added brominated phospholipids. X-ray structural analysis of these crystals has revealed the presence of two lipid binding sites from the characteristic strong X-ray scattering from the bromine atoms. These results demonstrate the usefulness of this approach to mapping lipid binding sites at the surface of membrane proteins.

  2. Supported lipid bilayer nanosystems: stabilization by undulatory-protrusion forces and destabilization by lipid bridging.

    Science.gov (United States)

    Savarala, Sushma; Monson, Frederick; Ilies, Marc A; Wunder, Stephanie L

    2011-05-17

    Control of the stabilization/destabilization of supported lipid bilayers (SLBs) on nanoparticles is important for promotion of their organized assembly and for their use as delivery vehicles. At the same time, understanding the mechanism of these processes can yield insight into nanoparticle-cell interactions and nanoparticle toxicity. In this study, the suspension/precipitation process of zwitterionic lipid/SiO(2) nanosystems was analyzed as a function of ionic strength and as a function of the ratio of lipid/SiO(2) surface areas, at pH = 7.6. Salt is necessary to induce supported lipid bilayer (SLB) formation for zwitterionic lipids on silica (SiO(2)) (Seantier, B.; Kasemo, B., Influence of Mono- and Divalent Ions on the Formation of Supported Phospholipid Bilayers via Vesicle Adsorption. Langmuir 2009, 25 (10), 5767-5772). However, for zwitterionic SLBs on SiO(2) nanoparticles, addition of salt can cause precipitation of the SLBs, due to electrostatic shielding by both the lipid and the salt and to the suppression of thermal undulation/protrusion repulsive forces for lipids on solid surfaces. At ionic strengths that cause precipitation of SLBs, it was found that addition of excess SUVs, at ratios where there were equal populations of SUVs and SLBs, restored the undulation/protrusion repulsive forces and restabilized the suspensions. We suggest that SUVs separate SLBs in the suspension, as observed by TEM, and that SLB-SLB interactions are replaced by SLB-SUV interactions. Decreasing the relative amount of lipid, to the extent that there was less lipid available than the amount required for complete bilayer coverage of the SiO(2), resulted in precipitation of the nanosystem by a process of nanoparticle lipid bridging. For this case, we postulate a process in which lipid bilayer patches on one nanoparticle collide with bare silica patches on another SiO(2) nanoparticle, forming a single bilayer bridge between them. TEM data confirmed these findings, thus

  3. Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC).

    Science.gov (United States)

    Fang, Jia-You; Fang, Chia-Lang; Liu, Chi-Hsien; Su, Yu-Han

    2008-10-01

    Solid lipid nanoparticles (SLN) were developed by using Precirol ATO 5 as the solid core of the particles for topical psoralen delivery. Nanostructured lipid carriers (NLC) consisting of Precirol and squalene, a liquid lipid, were also prepared for comparison. SLN and NLC showed respective mean particle sizes of approximately 300 and 200nm, respectively. Viscosity, polarity, and differential scanning calorimetry (DSC) studies were performed to characterize the physicochemical properties of the SLN and NLC. The viscosity of all nanoparticulate systems exhibited Newtonian behavior except the NLC with Tween 80 and soybean phospholipids as the emulsifiers (NLC-Tw). According to the DSC thermograms, the melting peak of Precirol shifted from 58 to 55 degrees C after incorporating squalene into the solid lipid cores (of NLC), which suggests defects in the crystalline lattice of the lipid cores and smaller particle sizes. Three psoralen derivatives for psoriasis treatments were loaded in SLN and NLC to examine their ability to permeate skin. The permeability of psoralens increased in the order of 8-methoxypsoralen (8-MOP)>5-methoxypsoralen (5-MOP)>4,5,8-trimethylpsoralen (TMP). Enhanced permeation and controlled release of psoralen delivery were both achieved using the NLC. The in vitro permeation results showed that NLC-Tw increased the 8-MOP flux 2.8 times over that of a conventional emulsion. Hyperproliferative or psoriasis-like skin produced by repeated strippings in the dorsal skin of nude mouse was also used as a permeation barrier. The results showed that the entrapment of 8-MOP in nanoparticulate systems could minimize the permeation differentiation between normal and hyperproliferative skin compared to the free drug in an aqueous control.

  4. Calanus hyperboreus and the lipid pump

    DEFF Research Database (Denmark)

    Visser, Andre; Grønning, Josephine Bøgeskov; Jonasdottir, Sigrun

    2017-01-01

    Lipid-fuelled overwintering by copepods can be a regionally important contribution to carbon sequestration in the deep oceans. Here, we estimate the contribution for Calanus hyperboreus, found in abundance in the northern reaches of the North Atlantic and Arctic Ocean. Estimates for regions with ...

  5. Lipid nanoparticles for dermal drug delivery.

    Science.gov (United States)

    Kakadia, Pratibha G; Conway, Barbara R

    2015-01-01

    Lipid based drug delivery systems have been widely studied and reported over the past decade and offer a useful alternative to other colloidal drug delivery systems. Skin is a popular route of drug delivery for locally and systemically acting drugs and nanoparticles are reported as a potential formulation strategy for dermal delivery. Although the skin acts as a natural physical barrier against penetration of foreign materials, including particulates, opportunities exist for the delivery of therapeutic nanoparticles, especially in diseased and damaged skin and via appendageal routes such as the openings of hair follicles. The extent and ability of nanoparticles to penetrate into the underlying viable tissue is still the subject of debate although recent studies have identified the follicular route as the most likely route of entry; this influences the potential applications of these dosage forms as a drug delivery strategy. This paper reviews present state of art of lipid-based nanocarriers focussing on solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, their production methods, potential advantages and applications in dermal drug delivery.

  6. Engineering Lipid Bilayer Membranes for Protein Studies

    Directory of Open Access Journals (Sweden)

    Muhammad Shuja Khan

    2013-10-01

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

  7. Lipid contents of the sponge Haliclona sp.

    Digital Repository Service at National Institute of Oceanography (India)

    Parameswaran, P.S.; Das, B.; Kamat, S.Y.

    Several fatty acids, sterols, batyl alcohol and its analogs and an N-acylated sphingosine (ceramide) have been isolated from the lipid fraction of the extract of the sponge Haliclona sp. The major sterol is found to be cholesterol (54%), followed...

  8. DNA nanotechnology: Bringing lipid bilayers into shape

    Science.gov (United States)

    Howorka, Stefan

    2017-07-01

    Lipid bilayers form the thin and floppy membranes that define the boundary of compartments such as cells. Now, a method to control the shape and size of bilayers using DNA nanoscaffolds has been developed. Such designer materials advance synthetic biology and could find use in membrane research.

  9. [Residual lipid profile in recurrent ischemic cardiopathy].

    Science.gov (United States)

    Millán, Jesús; Pedro-Botet, Juan; Muñoz, Anna; Corbella, Emili; Mangas, Alipio; Zúñiga, Manuel; Hernández-Mijares, Antonio; Pintó, Xavier

    2012-03-17

    In this paper we analyze the lipid profile of a cohort of patients attended in different tertiary hospitals with acute coronary syndrome (angor pectoris or acute myocardial infarction). We have analysed different variables of patients with acute coronary syndrome, related with the prevalence and grade of main cardiovascular risk factors, and related with different treatments. We have analysed the lipid profile, and stratified the results according with the status of the first acute coronary event or recurrent coronary event. Patients with recurrent disease showed lower levels of total cholesterol and LDL-c, and similar levels of HDL-c and triglycerides in relation with patients with a first event. We found similar HDL-c and triglycerides levels in both groups of patients meaning that, despite a standard statins treatment, patients with a first coronary event did not modify such a lipid profile. It is necessary to do a more intensive therapeutic effort over all the lipid fractions with the aim to reduce the recurrences of coronary events. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  10. Perfluorooctanoic acid rigidifies a model lipid membrane

    NARCIS (Netherlands)

    Brüning, B.A.; Farago, B.

    2014-01-01

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

  11. Fragmented state of lipid bilayers in water

    DEFF Research Database (Denmark)

    Helfrich, W.; Thimmel, J.; Klösgen, Beate Maria

    1999-01-01

    The bilayers of some typical biological membrane lipids such as PC and DGDG disintegrate in a large excess of water to form an optically invisible dispersive bilayer phase. `Dark bodies' can be reversibly precipitated from it by raising the temperature. The dispersive phase probably consists...

  12. Perfluorooctanoic acid rigidifies a model lipid membrane

    NARCIS (Netherlands)

    Brüning, B.A.; Farago, B.

    2014-01-01

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

  13. Lipid organization of the plasma membrane

    NARCIS (Netherlands)

    Ingólfsson, Helgi I; Melo, Manuel N; van Eerden, Floris J; Arnarez, Clément; Lopez, Cesar A; Wassenaar, Tsjerk A; Periole, Xavier; de Vries, Alex H; Tieleman, D Peter; Marrink, Siewert J

    2014-01-01

    The detailed organization of cellular membranes remains rather elusive. Based on large-scale molecular dynamics simulations, we provide a high-resolution view of the lipid organization of a plasma membrane at an unprecedented level of complexity. Our plasma membrane model consists of 63 different

  14. Self-assembly models for lipid mixtures

    Science.gov (United States)

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

    2006-03-01

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

  15. Statistical mechanics of a lipid monolayer

    NARCIS (Netherlands)

    Kox, A.J.; Wiegel, F.W.

    1978-01-01

    We calculate from first principles the equation of state of a simple type of membrane: a monolayer consisting of lipid chain molecules with short-range repulsive and long-range attractive forces. An approximate solution to the packing problem of the hydrocarbon chains is obtained by using a mathemat

  16. Variation in seed lipids in Calendula germplasm

    Science.gov (United States)

    Calendula officinalis (pot marigold) has considerable promise as an industrial crop, with a long history as an ornamental and medicinal plant. It is also marketed as an ingredient in cosmetics and a colorant. It produces unusual seed lipids, which can provide an additional market for commercial Ca...

  17. Stability of lipid encapsulated ferulic acid particles

    Science.gov (United States)

    Encapsulation of bioactive compounds by a solid lipid matrix provides stability and a mechanism for controlled release in formulated products. Phenolic compounds exhibit antioxidant and antimicrobial activities and have applications as functional food and feed additives. Ferulic acid, a common pheno...

