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Sample records for activated fatty acids

  1. Physiological activities of hydroxyl fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the search of value-added products from surplus soybean oil, we produced many new hydroxy fatty acids through microbial bioconversion. Hydroxy fatty acids are used in a wide range of industrial products, such as resins, waxes, nylons plastics, lubricants, cosmetics, and additives in coatings and...

  2. Synthesis and antituberculosis activity of new fatty acid amides.

    PubMed

    D'Oca, Caroline Da Ros Montes; Coelho, Tatiane; Marinho, Tamara Germani; Hack, Carolina Rosa Lopes; Duarte, Rodrigo da Costa; da Silva, Pedro Almeida; D'Oca, Marcelo Gonçalves Montes

    2010-09-01

    This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H(37)Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 microg/mL for resistance strains. PMID:20667727

  3. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

    PubMed

    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer. PMID:25510639

  4. Polyunsaturated fatty acid inhibition of fatty acid synthase transcription is independent of PPAR activation.

    TOXLINE Toxicology Bibliographic Information

    Clarke SD; Turini M; Jump DB; Abraham S; Reedy M

    1998-01-01

    Polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families inhibit the rate of gene transcription for a number of hepatic lipogenic and glycolytic genes, e.g., fatty acid synthase (FAS). In contrast, saturated and monounsaturated fatty acids have no inhibitory capability. The suppression of gene transcription resulting from the addition of PUFA to a high carbohydrate diet: occurs quickly (< 3 h) after its addition to a high glucose diet; can be recreated with hepatocytes cultured in a serum-free medium containing insulin and glucocorticoids; can be demonstrated in diabetic rats fed fructose; and is independent of glucagon. While the nature of the intracellular PUFA inhibitor is unclear, it appears that delta-6 desaturation is a required step in the process. Recently, the fatty acid activated nuclear factor, peroxisome-proliferator activated receptor (PPAR) was suggested to be the PUFA-response factor. However, the potent PPAR activators ETYA and Wy-14643 did not suppress hepatic expression of FAS, but did induce the PPAR-responsive gene, acyl-CoA oxidase (AOX). Similarly, treating rat hepatocytes with 20:4 (n-6) suppressed FAS expression but had no effect on AOX. Thus, it appears that the PUFA regulation of gene transcription involves a PUFA-response factor that is independent from PPAR.

  5. Fatty Acid Activation in Cyanobacteria Mediated by Acyl-Acyl Carrier Protein Synthetase Enables Fatty Acid Recycling1[W

    PubMed Central

    Kaczmarzyk, Danuta; Fulda, Martin

    2010-01-01

    In cyanobacteria fatty acids destined for lipid synthesis can be synthesized de novo, but also exogenous free fatty acids from the culture medium can be directly incorporated into lipids. Activation of exogenous fatty acids is likely required prior to their utilization. To identify the enzymatic activity responsible for activation we cloned candidate genes from Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 and identified the encoded proteins as acyl-acyl carrier protein synthetases (Aas). The enzymes catalyze the ATP-dependent esterification of fatty acids to the thiol of acyl carrier protein. The two protein sequences are only distantly related to known prokaryotic Aas proteins but they display strong similarity to sequences that can be found in almost all organisms that perform oxygenic photosynthesis. To investigate the biological role of Aas activity in cyanobacteria, aas knockout mutants were generated in the background of Synechocystis sp. PCC 6803 and S. elongatus PCC 7942. The mutant strains showed two phenotypes characterized by the inability to utilize exogenous fatty acids and by the secretion of endogenous fatty acids into the culture medium. The analyses of extracellular and intracellular fatty acid profiles of aas mutant strains as well as labeling experiments indicated that the detected free fatty acids are released from membrane lipids. The data suggest a considerable turnover of lipid molecules and a role for Aas activity in recycling the released fatty acids. In this model, lipid degradation represents a third supply of fatty acids for lipid synthesis in cyanobacteria. PMID:20061450

  6. Reconciling Ligase Ribozyme Activity with Fatty Acid Vesicle Stability

    PubMed Central

    Anella, Fabrizio; Danelon, Christophe

    2014-01-01

    The “RNA world” and the “Lipid world” theories for the origin of cellular life are often considered incompatible due to the differences in the environmental conditions at which they can emerge. One obstacle resides in the conflicting requirements for divalent metal ions, in particular Mg2+, with respect to optimal ribozyme activity, fatty acid vesicle stability and protection against RNA strand cleavage. Here, we report on the activity of a short L1 ligase ribozyme in the presence of myristoleic acid (MA) vesicles at varying concentrations of Mg2+. The ligation rate is significantly lower at low-Mg2+ conditions. However, the loss of activity is overcompensated by the increased stability of RNA leading to a larger amount of intact ligated substrate after long reaction periods. Combining RNA ligation assays with fatty acid vesicles we found that MA vesicles made of 5 mM amphiphile are stable and do not impair ligase ribozyme activity in the presence of approximately 2 mM Mg2+. These results provide a scenario in which catalytic RNA and primordial membrane assembly can coexist in the same environment. PMID:25513761

  7. Intracellular activation of EGFR by fatty acid synthase dependent palmitoylation

    PubMed Central

    Bollu, Lakshmi Reddy; Katreddy, Rajashekhara Reddy; Blessing, Alicia Marie; Pham, Nguyen; Zheng, Baohui; Wu, Xu; Weihua, Zhang

    2015-01-01

    Epidermal growth factor receptor (EGFR) is an oncogenic receptor tyrosine kinase. Canonically, the tyrosine kinase activity of EGFR is regulated by its extracellular ligands. However, ligand-independent activation of EGFR exists in certain cancer cells, and the underlying mechanism remains to be defined. In this study, using PC3 and A549 cells as a model, we have found that, in the absence of extracellular ligands, a subpopulation of EGFR is constitutively active, which is needed for maintaining cell proliferation. Furthermore, we have found that fatty acid synthase (FASN)-dependent palmitoylation of EGFR is required for EGFR dimerization and kinase activation. Inhibition of FASN or palmitoyl acyltransferases reduced the activity and down-regulated the levels of EGFR, and sensitized cancer cells to EGFR tyrosine kinase inhibitors. It is concluded that EGFR can be activated intracellularly by FASN-dependent palmitoylation. This mechanism may serve as a new target for improving EGFR-based cancer therapy. PMID:26378037

  8. Arachidonic Acid and Other Fatty Acids Directly Activate Potassium Channels in Smooth Muscle Cells

    NASA Astrophysics Data System (ADS)

    Ordway, Richard W.; Walsh, John V.; Singer, Joshua J.

    1989-06-01

    Arachidonic acid, as well as fatty acids that are not substrates for cyclooxygenase and lipoxygenase enzymes, activated a specific type of potassium channel in freshly dissociated smooth muscle cells. Activation occurred in excised membrane patches in the absence of calcium and all nucleotides. Therefore signal transduction pathways that require such soluble factors, including the NADPH-dependent cytochrome P450 pathway, do not mediate the response. Thus, fatty acids directly activate potassium channels and so may constitute a class of signal molecules that regulate ion channels.

  9. Binding of acyl CoA by fatty acid binding protein and the effect on fatty acid activation

    SciTech Connect

    Burrier, R.E.; Manson, C.R.; Brecher, P.

    1987-05-01

    The ability of purified rat liver and heart fatty acid binding proteins (FABPs) to bind oleoyl CoA and modulate acyl CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart FABP was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver FABP has a single binding site for acyl CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver FABP stimulated acyl CoA production whereas heart FABP did not stimulate production over control values. /sup 14/C-Fatty acid-FABP complexes were prepared, incubated with membranes and acyl CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl CoA in the presence of liver FABP but in the presence of heart FABP, only 45% of the fatty acid was converted. The amount of product formed was not changed by additional membrane, enzyme cofactor, or incubation time. Liver but not heart FABP bound the acyl CoA formed and removed it from the membranes. These studies suggest that liver FABP can increase the amount of acyl CoA by binding this ligand thereby removing it from the membrane and possibly aiding transport within the cell.

  10. Anti-cancer Activities of ω-6 Polyunsaturated Fatty Acids

    PubMed Central

    Xu, Yi; Qian, Steven Y.

    2014-01-01

    The ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are two major families of PUFAs present as essential cellular components which possess diverse bioactivities. The ω-3s, mainly found in seafood, are associated with many beneficial effects on human health, while the ω-6s are more abundant in our daily diet and could be implicated in many pathological processes including cancer development. Increasing evidence suggests that the adverse effects of ω-6s may be largely attributed to arachidonic acid (AA, a downstream ω-6) and the metabolite prostaglandin E2 (PGE2) that stems from its cyclooxygenase (COX)-catalyzed lipid peroxidation. On the other hand, two of AA’s upstream ω-6s, γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA), are shown to possess certain anti-cancer activities, including inducing cell apoptosis and inhibiting cell proliferation. In this paper, we review the documented anti-cancer activities of ω-6 PUFAs, including the recent findings regarding the anti-cancer effects of free radical-mediated DGLA peroxidation. The possible mechanisms and applications of DGLA (and other ω-6s) in inducing anti-cancer activity are also discussed. Considering the wide availability of ω-6s in our daily diet, the study of the potential beneficial effect of ω-6 PUFAs may guide us to develop an ω-6–based diet care strategy for cancer prevention and treatment. PMID:24923568

  11. Antimicrobial activity of fatty acid methyl esters of some members of Chenopodiaceae.

    PubMed

    Chandrasekaran, Manivachagam; Kannathasan, Krishnan; Venkatesalu, Venugopalan

    2008-01-01

    Fatty acid methyl ester (FAME) extracts of four halophytic plants, viz. Arthrocnemum indicum, Salicornia brachiata, Suaeda maritima and Suaeda monoica belonging to the family Chenopodiaceae, were prepared and their composition was analyzed by GC-MS. The FAME extracts were also screened for antibacterial and antifungal activities. The GC-MS analysis revealed the presence of more saturated fatty acids than unsaturated fatty acids. Among the fatty acids analyzed, the relative percentage of lauric acid was high in S. brachiata (61.85%). The FAME extract of S. brachiata showed the highest antibacterial and antifungal activities among the extracts tested. The other three extracts showed potent antibacterial and moderate anticandidal activities. PMID:18669016

  12. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  13. Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxygenated fatty acids are useful as specialty chemicals, plasticizers, and biomedicals. Microbial enzymes convert fatty acids to mono-, di-, and trihydroxy fatty acid products. Among them, Bacillus megaterium ALA2 converted n-6 and n-3 PUFAs to many new oxygenated fatty acids. Linoleic acid was ...

  14. Understanding fatty acid metabolism through an active learning approach.

    PubMed

    Fardilha, M; Schrader, M; da Cruz E Silva, O A B; da Cruz E Silva, E F

    2010-03-01

    A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less emphasis is placed on transmitting information and the focus is shifted toward developing higher order thinking (analysis, synthesis, and evaluation). However, MALA should always involve clearly identified objectives and well-defined targets. Understanding fatty acid metabolism was one of the proposed goals of the Medical Biochemistry unit. To this end, students were challenged with a variety of learning strategies to develop skills associated with group conflict resolution, critical thinking, information access, and retrieval, as well as oral and written communication skills. Overall, students and learning facilitators were highly motivated by the diversity of learning activities, particularly due to the emphasis on correlating theoretical knowledge with human health and disease. As a quality control exercise, the students were asked to answer a questionnaire on their evaluation of the whole teaching/learning experience. Our initial analysis of the learning outcomes permits us to conclude that the approach undertaken yields results that surpass the traditional teaching methods. PMID:21567798

  15. Bactericidal Activity of the Human Skin Fatty Acid cis-6-Hexadecanoic Acid on Staphylococcus aureus

    PubMed Central

    Cartron, Michaël L.; England, Simon R.; Chiriac, Alina Iulia; Josten, Michaele; Turner, Robert; Rauter, Yvonne; Hurd, Alexander; Sahl, Hans-Georg; Jones, Simon

    2014-01-01

    Human skin fatty acids are a potent aspect of our innate defenses, giving surface protection against potentially invasive organisms. They provide an important parameter in determining the ecology of the skin microflora, and alterations can lead to increased colonization by pathogens such as Staphylococcus aureus. Harnessing skin fatty acids may also give a new avenue of exploration in the generation of control measures against drug-resistant organisms. Despite their importance, the mechanism(s) whereby skin fatty acids kill bacteria has remained largely elusive. Here, we describe an analysis of the bactericidal effects of the major human skin fatty acid cis-6-hexadecenoic acid (C6H) on the human commensal and pathogen S. aureus. Several C6H concentration-dependent mechanisms were found. At high concentrations, C6H swiftly kills cells associated with a general loss of membrane integrity. However, C6H still kills at lower concentrations, acting through disruption of the proton motive force, an increase in membrane fluidity, and its effects on electron transfer. The design of analogues with altered bactericidal effects has begun to determine the structural constraints on activity and paves the way for the rational design of new antistaphylococcal agents. PMID:24709265

  16. Ileal and colonic fatty acid profiles in patients with active Crohn's disease.

    PubMed Central

    Bühner, S; Nagel, E; Körber, J; Vogelsang, H; Linn, T; Pichlmayr, R

    1994-01-01

    In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event. PMID:7959199

  17. Adenylate cyclase activity, membrane fluidity and fatty acid composition of rat heart in essential fatty acid deficiency.

    PubMed

    Alam, S Q; Alam, B S; Ren, Y F

    1987-05-01

    Three groups of male, weanling, Sprague-Dawley rats were fed diets containing 7% hydrogenated coconut oil, 6.6% hydrogenated coconut oil + 0.4% corn oil, or 7% corn oil for 8-17 weeks. These diets provided 0% (EFAD group), 0.5% (MEFAD group) or 5% (CONTROL group) of the total energy as linoleic acid, respectively. Crude plasma membranes were prepared from heart and assayed for adenylate cyclase activity. Both basal and fluoride-stimulated activity was lower in the membranes from EFAD and MEFAD rats than that of the controls. The double bond index of total lipids and phospholipids, and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) were not appreciably different in the membranes from the three dietary groups. The fatty acid composition of total phospholipids of the membranes, however, was quite different and indicative of biochemical changes typical of an EFA deficiency. Feeding of the control diet to the EFAD or MEFAD rats for up to 6 weeks did not alleviate completely the changes in adenylate cyclase activity although the fatty acid patterns were restored to the normal levels. There was also a decrease in the number of [3H]-DHA binding sites in heart of EFAD rats as compared with their controls. The results suggest that the changes induced by EFA deficiency in the acyl group composition of membrane phospholipids and in the number of beta-adrenergic receptors may be important in regulating adenylate cyclase activity in the heart. PMID:3625782

  18. Long-Chain Fatty Acids Activate Calcium Channels in Ventricular Myocytes

    NASA Astrophysics Data System (ADS)

    Huang, James Min-Che; Xian, Hu; Bacaner, Marvin

    1992-07-01

    Nonesterified fatty acids accumulate at sites of tissue injury and necrosis. In cardiac tissue the concentrations of oleic acid, arachidonic acid, leukotrienes, and other fatty acids increase greatly during ischemia due to receptor or nonreceptor-mediated activation of phospholipases and/or diminished reacylation. In ischemic myocardium, the time course of increase in fatty acids and tissue calcium closely parallels irreversible cardiac damage. We postulated that fatty acids released from membrane phospholipids may be involved in the increase of intracellular calcium. We report here that low concentrations (3-30 μM) of each long-chain unsaturated (oleic, linoleic, linolenic, and arachidonic) and saturated (palmitic, stearic, and arachidic) fatty acid tested induced multifold increases in voltage-dependent calcium currents (ICa) in cardiac myocytes. In contrast, neither short-chain fatty acids (<12 carbons) or fatty acid esters (oleic and palmitic methyl esters) had any effect on ICa, indicating that activation of calcium channels depended on chain length and required a free carboxyl group. Inhibition of protein kinases C and A, G proteins, eicosanoid production, or nonenzymatic oxidation did not block the fatty acid-induced increase in ICa. Thus, long-chain fatty acids appear to directly activate ICa, possibly by acting at some lipid sites near the channels or directly on the channel protein itself. We suggest that the combined effects of fatty acids released during ischemia on ICa may contribute to ischemia-induced pathogenic events on the heart that involve calcium, such as arrhythmias, conduction disturbances, and myocardial damage due to cytotoxic calcium overload.

  19. Novel hybrid DHPM-fatty acids: synthesis and activity against glioma cell growth in vitro.

    PubMed

    Treptow, Tamara G M; Figueiró, Fabrício; Jandrey, Elisa H F; Battastini, Ana M O; Salbego, Christianne G; Hoppe, Juliana B; Taborda, Priscila S; Rosa, Sabrina B; Piovesan, Luciana A; Montes D'Oca, Caroline Da R; Russowsky, Dennis; Montes D'Oca, Marcelo G

    2015-05-01

    We described the first synthesis of fatty acid 3,4-dihydropyrimidinones (DHPM-fatty acids) using the Biginelli multicomponent reaction. Antiproliferative activity on two glioma cell lines (C6 rat and U-138-MG human) was also reported. The novel DHPM-fatty acids reduced glioma cell viability relative to temozolomide. Hybrid oxo-monastrol-palmitic acid was the most potent, reducing U-138-MG human cell viability by ca. 50% at 10 μM. In addition, the DHPM-fatty acids showed a large safety range to neural cells, represented by the organotypic hippocampal culture. These results suggest that the increased lipophilicity of DHPM-fatty acids offer a promising approach to overcoming resistance to chemotherapy and may play an important role in the development of new antitumor drugs. PMID:25863023

  20. Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

    PubMed Central

    Boshtam, Maryam; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

    2013-01-01

    Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health. PMID:24167374

  1. Plant fatty acid hydroxylases

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank

    2001-01-01

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  2. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    SciTech Connect

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki; Kawada, Teruo

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected effects of PPAR{alpha} activation are very valuable for managing diabetic conditions accompanied by obesity, because PPAR{gamma} agonists, usually used as antidiabetic drugs, induce excessive lipid accumulation in adipocytes in addition to improvement of insulin resistance.

  3. Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity

    SciTech Connect

    Hopperton, Kathryn E.; Duncan, Robin E.; Bazinet, Richard P.; Archer, Michael C.

    2014-01-15

    Fatty acid synthase is over-expressed in many cancers and its activity is required for cancer cell survival, but the role of endogenously synthesized fatty acids in cancer is unknown. It has been suggested that endogenous fatty acid synthesis is either needed to support the growth of rapidly dividing cells, or to maintain elevated glycolysis (the Warburg effect) that is characteristic of cancer cells. Here, we investigate both hypotheses. First, we compared utilization of fatty acids synthesized endogenously from {sup 14}C-labeled acetate to those supplied exogenously as {sup 14}C-labeled palmitate in the culture medium in human breast cancer (MCF-7 and MDA-MB-231) and untransformed breast epithelial cells (MCF-10A). We found that cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, that these fatty acids are esterified to the same lipid and phospholipid classes in the same proportions, and that their distribution within neutral lipids is not different from untransformed cells. These results suggest that endogenously synthesized fatty acids do not fulfill a specific function in cancer cells. Furthermore, we observed that cancer cells excrete endogenously synthesized fatty acids, suggesting that they are produced in excess of requirements. We next investigated whether lipogenic activity is involved in the maintenance of high glycolytic activity by culturing both cancer and non-transformed cells under anoxic conditions. Although anoxia increased glycolysis 2–3 fold, we observed no concomitant increase in lipogenesis. Our results indicate that breast cancer cells do not have a specific qualitative or quantitative requirement for endogenously synthesized fatty acids and that increased de novo lipogenesis is not required to sustain elevations in glycolytic activity induced by anoxia in these cells. - Highlights: • Fatty acid synthase (FASN) is over-expressed in cancer but its function is unknown. • We compare utilization of fatty acids produced by FASN to those derived exogenously. • Cancer cells do not have a specific requirement for fatty acids produced by FASN. • Fatty acids produced by FASN are in excess of cell requirements and are excreted. • Increased FASN activity is not required to sustain elevations in glycolysis.

  4. Fatty acid-binding protein activities in bovine muscle, liver and adipose tissue

    SciTech Connect

    Smith, S.B.; Ekeren, P.A.; Sanders, J.O.

    1985-11-01

    Subcutaneous adipose tissue, sternomandibularis muscle and liver were obtained from steers immediately postmortem. Muscle strips and adipose tissue snips were incubated with 0.75 mM (1- UC)palmitate and 5 mM glucose. Muscle strips esterified palmitate at the rate of 2.5 nmol/min per gram tissue, which was 30% of the rate observed for adipose tissue. Fatty acid-binding protein activity was measured in 104,000 x g supernatant fractions of liver, muscle and adipose tissue homogenates. Muscle and adipose tissue fractions bound 840 and 140 pmol (1- UC)palmitoyl-CoA per gram tissue, respectively. Fatty acid-binding protein activity was greater in adipose tissue than in muscle when data were expressed per milligram protein. Fatty acid binding-protein activity was correlated with the rate of palmitate esterification within each tissue. Liver contained the highest fatty acid-binding protein activity.