  18. Design of lipid matrix particles for fenofibrate

    DEFF Research Database (Denmark)

    Xia, Dengning; Cui, Fude; Gan, Yong

    2014-01-01

    The effect of polymorphism of glycerol monostearate (GMS) on drug incorporation and release from lipid matrix particles (LMPs) was investigated using fenofibrate as a model drug. X-ray powder diffraction and differential scanning calorimetry were used to study the polymorphism change of GMS and t...

  19. Lipid organization of the plasma membrane

    NARCIS (Netherlands)

    Ingólfsson, Helgi I; Melo, Manuel N; van Eerden, Floris J; Arnarez, Clément; Lopez, Cesar A; Wassenaar, Tsjerk A; Periole, Xavier; de Vries, Alex H; Tieleman, D Peter; Marrink, Siewert J

    2014-01-01

    The detailed organization of cellular membranes remains rather elusive. Based on large-scale molecular dynamics simulations, we provide a high-resolution view of the lipid organization of a plasma membrane at an unprecedented level of complexity. Our plasma membrane model consists of 63 different li

  20. Bright Ion Channels and Lipid Bilayers

    NARCIS (Netherlands)

    Szymanski, Wiktor; Yilmaz, Duygu; Kocer, Armagan; Feringa, Ben L.

    2013-01-01

    If we look at a simple organism such as a zebrafish under a microscope, we would see many cells working in harmony. If we zoomed in, we would observe each unit performing its own tasks in a special aqueous environment isolated from the other units by a lipid bilayer approximately 5 nm thick. These

  1. Nonadditive Compositional Curvature Energetics of Lipid Bilayers

    Science.gov (United States)

    Sodt, A. J.; Venable, R. M.; Lyman, E.; Pastor, R. W.

    2016-09-01

    The unique properties of the individual lipids that compose biological membranes together determine the energetics of the surface. The energetics of the surface, in turn, govern the formation of membrane structures and membrane reshaping processes, and thus they will underlie cellular-scale models of viral fusion, vesicle-dependent transport, and lateral organization relevant to signaling. The spontaneous curvature, to the best of our knowledge, is always assumed to be additive. We describe observations from simulations of unexpected nonadditive compositional curvature energetics of two lipids essential to the plasma membrane: sphingomyelin and cholesterol. A model is developed that connects molecular interactions to curvature stress, and which explains the role of local composition. Cholesterol is shown to lower the number of effective Kuhn segments of saturated acyl chains, reducing lateral pressure below the neutral surface of bending and favoring positive curvature. The effect is not observed for unsaturated (flexible) acyl chains. Likewise, hydrogen bonding between sphingomyelin lipids leads to positive curvature, but only at sufficient concentration, below which the lipid prefers negative curvature.

  2. High fat intake and equine lipid metabolism

    NARCIS (Netherlands)

    Geelen, Suzanne Nicole Jeanne

    2001-01-01

    This thesis deals with the influence of fat feeding on lipid metabolism in horses. Highfat diets have attained considerable interest as a potential tool to improve performance.Many factors affect performance so that large numbers of horses are needed to unequivocally determine the effect of diet on

  3. Immune modulation by parenteral lipid emulsions.

    NARCIS (Netherlands)

    Wanten, G.J.A.; Calder, P.C.

    2007-01-01

    Total parenteral nutrition is the final option for nutritional support of patients with severe intestinal failure. Lipid emulsions constitute the main source of fuel calories and fatty acids (FAs) in parenteral nutrition formulations. However, adverse effects on patient outcomes have been attributed

  4. Editorial; Lipids in Metabolic Health and Disease

    NARCIS (Netherlands)

    Glatz, Jan; De Groot, Renate; Hesselink, Matthijs; Schrauwen, Patrick

    2012-01-01

    Glatz, J. F. C., De Groot, R. H. M., Hesselink, K. C., & Schrauwen, P. (2011). Editorial; Lipids in Metabolic Health and Disease. Prostaglandines, Leukotrienes and Essential fatty Acids, 85, 195. DOI: 10.1016/j.plefa.2011.04.006

  5. Voltage-gated lipid ion channels

    DEFF Research Database (Denmark)

    Blicher, Andreas; Heimburg, Thomas Rainer

    2013-01-01

    Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current...

  6. LIPID BIOMARKER ANALYSIS OF MARINE DINOFLAGELLATES

    Science.gov (United States)

    Many marine eukaryotic algae have been shown to possess characteristic chemotaxonomic lipid biomarkers. Dinoflagellates in particular are often characterized by the presence of sterols and pigments that are rarely found in other classes of algae. To evaluate the utility of chemic...

  7. Pollen viability and membrane lipid composition.

    NARCIS (Netherlands)

    Bilsen, van D.G.J.L.

    1993-01-01

    In this thesis membrane lipid composition is studied in relation to pollen viability during storage. Chapter 1 reviews pollen viability, membranes in the dry state and membrane changes associated with cellular aging. This chapter is followed by a study of age-related changes in phospholipid composit

  8. Polar Lipid Profile of Nannochloropsis oculata Determined Using a Variety of Lipid Extraction Procedures.

    Science.gov (United States)

    Servaes, K; Maesen, M; Prandi, B; Sforza, S; Elst, K

    2015-04-22

    Lipid compositions obtained from microalgae species are affected by both the cultivation conditions and the extraction method used. In this study, the extraction of lipids from Nannochloropsis oculata using traditional and modern extraction technologies with several solvents has been compared. Because important polyunsaturated fatty acids are bound to polar lipids, these polar lipids were the main focus of this study. The dominant compounds in the glycolipid fractions were monogalactosyldiglycerides and digalactosyldiglycerides bearing fatty acid chains containing at least one site of unsaturation. Phosphatidylcholine and trimethylhomoserines were detected in the phospholipid fractions. The fatty acid profile comprised large fractions of C16:0, C16:1, C20:5, and C18:3. Extraction of specific compounds was determined by extraction efficiency as well as differences in the selectivity of the method used. The composition derived from a glycolipid fraction was observed to be affected by the method used to a greater extent than the phospholipid fraction.

  9. Nanostructured Silica–Lipid Hybrid Microparticles: A Supersaturating Carrier for Water- and Lipid-resistant Compounds

    National Research Council Canada - National Science Library

    Tan, Angel; Prestidge, Clive

    2012-01-01

    Nanostructured silica–lipid hybrid (SLH) microparticles, which are fabricated based on Pickering emulsion templates, are reported to enhance the encapsulation efficiency of a weak base anthelmintic, albendazole (ABZ...

  10. Tubular lipid membranes pulled from vesicles: Dependence of system equilibrium on lipid bilayer curvature

    Science.gov (United States)

    Golushko, I. Yu.; Rochal, S. B.

    2016-01-01

    Conditions of joint equilibrium and stability are derived for a spherical lipid vesicle and a tubular lipid membrane (TLM) pulled from this vesicle. The obtained equations establish relationships between the geometric and physical characteristics of the system and the external parameters, which have been found to be controllable in recent experiments. In particular, the proposed theory shows that, in addition to the pressure difference between internal and external regions of the system, the variable spontaneous average curvature of the lipid bilayer (forming the TLM) also influences the stability of the lipid tube. The conditions for stability of the cylindrical phase of TLMs after switching off the external force that initially formed the TLM from a vesicle are discussed. The loss of system stability under the action of a small axial force compressing the TLM is considered.

  11. Atomistic study of lipid membranes containing chloroform: looking for a lipid-mediated mechanism of anesthesia.

    Directory of Open Access Journals (Sweden)

    Ramon Reigada

    Full Text Available The molecular mechanism of general anesthesia is still a controversial issue. Direct effect by linking of anesthetics to proteins and indirect action on the lipid membrane properties are the two hypotheses in conflict. Atomistic simulations of different lipid membranes subjected to the effect of small volatile organohalogen compounds are used to explore plausible lipid-mediated mechanisms. Simulations of homogeneous membranes reveal that electrostatic potential and lateral pressure transversal profiles are affected differently by chloroform (anesthetic and carbon tetrachloride (non-anesthetic. Simulations of structured membranes that combine ordered and disordered regions show that chloroform molecules accumulate preferentially in highly disordered lipid domains, suggesting that the combination of both lateral and transversal partitioning of chloroform in the cell membrane could be responsible of its anesthetic action.

  12. Lipid emulsion therapy: non-nutritive uses of lipid emulsions in ...

    African Journals Online (AJOL)

    toxicity.1 However, the non-nutritive therapeutic roles of lipid emulsions have ... solving the toxicity associated with previous intravenous fat solutions.2 ..... Hu ZY, Peng XY, Liu F, et al. Emulsified ... prostaglandin metabolism. Chest. 1991 ...

  13. The emerging roles of lipids in circadian control.

    Science.gov (United States)

    Adamovich, Yaarit; Aviram, Rona; Asher, Gad

    2015-08-01

    Lipids play vital roles in a wide variety of cellular functions. They act as structural components in cell membranes, serve as a major form of energy storage, and function as key signaling molecules. Mounting evidence points towards a tight interplay between lipids and circadian clocks. In mammals, circadian clocks regulate the daily physiology and metabolism, and disruption of circadian rhythmicity is associated with altered lipid homeostasis and pathologies such as fatty liver and obesity. Concomitantly, emerging evidence suggest that lipids are embedded within the core clock circuitry and participate in circadian control. Recent advances in lipidomics methodologies and their application in chronobiology studies have shed new light on the cross talk between circadian clocks and lipid homeostasis. We review herein the latest literature related to the involvement of lipids in circadian clock's function and highlight the contribution of circadian lipidomics studies to our understanding of circadian rhythmicity and lipid homeostasis. This article is part of a Special Issue entitled Brain Lipids.

  14. Lipid-related markers and cardiovascular disease prediction

    DEFF Research Database (Denmark)

    Di Angelantonio, Emanuele; Gao, Pei; Pennells, Lisa

    2012-01-01

    The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated.......The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated....

  15. The role of the kidney in lipid metabolism

    DEFF Research Database (Denmark)

    Moestrup, Søren K; Nielsen, Lars Bo

    2005-01-01

    PURPOSE OF REVIEW: Cellular uptake of plasma lipids is to a large extent mediated by specific membrane-associated proteins that recognize lipid-protein complexes. In the kidney, the apical surface of proximal tubules has a high capacity for receptor-mediated uptake of filtered lipid-binding plasma...... proteins. We describe the renal receptor system and its role in lipid metabolism in health and disease, and discuss the general effect of the diseased kidney on lipid metabolism. RECENT FINDINGS: Megalin and cubilin are receptors in the proximal tubules. An accumulating number of lipid......-binding and regulating proteins (e.g. albumin, apolipoprotein A-I and leptin) have been identified as ligands, suggesting that their receptors may directly take up lipids in the proximal tubules and indirectly affect plasma and tissue lipid metabolism. Recently, the amnionless protein was shown to be essential...

  16. Influence of Atorvastatin/Probucol Combination on Blood Lipid and ...

    African Journals Online (AJOL)

    Lipid and Serum C-Reactive Protein Levels in Patients with. Cerebral Infarction ... analyzed the influence of atorvastatin combined ... Comparison of blood fat level of two groups before and after .... plaque focuses on lipid regulation, oxidation.

  17. Variations in plasma lipids and lipoproteins among cardiovascular ...

    African Journals Online (AJOL)

    Variations in plasma lipids and lipoproteins among cardiovascular disease patients in ... This study was designed to assess the changes in plasma lipids and lipoproteins, in particular highdensity lipoprotein (HDLC) in patients ... Article Metrics.

  18. Evaluation of HIV therapeutic agents on immunological, lipid and ...

    African Journals Online (AJOL)

    Evaluation of HIV therapeutic agents on immunological, lipid and lipoprotein indices in Ghanaian HIV-1 infected patients. ... lipid and lipoprotein changes as well as the atherogenic indices of Ghanaian HIV-1 infected patients. ... Article Metrics.

  19. Evaluation of plasma lipids and lipoproteins in nigerians suffering ...

    African Journals Online (AJOL)

    Evaluation of plasma lipids and lipoproteins in nigerians suffering from depressive illness. ... Very little is known about the lipid and lipoprotein status in Nigerian adults suffering from depression. One hundred subjects ... Article Metrics.

  20. In search of lipid translocases and their biological functions

    NARCIS (Netherlands)

    Hoekstra, D; van Ijzendoorn, SCD

    2003-01-01

    In plasma membranes, lipids distribute asymmetrically across the bilayer, a process that requires proteins. Recent work identified novel lipid translocators in yeast, and their activity was functionally correlated to endocytosis, thus boosting investigations on identity, mechanism, and function of l

  1. Comparative lipid composition of heterotrophically and autotrophically grown Sulfolobus acidocaldarius.

    Science.gov (United States)

    Langworthy, T A

    1977-06-01

    Complex lipids from the thermoacidophilic facultative autotroph Sulfolobus acidocaldarius, as well as a strictly autotrophic isolate, were compared between cells grown on yeast extract and elemental sulfur. Lipids from both organisms grown autotrophically were nearly identical. Each contained about 15% neutral lipids, 35% glycolipids, and 50% acidic lipids. Glycolipids and acidic lipids contained C40H82-76-derived glycerol ether residues. Major glycolipids included the glycerol ether analogues of glucosyl galactosyl diglyceride (5%) and glucosyl polyol diglyceride (75%). Acidic lipids were comprised mainly of the glycerol ether analogues of phosphatidyl inositol (7%), inositolphosphoryl glucosyl polyol diglyceride (72%), and a partially characterized sulfate- and phosphate-containing derivative of glucosyl polyol diglyceride (13%). The lipids from cells grown heterotrophically were similar to those from autotrophically grown cells, except that the partially characterized acidic lipid was absent. In addition, the two glycolipids as well as the respective inositolphosphoryl derivatives were each present in nearly equal proportions.

  2. The molecular face of lipid rafts in model membranes

    NARCIS (Netherlands)

    Risselada, H. Jelger; Marrink, Siewert J.

    2008-01-01

    Cell membranes contain a large number of different lipid species. Such a multicomponent mixture exhibits a complex phase behavior with regions of structural and compositional heterogeneity. Especially domains formed in ternary mixtures, composed of saturated and unsaturated lipids together with

  3. Lipid-binding analysis using a fat blot assay.

    NARCIS (Netherlands)

    Munnik, T.; Wierzchowiecka, M.

    2013-01-01

    Protein-lipid interactions play an important role in lipid metabolism, membrane trafficking and cell -signaling by regulating protein localization, activation, and function. The Fat Blot assay is a relatively simple and inexpensive method to examine these interactions using nitrocellulose

  4. Ion dynamics in cationic lipid bilayer systems in saline solutions

    DEFF Research Database (Denmark)

    Miettinen, Markus S; Gurtovenko, Andrey A; Vattulainen, Ilpo

    2009-01-01

    mixture of cationic dimyristoyltrimethylammoniumpropane (DMTAP) and zwitterionic (neutral) dimyristoylphosphatidylcholine (DMPC) lipids. Using atomistic molecular dynamics simulations, we address the effects of bilayer composition (cationic to zwitterionic lipid fraction) and of NaCl electrolyte...

  5. Importance of the hexagonal lipid phase in biological membrane organisation

    Directory of Open Access Journals (Sweden)

    Juliette eJouhet

    2013-12-01

    Full Text Available Abstract:Domains are present in every natural membrane. They are characterised by a distinctive protein and/or lipid composition. Their size is highly variable from the nano- to the micrometer scale. The domains confer specific properties to the membrane leading to original structure and function. The determinants leading to domain organisation are therefore important but remain obscure. This review presents how the ability of lipids to organize into hexagonal II or lamellar phases can promote particular local structures within membranes. Since biological membranes are composed of a mixture of lipids, each with distinctive biophysical properties, lateral and transversal sorting of lipids can promote creation of domains inside the membrane through local modulation of the lipid phase. Lipid biophysical properties have been characterized for long based on in vitro analyses using non-natural lipid molecules; their re-examinations using natural lipids might open interesting perspectives on membrane architecture occurring in vivo in various cellular and physiological contexts.

  6. Recent advances in the field of omega-3-lipids

    DEFF Research Database (Denmark)

    Jacobsen, Charlotte

    During the last 15-20 years the use of fish and algae oils for human applications has received increasing attention from academia, industry and consumers. This is due to the fact that a growing body of evidence supports that marine omega-3 lipids have a wide range of health beneficial effects...... consumption. Due to their polyunsaturated nature omega-3 lipids are highly susceptible to lipid oxidation. The last part of the presentation will discuss possible means to prevent or reduce lipid oxidation in omega-3 lipids in dietary supplements and in foods enriched with these healthy lipids. Possible means......, and at the same time the intake of these healthy lipids is far below the recommendable level in many parts of the world. This presentation will provide a brief overview of recent advances in the body of knowledge about the health benefits of omega-3 lipids. For many years fish oil produced from wild fish has been...

  7. Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators

    Science.gov (United States)

    Ramírez-López, María T.; Arco, Rocío; Decara, Juan; Vázquez, Mariam; Rivera, Patricia; Blanco, Rosario Noemi; Alén, Francisco; Gómez de Heras, Raquel; Suárez, Juan; Rodríguez de Fonseca, Fernando

    2016-01-01

    Maternal malnutrition causes long-lasting alterations in feeding behavior and energy homeostasis in offspring. It is still unknown whether both, the endocannabinoid (eCB) machinery and the lipid metabolism are implicated in long-term adaptive responses to fetal reprogramming caused by maternal undernutrition. We investigated the long-term effects of maternal exposure to a 20% standard diet restriction during preconceptional and gestational periods on the metabolically-relevant tissues hypothalamus, liver, and perirenal fat (PAT) of male and female offspring at adulthood. The adult male offspring from calorie-restricted dams (RC males) exhibited a differential response to the CB1 antagonist AM251 in a chocolate preference test as well as increased body weight, perirenal adiposity, and plasma levels of triglycerides, LDL, VLDL, bilirubin, and leptin. The gene expression of the cannabinoid receptors Cnr1 and Cnr2 was increased in RC male hypothalamus, but a down-expression of most eCBs-metabolizing enzymes (Faah, Daglα, Daglβ, Mgll) and several key regulators of fatty-acid β-oxidation (Cpt1b, Acox1), mitochondrial respiration (Cox4i1), and lipid flux (Pparγ) was found in their PAT. The female offspring from calorie-restricted dams exhibited higher plasma levels of LDL and glucose as well as a reduction in chocolate and caloric intake at post-weaning periods in the feeding tests. Their liver showed a decreased gene expression of Cnr1, Pparα, Pparγ, the eCBs-degrading enzymes Faah and Mgll, the de novo lipogenic enzymes Acaca and Fasn, and the liver-specific cholesterol biosynthesis regulators Insig1 and Hmgcr. Our results suggest that the long-lasting adaptive responses to maternal caloric restriction affected cannabinoid-regulated mechanisms involved in feeding behavior, adipose β-oxidation, and hepatic lipid and cholesterol biosynthesis in a sex-dependent manner. PMID:28082878

  8. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice.

    Directory of Open Access Journals (Sweden)

    Elise F Hoek-van den Hil

    Full Text Available Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD. In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control or with supplementation of 0.33% (w/w quercetin for 12 weeks. Gas chromatography and (1H nuclear magnetic resonance were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify possible mechanisms underlying altered circulating lipid levels. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, triglycerides (TG were decreased with 14% (p<0.001 and total poly unsaturated fatty acids (PUFA were increased with 13% (p<0.01. Palmitic acid, oleic acid, and linoleic acid were all decreased by 9-15% (p<0.05 in quercetin-fed mice. Both palmitic acid and oleic acid can be oxidized by omega (ω-oxidation. Gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially ω-oxidation. At the gene level, this was reflected by the up-regulation of cytochrome P450 (Cyp 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3. Two relevant regulators, cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s and the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3 were also up-regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid ω-oxidation and lowered corresponding circulating lipid levels, which may contribute to potential beneficial effects on CVD.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-14

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

  10. Association of glycosylated hemoglobin level with lipid ratio and individual lipids in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    Zhe Yan; Yang Liu; Hui Huang

    2012-01-01

    Objective:To study the correlation of lipid ratios and individual lipid indexes of patients with type2 diabetes with glycosylated hemoglobin (HbA1c).Methods:Samples were collected from 128 type2 diabetic patients (aged19-90 years; male 72, female56). The sera were analyzed for HbA1c, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). According to theHbA1c level, the patients were divided into three groups, groupA (HbA1c 10%,n=49). The correlation ofHbA1cwith lipid ratios & individual lipid indexes were analyzed.Results:With the increased level ofHbA1c,LDL-C had a significantly increasing trend (P<0.05); whereasTC went up with the increasedHbA1c, without any significant differences between three groups. There was no significant correlation betweenHbA1c andTG or HDL-C. With the increased level ofHbA1c,TC/HDL-C,LDL-C/HDL-C ratios were gradually increased, with significant differences among groups (P<0.05). The lipid ratios, especiallyLDL-C/HDL-C ratio was more susceptible to impaired lipid metabolism inT2DM patients than individual lipid. Conclusions:LDL-C/HDL-C ratio is helpful in assessing and reducing the risk of cardiovascular disease caused by impaired lipid metabolism in type2 diabetic patients.