  5. Brain microsomal fatty acid elongation is increased in abcd1-deficient mouse during active myelination phase.

    PubMed

    Morita, Masashi; Kawamichi, Misato; Shimura, Yusuke; Kawaguchi, Kosuke; Watanabe, Shiro; Imanaka, Tsuneo

    2015-12-01

    The dysfunction of ABCD1, a peroxisomal ABC protein, leads to the perturbation of very long chain fatty acid (VLCFA) metabolism and is the cause of X-linked adrenoleukodystrophy. Abcd1-deficient mice exhibit an accumulation of saturated VLCFAs, such as C26:0, in all tissues, especially the brain. The present study sought to measure microsomal fatty acid elongation activity in the brain of wild-type (WT) and abcd1-deficient mice during the course of development. The fatty acid elongation activity in the microsomal fraction was measured by the incorporation of [2-(14)C]malonyl-CoA into fatty acids in the presence of C16:0-CoA or C20:0-CoA. Cytosolic fatty acid synthesis activity was completely inhibited by the addition of N-ethylmaleimide (NEM). The microsomal fatty acid elongation activity in the brain was significantly high at 3 weeks after birth and decreased substantially at 3 months after birth. Furthermore, we detected two different types of microsomal fatty acid elongation activity by using C16:0-CoA or C20:0-CoA as the substrate and found the activity toward C20:0-CoA in abcd1-deficient mice was higher than the WT 3-week-old animals. These results suggest that during the active myelination phase the microsomal fatty acid elongation activity is stimulated in abcd1-deficient mice, which in turn perturbs the lipid composition in myelin. PMID:26108493

  6. Insulin activation of plasma non-esterified fatty acid uptake in metabolic syndrome

    PubMed Central

    Ramos-Roman, Maria A.; Lapidot, Smadar A.; Phair, Robert D.; Parks, Elizabeth J.

    2012-01-01

    Objectives Insulin control of fatty acid metabolism has long been deemed dominated by suppression of adipose lipolysis. This studys goal was to test the hypothesis that this single role of insulin is insufficient to explain observed fatty acid dynamics. Methods and Results Fatty acid kinetics were measured during a meal-tolerance test and insulin sensitivity assessed by IVGTT in overweight human subjects (n=15, BMI 35.8 7.1 kg/m2). Non-steady state tracer kinetic models were formulated and tested using ProcessDB software. Suppression of adipose release alone could not account for NEFA concentration changes postprandially, but when combined with insulin activation of fatty acid uptake was consistent with the NEFA data. The observed insulin Km for NEFA uptake was inversely correlated with both insulin sensitivity of glucose uptake (IVGTT Si) (r=?0.626, P=0.01), and whole body fat oxidation after the meal (r=?0.538, P=0.05). Conclusions These results support insulin regulation of fatty acid turnover by both release and uptake mechanisms. Activation of fatty acid uptake is consistent with the human data, has mechanistic precedent in cell culture, and highlights a new potential target for therapies aimed at improving the control of fatty acid metabolism in insulin-resistant disease states. PMID:22723441

  7. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance.

    PubMed

    Moreel, Xavier; Allaire, Janie; Léger, Caroline; Caron, André; Labonté, Marie-Ève; Lamarche, Benoît; Julien, Pierre; Desmeules, Patrice; Têtu, Bernard; Fradet, Vincent

    2014-07-01

    The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer. PMID:24824038

  8. Dietary trans fatty acids increase serum cholesterylester transfer protein activity in man.

    PubMed

    van Tol, A; Zock, P L; van Gent, T; Scheek, L M; Katan, M B

    1995-05-01

    The average diet may provide some 8-10 g/day of unsaturated fatty acids with a trans double bond. Previous studies showed that dietary trans fatty acids may simultaneously raise low-density lipoprotein (LDL) cholesterol and reduce high-density lipoprotein (HDL) cholesterol. Human plasma contains a protein (CETP) which transfers cholesterylesters from HDL to lipoproteins of lower density. We hypothesized that CETP could play a role in the effect of trans fatty acids on lipoproteins and measured the activity levels of CETP in serum samples from a 9-week study in which 55 volunteers were fed three controlled diets with different fatty acid profiles. Mean activity was 114 (% of reference serum) after consumption of a high trans fatty acid diet, as opposed to 96 after linoleic acid and 97 after stearic acid (P < 0.02). We conclude that the increased activity of CETP may contribute to the rise in LDL cholesterol and the fall in HDL cholesterol seen on diets with high contents of trans fatty acids. PMID:7669083

  9. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  10. Omega-3 Fatty Acids

    MedlinePlus

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount ... the blood in people with very high triglycerides. Omega-3 fatty acids are in a class of medications ...

  11. The effects of nutritional polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats.

    PubMed

    Hauser, Joachim; Makulska-Gertruda, Ewelina; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

    2014-06-01

    The present study investigated the effects of nutritional omega-3 polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats (SHRs), which are used as an animal model of attention-deficit/hyperactivity disorder (ADHD). For 6 weeks, two groups of randomly assigned SHRs received food either enriched with or deficient in omega-3 fatty acids (based on the American Institute of Nutrition-93 G/AIN93G). Using an open field, locomotor activity was subsequently assessed for 6 days. A marked difference in locomotor activity as assessed by the distance travelled in the open field was found between the two groups of rats. In comparison with rats fed with omega-3 fatty acid-enriched food, the animals on the omega-3 fatty acid-deficient diet showed a significantly higher locomotor activity. The present findings demonstrated that nutritional enrichment with omega-3 fatty acids was associated with reduced motor activity in an established animal model of ADHD and support the notion that omega-3 polyunsaturated fatty acids may play a role in the pathophysiology of ADHD. PMID:24415401

  12. Effect of low temperature on highly unsaturated fatty acid biosynthesis in activated sludge.

    PubMed

    He, Su; Ding, Li-Li; Xu, Ke; Geng, Jin-Ju; Ren, Hong-Qiang

    2016-07-01

    Low temperature is a limiting factor for the microbial activity of activated sludge for sewage treatment plant in winter. Highly unsaturated fatty acid (UFA) biosynthesis, phospholipid fatty acid (PLFA) constituents and microbial structure in activated sludge at low temperature were investigated. Over 12 gigabases of metagenomic sequence data were generated with the Illumina HiSeq 2000 platform. The result showed 43.11% of phospholipid fatty acid (PLFA) in the activated sludge participated in UFA biosynthesis, and γ-Linolenic could be converted to Arachidonic acid at low temperature. The highly UFA biosynthesis in activated sludge was n-6 highly UFA biosynthesis, rather than n-3 highly UFA biosynthesis. The microbial community structures of activated sludge were analyzed by PLFA and high-throughput sequencing (HiSeq) simultaneously. Acidovorax, Pseudomonas, Flavobacterium and Polaromonas occupied higher percentage at 5°C, and genetic changes of highly UFA biosynthesis derived from microbial community structures change. PMID:27035483

  13. Nitrogen dioxide induced changes in level of free fatty acids, triglyceride, esterified fatty acid, ganglioside and lipase activity in the guinea pig brain

    SciTech Connect

    Farahani, H.; Hasan, M. )

    1992-02-01

    The biochemical response to controlled inhalation of nitrogen dioxide (NO2) was studied in 18 male guinea pigs. Animals were exposed to 2.5, 5.0, and 10 ppm NO2 for 2h daily for 35 consecutive days, and the results compared with six control animals exposed to filtered air for 2h daily for same period. Five biochemical parameters, including triglyceride, free fatty acids, esterified fatty acid, ganglioside and lipase activity were measured immediately after the last day of exposure. At 2.5 ppm NO2 inhalation no significant changes occurred in any region of the central nervous system (CNS). While as the dose concentration was increased to 5 and 10 ppm nitrogen dioxide, significant dose-related alteration were observed in the levels of triglyceride, free fatty acid, esterified fatty acid, ganglioside and lipase activity in the different regions of the guinea pig CNS.

  14. Saturated fatty acids activate TLR-mediated pro-inflammatory signaling pathways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Toll-like receptor 4 (TLR4) and TLR2 were shown to be activated by saturated fatty acids (SFAs) but inhibited by docosahexaenoic acid (DHA). However, one report (ATVB 11:1944, 2009) suggested that SFA-induced TLR activation in cell culture systems is due to contaminants in BSA used for conjugating f...

  15. Influence of ethylenediamine-n,n’-disuccinic acid (EDDS) concentration on the bactericidal activity of fatty acids in vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The antibacterial activity of mixtures of ethylenediamine-N,N’-disuccinic acid (EDDS) and antibacterial fatty acids (FA) was examined using the agar diffusion assay. Solutions of caproic, caprylic, capric, and lauric acids dissolved in potassium hydroxide (KOH) were supplemented with 0, 5, or 10 mM ...

  16. Bactericidal activity of alkaline salts of fatty acids towards bacteria associated with poultry processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibacterial activity of alkaline salts of caproic, caprylic, capric, lauric, and myristic acids were determined using the agar diffusion assay. A 0.5M concentration of each fatty acid (FA) was dissolved in 1.0 M potassium hydroxide (KOH), and pH of the mixtures was adjusted to 10.5 with citric aci...

  17. The biological activities of protein/oleic acid complexes reside in the fatty acid.

    PubMed

    Fontana, Angelo; Spolaore, Barbara; Polverino de Laureto, Patrizia

    2013-06-01

    A complex formed by human α-lactalbumin (α-LA) and oleic acid (OA), named HAMLET, has been shown to have an apoptotic activity leading to the selective death of tumor cells. In numerous publications it has been reported that in the complex α-LA is monomeric and adopts a partly folded or "molten globule" state, leading to the idea that partly folded proteins can have "beneficial effects". The protein/OA molar ratio initially has been reported to be 1:1, while recent data have indicated that the OA-complex is given by an oligomeric protein capable of binding numerous OA molecules per protein monomer. Proteolytic fragments of α-LA, as well as other proteins unrelated to α-LA, can form OA-complexes with biological activities similar to those of HAMLET, thus indicating that a generic protein can form a cytotoxic complex under suitable experimental conditions. Moreover, even the selective tumoricidal activity of HAMLET-like complexes has been questioned. There is recent evidence that the biological activity of long chain unsaturated fatty acids, including OA, can be ascribed to their effect of perturbing the structure of biological membranes and consequently the function of membrane-bound proteins. In general, it has been observed that the cytotoxic effects exerted by HAMLET-like complexes are similar to those reported for OA alone. Overall, these findings can be interpreted by considering that the protein moiety does not have a toxic effect on its own, but merely acts as a solubilising agent for the inherently toxic fatty acid. PMID:23499846

  18. Omega-3 Fatty Acids Moderate Effects of Physical Activity on Cognitive Function

    PubMed Central

    Leckie, Regina L.; Manuck, Stephen B.; Bhattacharee, Neha; Muldoon, Matthew F.; Flory, Janine M.; Erickson, Kirk I.

    2014-01-01

    Greater amounts of physical activity (PA) and omega-3 fatty acids have both been independently associated with better cognitive performance. Because of the overlapping biological effects of omega-3 fatty acids and PA, fatty acid intake may modify the effects of PA on neurocognitive function. The present study tested this hypothesis by examining whether the ratio of serum omega-6 to omega-3 fatty acid levels would moderate the association between PA and executive and memory functions in 344 participants (Mean age = 44.42 years, SD = 6.72). The Paffenbarger Physical Activity Questionnaire (PPAQ), serum fatty acid levels, and performance on a standard neuropsychological battery were acquired on all subjects. A principal component analysis reduced the number of cognitive outcomes to three factors: n-back working memory, Trail Making test, and Logical Memory. We found a significant interaction between PA and the ratio of omega-6 to omega-3 fatty acid serum levels on Trail Making performance and n-back performance, such that higher amounts of omega-3 levels offset the deleterious effects of lower amounts of PA. These effects remained significant in a subsample (n=299) controlling for overall dietary fat consumption. There were no significant additive or multiplicative benefits of higher amounts of both omega-3 and PA on cognitive performance. Our results demonstrate that a diet high in omega-3 fatty acids might mitigate the effect of lower levels of PA on cognitive performance. This study illuminates the importance of understanding dietary and PA factors in tandem when exploring their effects on neurocognitive health. PMID:24813150

  19. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.

    PubMed

    Yamauchi, T; Kamon, J; Minokoshi, Y; Ito, Y; Waki, H; Uchida, S; Yamashita, S; Noda, M; Kita, S; Ueki, K; Eto, K; Akanuma, Y; Froguel, P; Foufelle, F; Ferre, P; Carling, D; Kimura, S; Nagai, R; Kahn, B B; Kadowaki, T

    2002-11-01

    Adiponectin (Ad) is a hormone secreted by adipocytes that regulates energy homeostasis and glucose and lipid metabolism. However, the signaling pathways that mediate the metabolic effects of Ad remain poorly identified. Here we show that phosphorylation and activation of the 5'-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full-length Ad in the liver. In parallel with its activation of AMPK, Ad stimulates phosphorylation of acetyl coenzyme A carboxylase (ACC), fatty-acid oxidation, glucose uptake and lactate production in myocytes, phosphorylation of ACC and reduction of molecules involved in gluconeogenesis in the liver, and reduction of glucose levels in vivo. Blocking AMPK activation by dominant-negative mutant inhibits each of these effects, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK. Our data may provide a novel paradigm that an adipocyte-derived antidiabetic hormone, Ad, activates AMPK, thereby directly regulating glucose metabolism and insulin sensitivity in vitro and in vivo. PMID:12368907

  20. Effects of exogenous fatty acids and cholesterol on aminopeptidase activities in rat astroglia.

    PubMed

    Ramírez-Expósito, M J; García, M J; Mayas, M D; Ramírez, M; Martínez-Martos, J M

    2002-12-01

    Several studies have addressed the interaction between fatty acids and lipids with central nervous system peptides. Because aminopeptidases (AP) are involved in the regulation of neuropeptides, this work studies several AP expressed in cultured astroglia, after exogenous addition of oleic and linoleic fatty acids and cholesterol to the culture medium. Alanyl-AP, arginyl-AP, cystyl-AP, leucyl-AP, tyrosyl-AP and pyroglutamyl-AP activities were analysed in whole cells using the corresponding aminoacyl-beta-naphthylamides as substrates. Oleic acid inhibits alanyl-AP, cystyl-AP and leucyl-AP activities, whereas linoleic acid inhibits alanyl-AP, arginyl-AP and tyrosyl-AP activities. Neither oleic acid nor linoleic acid modifies pyroglutamyl-AP activity. In contrast, cholesterol increases arginyl-AP, cystyl-AP, leucyl-AP, tyrosyl-AP and pyroglutamyl-AP activities, although it does not modify alanyl-AP activity. The changes reported here suggest that oleic and linoleic fatty acids and cholesterol can modulate peptide activities via their degradation route involving aminopeptidases; each of them being differentially regulated. PMID:12415561

  1. Pure short-chain glycerol fatty acid esters and glycerylic cyclocarbonic fatty acid esters as surface active and antimicrobial coagels protecting surfaces by promoting superhydrophilicity.

    PubMed

    Valentin, Romain; Alignan, Marion; Giacinti, Géraldine; Renaud, François N R; Raymond, Bernard; Mouloungui, Zéphirin

    2012-01-01

    Pure glycerol fatty acid esters and glycerylic cyclocarbonic fatty acid esters have an amphiphilic structure, giving these biomolecules a broad range of physico-chemical and biological properties. Physico-chemical properties depend on chain lengths, odd or even carbon numbers on the chain, and glyceryl or cyclocarbonic polar heads. The spectrum of melting-point values for these molecules is large. Surface-activity is very important and through determination of the critical aggregation concentration (CAC), some fatty-acid esters are considered as solvo-surfactant biomolecules. Coupling these self-aggregation and crystallization properties, superhydrophilic surfaces were obtained. An efficient durable water repellent coating of various metallic and polymeric surfaces was allowed. Moreover, these fatty acid esters promoting superhydrophilicity showed biological activity against Gram positive, Gram negative, and yeast-like micro-organisms. Such surfaces coated by self-assembled fatty acid esters in a stable coagel state present a novel solution to surface-contamination risks from pathogen proliferation. PMID:21968402

  2. Active role of fatty acid amino acid conjugates in nitrogen metabolidm by Spodoptera litura larvae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since the first fatty acid amino acid conjugate (FAC) was isolated from regurgitant of Spodoptera exigua larvae in 1997 [volicitin: N-(17-hydroxylinolenoyl)- L-glutamine], their role as elicitors of induced responses in plants has been well documented. However, studies of the biosyntheses as well as...

  3. New bioactive fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  4. New Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to new compounds, 7,10-dihydroxy-8(E)-octadecen...

  5. Fats and fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The absolute fat requirement of the human species is the amount of essential fatty acids needed to maintain optimal fatty acid composition of all tissues and normal eicosanoid synthesis. At most, this requirement is no more than about 5% of an adequate energy intake. However, fat accounts for appro...

  6. Esterification and Transesterification of greases to fatty acid methyl esters with highly active diphenylamine salts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diphenylamine sulfate (DPAS) and diphenylamine hydrochloride (DPACl) salts were found to be highly active catalysts for esterification and transesterification of inexpensive greases to fatty acid methyl esters (FAME). In the presence of catalytic amounts of DPAS or DPACl and excess methanol, the fr...

  7. Esterification and transesterification of greases to fatty acid methyl esters with highly active diphanylammonium salts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have conducted an investigation designed to identify alternate catalysts for the production of fatty acid methyl esters (FAME) to be used as biodiesel. Diphenylammonium sulfate (DPAS) and diphenylammonium chloride (DPA-HCl) salts were found to be highly active homogeneous catalysts for the simu...

  8. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    PubMed

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged. PMID:26041126

  9. Production of Biologically Active Hydroxy Fatty Acids from Vegetable Oils by Pseudomonas aeruginosa PR3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydroxy fatty acids have gained industrial attention because of their special properties such as higher viscosity and reactivity compared with other non-hydroxy fatty acids. The bacterial isolate Pseudomonas aeruginosa (PR3) had been reported to produce mono-, di-, and tri-hydroxy fatty acids from ...

  10. Production of Biologically Active Hydroxy Fatty Acids by Pseudomonas aeruginosa PR3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydroxy fatty acids (HFA) have gained important attentions because of their special properties such as higher viscosity and reactivity compared with other non-hydroxy fatty acids. Pseudomonas aeruginosa (PR3) had been reported to produce mono-, di-, and tri-hydroxy fatty acids from different unsatu...

  11. Cytochrome b5 Coexpression Increases Tetrahymena thermophila Δ6 Fatty Acid Desaturase Activity in Saccharomyces cerevisiae

    PubMed Central

    Dahmen, Jeremy L.; Olsen, Rebecca; Fahy, Deirdre; Wallis, James G.

    2013-01-01

    Very-long-chain polyunsaturated fatty acids such as arachidonic, eicosapentaenoic, and docosahexaenoic acids, are important to the physiology of many microorganisms and metazoans and are vital to human development and health. The production of these and related fatty acids depends on Δ6 desaturases, the final components of an electron transfer chain that introduces double bonds into 18-carbon fatty acid chains. When a Δ6 desaturase identified from the ciliated protist Tetrahymena thermophila was expressed in Saccharomyces cerevisiae cultures supplemented with the 18:2Δ9,12 substrate, only 4% of the incorporated substrate was desaturated. Cytochrome b5 protein sequences identified from the genome of T. thermophila included one sequence with two conserved cytochrome b5 domains. Desaturation by the Δ6 enzyme increased as much as 10-fold when T. thermophila cytochrome b5s were coexpressed with the desaturase. Coexpression of a cytochrome b5 from Arabidopsis thaliana with the Δ6 enzyme also increased desaturation. A split ubiquitin growth assay indicated that the strength of interaction between cytochrome b5 proteins and the desaturase plays a vital role in fatty acid desaturase activity, illustrating the importance of protein-protein interactions in this enzyme activity. PMID:23584993

  12. Essential-oil and fatty-acid composition, and antioxidant activity of extracts of Ficaria kochii.

    PubMed

    Tavakoli, Rahmatollah; Mohadjerani, Maryam; Hosseinzadeh, Rahman; Tajbakhsh, Mahmood; Naqinezhad, Alireza

    2012-12-01

    The essential-oil and fatty-acid composition of the aerial parts of Ficaria kochii (Ledeb.) Iranshahr & Rech.f. native to Iran, and the antioxidant activity of various extracts of this plant were examined. The study by GC-FID and GC/MS analysis of the essential oil resulted in the identification of 61 compounds, representing 86.01% of the total oil composition. Phytol (10.49%), farnesol (7.72%), methyl linoleate (5.57%), and α-farnesene (4.96%) were the main components. The fatty-acid composition of the aerial parts of F. kochii was also analyzed by GC/MS. The major components were palmitic acid (25.9%), linolenic acid (25.3%), and linoleic acid (17.5%). Polyunsaturated fatty acids (PUFAs) were found in higher amounts than saturated fatty acids. The possible antioxidant activity of various extracts (prepared by using solvents with different polarity) of the F. kochii aerial parts was evaluated by screening for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, Fe(III) -reducing power, total antioxidant activity, and inhibitory activity in the linoleic acid-peroxidation system. H(2) O proved to be the most efficient solvent for the extraction of antioxidants, as the H(2) O extract contained the highest amount of phenolic compounds (2.78±0.23 GAE/g dry matter) and also exhibited the strongest antioxidant capacity in all the assays used. The results of the present investigation demonstrated that the aerial parts of F. kochii can be used as natural and safe nutrition supplement in place of synthetic ones. PMID:23255443

  13. Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation

    PubMed Central

    Sui, Yong-Heng; Luo, Wen-Jing; Xu, Qin-Yu; Hua, Jing

    2016-01-01

    AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation. METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids (SFAs) or PUFAs as well as combined with lipopolysaccharide (LPS). The expression of NOD-like receptor protein 3 (NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B (NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured. RESULTS: High-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid (PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid (DHA) had the potential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a high-fat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but DHA decreased phosphorylated NF-κB p65 protein expression in hepatocytes. CONCLUSION: Hepatic NLRP3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB. PMID:26937141

  14. Trans Fatty Acids

    NASA Astrophysics Data System (ADS)

    Doyle, Ellin

    1997-09-01

    Fats and their various fatty acid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fatty acids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fatty acids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fatty acids was also recommended. Although the actual health effects of trans fatty acids remain uncertain, experimental evidence indicates that consumption of trans fatty acids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fatty acids should be minimized.