  11. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery.

    Science.gov (United States)

    Cheng, Xinwei; Lee, Robert J

    2016-04-01

    Lipid nanoparticles (LNPs) have shown promise as delivery vehicles for therapeutic oligonucleotides, including antisense oligos (ONs), siRNA, and microRNA mimics and inhibitors. In addition to a cationic lipid, LNPs are typically composed of helper lipids that contribute to their stability and delivery efficiency. Helper lipids with cone-shape geometry favoring the formation hexagonal II phase, such as dioleoylphosphatidylethanolamine (DOPE), can promote endosomal release of ONs. Meanwhile, cylindrical-shaped lipid phosphatidylcholine can provide greater bilayer stability, which is important for in vivo application of LNPs. Cholesterol is often included as a helper that improves intracellular delivery as well as LNP stability in vivo. Inclusion of a PEGylating lipid can enhance LNP colloidal stability in vitro and circulation time in vivo but may reduce uptake and inhibit endosomal release at the cellular level. This problem can be addressed by choosing reversible PEGylation in which the PEG moiety is gradually released in blood circulation. pH-sensitive anionic helper lipids, such as fatty acids and cholesteryl hemisuccinate (CHEMS), can trigger low-pH-induced changes in LNP surface charge and destabilization that can facilitate endosomal release of ONs. Generally speaking, there is no correlation between LNP activity in vitro and in vivo because of differences in factors limiting the efficiency of delivery. Designing LNPs requires the striking of a proper balance between the need for particle stability, long systemic circulation time, and the need for LNP destabilization inside the target cell to release the oligonucleotide cargo, which requires the proper selection of both the cationic and helper lipids. Customized design and empirical optimization is needed for specific applications.

  12. The effects of short term lipid infusion on plasma and hepatic bile lipids in humans

    OpenAIRE

    Pakula, R; Konikoff, F.; Moser, A.; Greif, F.; Tietz, A; Gilat, T; Rubin, M

    1999-01-01

    BACKGROUND—Patients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder.
AIMS—To determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy...

  13. Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice.

    Science.gov (United States)

    Hoek-van den Hil, Elise F; Keijer, Jaap; Bunschoten, Annelies; Vervoort, Jacques J M; Stankova, Barbora; Bekkenkamp, Melissa; Herreman, Laure; Venema, Dini; Hollman, Peter C H; Tvrzicka, Eva; Rietjens, Ivonne M C M; van Schothorst, Evert M

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and (1)H nuclear magnetic resonance were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify possible mechanisms underlying altered circulating lipid levels. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, triglycerides (TG) were decreased with 14% (p<0.001) and total poly unsaturated fatty acids (PUFA) were increased with 13% (p<0.01). Palmitic acid, oleic acid, and linoleic acid were all decreased by 9-15% (p<0.05) in quercetin-fed mice. Both palmitic acid and oleic acid can be oxidized by omega (ω)-oxidation. Gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially ω-oxidation. At the gene level, this was reflected by the up-regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3) were also up-regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid ω-oxidation and lowered corresponding circulating lipid levels, which may contribute to potential beneficial effects on CVD.

  14. Subretinal lipid exudation associated with untreated choroidal melanoma

    Directory of Open Access Journals (Sweden)

    C K Minija

    2011-01-01

    Full Text Available Subretinal lipid exudation in an untreated choroidal melanoma is very rare. It is seen following plaque radiotherapy in choroidal melanoma. There is only one case report of untreated choroidal melanoma with massive lipid exudation in a patient with metastatic hypernephroma. We report here a rare case of untreated choroidal melanoma with lipid exudation. Subretinal exudation that is rarely seen following plaque brachytherapy was noted at the borders of this untreated tumor. Lipid exudation partially resolved following brachytherapy.

  15. Characteristics of lipids and their feeding value in swine diets

    OpenAIRE

    Kerr, Brian J; Kellner, Trey A.; Shurson, Gerald C

    2015-01-01

    In livestock diets, energy is one of the most expensive nutritional components of feed formulation. Because lipids are a concentrated energy source, inclusion of lipids are known to affect growth rate and feed efficiency, but are also known to affect diet palatability, feed dustiness, and pellet quality. In reviewing the literature, the majority of research studies conducted on the subject of lipids have focused mainly on the effects of feeding presumably high quality lipids on growth perform...

  16. SOLID LIPID NANOPARTICLES: AN ADVANCED DRUG DELIVERY SYSTEM

    OpenAIRE

    Raghu Nandan Reddy* and Arshia Shariff

    2013-01-01

    Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, research and clinical medicine, as well as in other varied sciences. Solid lipid nanoparticle (SLN) dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. Solid lipid nanoparticles (SLNs) technology represents a promising new approach to lipophilic drug delivery. Solid lipid nanopa...

  17. The dynamic of lipid oxidation in human myotubes

    DEFF Research Database (Denmark)

    Gaster, Michael

    2009-01-01

    Both endogenous and exogenous lipid levels may be regulators of total lipid oxidation in skeletal muscles. We studied the dynamics of lipid oxidation in human myotubes established from healthy, lean subjects exposed to acutely and chronically increased palmitate concentrations. The intramyocellul...... oxidation in human myotubes. A reduced exogenous lipid oxidation, secondary to increased triacylglycerol levels, may redirect free fatty acids into esterification and oxidation from intracellular stores, thereby protecting myotubes from FFA lipotoxic effects....

  18. Lipid Quality in Infant Nutrition: Current Knowledge and Future Opportunities

    OpenAIRE

    Delplanque, Bernadette; Gibson, Robert; Koletzko, Berthold; Lapillonne, Alexandre; Strandvik, Birgitta

    2015-01-01

    Abstract Dietary lipids are key for infants to not only meet their high energy needs but also fulfill numerous metabolic and physiological functions critical to their growth, development, and health. The lipid composition of breast milk varies during lactation and according to the mother's diet, whereas the lipid composition of infant formulae varies according to the blend of different fat sources. This report compares the compositions of lipids in breast milk and infant formulae, and highlig...

  19. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-12-1-0168 TITLE: Imaging prostatic lipids to distinguish aggressive prostate cancer PRINCIPAL INVESTIGATOR: Jackilen...Imaging prostatic lipids to distinguish aggressive prostate Cancer 5a. CONTRACT NUMBER W81XWH-12-1-0168 5b. GRANT NUMBER PC110361 5c. PROGRAM...Mechanisms linking fatty acid synthase overexpression, lipid accumulation, lipid oxidation, and tumor aggressiveness will be explored using

  20. MR-Visible Lipids and the Tumor Microenvironment

    Science.gov (United States)

    Delikatny, E. James; Chawla, Sanjeev; Leung, Daniel-Joseph; Poptani, Harish

    2013-01-01

    MR-visible lipids or mobile lipids are defined as lipids that are observable using proton magnetic resonance spectroscopy in cells and in tissues. These MR-visible lipids are composed of triglycerides and cholesterol esters that accumulate in intracellular neutral lipid droplets, where their MR visibility is conferred as a result of the increased molecular motion available in this unique physical environment. This review will discuss factors that lead to the biogenesis of MR-visible lipids in cancer cells and in other cell types such as immune cells and fibroblasts. We focus on the accumulations of mobile lipids that are inducible in cultured cells by a number of stresses, including culture conditions and in response to activating stimuli or apoptotic cell death induced by anticancer drugs. This is compared with animal tumor models, where increases in mobile lipids are observed in response to chemo and radiotherapy, and to human tumors where mobile lipids are observed predominantly in high-grade brain tumors and in regions of necrosis. Conducive conditions for mobile lipid formation in the tumor microenvironment will be discussed including low pH, oxygen availability and the presence of inflammatory cells. It is concluded that MR-visible lipids appear in cancer cells and human tumors as a stress response. Mobile lipids stored as neutral lipid droplets may play a role in detoxification of the cell or act as an alternate energy source, especially in cancer cells, which often grow in ischemic/hypoxic environments. The role of MR-visible lipids in cancer diagnosis and assessment of treatment response both in animal models of cancer as well as human brain tumors will also be discussed. Although technical limitations exist in the accurate detection of intratumoral mobile lipids, early increases in mobile lipids after therapeutic interventions may be used as a potential biomarker for assessing treatment response in cancer. PMID:21538631

  1. Assay of flippase activity in proteoliposomes using fluorescent lipid derivatives

    DEFF Research Database (Denmark)

    Marek, Magdalena; Günther-Pomorski, Thomas

    2016-01-01

    Specific membrane proteins, termed lipid flippases, play a central role in facilitating the movement of lipids across cellular membranes. In this protocol, we describe the reconstitution of ATP-driven lipid flippases in liposomes and the analysis of their in vitro flippase activity based on the use...... of fluorescent lipid derivatives. Working with purified and reconstituted systems provides a well-defined experimental setup and allows to directly characterize these membrane proteins at the molecular level....

  2. Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

    Science.gov (United States)

    Michalski, M C; Genot, C; Gayet, C; Lopez, C; Fine, F; Joffre, F; Vendeuvre, J L; Bouvier, J; Chardigny, J M; Raynal-Ljutovac, K

    2013-10-01

    On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen.

  3. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2013-01-01

    Full Text Available Diclofenac sodium loaded solid lipid nanoparticles (SLNs were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG and plain carbopol gel containing drug (CG for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1 and stearic acid nanoparticle 1 (SAN-1 gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3 showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  4. Lipid Vesicles for the Skin Delivery of Diclofenac: Cerosomes vs. Other Lipid Suspensions

    Directory of Open Access Journals (Sweden)

    Anahita Fathi-Azarbayjani

    2015-03-01

    Full Text Available Purpose: Lipid suspensions as drug carriers, including conventional liposomes, ethosomes, transferosomes, proniosomes, niosomes, PEG-PPG-PEG niosomes and stratum corneum liposomes (cerosomes, were formulated and compared. Methods: Lipid vesicles were formulated and assessed with regards to enhancement of skin permeation of diclofenac and stability profiles of the formulations. Formulation-induced changes of the biophysical structure of excised human skin were monitored using the Fourier transform infrared spectroscopy. Results: The stability profiles of these suspensions over 12 weeks did not show any significant drug leakage from the vesicles of interest (p > 0.05. FTIR observations indicated that the vesicles increased stratum corneum (SC lipid fluidization and altered protein conformation. Skin permeability experiments showed that the free unencapsulated drug in the cerosomal formulations caused significant increase in drug permeation across the skin (p < 0.01. Low skin permeability of drug from the other lipid suspensions could be due to the entrapment of diclofenac within these vesicles which decreased the solubility of the hydrophilic drug in the skin lipids and the partition coefficient of the drug from these vesicles into the SC. Conclusion: Optimal drug entrapment in vesicles or alteration of the skin structure may not necessarily enhance the permeation of hydrophilic drugs across the human skin. These lipid vesicles may be further developed into carriers of both hydrophilic and hydrophobic drugs for topical and transdermal delivery, respectively.

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

    Science.gov (United States)

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

    2017-03-01

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

  6. Polymerized planar suspended lipid bilayers for single ion channel recordings: comparison of several dienoyl lipids.

    Science.gov (United States)

    Heitz, Benjamin A; Xu, Juhua; Jones, Ian W; Keogh, John P; Comi, Troy J; Hall, Henry K; Aspinwall, Craig A; Saavedra, S Scott

    2011-03-01

    The stabilization of suspended planar lipid membranes, or black lipid membranes (BLMs), through polymerization of mono- and bis-functionalized dienoyl lipids was investigated. Electrical properties, including capacitance, conductance, and dielectric breakdown voltage, were determined for BLMs composed of mono-DenPC, bis-DenPC, mono-SorbPC, and bis-SorbPC both prior to and following photopolymerization, with diphytanoyl phosphocholine (DPhPC) serving as a control. Poly(lipid) BLMs exhibited significantly longer lifetimes and increased the stability of air-water transfers. BLM stability followed the order bis-DenPC > mono-DenPC ≈ mono-SorbPC > bis-SorbPC. The conductance of bis-SorbPC BLMs was significantly higher than that of the other lipids, which is attributed to a high density of hydrophilic pores, resulting in relatively unstable membranes. The use of poly(lipid) BLMs as matrices for supporting the activity of an ion channel protein (IC) was explored using α-hemolysin (α-HL), a model IC. Characteristic i-V plots of α-HL were maintained following photopolymerization of bis-DenPC, mono-DenPC, and mono-SorbPC, demonstrating the utility of these materials for preparing more durable BLMs for single-channel recordings of reconstituted ICs.

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

    Science.gov (United States)

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

    2014-02-25

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

  8. Lipid Vesicles for the Skin Delivery of Diclofenac: Cerosomes vs. Other Lipid Suspensions

    Science.gov (United States)

    Fathi-Azarbayjani, Anahita; Ng, Kai Xin; Chan, Yew Weng; Chan, Sui Yung

    2015-01-01

    Purpose: Lipid suspensions as drug carriers, including conventional liposomes, ethosomes, transferosomes, proniosomes, niosomes, PEG-PPG-PEG niosomes and stratum corneum liposomes (cerosomes), were formulated and compared. Methods: Lipid vesicles were formulated and assessed with regards to enhancement of skin permeation of diclofenac and stability profiles of the formulations. Formulation-induced changes of the biophysical structure of excised human skin were monitored using the Fourier transform infrared spectroscopy. Results: The stability profiles of these suspensions over 12 weeks did not show any significant drug leakage from the vesicles of interest (p > 0.05). FTIR observations indicated that the vesicles increased stratum corneum (SC) lipid fluidization and altered protein conformation. Skin permeability experiments showed that the free unencapsulated drug in the cerosomal formulations caused significant increase in drug permeation across the skin (p < 0.01). Low skin permeability of drug from the other lipid suspensions could be due to the entrapment of diclofenac within these vesicles which decreased the solubility of the hydrophilic drug in the skin lipids and the partition coefficient of the drug from these vesicles into the SC. Conclusion: Optimal drug entrapment in vesicles or alteration of the skin structure may not necessarily enhance the permeation of hydrophilic drugs across the human skin. These lipid vesicles may be further developed into carriers of both hydrophilic and hydrophobic drugs for topical and transdermal delivery, respectively. PMID:25789216

  9. Characterization of Microalgal Lipids for Optimization of Biofuels

    Science.gov (United States)

    2014-05-09

    ABSTRACT This research project investigates the lipid content and composition of extremophilic and estuarine microalgae under different growth...extremophilic and estuarine microalgae under different growth conditions for suitability as biofuel feedstocks. Fatty acid content and lipid...estuarine microalgae for suitability as biofuel feedstocks and assess the impact of varying growth conditions on lipid content and composition

  10. Microemulsion extrusion technique : a new method to produce lipid nanoparticles

    NARCIS (Netherlands)

    de Jesus, Marcelo Bispo; Radaic, Allan; Zuhorn, Inge S.; de Paula, Eneida

    2013-01-01

    Solid lipid nanoparticles (SLN) and nano-structured lipid carriers (NLC) have been intensively investigated for different applications, including their use as drug and gene delivery systems. Different techniques have been employed to produce lipid nanoparticles, of which high pressure homogenization

  11. Tocopherol isoforms in parenteral lipid emulsions and neutrophil activation.

    NARCIS (Netherlands)

    Wanten, G.J.A.; Beunk, J.; Naber, A.H.J.; Swinkels, D.W.

    2002-01-01

    BACKGROUND AND AIMS: Tocopherol is a lipid-soluble anti-oxidant that exists in several isoforms. Patients on total parenteral nutrition depend on lipid emulsions for their tocopherol intake. In the present study, we analysed the content of tocopherol isoforms in various lipid emulsions. We also

  12. Microemulsion extrusion technique : a new method to produce lipid nanoparticles

    NARCIS (Netherlands)

    de Jesus, Marcelo Bispo; Radaic, Allan; Zuhorn, Inge S.; de Paula, Eneida

    2013-01-01

    Solid lipid nanoparticles (SLN) and nano-structured lipid carriers (NLC) have been intensively investigated for different applications, including their use as drug and gene delivery systems. Different techniques have been employed to produce lipid nanoparticles, of which high pressure homogenization

  13. Lipids from yeasts and fungi: Tomorrow's source of Biodiesel?

    NARCIS (Netherlands)

    Meeuwse, P.; Sanders, J.P.M.; Tramper, J.; Rinzema, A.

    2013-01-01

    In the search for new transport fuels from renewable resources, biodiesel from microbial lipids comes into view. We have evaluated the lipid yield and energy use of a process for production of biodiesel from agricultural waste using lipid-accumulating yeast and fungi. We included different

  14. Effective lipid extraction from algae cultures using switchable solvents

    NARCIS (Netherlands)

    Samori, Chiara; Lopez Barreiro, Diego; Vet, Robin; Pezzolesi, Laura; Brilman, Derk W.F. (Wim); Galletti, Paola; Tagliavini, Emilio

    2013-01-01

    A new procedure based on switchable polarity solvents (SPS) was proposed for lipid extraction of wet algal samples or cultures, thereby circumventing the need for an energy intensive drying step and facilitating easy recovery of the lipids from the extraction liquid. Lipids were extracted by using N

  15. Lipid Oxidation Promotes Acrylamide Formation in Fat-Rich Systems

    NARCIS (Netherlands)

    Capuano, Edoardo

    2016-01-01

    Evidence from model systems suggests that lipid oxidation can contribute to acrylamide (AA) formation through the generation of secondary lipid oxidation carbonyl products, mainly aldehydes, which are able to degrade asparagine to AA. In this respect, factors affecting the extent of lipid

  16. Lipid Oxidation Promotes Acrylamide Formation in Fat-Rich Systems

    NARCIS (Netherlands)

    Capuano, Edoardo

    2016-01-01

    Evidence from model systems suggests that lipid oxidation can contribute to acrylamide (AA) formation through the generation of secondary lipid oxidation carbonyl products, mainly aldehydes, which are able to degrade asparagine to AA. In this respect, factors affecting the extent of lipid oxidati

  17. Lipid Oxidation Promotes Acrylamide Formation in Fat-Rich Systems

    NARCIS (Netherlands)

    Capuano, Edoardo

    2016-01-01

    Evidence from model systems suggests that lipid oxidation can contribute to acrylamide (AA) formation through the generation of secondary lipid oxidation carbonyl products, mainly aldehydes, which are able to degrade asparagine to AA. In this respect, factors affecting the extent of lipid oxidati

  18. Final Report: 17th international Symposium on Plant Lipids

    Energy Technology Data Exchange (ETDEWEB)

    Christoph Benning

    2007-03-07

    This meeting covered several emerging areas in the plant lipid field such as the biosynthesis of cuticle components, interorganelle lipid trafficking, the regulation of lipid homeostasis, and the utilization of algal models. Stimulating new insights were provided not only based on research reports based on plant models, but also due to several excellent talks by experts from the yeast field.

  19. Sphingolipid management by an orchestra of lipid transfer proteins

    NARCIS (Netherlands)

    Neumann, S.; van Meer, G.