  15. Fatty acid composition, antioxidant and antibacterial activities of Adonis wolgensis L. extract

    PubMed Central

    Mohadjerani, Maryam; Tavakoli, Rahmatollah; Hosseinzadeh, Rahman

    2014-01-01

    Objectives: The objective of this study was to analyze the fatty acid content, antioxidant, and antibacterial activities of hydro-methanolic extract of Adonis wolgensis L. (A. wolgensis L.) growing wild in north of Iran. Materials and Methods: Oils of A. wolgensis L. was obtained by means of Soxhlet apparatus from leaves and stems. Methyl esters were derived from the oily mixtures by trans-esterification process and were analyzed by GC/FID and GC/MS systems. Phenolic compounds extraction was done with aqueous methanol (90%). This extract was investigated for antioxidant activity using DPPH radical scavenging and reducing power methods and was also tested against a panel of microorganisms. Results: Linolenic acid (45.83%) and oleic acid (47.54%) were the most abundant fatty acids in leaves and stems, respectively. Hydro-methanolic extract with the high amount of total phenolics (9.20 0.011 mg GAE per dry matter) was the potent antioxidant in the assays. Results obtained from measurements of MIC for extract, indicated that E. coli, S. aureus, and S. enteritidis were the most sensitive microorganisms tested, but no activity was observed against Gram-positive microorganism (B. subtilis). Conclusion: The results obtained from the present study indicated that the oil of A. wolgensis leaves and stems contained a high source of poly-unsaturated fatty acids (PUFAs). These results also showed that hydro-methanolic extract of this plant contained significant antioxidant and antibacterial activities. PMID:25050298

  16. Two new peroxy fatty acids with antibacterial activity from Ophioglossum thermale Kom.

    PubMed

    Dong, Jian-Wei; Cai, Le; Li, Xue-Jiao; Peng, Li; Xing, Yun; Mei, Rui-Feng; Wang, Jia-Peng; Ding, Zhong-Tao

    2016-03-01

    Two new peroxy fatty acids, thermalic acids A (1) and B (2), together with eight known compounds, (3β)-methyl-3-hydroxy-urs-11-en-28 oate (3), luteolin (4), quercetin (5), 3-methoxyquercetin (6), ophioglonol (7), ophioglonol 4'-O-α-D-glucopyranoside (8), pedunculosumoside B (9), syringol (10), were isolated from the herba of Ophioglossum thermale Kom. The structures of 1 and 2 were identified by HRESIMS, EIMS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectra. Both two acids exhibited potential antibacterial activities against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. This is the first report of peroxy fatty acids isolated from herbaceous plants of Ophioglossaceae. PMID:26742995

  17. Recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids.

    PubMed

    Carballeira, Nstor M

    2013-01-01

    The 2-alkynoic fatty acids are an interesting group of synthetic compounds that display antimycobacterial, antifungal, anticancer, and pesticidal activities but their antiprotozoal activity has received little attention until recently. In this review we have summarized our present knowledge of the biomedical potential of the 2-hexadecynoic acid (2-HDA) and 2-octadecynoic acid (2-ODA) together with several mechanistic pieces of work attesting to the fact that these compounds, and their metabolites, are good fatty acid biosynthesis inhibitors. The antiprotozoal activity of 2-HDA and 2-ODA against Leishmania donovani and Plasmodium falciparum, parasites responsible for visceral leishmaniasis and malaria, respectively, is also reviewed. The evidence obtained so far supports the fact that these fatty acids are good inhibitors of the L. donovani DNA topoisomerase IB enzyme (LdTopIB) and the potency of LdTopIB inhibition is chain length dependent. We also demonstrate the generality of the antiprotozoal activity of 2-HDA and 2-ODA against P. falciparum, and review our present knowledge of their inhibition of key P. falciparum enzymes such as PfFabZ, PfFabG, and PfFabI together with some possible modes of inhibition. Recent research by our group has also demonstrated that 2-ODA displays antineoplastic activity, specifically against the neuroblastoma SH-SY5Y cell line via lactate dehydrogenase (LDH) release, which is a cell death mechanism principally associated to necrosis. This is the first comprehensive review of the medicinal chemistry of this interesting group of acetylenic fatty acids. PMID:23727443

  18. In vitro biological activities and fatty acid profiles of Pistacia terebinthus fruits and Pistacia khinjuk seeds.

    PubMed

    Hacıbekiroğlu, Işil; Yılmaz, Pelin Köseoğlu; Haşimi, Nesrin; Kılınç, Ersin; Tolan, Veysel; Kolak, Ufuk

    2015-01-01

    This study reports in vitro anticholinesterase, antioxidant and antimicrobial effects of the n-hexane, dichloromethane, ethanol and ethanol-water extracts prepared from Pistacia terebinthus L. fruits and Pistacia khinjuk Stocks seeds as well as their total phenolic and flavonoid contents, and fatty acid compositions. Ethanol and ethanol-water extracts of both species exhibited higher anticholinesterase activity than galanthamine. Among ABTS, DPPH and CUPRAC assays, the highest antioxidant capacity of the extracts was found in the last one. P. terebinthus ethanol extract being rich in flavonoid content showed the best cupric reducing effect. All extracts possessed no antimicrobial activity. The main fatty acid in P. terebinthus fruits (52.52%) and P. khinjuk seeds (59.44%) was found to be oleic acid. Our results indicate that P. terebinthus fruits and P. khinjuk seeds could be a good source of anticholinesterase compounds, and could be phytochemically investigated. PMID:25115646

  19. The influence of dietary fat on the lipogenic activity and fatty acid composition of rat white adipose tissue.

    PubMed

    Nelson, G J; Kelley, D S; Schmidt, P C; Serrato, C M

    1987-05-01

    The in vivo fatty acid synthesis rate, selected enzyme activities and fatty acid composition of rat white adipose tissue from animals fed semisynthetic diets of differing fat type and content were studied. All animals were starved for 48 hr and then refed a fat-free (FF) diet for 48 hr. They were then divided into three groups. One group was continued on the FF diet for 48 hr. Another group was fed a diet containing 44% of calories from corn oil (CO). The final group was fed a diet containing 44% of calories from completely hydrogenated soybean oil (HSO). The animals on the FF diet had a marked increase in adipose tissue fatty acid synthesis during the 96-hr feeding period (as measured by 3H incorporation into adipose fatty acids). Addition of either CO or HSO to the diets did not significantly inhibit fatty acid synthesis in dorsal or epididymal adipose tissue. The activities of the enzymes' fatty acid synthetase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase increased on the FF diet and generally were not inhibited significantly by the addition of either fat to the diets. Linoleic acid was the major polyunsaturated fatty acid (ca. 22%) in adipose tissue. Monounsaturated fatty acids (palmitoleic, oleic, cis-vaccenic) made up ca. 38% of the total adipose fatty acids, while saturated fatty acids accounted for about 32% (myristic, palmitic and stearic). White adipose tissue in mature male rats was a major depot for n-3 fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3600209

  20. Abiotic synthesis of fatty acids

    NASA Technical Reports Server (NTRS)

    Leach, W. W.; Nooner, D. W.; Oro, J.

    1978-01-01

    The formation of fatty acids by Fischer-Tropsch-type synthesis was investigated with ferric oxide, ammonium carbonate, potassium carbonate, powdered Pueblito de Allende carbonaceous chondrite, and filings from the Canyon Diablo meteorite used as catalysts. Products were separated and identified by gas chromatography and mass spectrometry. Iron oxide, Pueblito de Allende chondrite, and Canyon Diablo filings in an oxidized catalyst form yielded no fatty acids. Canyon Diablo filings heated overnight at 500 C while undergoing slow purging by deuterium produced fatty acids only when potassium carbonate was admixed; potassium carbonate alone also produced these compounds. The active catalytic combinations gave relatively high yields of aliphatic and aromatic hydrocarbons; substantial amounts of n-alkenes were almost invariably observed when fatty acids were produced; the latter were in the range C6 to C18, with maximum yield in C9 or 10.

  1. Fatty acid composition of plasma lipids and erythrocyte membranes during simulated extravehicular activity

    NASA Astrophysics Data System (ADS)

    Skedina, M. A.; Katuntsev, V. P.; Buravkova, L. B.; Naidina, V. P.

    Ten subjects (from 27 to 41 years) have been participated in 32 experiments. They were decompressed from ground level to 40-35 kPa in altitude chamber when breathed 100% oxygen by mask and performed repeated cycles of exercises (3.0 Kcal/min). The intervals between decompressions were 3-5 days. Plasma lipid and erythrocyte membrane fatty acid composition was evaluated in the fasting venous blood before and immediately after hypobaric exposure. There were 7 cases decompression sickness (DCS). Venous gas bubbles (GB) were detected in 27 cases (84.4%). Any significant changes in the fatty acid composition of erythrocyte membranes and plasma didn't practically induce after the first decompression. However, by the beginning of the second decompression the total lipid level in erythrocyte membranes decreased from 54.6 mg% to 40.4 mg% in group with DCS symptoms and from 51.2 mg% to 35.2 mg% (p < 0.05) without DCS symptoms. In group with DCS symptoms a tendency to increased level of saturated fatty acids in erythrocyte membranes (16:0, 18:0), the level of the polyunsaturated linoleic fatty acid (18:2) and arachidonic acid (20:4) tended to be decreased by the beginning of the second decompression. Insignificant changes in blood plasma fatty acid composition was observed in both groups. The obtained biochemical data that indicated the simulated extravehicular activity (EVA) condition is accompanied by the certain changes in the blood lipid metabolism, structural and functional state of erythrocyte membranes, which are reversible. The most pronounced changes are found in subjects with DCS symptoms.

  2. Omega-6 Fatty Acids

    MedlinePlus

    ... 3 fatty acids for 3 months can improve reading, spelling, and behavior, but not coordination or movement in children with DCD. Laser eye surgery. Early research suggests that taking a tablet that contains an ...

  3. Trans fatty acids (image)

    MedlinePlus

    Trans fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They may be particularly dangerous for ...

  4. Mouse very long-chain Acyl-CoA synthetase 3/fatty acid transport protein 3 catalyzes fatty acid activation but not fatty acid transport in MA-10 cells.

    PubMed

    Pei, Zhengtong; Fraisl, Peter; Berger, Johannes; Jia, Zhenzhen; Forss-Petter, Sonja; Watkins, Paul A

    2004-12-24

    The family of proteins that includes very long-chain acyl-CoA synthetases (ACSVL) consists of six members. These enzymes have also been designated fatty acid transport proteins. We cloned full-length mouse Acsvl3 cDNA and characterized its protein product ACSVL3/fatty acid transport protein 3. The predicted amino acid sequence contains two highly conserved motifs characteristic of acyl-CoA synthetases. Northern blot analysis revealed that the mouse Acsvl3 mRNA is highly expressed in adrenal gland, testis, and ovary, with lower expression in the brain of adult mice. A developmental Northern blot revealed that Acsvl3 mRNA levels were significantly higher in embryonic mouse brain (embryonic days 12-14) than in newborn or adult mice, suggesting a possible role in nervous system development. Immunohistochemistry revealed high ACSVL3 expression in adrenal cortical cells, spermatocytes and interstitial cells of the testis, theca cells of the ovary, cerebral cortical neurons, and cerebellar Purkinje cells. Endogenous ACSVL3 was found primarily in mitochondria of MA-10 and Neuro2a cells by both Western blot analysis of subcellular fractions and immunofluorescence analysis. In MA-10 cells, loss-of-function studies using RNA interference confirmed that endogenous ACSVL3 is an acyl-CoA synthetase capable of activating both long-chain (C16:0) and very long-chain (C24:0) fatty acids. However, despite decreased acyl-CoA synthetase activity, initial rates of fatty acid uptake were unaffected by knockdown of Acsvl3 expression in MA-10 cells. These studies cast doubt on the designation of ACSVL3 as a fatty acid transport protein. PMID:15469937

  5. Antibacterial activity of selected fatty acids and essential oils against six meat spoilage organisms.

    PubMed

    Ouattara, B; Simard, R E; Holley, R A; Piette, G J; Bgin, A

    1997-07-22

    The antibacterial activity of selected fatty acids and essential oils was examined against two gram-negative (Pseudomonas fluorescens and Serratia liquefaciens) and four gram-positive (Brochothrix thermosphacta, Carnobacterium piscicola, Lactobacillus curvatus, and Lactobacillus sake) bacteria involved in meat spoilage. Various amounts of each preservative were added to brain heart infusion or MRS (deMan, Rogosa and Sharpe) agars, and the minimum inhibitory concentration was determined for each organism. Essential oils were analysed by gas-liquid chromatography to determine the concentration of selected components commonly found in spices. B. thermosphacta, P. fluorescens and S. liquefaciens were not affected by fatty acids, and generally overcame the inhibitory effect of essential oils after 24 h of exposure. Among the fatty acids, lauric and palmitoleic acids exhibited the greatest inhibitory effect with minimum inhibitory concentrations of 250 to 500 micrograms/ml, while myristic, palmitic, stearic and oleic acids were completely ineffective. For essential oils, clove, cinnamon, pimento, and rosemary were found to be the most active. The 1/100 dilution of those oils inhibited at least five of the six tested organisms. A relationship was found between the inhibitory effect of essential oils and the presence of eugenol and cinnamaldehyde. PMID:9310850

  6. Omega-3 fatty acid supplementation augments sympathetic nerve activity responses to physiological stressors in humans.

    PubMed

    Monahan, Kevin D; Wilson, Thad E; Ray, Chester A

    2004-11-01

    An inverse relation exists between omega-3 fatty acid intake and risk of cardiovascular disease development/mortality and sudden cardiac death in humans. Mechanisms underlying this cardioprotective effect are unknown, but could involve the autonomic nervous system. We tested the hypothesis that omega-3 fatty acid supplementation ("fish oil") would reduce muscle sympathetic nerve activity (MSNA) at rest and attenuate increases during physiological stressors. MSNA (peroneal microneurography) was measured during rest, ischemic handgrip to fatigue (IHG), and a cold pressor test (CPT). Measurements were obtained before (PRE) and after (POST) 1 month of daily ingestion of either fish oil (experimental group, n=9) or olive oil capsules (control group, n=9). MSNA at rest was comparable PRE and POST in control (3+/-1 versus 3+/-1 bursts/30 seconds) and experimental (4+/-1 versus 5+/-1 bursts/30 seconds) subjects. IHG and CPT increased MSNA in both groups PRE and POST. MSNA, arterial blood pressure, and heart rate responses to the stressors were similar PRE and POST in the control group. In contrast, MSNA responses to IHG (Delta4+/-2 and Delta9+/-2 bursts/30 seconds; P<0.05 for PRE and POST, respectively) and CPT (Delta4+/-1 versus Delta10+/-2 bursts/30 seconds; P<0.05) were augmented after omega-3 fatty acid supplementation whereas arterial blood pressure and heart rate responses were unchanged. These data indicate that 1 month of omega-3 fatty acid supplementation does not change MSNA at rest but augments sympathetic outflow to physiological stressors. The mechanism underlying augmented MSNA responses to physiological stressors after omega-3 fatty acid supplementation is unknown, but may involve impaired peripheral vasoconstriction. PMID:15452023

  7. Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPARγ and Fatty Acid Uptake.

    PubMed

    Labrie, Marilyne; Lalonde, Simon; Najyb, Ouafa; Thiery, Maxime; Daneault, Caroline; Des Rosiers, Chrisitne; Rassart, Eric; Mounier, Catherine

    2015-01-01

    Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice. Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation. Expression of the fatty acid transporter CD36, another PPARgamma target, is also increased in Tg mice associated with elevated fatty acid uptake as measured in primary hepatocytes. Elevated expression of AMPK in the liver of Tg leads to phosphorylation of acetyl CoA carboxylase, indicating a decreased activity of the enzyme. Fatty acid synthase expression is also induced but the hepatic lipogenesis measured in vivo is not significantly different between WT and Tg mice. In addition, expression of carnitine palmitoyl transferase 1, the rate-limiting enzyme of beta-oxidation, is slightly upregulated. Finally, we show that overexpressing H-apoD in HepG2 cells in presence of arachidonic acid (AA), the main apoD ligand, increases the transcriptional activity of PPARγ. Supporting the role of apoD in AA transport, we observed enrichment in hepatic AA and a decrease in plasmatic AA concentration. Taken together, our results demonstrate that the hepatic steatosis observed in apoD Tg mice is a consequence of increased PPARγ transcriptional activity by AA leading to increased fatty acid uptake by the liver. PMID:26083030

  8. Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPARγ and Fatty Acid Uptake

    PubMed Central

    Labrie, Marilyne; Lalonde, Simon; Najyb, Ouafa; Thiery, Maxime; Daneault, Caroline; Des Rosiers, Chrisitne; Rassart, Eric; Mounier, Catherine

    2015-01-01

    Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice. Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation. Expression of the fatty acid transporter CD36, another PPARgamma target, is also increased in Tg mice associated with elevated fatty acid uptake as measured in primary hepatocytes. Elevated expression of AMPK in the liver of Tg leads to phosphorylation of acetyl CoA carboxylase, indicating a decreased activity of the enzyme. Fatty acid synthase expression is also induced but the hepatic lipogenesis measured in vivo is not significantly different between WT and Tg mice. In addition, expression of carnitine palmitoyl transferase 1, the rate-limiting enzyme of beta-oxidation, is slightly upregulated. Finally, we show that overexpressing H-apoD in HepG2 cells in presence of arachidonic acid (AA), the main apoD ligand, increases the transcriptional activity of PPARγ. Supporting the role of apoD in AA transport, we observed enrichment in hepatic AA and a decrease in plasmatic AA concentration. Taken together, our results demonstrate that the hepatic steatosis observed in apoD Tg mice is a consequence of increased PPARγ transcriptional activity by AA leading to increased fatty acid uptake by the liver. PMID:26083030

  9. Activity of Bradykinin B2 Receptor Is Regulated by Long-Chain Polyunsaturated Fatty Acids.

    PubMed

    Candelario, Jose; Chachisvilis, Mirianas

    2013-01-01

    The molecular and cellular mechanisms by which long-chain polyunsaturated fatty acids (LCPUFA) exert their beneficial effects on cardiovascular health remain obscure. While both LCPUFA and bradykinin (BK) signaling pathway play a role in the cardiovascular system, any direct link between the two is yet to be established. Using picosecond time-resolved fluorescence microscopy and a genetically engineered bradykinin B2 receptor (B2R) sensor (B2K-CC), we detected LCPUFA-induced conformational responses in the B2R similar to those caused by its cognate ligand, BK. The selective B2R antagonist (HOE-140) blocked the eicosapentaenoic acid (EPA, C20∶5, n-3) induced conformational response of the B2K-CC. Further analysis suggests that LCPUFA are capable of direct, B2R-dependent activation of extracellular ligand-regulated kinases (ERK). From a wide range of fatty acids studied, varying in chain length, saturation, and position of double bonds, EPA, docosahexaenoic (DHA, C22∶6, n-3), docosadienoic (DDA, C22∶2, n-6), and dihomo-gamma linoleic (DGLA, C20∶3, n-6) fatty acids caused the highest ERK phosphorylation. EPA or DHA dependent ERK phosphorylation was inhibited by the selective B2R antagonist. We show that LCPUFA stimulates downstream signaling by B2R such as B2R-dependent phosphorylation and expression regulation of endothelial nitric-oxide synthase (eNOS). Further analysis indicated that LCPUFA also alters levels of the eNOS transcription factor, kruppel-like factor 2 (KLF2). Moreover we show that EPA increases membrane fluidity on the same time scale as B2R conformational response, suggesting that partitioning of LCPUFA into bilayer is a primary step required for receptor activation. In summary our data show that LCPUFA activate B2R receptor at nanomolar concentrations suggesting a novel molecular mechanism by which fatty acids may affect the cardiovascular system. PMID:23826374

  10. Understanding Fatty Acid Metabolism through an Active Learning Approach

    ERIC Educational Resources Information Center

    Fardilha, M.; Schrader, M.; da Cruz e Silva, O. A. B.; da Cruz e Silva, E. F.

    2010-01-01

    A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less

  11. Understanding Fatty Acid Metabolism through an Active Learning Approach

    ERIC Educational Resources Information Center

    Fardilha, M.; Schrader, M.; da Cruz e Silva, O. A. B.; da Cruz e Silva, E. F.