    2008-01-01

    The various membranes in eukaryotic cells have unique lipid compositions. Despite important discoveries in lipid research over recent decades, the basic principles by which cells define their membrane compositions are essentially unknown. Cells must sense the concentration of each lipid, integrate s

  20. Effective lipid extraction from algae cultures using switchable solvents

    NARCIS (Netherlands)

    Samori, Chiara; Lopez Barreiro, D.; Vet, Robin; Pezzolesi, Laura; Brilman, Derk Willem Frederik; Galletti, Paola; Tagliavini, Emilio

    2013-01-01

    A new procedure based on switchable polarity solvents (SPS) was proposed for lipid extraction of wet algal samples or cultures, thereby circumventing the need for an energy intensive drying step and facilitating easy recovery of the lipids from the extraction liquid. Lipids were extracted by using

  1. Radioinduced lipid peroxidation: factors determining the oxidizability of lipids; De la peroxydation lipidique radioinduite: les facteurs determinant l'oxydabilite des lipides

    Energy Technology Data Exchange (ETDEWEB)

    Remita, S. [Lab. de Chimie et Biochimie Pharmacologiques et Toxicologiques, Groupe de Chimie-Physique, Unite Mixte de Recherche, Centre National de la Recherche Scientifique, Univ. Paris (France)

    2001-02-01

    Lipids are the essential components of cell membranes and lipoproteins. Their peroxidation plays an important role in numerous pathologies in which oxidative stress is involved. Lipid peroxidation occurs through a chain reaction that contributes to membrane damage in cells. It results in the conversion of fatty acids to polar hydroperoxides and leads to the breakdown or malfunction of the membrane. Lipids are amphiphilic molecules that aggregate in aqueous solutions into micelles and liposoms. The effect of this structural organization is significant in studies of radiation-induced peroxidation damage in highly ordered biological systems such as biological membranes. In this paper, a synthesis of the data concerning radioinduced lipid peroxidation is completed by an original review of the different parameters that determine lipid oxidizability. In addition, the influence of lipid aggregation and the effect of molecular packing are discussed. (author)

  2. Unusual polar lipids of Micrococcus radiodurans strain Sark.

    Science.gov (United States)

    Thompson, B G; Anderson, R; Murray, R G

    1980-12-01

    The polar lipids of Micrococcus radiodurans strain Sark appear to be unique in that common bacterial phospholipids such as phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, and phosphatidylinositol are absent. Of the 13 polar lipids detected, 5 contain phosphorus and carbohydrate, 4 contain carbohydrate and no phosphorus, and 1 contains phosphorus as well as sulfur. None of the polar lipids contain free choline or amino groups and none are sensitive to phospholipases C or D. Of eight selected polar lipids tested, all were found to be labile to milk alkali, suggesting the presence of ester linkages. It is suggested that the unusual lipid profile of M. radiodurans strain Sark may be useful in taxonomic considerations.

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

    Science.gov (United States)

    Baowan, Duangkamon; Thamwattana, Ngamta

    2014-02-01

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

  4. The Ins and Outs of Lipid Flip-Flop.

    Science.gov (United States)

    Allhusen, John S; Conboy, John C

    2017-01-17

    Our current view of cellular membranes centers on the fluid-mosaic model, which envisions the cellular membrane as a "liquidlike" bilayer of lipids, cholesterol, and proteins that freely diffuse in two dimensions. In stark contrast, the exchange of materials between the leaflets of a bilayer was presumed to be prohibited by the large enthalpic barrier associated with translocating hydrophilic materials, such as a charged lipid headgroup, through the hydrophobic membrane core. This static picture with regard to lipid translocation (or "flip-flop" as it is affectionately known) has been a long-held belief in the study of membrane dynamics. The current accepted membrane model invokes specific protein flippase (inward moving), floppase (outward moving), and scramblase (bidirectional) enzymes that assist in the movement of lipids between the leaflets of cellular membranes. The low rate of protein-free lipid flip-flop has also been a cornerstone of our understanding of the bilateral organization of cellular membrane components, specifically the asymmetric distribution of lipid species found in the luminal and extracellular leaflets of the plasma membrane of eukaryotic cells. Much of the previous work contributing to our current understanding of lipid flip-flop has utilized fluorescent- or spin-labeled lipids. However, there is growing evidence that these lipid probes do not accurately convey the dynamics and thermodynamics of native (unlabeled) lipid motion. This Account summarizes our research efforts directed toward developing a deep physical and chemical understanding of protein-free lipid flip-flop in phospholipid membrane models using sum-frequency vibrational spectroscopy (SFVS). Our use of SFVS enables the direct measurement of native lipid flip-flop in model membranes. In particular, we have explored the kinetic rates and activation thermodynamics of lipid translocation as a means of deciphering the underlying chemical and physical directors governing this

  5. A quick colorimetric method for total lipid quantification in microalgae.

    Science.gov (United States)

    Byreddy, Avinesh R; Gupta, Adarsha; Barrow, Colin J; Puri, Munish

    2016-06-01

    Discovering microalgae with high lipid productivity are among the key milestones for achieving sustainable biodiesel production. Current methods of lipid quantification are time intensive and costly. A rapid colorimetric method based on sulfo-phospho-vanillin (SPV) reaction was developed for the quantification of microbial lipids to facilitate screening for lipid producing microalgae. This method was successfully tested on marine thraustochytrid strains and vegetable oils. The colorimetric method results correlated well with gravimetric method estimates. The new method was less time consuming than gravimetric analysis and is quantitative for lipid determination, even in the presence of carbohydrates, proteins and glycerol.

  6. Multiscale molecular modeling of tertiary supported lipid bilayers

    Science.gov (United States)

    Ranz, Holden T.; Faller, Roland

    2015-08-01

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

  7. Lipid Rafts: Keys to Sperm Maturation, Fertilization, and Early Embryogenesis

    Directory of Open Access Journals (Sweden)

    Natsuko Kawano

    2011-01-01

    Full Text Available Cell membranes are composed of many different lipids and protein receptors, which are important for regulating intracellular functions and cell signaling. To orchestrate these activities, the cell membrane is compartmentalized into microdomains that are stably or transiently formed. These compartments are called “lipid rafts”. In gamete cells that lack gene transcription, distribution of lipids and proteins on these lipid rafts is focused during changes in their structure and functions such as starting flagella movement and membrane fusion. In this paper, we describe the role of lipid rafts in gamete maturation, fertilization, and early embryogenesis.

  8. Exercise Intensity Modulation of Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Fábio S. Lira

    2012-01-01

    Full Text Available Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL, ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge.

  9. Solid lipid nanoparticles: A drug carrier system

    Directory of Open Access Journals (Sweden)

    Rashmi R Kokardekar

    2011-01-01

    Full Text Available Solid lipid nanoparticles (SLN are a type of nanoparticles. They are submicron colloidal carriers which are composed of physiological lipids, dispersed in water or in aqueous surfactant solutions. SLN have wide range of advantages over other types of nanoparticles. These include availability of large-scale production methods and no signs of cytotoxicity, which are main hindrances in the application of other types of nanoparticles. Hot and cold homogenization techniques are mainly employed for its production. They are mainly evaluated on the basis of their drug release profile and particle internal structure. The products based on SLN are under development. They have a very wide range of applications in cosmetics and pharmaceuticals. They can be applied for any purpose, for which nanoparticles have a distinct advantage. Thus, SLN can be used extensively as an alternative to the existing drug carrier systems, providing more flexibility with respect to the area of applications and also aspects for commercialization.

  10. The role of lipids in mechanosensation.

    Science.gov (United States)

    Pliotas, Christos; Dahl, A Caroline E; Rasmussen, Tim; Mahendran, Kozhinjampara R; Smith, Terry K; Marius, Phedra; Gault, Joseph; Banda, Thandiwe; Rasmussen, Akiko; Miller, Samantha; Robinson, Carol V; Bayley, Hagan; Sansom, Mark S P; Booth, Ian R; Naismith, James H

    2015-12-01

    The ability of proteins to sense membrane tension is pervasive in biology. A higher-resolution structure of the Escherichia coli small-conductance mechanosensitive channel MscS identifies alkyl chains inside pockets formed by the transmembrane helices (TMs). Purified MscS contains E. coli lipids, and fluorescence quenching demonstrates that phospholipid acyl chains exchange between bilayer and TM pockets. Molecular dynamics and biophysical analyses show that the volume of the pockets and thus the number of lipid acyl chains within them decreases upon channel opening. Phospholipids with one acyl chain per head group (lysolipids) displace normal phospholipids (with two acyl chains) from MscS pockets and trigger channel opening. We propose that the extent of acyl-chain interdigitation in these pockets determines the conformation of MscS. When interdigitation is perturbed by increased membrane tension or by lysolipids, the closed state becomes unstable, and the channel gates.

  11. The Structure of Cholesterol in Lipid Rafts

    CERN Document Server

    Toppozini, Laura; Armstrong, Clare L; Yamani, Zahra; Kucerka, Norbert; Schmid, Friederike; Rheinstaedter, Maikel C

    2014-01-01

    Rafts, or functional domains, are transient nano- or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking and lipid/protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short-lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules we observe raft-like structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to orderin...

  12. Ageing mechanisms and associated lipid changes.

    Science.gov (United States)

    Kolovou, Genovefa; Katsiki, Niki; Pavlidis, Antonis; Bilianou, Helen; Goumas, George; Mikhailidis, Dimitri P

    2014-01-01

    Ageing is related to slowdown/breakdown of the somatotropic axis (i.e. the somatopause) leading to many physiological changes. The somatopause is accompanied by DNA and other macromolecule damage, and is characterized by a progressive decline in vitality and tissue function. We still do not have a definitive understanding of the mechanism( s) of ageing. Several overlapping theories have been proposed such as: 1) The free radical theory, 2) Mitochondrial Ageing, 3) The Glycation Theory, 4) Protein Damage and Maintenance in Ageing, and, 5) DNA Damage and Repair. Furthermore, several models of ageing were introduced such as genetically programmed senescence, telomere shortening, genomic instability, heterochromatin loss, altered epigenetic patterns and long lived cells. There are certain lipid modifications associated with the somatopause, characterized mainly by an increase in total cholesterol and triglyceride levels in both genders. In this review we consider the mechanisms of ageing and the associated changes in lipid metabolism according to gender.

  13. Membrane lipids and the origin of life

    Science.gov (United States)

    Oro, J.; Holzer, G.; Rao, M.; Tornabene, T. G.

    1981-01-01

    The current state of knowledge regarding the development of biological systems is briefly reviewed. At a crucial stage concerning the evolution of such systems, the mechanisms leading to more complex structures must have evolved within the confines of a protected microenvironment, similar to those provided by the contemporary cell membranes. The major components found normally in biomembranes are phospholipids. The structure of the biomembrane is examined, and attention is given to questions concerning the availability of the structural components which are necessary in the formation of primitive lipid membranes. Two approaches regarding the study of protomembranes are discussed. The probability of obtaining ether lipids under prebiotic conditions is considered, taking into account the formation of cyclic and acyclic isoprenoids by the irradiation of isoprene with UV.