    2010-01-01

    A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less…

  12. Fatty Acid Profile and Biological Activities of Linseed and Rapeseed Oils.

    PubMed

    Lewinska, Anna; Zebrowski, Jacek; Duda, Magdalena; Gorka, Anna; Wnuk, Maciej

    2015-01-01

    It has been postulated that fatty acids found in edible oils may exert beneficial health effects by the modulation of signaling pathways regulating cell differentiation and proliferation, especially in the treatment of cardiovascular diseases. In the present study, the biological effects of selected edible oils-linseed (LO) and rapeseed (RO) oils-were tested in vitro on fibroblast cells. The fatty acid profile of the oils was determined using gas chromatography and FTIR spectroscopy. LO was found to be rich in α-linolenic acid (ALA), whereas oleic acid was the most abundant species in RO. Fatty acids were taken up by the cells and promoted cell proliferation. No oxidative stress-mediated cytotoxic or genotoxic effects were observed after oil stimulation. Oils ameliorated the process of wound healing as judged by improved migration of fibroblasts to the wounding area. As ALA-rich LO exhibited the most potent wound healing activity, ALA may be considered a candidate for promoting the observed effect. PMID:26703545

  13. Modulation of peritoneal macrophage activity by the saturation state of the fatty acid moiety of phosphatidylcholine.

    PubMed

    Grando, F C C; Felício, C A; Twardowschy, A; Paula, F M; Batista, V G; Fernandes, L C; Curi, R; Nishiyama, A

    2009-07-01

    To determine the effects of saturated and unsaturated fatty acids in phosphatidylcholine (PC) on macrophage activity, peritoneal lavage cells were cultured in the presence of phosphatidylcholine rich in saturated or unsaturated fatty acids (sat PC and unsat PC, respectively), both used at concentrations of 32 and 64 microM. The treatment of peritoneal macrophages with 64 microM unsat PC increased the production of hydrogen peroxide by 48.3% compared to control (148.3 +/- 16.3 vs 100.0 +/- 1.8%, N = 15), and both doses of unsat PC increased adhesion capacity by nearly 50%. Moreover, 64 microM unsat PC decreased neutral red uptake by lysosomes by 32.5% compared to the untreated group (67.5 +/- 6.8 vs 100.0 +/- 5.5%, N = 15), while both 32 and 64 microM unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 +/- 2.6 vs 19.4 +/- 2.5 microM) and 46.4% (10.4 +/- 3.1 vs 19.4 +/- 2.5 microM), respectively. Unsat PC did not affect anion production in non-stimulated cells or phagocytosis of unopsonized zymosan particles. A different result pattern was obtained for macrophages treated with sat PC. Phorbol 12-miristate 13-acetate-elicited superoxide production and neutral red uptake were decreased by nearly 25% by 32 and 64 microM sat PC, respectively. Sat PC did not affect nitric oxide or hydrogen peroxide production, adhesion capacity or zymosan phagocytosis. Thus, PC modifies macrophage activity, but this effect depends on cell activation state, fatty acid saturation and esterification to PC molecule and PC concentration. Taken together, these results indicate that the fatty acid moiety of PC modulates macrophage activity and, consequently, is likely to affect immune system regulation in vivo. PMID:19466285

  14. Surface-Active and Performance Properties of Cationic Imidazolinium Surfactants Based on Different Fatty Acids

    NASA Astrophysics Data System (ADS)

    Bajpai, Divya; Tyagi, V. K.

    Imidazoline surfactants belong to the category of cationic surfactants. Cationic surfactants are often quaternary nitrogen salts and are widely used both in nonaqueous systems and in applications such as textile softeners, dispersants, and emulsifiers. This study describes the surface-active properties of cationic imidazolinium surfactants synthesized from different fatty acids. Their laundry performance in combination with nonionic surfactants like detergency, foaming property, softening property, rewettability etc., is also emphasized.

  15. Antifungal Hydroxy Fatty Acids Produced during Sourdough Fermentation: Microbial and Enzymatic Pathways, and Antifungal Activity in Bread

    PubMed Central

    Black, Brenna A.; Zannini, Emanuele; Curtis, Jonathan M.

    2013-01-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli grown in modified De Man Rogosa Sharpe medium or sourdough were assayed for antifungal activity. Lactobacillus hammesii exhibited increased antifungal activity upon the addition of linoleic acid as a substrate. Bioassay-guided fractionation attributed the antifungal activity of L. hammesii to a monohydroxy C18:1 fatty acid. Comparison of its antifungal activity to those of other hydroxy fatty acids revealed that the monohydroxy fraction from L. hammesii and coriolic (13-hydroxy-9,11-octadecadienoic) acid were the most active, with MICs of 0.1 to 0.7 g liter?1. Ricinoleic (12-hydroxy-9-octadecenoic) acid was active at a MIC of 2.4 g liter?1. L. hammesii accumulated the monohydroxy C18:1 fatty acid in sourdough to a concentration of 0.73 0.03 g liter?1 (mean standard deviation). Generation of hydroxy fatty acids in sourdough also occurred through enzymatic oxidation of linoleic acid to coriolic acid. The use of 20% sourdough fermented with L. hammesii or the use of 0.15% coriolic acid in bread making increased the mold-free shelf life by 2 to 3 days or from 2 to more than 6 days, respectively. In conclusion, L. hammesii converts linoleic acid in sourdough and the resulting monohydroxy octadecenoic acid exerts antifungal activity in bread. PMID:23315734

  16. Antioxidant activity and fatty acid profile of fermented milk prepared by Pediococcus pentosaceus.

    PubMed

    Balakrishnan, Gayathri; Agrawal, Renu

    2014-12-01

    Probiotics are the class of beneficial microorganisms that have positive influence on the health when ingested in adequate amounts. Probiotic fermented milk is one of the dairy products that is prepared by using probiotic lactic acid bacteria. The study comprised preparation of fermented milk from various sources such as cow, goat and camel. Pediococcus pentosaceus which is a native laboratory isolate from cheese was utilized for the product formation. Changes in functional properties in the fermented milks obtained from three different species were evaluated. Antioxidant activity determined by DPPH assay showed activity in probiotic fermented milk obtained from all the products being highest in goat milk (93 %) followed by product from camel milk (86 %) and then product from cow milk (79 %). The composition of beneficial fatty acids such as stearic acid, oleic acid and linoleic acid were higher in fermented milk than the unfermented ones. Results suggested that probiotic bacteria are able to utilize the nutrients in goat and camel milk more efficiently compared to cow milk. Increase in antioxidant activity and fatty acid profile of fermented milks enhances the therapeutic value of the products. PMID:25477694

  17. Bioconversion of volatile fatty acids derived from waste activated sludge into lipids by Cryptococcus curvatus.

    PubMed

    Liu, Jia; Liu, Jia-Nan; Yuan, Ming; Shen, Zi-Heng; Peng, Kai-Ming; Lu, Li-Jun; Huang, Xiang-Feng

    2016-07-01

    Pure volatile fatty acid (VFA) solution derived from waste activated sludge (WAS) was used to produce microbial lipids as culture medium in this study, which aimed to realize the resource recovery of WAS and provide low-cost feedstock for biodiesel production simultaneously. Cryptococcus curvatus was selected among three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by struvite precipitation. The lipid content further increased to 39.6% and the biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA solution contained nearly 50% of monounsaturated fatty acids, including palmitic acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic acid, which showed the adequacy of biodiesel production. PMID:27038264

  18. UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis

    PubMed Central

    Moon, Jong-Seok; Lee, Seonmin; Park, Mi-Ae; Siempos, Ilias I.; Haslip, Maria; Lee, Patty J.; Yun, Mijin; Kim, Chun K.; Howrylak, Judie; Ryter, Stefan W.; Nakahira, Kiichi; Choi, Augustine M.K.

    2015-01-01

    Cellular lipid metabolism has been linked to immune responses; however, the precise mechanisms by which de novo fatty acid synthesis can regulate inflammatory responses remain unclear. The NLRP3 inflammasome serves as a platform for caspase-1–dependent maturation and secretion of proinflammatory cytokines. Here, we demonstrated that the mitochondrial uncoupling protein-2 (UCP2) regulates NLRP3-mediated caspase-1 activation through the stimulation of lipid synthesis in macrophages. UCP2-deficient mice displayed improved survival in a mouse model of polymicrobial sepsis. Moreover, UCP2 expression was increased in human sepsis. Consistently, UCP2-deficient mice displayed impaired lipid synthesis and decreased production of IL-1β and IL-18 in response to LPS challenge. In macrophages, UCP2 deficiency suppressed NLRP3-mediated caspase-1 activation and NLRP3 expression associated with inhibition of lipid synthesis. In UCP2-deficient macrophages, inhibition of lipid synthesis resulted from the downregulation of fatty acid synthase (FASN), a key regulator of fatty acid synthesis. FASN inhibition by shRNA and treatment with the chemical inhibitors C75 and cerulenin suppressed NLRP3-mediated caspase-1 activation and inhibited NLRP3 and pro–IL-1β gene expression in macrophages. In conclusion, our results suggest that UCP2 regulates the NLRP3 inflammasome by inducing the lipid synthesis pathway in macrophages. These results identify UCP2 as a potential therapeutic target in inflammatory diseases such as sepsis. PMID:25574840

  19. Effect of fatty acids and their acyl-CoA esters on protein kinase C activity in fibroblasts: possible implications in fatty acid oxidation defects.

    PubMed

    Nesher, M; Boneh, A

    1994-03-10

    We studied the effect of fatty acids and their acyl-CoA esters on protein kinase C (PK-C) activity in human skin fibroblasts. Butyrate, octanoate, palmitate and oleate did not alter PK-C activity in either cytosolic or particulate fraction. In the presence of calcium, phosphatidylserine and diacylglycerol, both palmitoyl-CoA (Pal-CoA) and oleoyl-CoA (Ole-CoA) enhanced particulate PK-C activity by approx. 70% and octanoyl-CoA (Oct-CoA) by approx. 35%. Partially purified cytosolic PK-C activity was enhanced by 60-70% by 13.5 microM of either Pal-CoA or Ole-CoA. Basal histone phosphorylation (i.e., PK-C-independent phosphorylation) was decreased in the particulate fraction in the presence of these esters in a concentration-dependent manner. Both Pal-CoA and Ole-CoA fully substituted diacylglycerol in activating the kinase in both the cytosolic and particulate fractions, whereas Oct-CoA had a moderate effect. The pattern of endogenous cytosolic and particulate protein phosphorylation was altered in the presence of either Pal-CoA or Ole-CoA. We conclude that long-chain fatty acyl-CoA esters may activate PK-C in non-stimulated fibroblasts, i.e., in the absence of physiological diacylglycerol formation. Activation of PK-C in stimulated fibroblasts, i.e., in the presence of an elevated diacylglycerol concentration, is less pronounced. These results support the hypothesis that activation of PK-C and alteration of endogenous protein phosphorylation may play a role in the pathogenesis of diseases in which there is intracellular accumulation of fatty acyl-CoA esters, such as in inborn fatty-acid oxidation defects. PMID:8130278

  20. Discovery of essential fatty acids

    PubMed Central

    Spector, Arthur A.; Kim, Hee-Yong

    2015-01-01

    Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684

  1. An active site mutant of Escherichia coli cyclopropane fatty acid synthase forms new non-natural fatty acids providing insights on the mechanism of the enzymatic reaction.

    PubMed

    E, Guangqi; Drujon, Thierry; Correia, Isabelle; Ploux, Olivier; Guianvarc'h, Dominique

    2013-12-01

    We have produced and purified an active site mutant of the Escherichia coli cyclopropane fatty acid synthase (CFAS) by replacing the strictly conserved G236 within cyclopropane synthases, by a glutamate residue, which corresponds to E146 of the homologous mycolic acid methyltransferase, Hma, producing hydroxymethyl mycolic acids. The G236E CFAS mutant had less than 1% of the in vitro activity of the wild type enzyme. We expressed the G236E CFAS mutant in an E. coli (DE3) strain in which the chromosomal cfa gene had been deleted. After extraction of phospholipids and conversion into the corresponding fatty acid methyl esters (FAMEs), we observed the formation of cyclopropanated FAMEs suggesting that the mutant retained some of the normal activity in vivo. However, we also observed the formation of new C17 methyl-branched unsaturated FAMEs whose structures were determined using GC/MS and NMR analyses. The double bond was located at different positions 8, 9 or 10, and the methyl group at position 10 or 9. Thus, this new FAMEs are likely arising from a 16:1 acyl chain of a phospholipid that had been transformed by the G236E CFAS mutant in vivo. The reaction catalyzed by this G236E CFAS mutant thus starts by the methylation of the unsaturated acyl chain at position 10 or 9 yielding a carbocation at position 9 or 10 respectively. It follows then two competing steps, a normal cyclopropanation or hydride shift/elimination events giving different combinations of alkenes. This study not only provides further evidence that cyclopropane synthases (CSs) form a carbocationic intermediate but also opens the way to CSs engineering for the synthesis of non-natural fatty acids. PMID:23954860

  2. Aedes aegypti (Diptera: culicidae) biting deterrence: structure-activity relationship of saturated and unsaturated fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study we systematically evaluated for the first time the biting deterrent effects of a series of saturated and unsaturated fatty acids against Aedes aegypti [yellow fever mosquito (Diptera: Culicidae)] using the K & D bioassay system (Klun et al 2005). The saturated fatty acids (C6:0 to C16...

  3. Polyunsaturated Fatty Acids in Children

    PubMed Central

    2013-01-01

    Polyunsaturated fatty acids (PUFAs) are the major components of brain and retina, and are the essential fatty acids with important physiologically active functions. Thus, PUFAs should be provided to children, and are very important in the brain growth and development for fetuses, newborn infants, and children. Omega-3 fatty acids decrease coronary artery disease and improve blood flow. PUFAs have been known to have anti-inflammatory action and improved the chronic inflammation such as auto-immune diseases or degenerative neurologic diseases. PUFAs are used for metabolic syndrome related with obesity or diabetes. However, there are several considerations related with intake of PUFAs. Obsession with the intake of unsaturated fatty acids could bring about the shortage of essential fatty acids that are crucial for our body, weaken the immune system, and increase the risk of heart disease, arrhythmia, and stroke. In this review, we discuss types, physiologic mechanism of action of PUFAs, intake of PUFAs for children, recommended intake of PUFAs, and considerations for the intake of PUFAs. PMID:24224148

  4. Mechanisms of action of dietary fatty acids in regulating the activation of vascular endothelial cells during atherogenesis.

    PubMed

    Christon, Raymond A

    2003-08-01

    Dietary long chain omega-3 polyunsaturated fatty acids from fish oil appear to be clearly efficient in regulating endothelial dysfunction (or activation), which is the first stage of atherogenesis. Studies on endothelial cells in vitro have shown that the main dietary PUFA and oleic acid may prevent endothelium activation either by inhibiting the expression of adhesion molecules or by improving the nitric oxide production. Saturated fatty acids and also linoleic acid do not inhibit endothelium activation. The mechanisms involved in this inhibition could be related to endothelial cell membrane characteristics or redox status. However, these findings need to be confirmed in vivo. PMID:13677589

  5. Developmental effects of dietary n-3 fatty acids on activity and response to novelty.

    PubMed

    Levant, Beth; Zarcone, Troy J; Fowler, Stephen C

    2010-08-01

    Insufficient availability of n-3 polyunsaturated fatty acids (PUFA) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain. Low tissue levels of DHA are associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD). In this study, 1st- and 2nd-litter male Long-Evans rats were raised from conception on a Control diet containing alpha-linolenic acid (4.20 g/kg diet), the dietarily essential fatty acid precursor of DHA, or a diet Deficient in alpha-linolenic acid (0.38 g/kg diet). The Deficient diet resulted in a decrease in brain phospholipid DHA of 48% in 1st-litter pups and 65% in 2nd-litter pups. Activity, habituation, and response to spatial change in a familiar environment were assessed in a single-session behavioral paradigm at postnatal days 28 and 70, inclusive. Activity and habituation varied by age with younger rats exhibiting higher activity, less habituation, and less stimulation of activity induced by spatial novelty. During the first and second exposures to the test chamber, 2nd-litter Deficient pups exhibited higher levels of activity than Control rats or 1st-litter Deficient pups, and less habituation during the first exposure, but were not more active after introduction of a novel spatial stimulus. The higher level of activity in a familiar environment, but not after introduction of a novel stimulus is consistent with clinical observations in ADHD. The observation of this effect only in 2nd-litter rats fed the Deficient diet suggests that brain DHA content, rather than dietary n-3 PUFA content, likely underlies these effects. PMID:20457171

  6. Stable isotope liquid chromatography-tandem mass spectrometry assay for fatty acid amide hydrolase activity.

    PubMed

    Rakers, Christin; Zoerner, Alexander A; Engeli, Stefan; Batkai, Sandor; Jordan, Jens; Tsikas, Dimitrios

    2012-02-15

    Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the hydrolysis of the endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) to arachidonic acid (AA) and ethanolamine (EA). Published FAAH activity assays mostly employ radiolabeled anandamide or synthetic fluorogenic substrates. We report a stable isotope liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for specific, sensitive, and high-throughput capable FAAH activity measurements. The assay uses AEA labeled with deuterium on the EA moiety (d₄-AEA) as substrate and measures the specific reaction product tetradeutero-EA (d₄-EA) and the internal standard ¹³C₂-EA. Selected reaction monitoring of m/z 66→m/z 48 (d₄-EA) and m/z 64→m/z 46 (¹³C₂-EA) in the positive electrospray ionization mode after liquid chromatographic separation on a HILIC (hydrophilic interaction liquid chromatography) column is performed. The assay was developed and thoroughly validated using recombinant human FAAH (rhFAAH) and then was applied to human blood and dog liver samples. rhFAAH-catalyzed d₄-AEA hydrolysis obeyed Michaelis-Menten kinetics (K(M)=12.3 μM, V(max)=27.6 nmol/min mg). Oleoyl oxazolopyridine (oloxa) was a potent, partial noncompetitive inhibitor of rhFAAH (IC₅₀=24.3 nM). Substrate specificity of other fatty acid ethanolamides decreased with decreasing length, number of double bonds, and lipophilicity of the fatty acid skeleton. In human whole blood, we detected FAAH activity that was inhibited by oloxa. PMID:22146559

  7. Phytochemical Analysis, Antioxidant Activity, Fatty Acids Composition, and Functional Group Analysis of Heliotropium bacciferum

    PubMed Central

    Ahmad, Sohail; Ahmad, Shabir; Bibi, Ahtaram; Ishaq, Muhammad Saqib; Afridi, Muhammad Siddique; Kanwal, Farina; Zakir, Muhammad; Fatima, Farid

    2014-01-01

    Heliotropium bacciferum is paramount in medicinal perspective and belongs to Boraginaceae family. The crude and numerous fractions of leaves, stem, and roots of the plant were investigated for phytochemical analysis and DPPH radical scavenging activity. Phytochemical analysis of crude and fractions of the plant revealed the presence of alkaloids, saponins, tannins, steroids, terpenoids, flavonoids, glycosides, and phenols. The antioxidant (free radical scavenging) activity of various extracts of the Heliotropium bacciferum was resolute against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical with the avail of UV spectrophotometer at 517 nm. The stock solution (1000 mg/mL) and then several dilutions (50, 100, 150, 200, and 250 mg/mL) of the crude and fractions were prepared. Ascorbic acid was used as a standard. The plant leaves (52.59 ± 0.84 to 90.74 ± 1.00), stem (50.19 ± 0.92 to 89.42 ± 1.10), and roots extracts (49.19 ± 0.52 to 90.01 ± 1.02) divulged magnificent antioxidant activities. For the ascertainment of the fatty acid constituents a gas chromatograph hyphenated to mass spectrometer was used. The essential fatty acids for growth maintenance such as linoleic acid (65.70%), eicosadienoic acid (15.12%), oleic acid (8.72%), and palmitic acid (8.14%) were found in high percentage. The infrared spectra of all extracts of the plant were recorded by IR Prestige-21 FTIR model. PMID:25489605

  8. Inhibitory activities of omega-3 Fatty acids and traditional african remedies on keloid fibroblasts.

    PubMed

    Olaitan, Peter B; Chen, I-Ping; Norris, James E C; Feinn, Richard; Oluwatosin, Odunayo M; Reichenberger, Ernst J

    2011-04-01

    Keloids develop when scar tissue responds to skin trauma with proliferative fibrous growths that extend beyond the boundaries of the original wound and progress for several months or years. Keloids most frequently occur in individuals of indigenous sub-Saharan African origin. The etiology for keloids is still unknown and treatment can be problematic as patients respond differently to various treatment modalities. Keloids have a high rate of recurrence following surgical excision. Some West African patients claim to have had successful outcomes with traditional African remedies-boa constrictor oil (BCO) and shea butter-leading the authors to investigate their effects on cultured fibroblasts. The effects of emulsions of BCO, fish oil, isolated omega-3 fatty acids, and shea butter were tested in comparison to triamcinolone regarding inhibition of cell growth in keloid and control fibroblast cultures. In a series of controlled studies, it was observed that fish oil and BCO were more effective than triamcinolone, and that cis-5, 8, 11, 14, 17-eicosapentaenoic acid was more effective than -linolenic acid. While cell counts in control cultures continuously decreased over a period of 5 days, cell counts in keloid cultures consistently declined between day 1 and day 3, and then increased between day 3 and day 5 for all tested reagents except for fish oil. These results suggest that oils rich in omega-3 fatty acids may be effective in reducing actively proliferating keloid fibroblasts. Additional studies are warranted to investigate whether oils rich in omega-3 fatty acids offer effective and affordable treatment for some keloid patients, especially in the developing world. PMID:24489452

  9. Study on Synthesis, Characterization and Antiproliferative Activity of Novel Diisopropylphenyl Esters of Selected Fatty Acids.

    PubMed

    Reddy, Yasa Sathyam; Kaki, Shiva Shanker; Rao, Bala Bhaskara; Jain, Nishant; Vijayalakshmi, Penumarthy

    2016-01-01

    The present study describes the synthesis, characterization and evaluation of antiproliferative activity of novel diisopropylphenyl esters of alpha-linolenic acid (ALA), valproic acid (VA), butyric acid (BA) and 2-ethylhexanoic acid (2-EHA). These esters were chemically synthesized by the esterification of fatty acids with 2,6-diisopropylphenol and 2,4-diisopropylphenol (propofol). The structure of new conjugates viz. propofol-(alpha-linolenic acid) (2,6P-ALA and 2,4P-ALA), propofol-valproic acid (2,6P-VA and 2,4P-VA), propofol-butyric acid (2,6P-BA and 2,4P-BA) and propofol-(2-ethylhexanoic acid) (2,6P2-EHA and 2,4P-2-EHA) were characterized by FT-IR, NMR ((1)H, (13)C) and mass spectral data. The synthesized conjugates having more lipophilic character were tested for antiproliferative in vitro studies on A549, MDA-MB-231, HeLa, Mia-Pa-Ca and HePG2 cancer cell lines. All the conjugates showed specific growth inhibition on studied cancer cell lines. Among the synthesized esters, the conjugates synthesized from BA, VA and 2-EHA exhibited prominent growth inhibition against A549, HeLa, Mia-Pa-Ca and HePG2 cancer cell lines. The preliminary results suggest that the entire novel conjugates possess antiproliferative properties that reduce the proliferation of cancer cells in vitro. PMID:26666272

  10. Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo.

    PubMed

    Zadeh-Tahmasebi, Melika; Duca, Frank A; Rasmussen, Brittany A; Bauer, Paige V; Côté, Clémence D; Filippi, Beatrice M; Lam, Tony K T

    2016-04-15

    Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fatty acids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fatty acid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo We further demonstrate that an ileal glucagon-like peptide-1 receptor-dependent neuronal network is necessary for ileal propionate and long chain fatty acid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fatty acid sensing machinery in the ileum to regulate glucose homeostasis. PMID:26896795

  11. One-step production of a biologically active novel furan fatty acid from 7,10-dihydroxy-8(E)-octadecenoic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Furan fatty acids (F-acids) gain special attentions since they are known to play important roles in biological systems including humans. Specifically F-acids are known to have strong antioxidant activity like radical scavenging activity. Although widely distributed in most biological systems, F-ac...

  12. (Radioiodinated free fatty acids)

    SciTech Connect

    Knapp, Jr., F. F.

    1987-12-11

    The traveler participated in the Second International Workshop on Radioiodinated Free Fatty Acids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fatty acids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.

  13. PGC-1β suppresses saturated fatty acid-induced macrophage inflammation by inhibiting TAK1 activation.

    PubMed

    Chen, Hongen; Liu, Yan; Li, Di; Song, Jiayi; Xia, Min

    2016-02-01

    Inflammation of infiltrated macrophages in adipose tissue is a key contributor to the initiation of adipose insulin resistance. These macrophages are exposed to high local concentrations of free fatty acids (FFAs) and can be proinflammatory activated by saturated fatty acids (SFAs). However, the regulatory mechanisms on SFA-induced macrophage inflammation are still elusive. Peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β) is a member of the PGC-1 family of transcriptional coactivators and has been reported to play a key role in SFAs metabolism and in the regulation of inflammatory signaling. However, it remains unclear whether PGC-1β is involved in SFA-induced macrophage inflammation. In this study, we found that PGC-1β expression was significantly decreased in response to palmitic acid (PA) in macrophages in a dose dependent manner. PGC-1β inhibited PA induced TNFα, MCP-1, and IL-1β mRNA and protein expressions. Furthermore, PGC-1β significantly antagonized PA induced macrophage nuclear factor-κB (NF-κB) p65 and JUN N-terminal kinase activation. Mechanistically, we revealed that TGF-β-activated kinase 1 (TAK1) and its adaptor protein TAK1 binding protein 1 (TAB1) played a dominant role in the regulatory effects of PGC-1β. We confirmed that PGC-1β inhibited downstream inflammatory signals via binding with TAB1 and thus preventing TAB1/TAK1 binding and TAK1 activation. Finally, we showed that PGC-1β overexpression in PA treated macrophages improved adipocytes PI3K-Akt insulin signaling in a paracrine fashion. Collectively, our results uncovered a novel mechanism on how macrophage inflammation induced by SFAs was regulated and suggest a potential target in the treatment of obesity induced insulin resistance. © 2016 IUBMB Life, 68(2):145-155, 2016. PMID:26748475

  14. Type I and type II fatty acid biosynthesis in Eimeria tenella : enoyl reductase activity and structure

    PubMed Central

    Lu, J. Z.; Muench, S. P.; Allary, M.; Campbell, S.; Roberts, C. W.; Mui, E.; McLeod, R. L.; Rice, D. W.; Prigge, S. T.

    2009-01-01

    SUMMARY Apicomplexan parasites of the genus Eimeria are the major causative agent of avian coccidiosis, leading to high economic losses in the poultry industry. Recent results show that Eimeria tenella harbours an apicoplast organelle, and that a key biosynthetic enzyme, enoyl reductase, is located in this organelle. In related parasites, enoyl reductase is one component of a type II fatty acid synthase (FAS) and has proven to be an attractive target for antimicrobial compounds. We cloned and expressed the mature form of E. tenella enoyl reductase (EtENR) for biochemical and structural studies. Recombinant EtENR exhibits NADH-dependent enoyl reductase activity and is inhibited by triclosan with an IC50 value of 60 nM. The crystal structure of EtENR reveals overall similarity with other ENR enzymes; however, the active site of EtENR is unoccupied, a state rarely observed in other ENR structures. Furthermore, the position of the central beta-sheet appears to block NADH binding and would require significant movement to allow NADH binding, a feature not previously seen in the ENR family. We analysed the E. tenella genomic database for orthologues of well-characterized bacterial and apicomplexan FAS enzymes and identified 6 additional genes, suggesting that E. tenella contains a type II FAS capable of synthesizing saturated, but not unsaturated, fatty acids. Interestingly, we also identified sequences that appear to encode multifunctional type I FAS enzymes, a feature also observed in Toxoplasma gondii, highlighting the similarity between these apicomplexan parasites. PMID:17697396

  15. Shc Proteins Influence the Activities of Enzymes Involved in Fatty Acid Oxidation and Ketogenesis

    PubMed Central

    Hagopian, Kevork; Tomilov, Alexey A.; Tomilova, Natalia; Kim, Kyoungmi; Taylor, Sandra L.; Lam, Adam K.; Cortopassi, Gino A.; McDonald, Roger B.; Ramsey, Jon J.

    2012-01-01

    Objective ShcKO mice have low body fat and resist weight gain on a high fat diet, indicating that Shc proteins may influence enzymes involved in β-oxidation. To investigate this idea, the activities of β-oxidation and ketone body metabolism enzymes were measured. Methods The activities of β-oxidation enzymes (acyl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and ketoacyl-CoA thiolase) in liver and hindlimb skeletal muscle, ketolytic enzymes (acetoacetyl-CoA thiolase, β-hydroxybutyrate dehydrogenase and 3-oxoacid-CoA transferase) in skeletal muscle, and ketogenic enzymes (acetoacetyl-CoA thiolase and β-hydroxybutyrate dehydrogenase) in liver were measured from wild-type and ShcKO mice. Results The activities of β-oxidation enzymes were increased (P < 0.05) in the ShcKO compared to wild-type mice in the fasted but not the fed state. In contrast, no uniform increases in the ketolytic enzyme activities were observed between ShcKO and wild-type mice. In liver, the activities of ketogenic enzymes were increased (P < 0.05) in ShcKO compared to wild-type mice in both the fed and fasted states. Levels of phosphorylated hormone sensitive lipase from adipocytes were also increased (P < 0.05) in fasted ShcKO mice. Conclusions These studies indicate that the low Shc levels in ShcKO mice result in increased liver and muscle β-oxidation enzyme activities in response to fasting and induce chronic increases in the activity of liver ketogenic enzymes. Decreases in the level of Shc proteins should be considered as possible contributors to the increase in activity of fatty acid oxidation enzymes in response to physiological conditions which increase reliance on fatty acids as a source of energy. PMID:22683097

  16. Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls

    PubMed Central

    Majkova, Zuzana; Layne, Joseph; Sunkara, Manjula; Morris, Andrew J.; Toborek, Michal; Hennig, Bernhard

    2011-01-01

    Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fatty acids, such as docosahexaenoic acid (DHA, 22:6ω-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fatty acid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-κB (NF-κB). A4/J4-neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH.. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH4), which concurrently abrogated A4/J4-NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1)by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A4/J4NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5ω-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2)and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A4/J4-NPs as mediators of omega-3 fatty acid-mediated protection against the endothelial toxicity of coplanar PCBs. PMID:21130106

  17. Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls

    SciTech Connect

    Majkova, Zuzana; Layne, Joseph; Sunkara, Manjula; Morris, Andrew J.; Toborek, Michal; Hennig, Bernhard

    2011-02-15

    Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fatty acids, such as docosahexaenoic acid (DHA, 22:6{omega}-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fatty acid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-{kappa}B (NF-{kappa}B). A{sub 4}/J{sub 4}-neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH{sub 4}), which concurrently abrogated A{sub 4}/J{sub 4}-NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A{sub 4}/J{sub 4} NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5{omega}-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2) and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A{sub 4}/J{sub 4}-NPs as mediators of omega-3 fatty acid-mediated protection against the endothelial toxicity of coplanar PCBs.

  18. Continuous volatile fatty acid production from waste activated sludge hydrolyzed at pH 12.

    PubMed

    Yang, Xue; Wan, Chunli; Lee, Duu-Jong; Du, Maoan; Pan, Xiangliang; Wan, Fang

    2014-09-01

    This study adopted rapid alkaline treatment at pH 12 to hydrolyze 66% of total chemical oxygen demands. Then the hydrolyzed liquor was fermented in a continuous-flow stirred reactor to produce volatile fatty acids (VFAs) at 8-h hydraulic retention time and at 35 °C. The maximum VFA productivity reached 365 mg VFAs g(-1) volatile suspended solids in a 45-d operation, with most produced VFAs being acetate and propionate, principally produced by protein degradation. The Bacteroidia, ε-proteobacteria and the Clostridia were identified to be the classes correlating with the fermentation processes. The fermented liquor was applied to denitrifying phosphorus removal process as alternative carbon source after excess phosphorus and nitrogen being recycled via struvite precipitation. Fermented liquors from alkaline hydrolysis-acid fermentation on waste activated sludge are a potential renewable resource for applications that need organic carbons. PMID:24630368

  19. Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against Mycobacterium tuberculosis.

    PubMed

    Sittiwong, Wantanee; Zinniel, Denise K; Fenton, Robert J; Marshall, Darrell D; Story, Courtney B; Kim, Bohkyung; Lee, Ji-Young; Powers, Robert; Barletta, Raúl G; Dussault, Patrick H

    2014-08-01

    Eleven fatty acid analogues incorporating four-membered carbocycles (cyclobutenes, cyclobutanes, cyclobutanones, and cyclobutanols) were investigated for the ability to inhibit the growth of Mycobacterium smegmatis (Msm) and Mycobacterium tuberculosis (Mtb). A number of the analogues displayed inhibitory activity against both mycobacterial species in minimal media. Several of the molecules displayed potent levels of inhibition against Mtb, with MIC values equal to or below those observed with the anti-tuberculosis drugs D-cycloserine and isoniazid. In contrast, two of the analogues that display the greatest activity against Mtb failed to inhibit E. coli growth under either set of conditions. Thus, the active molecules identified herein may provide the basis for the development of anti-mycobacterial agents against Mtb. PMID:24902951

  20. Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against Mycobacterium tuberculosis

    PubMed Central

    Sittiwong, Wantanee; Zinniel, Denise K.; Fenton, Robert J.; Marshall, Darrel; Story, Courtney B.; Kim, Bohkyung; Lee, Ji-Young; Powers, Robert; Barletta, Raúl G.

    2014-01-01

    Eleven fatty acid analogs incorporating four-membered carbocycles (cyclobutenes, cyclobutanes, cyclobutanones, and cyclobutanols) were investigated for the ability to inhibit growth of Mycobacterium smegmatis (Msm) and Mycobacterium tuberculosis (Mtb). A number of the analogs displayed inhibitory activity against both mycobacterial species in minimal media. Several of the molecules displayed potent levels of inhibition against Mtb with MIC values equal to or below those obtained with the anti-tuberculosis drugs D-cycloserine and isoniazid. In contrast, two of the analogs displaying the greatest activity against Mtb failed to inhibit E. coli growth under either set of conditions. Thus, the active molecules identified here (1, 2, 6, and 8) may provide the basis for development of anti-mycobacterial agents against Mtb. PMID:24902951

  1. Epoxide hydrolase activities and epoxy fatty acids in the mosquito Culex quinquefasciatus.

    PubMed

    Xu, Jiawen; Morisseau, Christophe; Yang, Jun; Mamatha, Dadala M; Hammock, Bruce D

    2015-04-01

    Culex mosquitoes have emerged as important model organisms for mosquito biology, and are disease vectors for multiple mosquito-borne pathogens, including West Nile virus. We characterized epoxide hydrolase activities in the mosquito Culex quinquefasciatus, which suggested multiple forms of epoxide hydrolases were present. We found EH activities on epoxy eicosatrienoic acids (EETs). EETs and other eicosanoids are well-established lipid signaling molecules in vertebrates. We showed EETs can be synthesized in vitro from arachidonic acids by mosquito lysate, and EETs were also detected in vivo both in larvae and adult mosquitoes by LC-MS/MS. The EH activities on EETs can be induced by blood feeding, and the highest activity was observed in the midgut of female mosquitoes. The enzyme activities on EETs can be inhibited by urea-based inhibitors designed for mammalian soluble epoxide hydrolases (sEH). The sEH inhibitors have been shown to play diverse biological roles in mammalian systems, and they can be useful tools to study the function of EETs in mosquitoes. Besides juvenile hormone metabolism and detoxification, insect epoxide hydrolases may also play a role in regulating lipid signaling molecules, such as EETs and other epoxy fatty acids, synthesized in vivo or obtained from blood feeding by female mosquitoes. PMID:25686802

  2. Epoxide hydrolase activities and epoxy fatty acids in the mosquito Culex quinquefasciatus

    PubMed Central

    Xu, Jiawen; Morisseau, Christophe; Yang, Jun; Mamatha, Dadala M.

    2015-01-01

    Culex mosquitoes have emerged as important model organisms for mosquito biology, and are disease vectors for multiple mosquito-borne pathogens, including West Nile virus. We characterized epoxide hydrolase activities in the mosquito Culex quinquefasciatus, which suggested multiple forms of epoxide hydrolases were present. We found EH activities on epoxy eicosatrienoic acids (EETs). EETs and other eicosanoids are well-established lipid signaling molecules in vertebrates. We showed EETs can be synthesized in vitro from arachidonic acids by mosquito lysate, and EETs were also detected in vivo both in larvae and adult mosquitoes by LC-MS/MS. The EH activities on EETs can be induced by blood feeding, and the highest activity was observed in the midgut of female mosquitoes. The enzyme activities on EETs can be inhibited by urea-based inhibitors designed for mammalian soluble epoxide hydrolases (sEH). The sEH inhibitors have been shown to play diverse biological roles in mammalian systems, and they can be useful tools to study the function of EETs in mosquitoes. Besides juvenile hormone metabolism and detoxification, insect epoxide hydrolases may also play a role in regulating lipid signaling molecules, such as EETs and other epoxy fatty acids, synthesized in vivo or obtained from blood feeding by female mosquitoes. PMID:25686802

  3. Variation of iron, copper, free fatty acid content and lipoxygenase activity in peanut kernels subjected to various pretreatments and roasting.

    PubMed

    Chen, M J; Chiou, R Y

    1995-05-01

    Peanut kernels subjected to pretreatment including rehydration, blanching and dehydration, and untreated kernels were roasted at 160 degrees C for times ranging from 0 to 90 min. For both peanuts, the iron content in oil and specific lipoxygenase activity in defatted peanut flour decreased, free fatty acid content increased and copper content changed insignificantly with roasting time. Changes of iron content, lipoxygenase activity and free fatty acid content were more significant in untreated peanuts than in pretreated peanuts. At each roasting time, iron, copper and free fatty acid contents in the oils and lipoxygenase activities in the defatted flours prepared from untreated peanuts were higher than in the oils and flours prepared from pretreated peanuts. PMID:7621086

  4. Synthesis and evaluation of fatty acid amides on the N-oleoylethanolamide-like activation of peroxisome proliferator activated receptor α.

    PubMed

    Takao, Koichi; Noguchi, Kaori; Hashimoto, Yosuke; Shirahata, Akira; Sugita, Yoshiaki

    2015-01-01

    A series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ(9)-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists. PMID:25832022

  5. Alteration of seed fatty acid composition by an ethyl methanesulfonate-induced mutation in Arabidopsis thaliana affecting diacylglycerol acyltransferase activity.

    PubMed Central

    Katavic, V; Reed, D W; Taylor, D C; Giblin, E M; Barton, D L; Zou, J; Mackenzie, S L; Covello, P S; Kunst, L

    1995-01-01

    In characterizing the enzymes involved in the formation of very long-chain fatty acids (VLCFAs) in the Brassicaceae, we have generated a series of mutants of Arabidopsis thaliana that have reduced VLCFA content. Here we report the characterization of a seed lipid mutant, AS11, which, in comparison to wild type (WT), has reduced levels of 20:1 and 18:1 and accumulates 18:3 as the major fatty acid in triacylglycerols. Proportions of 18:2 remain similar to WT. Genetic analyses indicate that the fatty acid phenotype is caused by a semidominant mutation in a single nuclear gene, designated TAG1, located on chromosome 2. Biochemical analyses have shown that the AS11 phenotype is not due to a deficiency in the capacity to elongate 18:1 or to an increase in the relative delta 15 or delta 12 desaturase activities. Indeed, the ratio of desaturase/elongase activities measured in vitro is virtually identical in developing WT and AS11 seed homogenates. Rather, the fatty acid phenotype of AS11 is the result of reduced diacylglycerol acyltransferase activity throughout development, such that triacylglycerol biosynthesis is reduced. This leads to a reduction in 20:1 biosynthesis during seed development, leaving more 18:1 available for desaturation. Thus, we have demonstrated that changes to triacylglycerol biosynthesis can result in dramatic changes in fatty acid composition and, in particular, in the accumulation of VLCFAs in seed storage lipids. PMID:7784510

  6. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

    PubMed Central

    Herms, Albert; Bosch, Marta; Reddy, Babu J.N.; Schieber, Nicole L.; Fajardo, Alba; Rupérez, Celia; Fernández-Vidal, Andrea; Ferguson, Charles; Rentero, Carles; Tebar, Francesc; Enrich, Carlos; Parton, Robert G.; Gross, Steven P.; Pol, Albert

    2015-01-01

    Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD–mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity. PMID:26013497

  7. Syntheses and biological activities of deoxy-d-allose fatty acid ester analogs.

    PubMed

    Chowdhury, Md Tazul Islam; Ando, Hikaru; Yanagita, Ryo C; Kawanami, Yasuhiro

    2016-04-01

    We describe the syntheses of three different deoxy-D-allose analogs [2-deoxy-D-allose (2-DOAll), 1,2-dideoxy-D-allose (1,2-DOAll), and 1,2-didehydro-1,2-dideoxy-D-allose (1,2-DHAll)] and their fatty acid esters via regioselective lipase-catalyzed transesterification. Among them, 2-DOAll and its decanoate (2-DOAll-C10) showed higher inhibitory activity on plant growth, which is similar to D-allose (All) and its decanoate (All-C10). Bioassay results of deoxy-All-C10 on four plant species suggest that the hydroxy group at the C-1 position might be important showing growth inhibitory activity. In addition, co-addition of gibberellin (GA3) with 1,2-DHAll-C10 and 2-DOAll-C10 recovered plant growth, suggesting that they might mainly inhibit biosynthesis of gibberellin. PMID:26822163

  8. Effects of Omega-3 Fatty Acids Supplement on Antioxidant Enzymes Activity in Type 2 Diabetic Patients

    PubMed Central

    TOORANG, Fatemeh; DJAZAYERY, Abolghassem; DJALALI, Mahmoud

    2016-01-01

    Background: Diabetes is a major cause of death. Oxidative stress mainly caused by hyperglycemia is the primary reason of related complications. Omega-3 fatty acids are prescribed in diabetes but the effect on antioxidant defense is controversial. This study investigated effects of omega-3 supplementation on antioxidant enzymes activity in type 2 diabetic patients. Methods: A randomized, placebo controlled, double blind clinical trial was performed on 90 type2 diabetic patients. The treatment group took, daily, three capsules of omega-3 for two mo, which totally provided 2714mg omega-3 (EPA=1548 mg, DHA=828 mg and 338 mg of other omega=3 fatty acids). Placebo contained 2100 mg sunflower oil (12% SFA, 65% linoleic acid, 23% MUFA), which is the main oil used in the study population. Food intakes, anthropometric and demographic characteristics, and therapeutic regimen data were recorded before and after the intervention. Fasting blood samples were taken before and after the intervention to measure super oxide dismutase, glutathione peroxidase, glutathione reductase, catalase and total antioxidant capacity in erythrocytes. Results: A total of 81 subjects completed the study. Two study groups were similar as regards duration of diabetes, age and the enzymes at baseline. Energy and macro- and micronutrients intakes, weight and hypoglycemic agent consumption were similar in the two groups at baseline and did not change. Supplementation had no effect on antioxidant enzyme status. Glycated hemoglobin showed a significant reduction by supplementation. Conclusion: Daily supplementation of 2714 mg mega-3 for two mo results in a significant reduction in HbA1c level in type2 diabetic patients with no effects on antioxidant enzymes activity.