  14. Computationally efficient prediction of area per lipid

    DEFF Research Database (Denmark)

    Chaban, Vitaly V.

    2014-01-01

    Area per lipid (APL) is an important property of biological and artificial membranes. Newly constructed bilayers are characterized by their APL and newly elaborated force fields must reproduce APL. Computer simulations of APL are very expensive due to slow conformational dynamics. The simulated d....... Thus, sampling times to predict accurate APL are reduced by a factor of 10. (C) 2014 Elsevier B.V. All rights reserved....

  15. Lipid Metabolism during Infection and Endotoxemia

    Science.gov (United States)

    1981-01-01

    membranes, emulsifying agents, and precursors for the synthesis of sterols, four vitamins and prostaglandins. Since lipids are organic compounds that are...only a brief description of the subject will be covered in this chapter. Ordinary dietary fats are emulsified by the bile secretions (conjugated bile...values (Lees et al., 1972). ZIn general, serum lecithin tended to be elevated in most bacterial infections in man and experimental animals (Beisel and

  16. Simulation Studies of Stratum Corneum Lipid Mixtures

    OpenAIRE

    Das, C; Noro, MG; Olmsted, PD

    2009-01-01

    We present atomistic molecular dynamics results for fully hydrated bilayers composed of ceramide NS-24:0, free fatty acid 24:0 and cholesterol, to address the effect of the different components in the stratum corneum (the outermost layer of skin) lipid matrix on its structural properties. Bilayers containing ceramide molecules show higher in-plane density and hence lower rate of passive transport compared to phospholipid bilayers. At physiological temperatures, for all composition ratios expl...

  17. Drug release mechanisms of compressed lipid implants.

    Science.gov (United States)

    Kreye, F; Siepmann, F; Siepmann, J

    2011-02-14

    The aim of this study was to elucidate the mass transport mechanisms controlling drug release from compressed lipid implants. The latter steadily gain in importance as parenteral controlled release dosage forms, especially for acid-labile drugs. A variety of lipid powders were blended with theophylline and propranolol hydrochloride as sparingly and freely water-soluble model drugs. Cylindrical implants were prepared by direct compression and thoroughly characterized before and after exposure to phosphate buffer pH 7.4. Based on the experimental results, an appropriate mathematical theory was identified in order to quantitatively describe the resulting drug release patterns. Importantly, broad release spectra and release periods ranging from 1 d to several weeks could easily be achieved by varying the type of lipid, irrespective of the type of drug. Interestingly, diffusion with constant diffusivities was found to be the dominant mass transport mechanism, if the amount of water within the implant was sufficient to dissolve all of the drug. In these cases an analytical solution of Fick's second law could successfully describe the experimentally measured theophylline and propranolol hydrochloride release profiles, even if varying formulation and processing parameters, e.g. the type of lipid, initial drug loading, drug particles size as well as compression force and time. However, based on the available data it was not possible to distinguish between drug diffusion control and water diffusion control. The obtained new knowledge can nevertheless significantly help facilitating the optimization of this type of advanced drug delivery systems, in particular if long release periods are targeted, which require time consuming experimental trials.

  18. Stabilization of Lipid Membranes With Dendritic Polymers

    Science.gov (United States)

    2004-12-01

    monolayer coverage was possible using the spin - coating procedure for concentrations of 10-5 w/w dendrimers in solution or lower. Higher coverages...The fluorescence intensity increased as coverage time before spin coating increased and as the dendrimer solution concentration increased (Fig...enhanced the adsorption of lipids to the substrate. Figure 7: Fluorescence intensity as a function of the PAMAM concentration used in the spin

  19. Collection and conversion of algal lipid

    Science.gov (United States)

    Lin, Ching-Chieh

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

  20. Rosiglitazone and Fenofibrate Additive Effects on Lipids

    Science.gov (United States)

    2011-10-01

    fasting TG, high-density lipoprotein cholesterol ( HDL -C), LDL -C, and plasma apolipoproteins A-I, A-II, and C-III level were compared after 12 weeks of...2 diabetic patients, the mean HDL -C increased by 6% and TG by 2%. The increase in the LDL -C concentration (9%) was accompanied by a shift in small...transaminases, fasting lipid profile, apolipoproteins, HDL size, LDL size, and statistical differ- ence from baseline. At this visit, subjects were

  1. Lipid raft: A floating island of death or survival

    Energy Technology Data Exchange (ETDEWEB)

    George, Kimberly S. [Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701 (United States); Department of Chemistry, Marietta College, Marietta, OH 45750 (United States); Wu, Shiyong, E-mail: wus1@ohio.edu [Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701 (United States)

    2012-03-15

    Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, as a major component of lipid rafts, is critical for the formation and configuration of lipid raft microdomains, which provide signaling platforms capable of activating both pro-apoptotic and anti-apoptotic signaling pathways. A change of cholesterol level can result in lipid raft disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels. Several anti-cancer drugs are able to suppress growth and induce apoptosis of tumor cells through alteration of lipid raft contents via disrupting lipid raft integrity. -- Highlights: ► The role of lipid rafts in apoptosis ► The pro- and anti-apoptotic effects of lipid raft disruption ► Cancer treatments targeting lipid rafts.

  2. Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production

    Directory of Open Access Journals (Sweden)

    Kimberly C. Lemmer

    2017-05-01

    Full Text Available Lipids from microbes offer a promising source of renewable alternatives to petroleum-derived compounds. In particular, oleaginous microbes are of interest because they accumulate a large fraction of their biomass as lipids. In this study, we analyzed genetic changes that alter lipid accumulation in Rhodobacter sphaeroides. By screening an R. sphaeroides Tn5 mutant library for insertions that increased fatty acid content, we identified 10 high-lipid (HL mutants for further characterization. These HL mutants exhibited increased sensitivity to drugs that target the bacterial cell envelope and changes in shape, and some had the ability to secrete lipids, with two HL mutants accumulating ~60% of their total lipids extracellularly. When one of the highest-lipid-secreting strains was grown in a fed-batch bioreactor, its lipid content was comparable to that of oleaginous microbes, with the majority of the lipids secreted into the medium. Based on the properties of these HL mutants, we conclude that alterations of the cell envelope are a previously unreported approach to increase microbial lipid production. We also propose that this approach may be combined with knowledge about biosynthetic pathways, in this or other microbes, to increase production of lipids and other chemicals.

  3. Preparation of artificial plasma membrane mimicking vesicles with lipid asymmetry.

    Directory of Open Access Journals (Sweden)

    Qingqing Lin

    Full Text Available Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM and/or phosphatidylcholine (PC outside/phosphatidylethanolamine (PE and phosphatidylserine (PS inside, and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes "artificial plasma membrane mimicking" ("PMm" vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.

  4. Preparation of artificial plasma membrane mimicking vesicles with lipid asymmetry.

    Science.gov (United States)

    Lin, Qingqing; London, Erwin

    2014-01-01

    Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM) and/or phosphatidylcholine (PC) outside/phosphatidylethanolamine (PE) and phosphatidylserine (PS) inside), and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes "artificial plasma membrane mimicking" ("PMm") vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.

  5. A systematic survey of lipids across mouse tissues

    Science.gov (United States)

    Jain, Mohit; Ngoy, Soeun; Sheth, Sunil A.; Swanson, Raymond A.; Rhee, Eugene P.; Liao, Ronglih; Clish, Clary B.; Mootha, Vamsi K.

    2014-01-01

    Lipids are a diverse collection of macromolecules essential for normal physiology, but the tissue distribution and function for many individual lipid species remain unclear. Here, we report a mass spectrometry survey of lipid abundance across 18 mouse tissues, detecting ∼1,000 mass spectrometry features, of which we identify 179 lipids from the glycerolipids, glycerophospholipids, lysophospholipids, acylcarnitines, sphingolipids, and cholesteryl ester classes. Our data reveal tissue-specific organization of lipids and can be used to generate testable hypotheses. For example, our data indicate that circulating triglycerides positively and negatively associated with future diabetes in humans are enriched in mouse adipose tissue and liver, respectively, raising hypotheses regarding the tissue origins of these diabetes-associated lipids. We also integrate our tissue lipid data with gene expression profiles to predict a number of substrates of lipid-metabolizing enzymes, highlighting choline phosphotransferases and sterol O-acyltransferases. Finally, we identify several tissue-specific lipids not present in plasma under normal conditions that may be of interest as biomarkers of tissue injury, and we show that two of these lipids are released into blood following ischemic brain injury in mice. This resource complements existing compendia of tissue gene expression and may be useful for integrative physiology and lipid biology. PMID:24518676

  6. Antimicrobial role of human meibomian lipids at the ocular surface.

    Science.gov (United States)

    Mudgil, Poonam

    2014-10-14

    Human meibomian lipids form the outermost lipid layer of the tear film and serve many important functions to maintain its integrity. Although not investigated earlier, these lipids may have antimicrobial properties that help in strengthening the innate host defense of tears at the ocular surface. The aim of this study was to investigate the antimicrobial role of human meibomian lipids. Ocular pathogenic bacteria, Staphylococcus aureus 31, Pseudomonas aeruginosa 19, Pseudomonas aeruginosa 20, and Serratia marcescens 35, were grown in the presence and absence of human meibomian lipids in an artificial tear solution at the physiological temperature. Viable counts were obtained to note the number of bacteria surviving the treatment with meibomian lipids. Bacterial cells were imaged using scanning electron microscopy to observe the damages caused by meibomian lipids. Viable count results showed that in the presence of meibomian lipids, growth of all bacteria was considerably lower. Scanning electron microscopy showed that meibomian lipids caused extensive cellular damage to bacteria as manifested in smaller size, loss of aggregation, abnormal phenotype, cellular distortion, damaged cell wall, and cell lysis. This is the first-ever report of the antimicrobial role of human meibomian lipids. These lipids possess antimicrobial properties against both Gram-positive and Gram-negative bacteria and are involved in the innate host defense of tears in protecting the ocular surface against microbial pathogens. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  7. Lipid Mediators in the Resolution of Inflammation

    Science.gov (United States)

    Serhan, Charles N.; Chiang, Nan; Dalli, Jesmond; Levy, Bruce D.