  9. n-3 Polyunsaturated fatty acids inhibit Fc ε receptor I-mediated mast cell activation.

    PubMed

    Wang, Xiaofeng; Ma, David W L; Kang, Jing X; Kulka, Marianna

    2015-12-01

    In vivo models show that n-3 polyunsaturated fatty acids (PUFA) inhibit some of the processes associated with allergic inflammation but the direct effect of n-3 PUFA on mast cells, the major effector cells in allergy, is poorly understood. We sought to determine the effect and mechanism of n-3 PUFA on Fc ε receptor I (FcεRI)-mediated signal transduction and mast cell activation. Bone marrow-derived mast cells (BMMC) were differentiated from bone marrow obtained from C57BL/6 wild-type (WT) and fat-1 transgenic mice. The fat-1 mice express fatty acid n-3 desaturase and produce endogenous n-3 PUFA. For comparison, exogenous n-3 PUFA were supplemented to WT BMMC and human mast cell (LAD2) cultures. Fat-1 BMMC released less β-hexosaminidase (β-hex) and cysteinyl leukotrienes and produced less tumor necrosis factor and chemokine (C-C motif) ligand 2. n-3 PUFA supplementation reduced LAD2 and BMMC degranulation (β-hex release) following FcεRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and FcεRI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell FcεRI was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced FcεRI localization to lipid rafts, and stimulation with antigen resulted in aberrant FcεRI shuttling to the rafts. Our results show that n-3 PUFA suppress FcεRI-mediated activation of mast cells, which results in reduced mediator release. This effect is associated with a decrease in LAT and Lyn expression as well as abnormal shuttling of FcεRI to lipid rafts. PMID:26363927

  10. Fatty acids and cardiovascular disease.

    PubMed

    Lecerf, Jean-Michel

    2009-05-01

    Fatty acids have been classified into "good" or "bad" groups according to their degree of unsaturation or whether they are "animal fat" or "vegetable fat". Today, it appears that the effects of fatty acids are complex and vary greatly according to the dose and the nature of the molecule. Monounsaturated fatty acids are still considered as having a "neutral" status, but any benefits may be related to the chemical environment of the source food or the associated overall food pattern. Controversy surrounds omega-6 polyunsaturated fatty acids, because even though they lower LDL cholesterol levels, excessive intakes do not appear to be correlated with cardiovascular benefit. The omega-3 fatty acids are known to exert cardiovascular protective effects. Dairy fat and its cardiovascular impact are being evaluated. This review examines the existing literature on the relationships between the different fatty acids and cardiovascular disease. PMID:19386031

  11. Benefits of Omega-3 Fatty Acids Supplementation on Serum Paraoxonase 1 Activity and Lipids Ratios in Polycystic Ovary Syndrome

    PubMed Central

    Mohammadi, Elahe; Rafraf, Maryam

    2012-01-01

    Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with increased risk of cardiovascular disease. The purpose of this study was to investigate the ef¬fects of omega-3 fatty acids on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Methods: This double-blind randomized controlled clinical trial was conducted on 64 PCOS pa¬tients with 20-35 years old. Thirty two of the subjects had taken 4 g/day omega -3 fatty acids and 32 patients were given placebo for 8 weeks. Fasting blood samples, anthropometric measure¬ments and dietary intakes were collected at the beginning and the end of the study. Serum total cholesterol, triglyceride, and HDL-C were measured using the enzymatic methods. LDL-C con¬centration was calculated by the Friedewald formula and arylesterase activity of serum PON1 was measured. Data were analyzed using SPSS software. Results: Omega-3 fatty acids significantly decreased TC/HDL-C and LDL-C/HDL-C ratios (P = 0.009 for both) and significantly increased serum PON1 activity (P = 0.048) compared with placebo. Changes in TG/HDL-C ratio were not statistically significant in omega-3 fatty acids group at the end of the study in comparison to placebo group. Reduction in TC/HDL-C, LDL-C/HDL-C and TG/HDL-C ratios and increase in serum PON1 activity were also significant in omega-3 fatty acids group at the end of the study compared with baseline values (P <0.001, P < 0.001, P = 0.004, and P = 0.001, respectively). Conclusion: Omega-3 fatty acids may decrease the risk for cardiovascular disease through the improvement in paraxonase-1 activity and reduction in some lipids ratio in PCOS women. PMID:24688934

  12. Hemolytic activity and solubilizing capacity of raffinose and melezitose fatty acid monoesters prepared by enzymatic synthesis.

    PubMed

    Carvalho, Luis; Morales, Juan C; Prez-Victoria, Jos M; Prez-Victoria, Ignacio

    2015-05-01

    The hemolytic activity and solubilizing capacity of two families of non-reducing trisaccharide fatty acid monoesters have been studied to assess their usefulness as surfactants for pharmaceutical applications. The carbohydrate-based surfactants investigated included homologous series of raffinose and melezitose monoesters bearing C10 to C18 acyl chains prepared by lipase-catalyzed synthesis in organic media. The hemolytic activity was determined in vitro using a static method based on the addition of the surfactants to an erythrocyte suspension and subsequent spectrophotometric determination of the released hemoglobin. The effect of the carbohydrate head group, the acyl chain length and the regioisomeric purity was investigated. In all cases, the carbohydrate monoester surfactants decreased their hemolytic activity (with respect to their critical micelle concentration) when increasing the length of the acyl chain. A very similar behaviour was observed either the carbohydrate head-group (raffinose and melezitose) or regardless of the regioisomeric purity. Interestingly, decanoyl (C10) and lauroyl (C12) monoesters were just marginally hemolytic at their critical micelle concentrations while the longer palmitoyl (C16) and (C18) stearoyl monoesters become hemolytic at concentrations much higher than their respective cmc. The palmitoyl and stearoyl monoesters also displayed higher solubilization capacity than the shorter acyl chain monoesters in a solubilization assay of a hydrophobic dye as a model drug mimic. These results suggest that raffinose and melezitose monoesters with long-chain fatty acids (C16 to C18) are promising surfactants for pharmaceutical applications and could be an alternative to the use of current commercial nonionic polyoxyethylene-based surfactants in parenteral formulations. PMID:25753196

  13. Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease

    PubMed Central

    Baratta, Francesco; Pastori, Daniele; Del Ben, Maria; Polimeni, Licia; Labbadia, Giancarlo; Di Santo, Serena; Piemonte, Fiorella; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95–1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61–1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51–0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004–1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241–5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248–0.866, p = 0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis. PMID:26288848

  14. Fatty acid synthesis is inhibited by inefficient utilization of unusual fatty acids for glycerolipid assembly

    PubMed Central

    Bates, Philip D.; Johnson, Sean R.; Cao, Xia; Li, Jia; Nam, Jeong-Won; Jaworski, Jan G.; Ohlrogge, John B.; Browse, John

    2014-01-01

    Degradation of unusual fatty acids through β-oxidation within transgenic plants has long been hypothesized as a major factor limiting the production of industrially useful unusual fatty acids in seed oils. Arabidopsis seeds expressing the castor fatty acid hydroxylase accumulate hydroxylated fatty acids up to 17% of total fatty acids in seed triacylglycerols; however, total seed oil is also reduced up to 50%. Investigations into the cause of the reduced oil phenotype through in vivo [14C]acetate and [3H]2O metabolic labeling of developing seeds surprisingly revealed that the rate of de novo fatty acid synthesis within the transgenic seeds was approximately half that of control seeds. RNAseq analysis indicated no changes in expression of fatty acid synthesis genes in hydroxylase-expressing plants. However, differential [14C]acetate and [14C]malonate metabolic labeling of hydroxylase-expressing seeds indicated the in vivo acetyl–CoA carboxylase activity was reduced to approximately half that of control seeds. Therefore, the reduction of oil content in the transgenic seeds is consistent with reduced de novo fatty acid synthesis in the plastid rather than fatty acid degradation. Intriguingly, the coexpression of triacylglycerol synthesis isozymes from castor along with the fatty acid hydroxylase alleviated the reduced acetyl–CoA carboxylase activity, restored the rate of fatty acid synthesis, and the accumulation of seed oil was substantially recovered. Together these results suggest a previously unidentified mechanism that detects inefficient utilization of unusual fatty acids within the endoplasmic reticulum and activates an endogenous pathway for posttranslational reduction of fatty acid synthesis within the plastid. PMID:24398521

  15. Bioproduction of volatile fatty acid from the fermentation of waste activated sludge for in situ denitritation.

    PubMed

    Wang, Bo; Peng, Yongzhen; Guo, Yuanyuan; Wang, Shuying

    2016-04-01

    Waste activated sludge (WAS) fermentation integrated with denitritation (the reduction of nitrite to dinitrogen gas) at different pHs was investigated in batch-mode reactors over a 24-day period. The results showed that in comparison with controlled pHs, the volatile fatty acid (VFA) bioproduction for in situ denitritation was significantly improved at uncontrolled pH. VFA fermented from WAS was quickly consumed by denitritation at uncontrolled pH, which accelerated sludge degradation. On the other hand, sludge digestion was benefited from the alkalinity produced from denitritation, while methanogenesis was prohibited by alkalinity and nitrite. The integrated sludge fermentation and denitritation can be cost-effectively applied to wastewater treatment plants, so that organic substrates (e.g., VFAs) are produced for denitritation via simultaneous sludge fermentation, which enables WAS reutilization and enhances nitrogen removal efficiency without the need of external carbon sources. PMID:26475401

  16. Volatile fatty acids produced by co-fermentation of waste activated sludge and henna plant biomass.

    PubMed

    Huang, Jingang; Zhou, Rongbing; Chen, Jianjun; Han, Wei; Chen, Yi; Wen, Yue; Tang, Junhong

    2016-07-01

    Anaerobic co-fermentation of waste activated sludge (WAS) and henna plant biomass (HPB) for the enhanced production of volatile fatty acids (VFAs) was investigated. The results indicated that VFAs was the main constituents of the released organics; the accumulation of VFAs was much higher than that of soluble carbohydrates and proteins. HPB was an advantageous substrate compared to WAS for VFAs production; and the maximum VFAs concentration in an HPB mono-fermentation system was about 2.6-fold that in a WAS mono-fermentation system. In co-fermentation systems, VFAs accumulation was positively related to the proportion of HPB in the mixed substrate, and the accumulated VFAs concentrations doubled when HPB was increased from 25% to 75%. HPB not only adjust the C/N ratio; the associated and/or released lawsone might also have a positive electron-shuttling effect on VFAs production. PMID:27003793

  17. Synthesis of Phenoxyacyl-Ethanolamides and Their Effects on Fatty Acid Amide Hydrolase Activity*

    PubMed Central

    Faure, Lionel; Nagarajan, Subbiah; Hwang, Hyeondo; Montgomery, Christa L.; Khan, Bibi Rafeiza; John, George; Koulen, Peter; Blancaflor, Elison B.; Chapman, Kent D.

    2014-01-01

    N-Acylethanolamines (NAEs) are involved in numerous biological activities in plant and animal systems. The metabolism of these lipids by fatty acid amide hydrolase (FAAH) is a key regulatory point in NAE signaling activity. Several active site-directed inhibitors of FAAH have been identified, but few compounds have been described that enhance FAAH activity. Here we synthesized two sets of phenoxyacyl-ethanolamides from natural products, 3-n-pentadecylphenolethanolamide and cardanolethanolamide, with structural similarity to NAEs and characterized their effects on the hydrolytic activity of FAAH. Both compounds increased the apparent Vmax of recombinant FAAH proteins from both plant (Arabidopsis) and mammalian (Rattus) sources. These NAE-like compounds appeared to act by reducing the negative feedback regulation of FAAH activity by free ethanolamine. Both compounds added to seedlings relieved, in part, the negative growth effects of exogenous NAE12:0. Cardanolethanolamide reduced neuronal viability and exacerbated oxidative stress-mediated cell death in primary cultured neurons at nanomolar concentrations. This was reversed by FAAH inhibitors or exogenous NAE substrate. Collectively, our data suggest that these phenoxyacyl-ethanolamides act to enhance the activity of FAAH and may stimulate the turnover of NAEs in vivo. Hence, these compounds might be useful pharmacological tools for manipulating FAAH-mediated regulation of NAE signaling in plants or animals. PMID:24558037

  18. The long chain fatty acid oleate activates mouse intestinal afferent nerves in vitro.

    PubMed

    Webster, W Andrew; Beyak, Michael J

    2013-05-01

    Vagal afferents innervating the gastrointestinal tract serve an important nutrient-sensing function, and these signals contribute to satiety. Detection of nutrients occurs largely through the release of mediators from specialized enteroendocrine cells within the mucosa of the gastrointestinal tract. The signaling pathways leading to vagal afferent activation are not clear; however, previous in-vivo studies have implicated a role for cholecystokinin (CCK). We used an in vitro intestinal afferent extracellular recording preparation to study the effect of luminal perfusion of the long chain fatty acid oleate on mouse intestinal afferent activity. Oleate activated intestinal afferents in a concentration-dependent fashion, with an EC50 value of approximately 25 mmol/L. The L-type calcium channel blocker nicardipine attenuated the effect of oleate. Vagotomy resulted in a significant (>60%) reduction of the responses to both oleate and CCK. The CCK-1 receptor antagonist lorglumide nearly abolished responses to CCK and oleate. Our experiments therefore suggest that oleate activates intestinal afferents, with vagal afferents primarily involved; however, nonvagal fibres also contribute. The activation is dependent on CCK release, likely via activation of L-type channels on mucosal enteroendocrine cells, finally resulting in activation of CCK-1 receptors on the afferent terminals. PMID:23656469

  19. Loss of Fatty Acid Binding Protein 4/aP2 Reduces Macrophage Inflammation Through Activation of SIRT3.

    PubMed

    Xu, Hongliang; Hertzel, Ann V; Steen, Kaylee A; Bernlohr, David A

    2016-03-01

    Activation of proinflammatory macrophages plays an important role in the pathogenesis of insulin resistance, type 2 diabetes, and atherosclerosis. Previous work using high fat-fed mice has shown that ablation of the adipocyte fatty acid binding protein (FABP4/aP2) in macrophages leads to an antiinflammatory state both in situ and in vivo, and the mechanism is linked, in part, to increased intracellular monounsaturated fatty acids and the up-regulation of uncoupling protein 2. Here, we show that loss of FABP4/aP2 in macrophages additionally induces sirtuin 3 (SIRT3) expression and that monounsaturated fatty acids (C16:1, C18:1) lead to increased SIRT3 protein expression. Increased expression of SirT3 in FABP4/aP2 null macrophages occurs at the protein level with no change in SirT3 mRNA. When compared with controls, silencing of SIRT3 in Raw246.7 macrophages leads to increased expression of inflammatory cytokines, inducible nitric oxide synthase and cyclooxygenase 2. In contrast, loss of SIRT3 in FABP4/aP2-deficient macrophages attenuates the suppressed inflammatory signaling, reduced reactive oxygen species production, lipopolysaccharide-induced mitochondrial dysfunction, and increased fatty acid oxidation. These results suggest that the antiinflammatory phenotype of FABP4/aP2 null mice is mediated by increased intracellular monounsaturated fatty acids leading to the increased expression of both uncoupling protein 2 and SirT3. PMID:26789108

  20. Isoproterenol stimulates 5'-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts.

    PubMed

    Jaswal, Jagdip S; Lund, Chad R; Keung, Wendy; Beker, Donna L; Rebeyka, Ivan M; Lopaschuk, Gary D

    2010-10-01

    Isoproterenol increases phosphorylation of LKB, 5'-AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC), enzymes involved in regulating fatty acid oxidation. However, inotropic stimulation selectively increases glucose oxidation in adult hearts. In the neonatal heart, fatty acid oxidation becomes a major energy source, while glucose oxidation remains low. This study tested the hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution (0.4 mM palmitate, 11 mM glucose, 0.5 mM lactate, and 100 mU/l insulin) with or without isoproterenol (300 nM). Isoproterenol increased myocardial O(2) consumption (in J·g dry wt(-1)·min(-1); 11.0 ± 1.4, n = 8 vs. 7.5 ± 0.8, n = 6, P < 0.05), and the phosphorylation of LKB (in arbitrary density units; 0.87 ± 0.09, n = 6 vs. 0.59 ± 0.08, n = 6, P < 0.05), AMPK (0.82 ± 0.08, n = 6 vs. 0.51 ± 0.06, n = 6, P < 0.05), and ACC-β (1.47 ± 0.14, n = 6 vs. 0.97 ± 0.07, n = 6, P < 0.05), with a concomitant decrease in malonyl-CoA levels (in nmol/g dry wt; 0.9 ± 0.9, n = 8 vs. 7.5 ± 1.3, n = 8, P < 0.05) and increase in palmitate oxidation (in nmol·g dry wt(-1)·min(-1); 272 ± 45, n = 8 vs. 114 ± 9, n = 6, P < 0.05). Glucose and lactate oxidation were increased (in nmol·g dry wt(-1)·min(-1); 253 ± 75, n = 8 vs. 63 ± 15, n = 9, P < 0.05 and 246 ± 43, n = 8 vs. 82 ± 11, n = 6, P < 0.05, respectively), independent of alterations in pyruvate dehydrogenase phosphorylation, but occurred secondary to a decrease in acetyl-CoA content and acetyl-CoA-to-free CoA ratio. As acetyl-CoA levels decrease in response to isoproterenol, despite an acceleration of the rates of palmitate and carbohydrate oxidation, these data suggest net rates of acetyl-CoA utilization exceed the net rates of acetyl-CoA generation. PMID:20656883

  1. Antibacterial activity of long-chain polyunsaturated fatty acids against Propionibacterium acnes and Staphylococcus aureus.

    PubMed

    Desbois, Andrew P; Lawlor, Keelan C

    2013-11-01

    New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32-1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15-30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

  2. Antibacterial Activity of Long-Chain Polyunsaturated Fatty Acids against Propionibacterium acnes and Staphylococcus aureus

    PubMed Central

    Desbois, Andrew P.; Lawlor, Keelan C.

    2013-01-01

    New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32–1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15–30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

  3. Fatty acid-producing hosts

    SciTech Connect

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  4. Nitrated Fatty Acids Reverse Cigarette Smoke-Induced Alveolar Macrophage Activation and Inhibit Protease Activity via Electrophilic S-Alkylation

    PubMed Central

    Reddy, Aravind T.; Lakshmi, Sowmya P.; Muchumarri, Ramamohan R.; Reddy, Raju C.

    2016-01-01

    Nitrated fatty acids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fatty acids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs’ electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease. PMID:27119365

  5. Intestinal metabolism of fatty acids

    PubMed Central

    Enser, M.

    1965-01-01

    1. The effect of concentration on the oxidation and incorporation into lipids of lauric acid and linoleic acid by rings of rat small intestine has been studied in vitro. 2. In the absence of glucose, the oxidation of lauric acid in the range 0·01–5·0mm showed a maximum at 0·1mm. In the presence of glucose the maximum was at 0·5mm. The oxidation of linoleic acid in the presence of glucose increased throughout the concentration range 0·01–5·0mm. 3. The incorporation of lauric acid into lipids was maximal at 0·5–0·6mm in the presence of glucose, but at 10mm in the absence of glucose. At 0·8mm-lauric acid, in the presence of glucose, over 75% of the incorporated lauric acid was in triglycerides, but at 10mm they only contained 30%. The incorporation of glucose carbon into glycerides paralleled the incorporation of lauric acid. 4. In the range 0·01–2·5mm-linoleic acid the quantity incorporated into lipids increased. In the range 0·01–0·4mm linoleic acid was incorporated predominantly into triglycerides, but between 0·4 and 1·0mm most was in diglycerides, and between 2·5 and 5·0mm most was in monoglycerides. 5. The relationship of fatty acid concentration to the mechanism of absorption is discussed, together with the correlation between the distribution of the absorbed fatty acids within the tissue lipids and the lipase activity of intestinal mucosa. PMID:5837779

  6. Omega-3 Free Fatty Acids Suppress Macrophage Inflammasome Activation by Inhibiting NF-κB Activation and Enhancing Autophagy

    PubMed Central

    Williams-Bey, Yolanda; Boularan, Cedric; Vural, Ali; Huang, Ning-Na; Hwang, Il-Young; Shan-Shi, Chong; Kehrl, John H.

    2014-01-01

    The omega-3 (ω3) fatty acid docosahexaenoic acid (DHA) can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR) 4 (also known as GPR120), a G-protein coupled receptor (GPR) known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity. PMID:24911523

  7. Fatty acid oxidation in brain is limited by the low activity of 3-ketoacyl-CoA thiolase

    SciTech Connect

    Yang, S.; He, X.; Schulz, H.

    1987-05-01

    In an attempt to establish why the brain is virtually incapable of oxidizing fatty acids, the activities of the ..beta..-oxidation enzymes in rat brain and rat heart mitochondria were measured and compared with each other. Although the apparent K/sub m/ values and chain-length specificities of the brain and heart enzymes are similar, the specific activities of all but one brain enzyme are between 4% and 50% of those observed in heart mitochondria. The exception is 3-ketoacyl-CoA thiolase (EC 2.3.1.16) whose specific activity in brain mitochondria is 125-times lower than in heart mitochondria. The partially purified brain 3-ketoacyl-CoA thiolase was shown to be catalytically and immunologically identical with the heart enzyme. The low rate of fatty acid oxidation in brain mitochondria estimated on the basis of palmitoylcarnitine-supported respiration and (1-/sup 14/C)palmitoylcarnitine degradation may be the consequence of the low activity of 3-ketoacyl-CoA thiolase. Inhibition of (1-/sup 14/C)palmitoylcarnitine oxidation by 4-bromocrotonic acid proves that the observed oxidation of fatty acids in brain is dependent on 3-ketoacyl-CoA thiolase and thus occurs via ..beta..-oxidation. Since the reactions catalyzed by carnitine palmitoyltransferase (EC 2.3.1.21) and acyl-CoA synthetase (EC 6.2.1.3) do not seem to restrict fatty acid oxidation in brain, it is concluded that the oxidation of fatty acids in rat brain is limited by the activity of the mitochondrial 3-ketoacyl-CoA thiolase.

  8. Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

    ERIC Educational Resources Information Center

    Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

    2009-01-01

    Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.

  9. Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

    ERIC Educational Resources Information Center

    Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

    2009-01-01

    Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

  10. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins.

    PubMed

    Hannukainen, Jarna C; Nuutila, Pirjo; Borra, Ronald; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 +/- 10% higher (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 +/- 4.3 versus 9.0 +/- 6.1 micromol (100 ml)(-1) min(-1), P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  11. Omega-3 fatty acids (image)

    MedlinePlus

    ... 3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. The body cannot make these ...

  12. Influence of spontaneous hypertension on n-3 delta-6-desaturase activity and fatty acid composition of rat hepatocytes.

    PubMed

    Narce, M; Asdrubal, P; Delachambre, M C; Gresti, J; Poisson, J P

    1995-11-01

    The first rate limiting step in the conversion of alpha-linolenic acid is catalyzed by the delta-6-desaturase enzyme. The activity of such an enzyme was studied in order to investigate the n-3 Polyunsaturated Fatty Acid biogenesis during hypertension. Rat isolated hepatocyte n-3 delta-6-desaturase activity was higher in 1 month old Spontaneously Hypertensive Rats -- prehypertensive period-as compared to normotensive Wistar Kyoto rats, whereas there was no significant differences at 12 months -- hypertensive period-. Our data indicate no correlation between the directly measured enzyme activity and the changes in hepatocyte n-3 fatty acid compositions. The loss of hepatocyte n-3 delta-6-desaturase activity in the Spontaneously Hypertensive Rat may be a key factor in the evolution of hypertension related to aging through altering the eicosanoid balance. PMID:8609913

  13. Biological denitrification of brine: the effect of compatible solutes on enzyme activities and fatty acid degradation.

    PubMed

    Cyplik, Paweł; Piotrowska-Cyplik, Agnieszka; Marecik, Roman; Czarny, Jakub; Drozdzyńska, Agnieszka; Chrzanowski, Łukasz

    2012-09-01

    The effect of the addition of compatible solutes (ectoine and trehalose) on the denitrification process of saline wastewater was studied. In saline wastewater, it was observed that the initial concentration of nitrates was 500 mg N l⁻¹. A fatty substance isolated from oiled bleaching earth (waste of vegetable oil refining process) was used as a source of carbon.The consortium, which was responsible for the denitrification process originated from the wastewater of the vegetable oil industry. The consortium of microorganisms was identified by the use of restriction fragment length polymorphism of 16S rRNA gene amplicons and sequencing techniques. It was noted that ectoine affects significantly the activity of lipase and nitrate reductase, and resulted in faster denitrification compared to saline wastewater with the addition of trehalose or control saline wastewater (without compatible solutes). It was observed that relative enzyme activities of lipase and nitrate reductase increased by 32 and 35%, respectively, in the presence of 1 mM ectoine. This resulted in an increase in specific nitrate reduction rate in the presence of 1 mM ectoine to 5.7 mg N g⁻¹ VSS h⁻¹, which was higher than in the absence of ectoine (3.2 mg N g⁻¹ VSS h⁻¹). The addition of trehalose did not have an effect on nitrate removals. Moreover, it was found that trehalose was used up completely by bacteria as a source of carbon in the denitrification process. The fatty acids were biodegraded by 74% in the presence of 1 mM ectoine. PMID:22286267

  14. Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids, desaturase activity indices, and urinary prostaglandin E in women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Compared to diets high in fat, low fat diets are associated with reduced risk of cardiovascular disease. We hypothesized that a low fat (LF; 20% fat) and a low fat high omega-3 (n-3) fatty acid diet (LFn3; 23% fat with 3% as ALA, EPA and DHA) would enhance n-3 composition of PLFA and reduce urinary ...

  15. Ligand-activated PPAR?-dependent DNA demethylation regulates the fatty acid ?-oxidation genes in the postnatal liver.

    PubMed

    Ehara, Tatsuya; Kamei, Yasutomi; Yuan, Xunmei; Takahashi, Mayumi; Kanai, Sayaka; Tamura, Erina; Tsujimoto, Kazutaka; Tamiya, Takashi; Nakagawa, Yoshimi; Shimano, Hitoshi; Takai-Igarashi, Takako; Hatada, Izuho; Suganami, Takayoshi; Hashimoto, Koshi; Ogawa, Yoshihiro

    2015-03-01

    The metabolic function of the liver changes sequentially during early life in mammals to adapt to the marked changes in nutritional environment. Accordingly, hepatic fatty acid ?-oxidation is activated after birth to produce energy from breast milk lipids. However, how it is induced during the neonatal period is poorly understood. Here we show DNA demethylation and increased mRNA expression of the fatty acid ?-oxidation genes in the postnatal mouse liver. The DNA demethylation does not occur in the fetal mouse liver under the physiologic condition, suggesting that it is specific to the neonatal period. Analysis of mice deficient in the nuclear receptor peroxisome proliferator-activated receptor ? (PPAR?) and maternal administration of a PPAR? ligand during the gestation and lactation periods reveal that the DNA demethylation is PPAR? dependent. We also find that DNA methylation of the fatty acid ?-oxidation genes are reduced in the adult human liver relative to the fetal liver. This study represents the first demonstration that the ligand-activated PPAR?-dependent DNA demethylation regulates the hepatic fatty acid ?-oxidation genes during the neonatal period, thereby highlighting the role of a lipid-sensing nuclear receptor in the gene- and life-stage-specific DNA demethylation of a particular metabolic pathway. PMID:25311726

  16. Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids.

    PubMed

    Beld, Joris; Abbriano, Raffaela; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D

    2016-04-22

    In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short precursors now gives us easy access to these extended molecules. PMID:26886879

  17. Fatty acids, essential oil and phenolics composition of Silybum marianum seeds and their antioxidant activities.

    PubMed

    Mhamdi, Baya; Abbassi, Feten; Smaoui, Abderrazak; Abdelly, Chedly; Marzouk, Brahim

    2016-05-01

    The presentstudydescribes the biochemical evaluation of Silybum marianum seed. The analysis of essential oil composition of Silybum marianum seed by Gas Chromatography-Mass Spectrometry GC-MS showed the presence of14 volatile components with the predominance of γ-cadinene (49.8%) and α-pinene (24.5%). Whereas, the analysis of fatty acids composition, showed the predominance of linoleic (50.5%) and oleic (30.2%) acids. Silybum marainum presented also an important polyphenol contents with 29mgGAE/g DW, a good antiradical activity (CI50=39μg/ml) but a lower reducing power ability. Flavonoid and condensed tannin contents were about 3.39mg EC/g DW and 1.8mg EC/gDW, respectively. The main phenolic compounds identified by RP-HPLC, were silybin A (12.2%), silybin B (17.67%), isosilybin A (21.9%), isosilybin B (12.8%), silychristin (7.9%) andsilydianin (7.5%). PMID:27166539

  18. Covalent Peroxisome Proliferator-activated Receptor γ Adduction by Nitro-fatty Acids

    PubMed Central

    Schopfer, Francisco J.; Cole, Marsha P.; Groeger, Alison L.; Chen, Chen-Shan; Khoo, Nicholas K. H.; Woodcock, Steven R.; Golin-Bisello, Franca; Motanya, U. Nkiru; Li, Yong; Zhang, Jifeng; Garcia-Barrio, Minerva T.; Rudolph, Tanja K.; Rudolph, Volker; Bonacci, Gustavo; Baker, Paul R. S.; Xu, H. Eric; Batthyany, Carlos I.; Chen, Y. Eugene; Hallis, Tina M.; Freeman, Bruce A.

    2010-01-01

    The peroxisome proliferator-activated receptor-γ (PPARγ) binds diverse ligands to transcriptionally regulate metabolism and inflammation. Activators of PPARγ include lipids and anti-hyperglycemic drugs such as thiazolidinediones (TZDs). Recently, TZDs have raised concern after being linked with increased risk of peripheral edema, weight gain, and adverse cardiovascular events. Most reported endogenous PPARγ ligands are intermediates of lipid metabolism and oxidation that bind PPARγ with very low affinity. In contrast, nitro derivatives of unsaturated fatty acids (NO2-FA) are endogenous products of nitric oxide (•NO) and nitrite (NO2−)-mediated redox reactions that activate PPARγ at nanomolar concentrations. We report that NO2-FA act as partial agonists of PPARγ and covalently bind PPARγ at Cys-285 via Michael addition. NO2-FA show selective PPARγ modulator characteristics by inducing coregulator protein interactions, PPARγ-dependent expression of key target genes, and lipid accumulation is distinctively different from responses induced by the TZD rosiglitazone. Administration of this class of signaling mediators to ob/ob mice revealed that NO2-FA lower insulin and glucose levels without inducing adverse side effects such as the increased weight gain induced by TZDs. PMID:20097754

  19. Cooperative interactions among intestinal GATA factors in activating the rat liver fatty acid binding protein gene.

    PubMed

    Divine, Joyce K; Staloch, Lora J; Haveri, Hanna; Rowley, Christopher W; Heikinheimo, Markku; Simon, Theodore C

    2006-08-01

    GATA-4, GATA-5, and GATA-6 are endodermal zinc-finger transcription factors that activate numerous enterocytic genes. GATA-4 and GATA-6 but not GATA-5 are present in adult murine small intestinal enterocytes, and we now report the simultaneous presence of all three GATA factors in murine small intestinal enterocytes before weaning age. An immunohistochemical survey detected enterocytic GATA-4 and GATA-6 at birth and 1 wk of age and GATA-5 at 1 wk but not birth. Interactions among GATA factors were explored utilizing a transgene constructed from the proximal promoter of the rat liver fatty acid binding protein gene (Fabp1). GATA-4 and GATA-5 but not GATA-6 activate the Fabp1 transgene through a cognate binding site at -128. A dose-response assay revealed a maximum in transgene activation by both factors, where additional factor did not further increase transgene activity. However, at saturated levels of GATA-4, additional transgene activation was achieved by adding GATA-5 expression construct, and vice versa. Similar cooperativity occurred with GATA-5 and GATA-6. Identical interactions were observed with a target transgene consisting of a single GATA site upstream of a minimal promoter. Furthermore, GATA-4 and GATA-5 or GATA-5 and GATA-6 bound to each other in solution. These results are consistent with tethering of one GATA factor to the Fabp1 promoter through interaction with a second GATA factor to produce increased target gene activation. Cooperative target gene activation was specific to an intestinal cell line and may represent a mechanism by which genes are activated in the small intestinal epithelium during the period before weaning. PMID:16603485

  20. Oil Content, Fatty Acid Composition and Distributions of Vitamin-E-Active Compounds of Some Fruit Seed Oils.

    PubMed

    Matthäus, Bertrand; Musazcan Özcan, Mehmet

    2015-01-01

    Oil content, fatty acid composition and the distribution of vitamin-E-active compounds of selected Turkish seeds that are typically by-products of the food processing industries (linseed, apricot, pear, fennel, peanut, apple, cotton, quince and chufa), were determined. The oil content of the samples ranged from 16.9 to 53.4 g/100 g. The dominating fatty acids were oleic acid (apricot seed oil, peanut oil, and chufa seed oil) in the range of 52.5 to 68.4 g/100 g and linoleic acid (pear seed oil, apple seed oil, cottonseed oil and quince seed oil) with 48.1 to 56.3 g/100 g, while in linseed oil mainly α-linolenic acid (53.2 g/100 g) and in fennel seed oil mainly 18:1 fatty acids (80.5 g/100 g) with petroselinic acid predominating. The total content of vitamin-E-active compounds ranged from 20.1 (fennel seed oil) to 96 mg/100 g (apple seed oil). The predominant isomers were established as α- and γ-tocopherol. PMID:26785341

  1. Oil Content, Fatty Acid Composition and Distributions of Vitamin-E-Active Compounds of Some Fruit Seed Oils

    PubMed Central

    Matthäus, Bertrand; Özcan, Mehmet Musa

    2015-01-01

    Oil content, fatty acid composition and the distribution of vitamin-E-active compounds of selected Turkish seeds that are typically by-products of the food processing industries (linseed, apricot, pear, fennel, peanut, apple, cotton, quince and chufa), were determined. The oil content of the samples ranged from 16.9 to 53.4 g/100 g. The dominating fatty acids were oleic acid (apricot seed oil, peanut oil, and chufa seed oil) in the range of 52.5 to 68.4 g/100 g and linoleic acid (pear seed oil, apple seed oil, cottonseed oil and quince seed oil) with 48.1 to 56.3 g/100 g, while in linseed oil mainly α-linolenic acid (53.2 g/100 g) and in fennel seed oil mainly 18:1 fatty acids (80.5 g/100 g) with petroselinic acid predominating. The total content of vitamin-E-active compounds ranged from 20.1 (fennel seed oil) to 96 mg/100 g (apple seed oil). The predominant isomers were established as α- and γ-tocopherol. PMID:26785341

  2. Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene with the maize transposon activator.

    PubMed Central

    James, D W; Lim, E; Keller, J; Plooy, I; Ralston, E; Dooner, H K

    1995-01-01

    The FATTY ACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the synthesis of very long chain fatty acids in the seed. The product of the FAE1 gene is presumed to be a condensing enzyme that extends the chain length of fatty acids from C18 to C20 and C22. We report here the cloning of FAE1 by directed transposon tagging with the maize element Activator (Ac). An unstable fae1 mutant was isolated in a line carrying Ac linked to the FAE1 locus on chromosome 4. Cosegregation and reversion analyses established that the new mutant was tagged by Ac. A DNA fragment flanking Ac was cloned by inverse polymerase chain reaction and used to isolate FAE1 genomic clones and a cDNA clone from a library made from immature siliques. The predicted amino acid sequence of the FAE1 protein shares homology with those of other condensing enzymes (chalcone synthase, stilbene synthases, and beta-ketoacyl-acyl carrier protein synthase III), supporting the notion that FAE1 is the structural gene for a synthase or condensing enzyme. FAE1 is expressed in developing seed, but not in leaves, as expected from the effect of the fae1 mutation on the fatty acid compositions of those tissues. PMID:7734965

  3. Characterisation of fatty acid, carotenoid, tocopherol/tocotrienol compositions and antioxidant activities in seeds of three Chenopodium quinoa Willd. genotypes.

    PubMed

    Tang, Yao; Li, Xihong; Chen, Peter X; Zhang, Bing; Hernandez, Marta; Zhang, Hua; Marcone, Massimo F; Liu, Ronghua; Tsao, Rong

    2015-05-01

    Composition of fatty acids, tocopherols, tocotrienols, and carotenoids, and their contribution to antioxidant activities were investigated in seeds of three coloured quinoa cultivars (white, red and black). The major components and individual compounds were significantly different, and their concentrations were higher in darker seeds (p < 0.05). The oil yield was 6.58-7.17% which contained predominantly unsaturated fatty acids (89.42%). The ratio of omega-6/omega-3 fatty acid was ca. 6/1. The total tocopherol content ranged from 37.49 to 59.82 μg/g and mainly consisted of γ-tocopherol. Trace amount of α- and β-tocotrienols was also found. Black quinoa had the highest vitamin E followed by red and white quinoas. Carotenoids, mainly trans-lutein (84.7-85.6%) and zeaxanthin were confirmed for the first time in quinoa seeds, and the concentration was also the highest in black seeds. The antioxidant activities of lipophilic extracts were positively correlated with polyunsaturated fatty acids, total carotenoids and total tocopherols. PMID:25529712

  4. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances.

    PubMed

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism. PMID:26742061

  5. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances

    PubMed Central

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism. PMID:26742061

  6. Fatty Acid Biosynthesis Revisited: Structure Elucidation and Metabolic Engineering

    PubMed Central

    Beld, Joris; Lee, D. John

    2014-01-01

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases’ many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field. PMID:25360565

  7. Relation of fatty acid composition in lead-exposed mallards to fat mobilization, lipid peroxidation and alkaline phosphatase activity

    USGS Publications Warehouse

    Mateo, R.; Beyer, W.N.; Spann, J.W.; Hoffman, D.J.

    2003-01-01

    The increase of n-6 polyunsaturated fatty acids (PUFA) in animal tissues has been proposed as a mechanism of Pb poisoning through lipid peroxidation or altered eicosanoids metabolism. We have studied fatty acid (FA) composition in liver and brain of mallards (Anas platyrhynchos) feeding for three weeks on diets containing combinations of low or high levels of vitamin E (20 or 200 UI/kg) and Pb (0 or 2 g/kg). Saturated FA, n-6 PUFA and total concentrations of FA were higher in livers of Pb-exposed mallards, but not in their brains. The percentage of n-6 PUFA in liver and brain was slightly higher in Pb-exposed mallards. The increase of n-6 PUFA in liver was associated with increased triglycerides and cholesterol in plasma, thus could be in part attributed to feed refusal and fat mobilization. The hepatic ratios between adrenic acid (22:4 n-6) and arachidonic acid (20:4 n-6) or between adrenic acid and linoleic acid (18:2 n-6) were higher in Pb exposed birds, supporting the existing hypothesis of increased fatty acid elongation by Pb. Among the possible consequences of increased n-6 PUFA concentration in tissues, we found increased lipid peroxidation in liver without important histopathological changes, and decreased plasma alkaline phosphatase activity that may reflect altered bone metabolism in birds.

  8. Improved bioproduction of short-chain fatty acids from waste activated sludge by perennial ryegrass addition.

    PubMed

    Jia, Shuting; Dai, Xiaohu; Zhang, Dong; Dai, Lingling; Wang, Rongchang; Zhao, Jianfu

    2013-09-01

    To improve short-chain fatty acids (SCFAs) production from waste activated sludge (WAS), studies that focus on pre-treatment methods, pH control or adding extra carbon like rice were reported. In this study, a kind of green waste (perennial ryegrass) was used as carbon source to adjust carbon to nitrogen ratio (C/N) in WAS to enhance SCFAs production. The effects of different C/N ratio ranging from 26/1 to 7/1 on SCFAs production and cellulose, hemicellulose, and lignin consumption were investigated in detail. It was observed that the maximal SCFAs yield was 368.71 g COD per kilogram of total solids (TS) at C/N 20/1 with fermentation time of 12 d, which was, respectively, over 4 and 12 times than that at C/N 26/1 (sole perennial ryegrass) and C/N 7/1 (sole WAS). Meanwhile, cellulose, hemicellulose and lignin consumptions were 109.12, 148.74, 20.90 g COD/kg TS, respectively, at C/N 20/1 with fermentation time of 12 d. The analysis of the composition of SCFAs showed that acetic acid ranked the first among other acids from C/N ratio of 26/1 to 18/1, whereas propionic acid was the dominant product from C/N ratio of 16/1 to 7/1. Because the results of this study were different from previous studies of SCFAs generation, the mechanism of improved SCFAs at C/N ratio of 20/1 by perennial ryegrass addition was investigated. Results showed that as soluble COD, soluble protein and soluble carbohydrate increased, more substrates were available for SCFAs production at C/N ratio of 20/1. In addition, with the drop of pH to 4.82, methane generating was inhabitant and the SCFAs production was therefore significantly enhanced. Additionally, the mechanism of improved SCFAs generation was analyzed from the view of enzyme activities and microbial community. The experiments revealed that at C/N ratio of 20/1 the activities of enzymes were the highest comparing with other C/N ratios and lignin was the rate-limiting steps in WAS anaerobic digestion by perennial ryegrass addition. The 16S rRNA gene clone library demonstrated that Clostridia, Spirochaetes, and Bacteroidetes were the dominant microbial community at C/N ratio of 20/1. PMID:23764607

  9. Synthesis of new optically active propargylic fluorides and application to the enantioselective synthesis of monofluorinated analogues of fatty acid metabolites.

    PubMed

    Prakesch, M; Grée, D; Grée, R

    2001-05-01

    A new approach to obtain optically active unsaturated or polyunsaturated systems with a single fluorine atom in an allylic or propargylic position is reported. Central to this strategy is the high regio- and stereocontrol observed during the fluorination of propargylic alcohols allowing a short and efficient synthesis of 1. Further, simple functional group transformations gave the enals 2 and 3. These three key intermediates were used for the preparation of optically active monofluorinated analogues of fatty acid metabolites. PMID:11325281

  10. Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I

    PubMed Central

    Boshoff, Helena I.; Mizrahi, Valerie; Barry, Clifton E.