    2015-01-01

    Mounting of the acute inflammatory response is crucial for host defense and pivotal to the development of chronic inflammation, fibrosis, or abscess formation versus the protective response and the need of the host tissues to return to homeostasis. Within self-limited acute inflammatory exudates, novel families of lipid mediators are identified, named resolvins (Rv), protectins, and maresins, which actively stimulate cardinal signs of resolution, namely, cessation of leukocytic infiltration, counterregulation of proinflammatory mediators, and the uptake of apoptotic neutrophils and cellular debris. The biosynthesis of these resolution-phase mediators in sensu stricto is initiated during lipid-mediator class switching, in which the classic initiators of acute inflammation, prostaglandins and leukotrienes (LTs), switch to produce specialized proresolving mediators (SPMs). In this work, we review recent evidence on the structure and functional roles of these novel lipid mediators of resolution. Together, these show that leukocyte trafficking and temporal spatial signals govern the resolution of self-limited inflammation and stimulate homeostasis. PMID:25359497

  8. Phytic Acid Inhibits Lipid Peroxidation In Vitro

    Directory of Open Access Journals (Sweden)

    Alicja Zajdel

    2013-01-01

    Full Text Available Phytic acid (PA has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II/ascorbate-induced peroxidation, as well as Fe(II/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II/ascorbate. The observed inhibitory effect of PA on Fe(II/ascorbate-induced lipid peroxidation was lower (10–20% compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II/ascorbate-induced peroxidation. In the absence of Fe(II/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.

  9. Phytic acid inhibits lipid peroxidation in vitro.

    Science.gov (United States)

    Zajdel, Alicja; Wilczok, Adam; Węglarz, Ludmiła; Dzierżewicz, Zofia

    2013-01-01

    Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II)/ascorbate. The observed inhibitory effect of PA on Fe(II)/ascorbate-induced lipid peroxidation was lower (10-20%) compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II)/ascorbate-induced peroxidation. In the absence of Fe(II)/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM) significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.

  10. Viscoelastic deformation of lipid bilayer vesicles†

    Science.gov (United States)

    Wu, Shao-Hua; Sankhagowit, Shalene; Biswas, Roshni; Wu, Shuyang; Povinelli, Michelle L.

    2015-01-01

    Lipid bilayers form the boundaries of the cell and its organelles. Many physiological processes, such as cell movement and division, involve bending and folding of the bilayer at high curvatures. Currently, bending of the bilayer is treated as an elastic deformation, such that its stress-strain response is independent of the rate at which bending strain is applied. We present here the first direct measurement of viscoelastic response in a lipid bilayer vesicle. We used a dual-beam optical trap (DBOT) to stretch 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) giant unilamellar vesicles (GUVs). Upon application of a step optical force, the vesicle membrane deforms in two regimes: a fast, instantaneous area increase, followed by a much slower stretching to an eventual plateau deformation. From measurements of dozens of GUVs, the average time constant of the slower stretching response was 0.225 ± 0.033 s (standard deviation, SD). Increasing the fluid viscosity did not affect the observed time constant. We performed a set of experiments to rule out heating by laser absorption as a cause of the transient behavior. Thus, we demonstrate here that the bending deformation of lipid bilayer membranes should be treated as viscoelastic. PMID:26268612

  11. Viscoelastic deformation of lipid bilayer vesicles.

    Science.gov (United States)

    Wu, Shao-Hua; Sankhagowit, Shalene; Biswas, Roshni; Wu, Shuyang; Povinelli, Michelle L; Malmstadt, Noah

    2015-10-07

    Lipid bilayers form the boundaries of the cell and its organelles. Many physiological processes, such as cell movement and division, involve bending and folding of the bilayer at high curvatures. Currently, bending of the bilayer is treated as an elastic deformation, such that its stress-strain response is independent of the rate at which bending strain is applied. We present here the first direct measurement of viscoelastic response in a lipid bilayer vesicle. We used a dual-beam optical trap (DBOT) to stretch 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) giant unilamellar vesicles (GUVs). Upon application of a step optical force, the vesicle membrane deforms in two regimes: a fast, instantaneous area increase, followed by a much slower stretching to an eventual plateau deformation. From measurements of dozens of GUVs, the average time constant of the slower stretching response was 0.225 ± 0.033 s (standard deviation, SD). Increasing the fluid viscosity did not affect the observed time constant. We performed a set of experiments to rule out heating by laser absorption as a cause of the transient behavior. Thus, we demonstrate here that the bending deformation of lipid bilayer membranes should be treated as viscoelastic.

  12. Roles of the Lipid Metabolism in Hepatic Stellate Cells Activation

    Institute of Scientific and Technical Information of China (English)

    Xin-yan Jing; Xue-feng Yang; Kai Qing; Yan Ou-Yang

    2013-01-01

    The lipids present in hepatic stellate cells (HSCs) lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80%of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracellular matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.

  13. Lipids in cell biology: how can we understand them better?

    Science.gov (United States)

    Muro, Eleonora; Atilla-Gokcumen, G. Ekin; Eggert, Ulrike S.

    2014-01-01

    Lipids are a major class of biological molecules and play many key roles in different processes. The diversity of lipids is on the same order of magnitude as that of proteins: cells express tens of thousands of different lipids and hundreds of proteins to regulate their metabolism and transport. Despite their clear importance and essential functions, lipids have not been as well studied as proteins. We discuss here some of the reasons why it has been challenging to study lipids and outline technological developments that are allowing us to begin lifting lipids out of their “Cinderella” status. We focus on recent advances in lipid identification, visualization, and investigation of their biophysics and perturbations and suggest that the field has sufficiently advanced to encourage broader investigation into these intriguing molecules. PMID:24925915

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

    Science.gov (United States)

    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

  15. Design of lipid microparticle dispersions based on the physicochemical properties of the lipid and aqueous phase.

    Science.gov (United States)

    Lauterbach, Andreas; Müller-Goymann, Christel C

    2015-10-15

    Lipid microparticle (LMP) dispersions may be utilized as novel pharmaceutical dosage forms for different administration routes. The particle size and particle size distribution of the LMPs can be classified to the most crucial specifications for therapeutical and research applications. The size parameters can be adjusted via the physicochemical properties of the inner lipid and the outer aqueous phase. In the present study, ten different solid lipids with incorporated lecithin and four concentrations of the surfactant poloxamer 407 (P407) were utilized for LMP dispersion preparation. Physicochemical properties of the bulk and dispersed lipid matrices as well as features of the P407 solutions were determined. Correlations between the mean particle size (mean) of the LMPs and the span as parameter for the particle size distribution as responses were identified by plotting against the measured physicochemical parameters. Most significant linear correlations were found between the mean and the micellization onset temperature (Tmicell) in the parent solution and the dynamic viscosity of the emulsifier solution at 25 °C and between the span and the Tmicell in the LMP dispersion. Consequently, P407 micelles as a reservoir for surfactant monomers and the overall viscosity as a separator between newly-formed lipid droplets are fundamental stabilizing parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  17. Brain lipids in rats fed a diet supplemented with hen eggs of modified lipid content

    Directory of Open Access Journals (Sweden)

    Hodžić Aida

    2012-01-01

    Full Text Available The aim of this study was to research the impact of a diet supplemented with egg yolks of modified content, having in mind the type of fat added to the laying hens diet, on the brain lipids and their fatty acid composition in rats. During four weeks of the experiment, 64 Wistar rats, divided into four groups of 16 animals each (eight animals of both sexes, were fed the commercial rat feed (group C, or the feed that contained 70% of the commercial rat feed and 30% of freshly boiled yolks from the eggs originating from laying hens fed with 3% fish oil (group F, 3% palm olein (group P or 3% lard (group L. Concentration and content of total lipids and total cholesterol, as well as the fatty-acid composition of the total brain lipids were determined in the lipid extracts of the rats brains. Under unfavourable conditions, which in our case could be high dietary intake of the total fat due to egg yolk addition, the amount of total fat in the brain tissue or the mass of the organ itself can be changed. Applied dietary treatments could also influence the level of de novo synthesis of total cholesterol in the rat brain. High dietary fat intake, as well as the fat quality regarding its fatty acid composition, appear to be able to significantly influence the fatty acid profile of the total brain lipids in adult rats, whereas the level and quality of the changes also depend on sex.

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

    Directory of Open Access Journals (Sweden)

    Zehra Kahveci

    2014-03-01

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

  19. Multiscale Modeling of Supported Lipid Bilayers

    Science.gov (United States)

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

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

  20. Maternal mid-pregnancy lipids and birthweight

    Science.gov (United States)

    Mudd, Lanay M.; Holzman, Claudia B.; Evans, Rhobert W.

    2015-01-01

    Objective To describe associations among maternal lipids and birthweight and to determine whether pre-pregnancy body mass index (BMI) modifies these associations. Design Cohort Study. Setting Multiple communities in Michigan, USA. Population Participants were a sub-cohort of women from the multi-community Pregnancy Outcomes and Community Health (POUCH) study (1998–2004). Methods Maternal total cholesterol, high-density lipoprotein (HDLc), and low-density lipoprotein (LDLc) cholesterol, and triglycerides were assessed at 16–27 weeks’ gestation. Women were classified as having normal (<25 kg/m2) or overweight/obese (≥25 kg/m2) pre-pregnancy BMI. Main Outcome Measures Sex- and gestational-age-specific BWz-score. Results Regression models examined associations among lipids (low: 1st quartile, referent: middle quartiles, high: 4th quartile) and BWz-scores for the total sample and stratified by pre-pregnancy BMI. In adjusted analyses (n=1207), low HDLc was associated with lower BWz-score (β=−0.23, 95%CI: −0.40 to −0.06) while high triglycerides was associated with higher BWz-score (β=0.23, 95%CI: 0.06–0.41). Once stratified by pre-pregnancy BMI, low total cholesterol was associated with lower BWz-score in normal BMI women (β= −0.25, 95%CI: −0.47 to −0.03), while in overweight/obese BMI women, high HDLc was inversely (β= −0.29, 95%CI: −0.54 to −0.04) and high triglycerides was directly associated with BWz-score (β=0.32, 95%CI: 0.07– 0.54). Removing women with gestational diabetes/hypertensive disorders did not alter the results. Conclusions The associations among maternal lipids and BWz-score vary by lipid measure and pre-pregnancy BMI. Future work should examine whether lipids and pre-pregnancy BMI make unique contributions to the fetal programming of disease. PMID:25912426