    2002-01-01

    The effects of low extracellular pH and intracellular accumulation of weak organic acids were compared with respect to fatty acid synthesis by whole cells of Mycobacterium tuberculosis and Mycobacterium smegmatis. The profile of fatty acids synthesized during exposure to benzoic, nicotinic, or pyrazinoic acids, as well as that observed during intracellular hydrolysis of the corresponding amides, was not a direct consequence of modulation of fatty acid synthesis by these compounds but reflected the response to inorganic acid stress. Analysis of fatty acid synthesis in crude mycobacterial cell extracts demonstrated that pyrazinoic acid failed to directly modulate the fatty acid synthase activity catalyzed by fatty acid synthase I (FAS-I). However, fatty acid synthesis was irreversibly inhibited by 5-chloro-pyrazinamide in a time-dependent fashion. Moreover, we demonstrate that pyrazinoic acid does not inhibit purified mycobacterial FAS-I, suggesting that this enzyme is not the immediate target of pyrazinamide. PMID:11914348

  11. An ortholog of farA of Aspergillus nidulans is implicated in the transcriptional activation of genes involved in fatty acid utilization in the yeast Yarrowia lipolytica

    SciTech Connect

    Poopanitpan, Napapol; Kobayashi, Satoshi; Fukuda, Ryouichi; Horiuchi, Hiroyuki; Ohta, Akinori

    2010-11-26

    Research highlights: {yields} POR1 is a Yarrowia lipolytica ortholog of farA involved in fatty acid response in A. nidulans. {yields} Deletion of POR1 caused growth defects on fatty acids. {yields} {Delta}por1 strain exhibited defects in the induction of genes involved in fatty acid utilization. -- Abstract: The yeast Yarrowia lipolytica effectively utilizes hydrophobic substrates such as fatty acids and n-alkanes. To identify a gene(s) regulating fatty acid utilization in Y. lipolytica, we first studied homologous genes to OAF1 and PIP2 of Saccharomyces cerevisiae, but their disruption did not change growth on oleic acid at all. We next characterized a Y. lipolytica gene, POR1 (primary oleate regulator 1), an ortholog of farA encoding a transcriptional activator that regulates fatty acid utilization in Aspergillus nidulans. The deletion mutant of POR1 was defective in the growth on various fatty acids, but not on glucose, glycerol, or n-hexadecane. It exhibited slight defect on n-decane. The transcriptional induction of genes involved in {beta}-oxidation and peroxisome proliferation by oleate was distinctly diminished in the {Delta}por1 strains. These data suggest that POR1 encodes a transcriptional activator widely regulating fatty acid metabolism in Y. lipolytica.

  12. Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels

    PubMed Central

    Hoshi, Toshinori; Wissuwa, Bianka; Tian, Yutao; Tajima, Nobuyoshi; Xu, Rong; Bauer, Michael; Heinemann, Stefan H.; Hou, Shangwei

    2013-01-01

    Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA), found abundantly in oily fish, may have diverse health-promoting effects, potentially protecting the immune, nervous, and cardiovascular systems. However, the mechanisms underlying the purported health-promoting effects of DHA remain largely unclear, in part because molecular signaling pathways and effectors of DHA are only beginning to be revealed. In vascular smooth muscle cells, large-conductance Ca2+- and voltage-activated K+ (BK) channels provide a critical vasodilatory influence. We report here that DHA with an EC50 of ?500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit ?1, increasing currents by up to ?20-fold. The DHA action is observed in cell-free patches and does not require voltage-sensor activation or Ca2+ binding but involves destabilization of the closed conformation of the ion conduction gate. DHA lowers blood pressure in anesthetized wild-type but not in Slo1 knockout mice. DHA ethyl ester, contained in dietary supplements, fails to activate BK channels and antagonizes the stimulatory effect of DHA. Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids, and these fatty acidsunlike their ethyl ester derivativesactivate the channels and lower blood pressure. This finding has practical implications for the use of omega-3 fatty acids as nutraceuticals for the general public and also for the critically ill receiving omega-3enriched formulas. PMID:23487785

  13. Structure–Activity Relationships of α-Keto Oxazole Inhibitors of Fatty Acid Amide Hydrolase

    PubMed Central

    Hardouin, Christophe; Kelso, Michael J.; Romero, F. Anthony; Rayl, Thomas J.; Leung, Donmienne; Hwang, Inkyu; Cravatt, Benjamin F.; Boger, Dale L.

    2008-01-01

    A systematic study of the structure–activity relationships (SAR) of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, Ki = 2.6 nM) with 5hh (aryl = 3-Cl-Ph, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally-restricted C2 side chains were examined and many provided exceptionally potent inhibitors of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteomic-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases. PMID:17559203

  14. Enhanced volatile fatty acids production of waste activated sludge under salinity conditions: Performance and mechanisms.

    PubMed

    Su, Gaoqiang; Wang, Shuying; Yuan, Zhiguo; Peng, Yongzhen

    2016-03-01

    Volatile fatty acids (VFAs) are essential for removing biological nitrogen and phosphorus in wastewater treatment plants. The purpose of this work was to investigate whether and how the addition of NaCl could improve the production of VFAs from waste activated sludge (WAS). Sludge solubilization was efficiently improved by the addition of NaCl. Both protein and carbohydrate in the fermentation liquid increased with the dosage of NaCl, and it provided a larger amount of organic compounds for the production of the VFAs. NaCl had inhibitory effects on the production of methane and a high dosage of NaCl could severely suppress the growth of methanogens, which decreased the consumption of the VFAs. Consequently, the production of VFAs was significantly enhanced by the addition of NaCl. The maximum production of VFAs was achieved with the highest dosage of NaCl (3316 mg (COD)/L at the NaCl dosage 0.5 mol/L; 783 mg (COD)/L without the addition of NaCl). Therefore, this study indicates that using NaCl could be an efficient method for improving the production of VFAs from WAS. PMID:26320405

  15. Increased Mitochondrial Activity in BMP7-Treated Brown Adipocytes, Due to Increased CPT1- and CD36-Mediated Fatty Acid Uptake

    PubMed Central

    Townsend, Kristy L.; An, Ding; Lynes, Matthew D.; Huang, Tian Lian; Zhang, Hongbin; Goodyear, Laurie J.

    2013-01-01

    Abstract Aims: Brown adipose tissue dissipates chemical energy in the form of heat and regulates triglyceride and glucose metabolism in the body. Factors that regulate fatty acid uptake and oxidation in brown adipocytes have not yet been fully elucidated. Bone morphogenetic protein 7 (BMP7) is a growth factor capable of inducing brown fat mitochondrial biogenesis during differentiation from adipocyte progenitors. Administration of BMP7 to mice also results in increased energy expenditure. To determine if BMP7 is able to affect the mitochondrial activity of mature brown adipocytes, independent of the differentiation process, we delivered BMP7 to mature brown adipocytes and measured mitochondrial activity. Results: We found that BMP7 increased mitochondrial activity, including fatty acid oxidation and citrate synthase activity, without increasing the mitochondrial number. This was accompanied by an increase in fatty acid uptake and increased protein expression of CPT1 and CD36, which import fatty acids into the mitochondria and the cell, respectively. Importantly, inhibition of either CPT1 or CD36 resulted in a blunting of the mitochondrial activity of BMP7-treated cells. Innovation: These findings uncover a novel pathway regulating mitochondrial activities in mature brown adipocytes by BMP7-mediated fatty acid uptake and oxidation. Conclusion: In conclusion, BMP7 increases mitochondrial activity in mature brown adipocytes via increased fatty acid uptake and oxidation, a process that requires the fatty acid transporters CPT1 and CD36. Antioxid. Redox Signal. 19, 243–257. PMID:22938691

  16. Signalling pathways controlling fatty acid desaturation.

    PubMed

    Mansilla, María Cecilia; Banchio, Claudia E; de Mendoza, Diego

    2008-01-01

    Microorganisms, plants and animals regulate the synthesis of unsaturated fatty acids (UFAs) during changing environmental conditions as well as in response to nutrients. Unsaturation of fatty acid chains has important structural roles in cell membranes: a proper ratio of saturated to UFAs contributes to membrane fluidity. Alterations in this ratio have been implicated in various disease states including cardiovascular diseases, immune disorders, cancer and obesity. They are also the major components of triglycerides and intermediates in the synthesis of biologically active molecules such as eicosanoids, which mediates fever, inflammation and neurotransmission. UFAs homeostasis in many organisms is achieved by feedback regulation of fatty acid desaturases gene transcription. Here, we review recently discovered components and mechanisms of the regulatory machinery governing the transcription of fatty acid desaturases in bacteria, yeast and animals. PMID:18751908

  17. Enhancement of E. coli acyl-CoA synthetase FadD activity on medium chain fatty acids.

    PubMed

    Ford, Tyler J; Way, Jeffrey C

    2015-01-01

    FadD catalyses the first step in E. coli beta-oxidation, the activation of free fatty acids into acyl-CoA thioesters. This activation makes fatty acids competent for catabolism and reduction into derivatives like alcohols and alkanes. Alcohols and alkanes derived from medium chain fatty acids (MCFAs, 6-12 carbons) are potential biofuels; however, FadD has low activity on MCFAs. Herein, we generate mutations in fadD that enhance its acyl-CoA synthetase activity on MCFAs. Homology modeling reveals that these mutations cluster on a face of FadD from which the co-product, AMP, is expected to exit. Using FadD homology models, we design additional FadD mutations that enhance E. coli growth rate on octanoate and provide evidence for a model wherein FadD activity on octanoate can be enhanced by aiding product exit. These studies provide FadD mutants useful for producing MCFA derivatives and a rationale to alter the substrate specificity of adenylating enzymes. PMID:26157619

  18. Enhancement of E. coli acyl-CoA synthetase FadD activity on medium chain fatty acids

    PubMed Central

    Way, Jeffrey C.

    2015-01-01

    FadD catalyses the first step in E. coli beta-oxidation, the activation of free fatty acids into acyl-CoA thioesters. This activation makes fatty acids competent for catabolism and reduction into derivatives like alcohols and alkanes. Alcohols and alkanes derived from medium chain fatty acids (MCFAs, 6–12 carbons) are potential biofuels; however, FadD has low activity on MCFAs. Herein, we generate mutations in fadD that enhance its acyl-CoA synthetase activity on MCFAs. Homology modeling reveals that these mutations cluster on a face of FadD from which the co-product, AMP, is expected to exit. Using FadD homology models, we design additional FadD mutations that enhance E. coli growth rate on octanoate and provide evidence for a model wherein FadD activity on octanoate can be enhanced by aiding product exit. These studies provide FadD mutants useful for producing MCFA derivatives and a rationale to alter the substrate specificity of adenylating enzymes. PMID:26157619

  19. Dietary long-chain (n-3) fatty acids facilitate immune cell activation in sedentary, but not exercise-trained rats.

    PubMed

    Robinson, L E; Field, C J

    1998-03-01

    Dietary long-chain (n-3) fatty acids from fish oil and low intensity exercise have been reported, independently, to inhibit tumor growth in rats. The mechanism for these effects is not known but may be related to diet and exercise-induced alterations in immune function. To study the individual and combined effects of these interventions on anticancer immune responses, healthy Fischer 344 rats were fed, for 4 wk, one of two semi-purified diets (polyunsaturated to saturated fatty acid ratio = 0.9), which differed only in the composition of fat (200 g/kg) and provided long-chain (n-3) fatty acids at 0 or 33 g/kg of total fat. Rats were randomly assigned to groups in a 2 x 2 experimental design to swim 3 h/d or to remain sedentary. For sedentary rats, dietary (n-3) fatty acids increased (P < 0.05) splenic natural killer (NK) cell cytotoxicity and the percentage of activated (CD71+) T and B cells and macrophages in spleen after concanavalin A stimulation. For exercise-trained rats, feeding the high (n-3) diet decreased (P < 0.05) the percentage of CD71+ T helper and B cells after stimulation. NK cell cytotoxicity, and the percentages of CD71+ T cells, B cells and macrophages after stimulation in the high (n-3)-fed exercise-trained group were not different than those of the low (n-3)-fed sedentary group. Thus individually, but not in combination, long-chain (n-3) fatty acids and low intensity exercise may be advantageous by augmenting cell-mediated immune function and NK cell cytotoxicity in healthy rats. PMID:9482755

  20. Identification and functional characterization of genes encoding omega-3 polyunsaturated fatty acid biosynthetic activities from unicellular microalgae.

    PubMed

    Vaezi, Royah; Napier, Johnathan A; Sayanova, Olga

    2013-12-01

    In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fatty acids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative "front-end" desaturases (Δ6 and Δ4) from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs) in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ6,9,12,15). These data confirm the functional characterization of omega-3 long chain polyunsaturated fatty acid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae. PMID:24351909

  1. Identification and Functional Characterization of Genes Encoding Omega-3 Polyunsaturated Fatty Acid Biosynthetic Activities from Unicellular Microalgae

    PubMed Central

    Vaezi, Royah; Napier, Johnathan A.; Sayanova, Olga

    2013-01-01

    In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fatty acids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative “front-end” desaturases (Δ6 and Δ4) from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs) in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ6,9,12,15). These data confirm the functional characterization of omega-3 long chain polyunsaturated fatty acid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae. PMID:24351909

  2. The liver-enriched transcription factor CREBH is nutritionally regulated and activated by fatty acids and PPAR{alpha}

    SciTech Connect

    Danno, Hirosuke; Ishii, Kiyo-aki; Nakagawa, Yoshimi; Mikami, Motoki; Yamamoto, Takashi; Yabe, Sachiko; Furusawa, Mika; Kumadaki, Shin; Watanabe, Kazuhisa; Shimizu, Hidehisa; Matsuzaka, Takashi; Kobayashi, Kazuto; Takahashi, Akimitsu; Yatoh, Shigeru; Suzuki, Hiroaki; Yamada, Nobuhiro; Shimano, Hitoshi

    2010-01-08

    To elucidate the physiological role of CREBH, the hepatic mRNA and protein levels of CREBH were estimated in various feeding states of wild and obesity mice. In the fast state, the expression of CREBH mRNA and nuclear protein were high and profoundly suppressed by refeeding in the wild-type mice. In ob/ob mice, the refeeding suppression was impaired. The diet studies suggested that CREBH expression was activated by fatty acids. CREBH mRNA levels in the mouse primary hepatocytes were elevated by addition of the palmitate, oleate and eicosapenonate. It was also induced by PPAR{alpha} agonist and repressed by PPAR{alpha} antagonist. Luciferase reporter gene assays indicated that the CREBH promoter activity was induced by fatty acids and co-expression of PPAR{alpha}. Deletion studies identified the PPRE for PPAR{alpha} activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay confirmed that PPAR{alpha} directly binds to the PPRE. Activation of CREBH at fasting through fatty acids and PPAR{alpha} suggest that CREBH is involved in nutritional regulation.

  3. Effects of synthetic alkamides on Arabidopsis fatty acid amide hydrolase activity and plant development.

    PubMed

    Faure, Lionel; Cavazos, Ronaldo; Khan, Bibi Rafeiza; Petros, Robby A; Koulen, Peter; Blancaflor, Elison B; Chapman, Kent D

    2015-02-01

    Alkamides and N-acylethanolamines (NAEs) are bioactive, amide-linked lipids that influence plant development. Alkamides are restricted to several families of higher plants and some fungi, whereas NAEs are widespread signaling molecules in both plants and animals. Fatty acid amide hydrolase (FAAH) has been described as a key contributor to NAE hydrolysis; however, no enzyme has been associated with alkamide degradation in plants. Herein reported is synthesis of 12 compounds structurally similar to a naturally occurring alkamide (N-isobutyl-(2E,6Z,8E)decatrienamide or affinin) with different acyl compositions more similar to plant NAEs and various amino alkyl head groups. These "hybrid" synthetic alkamides were tested for activity toward recombinant Arabidopsis FAAH and for their effects on plant development (i.e., cotyledon expansion and primary root length). A substantial increase in FAAH activity was discovered toward NAEs in vitro in the presence of some of these synthetic alkamides, such as N-ethyllauroylamide (4). This "enhancement" effect was found to be due, at least in part, to relief from product inhibition of FAAH by ethanolamine, and not due to an alteration in the oligomerization state of the FAAH enzyme. For several of these alkamides, an inhibition of seedling growth was observed with greater results in FAAH knockouts and less in FAAH over-expressing plants, suggesting that these alkamides could be hydrolyzed by FAAH in planta. The tight regulation of NAE levels in vivo appears to be important for proper seedling establishment, and as such, some of these synthetic alkamides may be useful pharmacological tools to manipulate the effects of NAEs in situ. PMID:25491532

  4. Fasciola hepatica Fatty Acid Binding Protein Induces the Alternative Activation of Human Macrophages

    PubMed Central

    Figueroa-Santiago, Olgary

    2014-01-01

    The liver fluke Fasciola hepatica is a highly evolved parasite that uses sophisticated mechanisms to evade the host immune response. The immunosuppressive capabilities of the parasite have been associated with antigens secreted through the parasite's tegument, called excretory-secretory products (ESPs). Proteomic studies have identified the fatty acid binding protein (FABP) as one of molecules present in the parasite ESPs. Although FABP has been investigated for potential use in the development of vaccines against fascioliasis, its direct interaction with cells of immune system has not been studied. In this study, FABP was purified in native form from soluble extracts of F. hepatica adult flukes using a combination of molecular sieving chromatography and preparative isoelectric focusing. The immunological effect of the purified protein, termed Fh12, was assayed in vitro using monocyte-derived macrophages (MDM) obtained from healthy human donors. Results from the assay indicate that Fh12 produced a significantly increased arginase expression and activity and induced the expression of chitinase-3-like protein (CHI3L1). The assay also showed that Fh12 downregulated the production of nitric oxide (NO) and the expression of nitric oxide synthase (NOS2). This indicates that Fh12 induced the production of alternatively activated macrophages (AAMϕ). The results also demonstrated the ability of Fh12 to downregulate the secretion of the proinflammatory and inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and IL-1βB, even after stimulation with lipopolysaccharide (LPS), as well as its ability to stimulate the overexpression of IL-10. These results suggest a potent anti-inflammatory role for Fh12, which could occur via targeting of Toll-like receptor 4 (TLR4). PMID:25225247

  5. Fasciola hepatica fatty acid binding protein induces the alternative activation of human macrophages.

    PubMed

    Figueroa-Santiago, Olgary; Espino, Ana M

    2014-12-01

    The liver fluke Fasciola hepatica is a highly evolved parasite that uses sophisticated mechanisms to evade the host immune response. The immunosuppressive capabilities of the parasite have been associated with antigens secreted through the parasite's tegument, called excretory-secretory products (ESPs). Proteomic studies have identified the fatty acid binding protein (FABP) as one of molecules present in the parasite ESPs. Although FABP has been investigated for potential use in the development of vaccines against fascioliasis, its direct interaction with cells of immune system has not been studied. In this study, FABP was purified in native form from soluble extracts of F. hepatica adult flukes using a combination of molecular sieving chromatography and preparative isoelectric focusing. The immunological effect of the purified protein, termed Fh12, was assayed in vitro using monocyte-derived macrophages (MDM) obtained from healthy human donors. Results from the assay indicate that Fh12 produced a significantly increased arginase expression and activity and induced the expression of chitinase-3-like protein (CHI3L1). The assay also showed that Fh12 downregulated the production of nitric oxide (NO) and the expression of nitric oxide synthase (NOS2). This indicates that Fh12 induced the production of alternatively activated macrophages (AAMϕ). The results also demonstrated the ability of Fh12 to downregulate the secretion of the proinflammatory and inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and IL-1βB, even after stimulation with lipopolysaccharide (LPS), as well as its ability to stimulate the overexpression of IL-10. These results suggest a potent anti-inflammatory role for Fh12, which could occur via targeting of Toll-like receptor 4 (TLR4). PMID:25225247

  6. Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes

    SciTech Connect

    Lynch, Caitlin; Pan, Yongmei; Li, Linhao; Heyward, Scott; Moeller, Timothy; Swaan, Peter W.; Wang, Hongbing

    2014-08-15

    Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods: Ligand-based structure–activity models were used for virtual screening of the Specs database ( (www.specs.net)) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results: Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fatty acid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion: Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fatty acid synthesis. Implications: Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. - Highlights: • Novel hCAR activators were identified by computational and biological approaches. • The role of hCAR in hepatic energy metabolism was examined. • hCAR activators repress gluconeogenesis but not lipogenesis and fatty acid synthesis. • Human and mouse CAR exhibit differential effects on energy metabolism.

  7. Influence of environmental temperature on the fatty acid desaturation and elongation activity of fish (Pimelodus maculatus) liver microsomes.

    PubMed

    de Torrengo, M; Brenner, R R

    1976-01-22

    The effect of environmental temperature on the activity of liver microsomes of fish (Pimelodus maculatus) to desaturate and elongate oleic, linoleic and alpha-linolenic acids was studied. It was found that: 1. Fish kept at 14-15 degrees C had higher desaturation and elongation activity than animals kept at 29-30 degrees C. The ratio of activity was the same for the three fatty acids. 2. A decrease of the environmental temperature increased the V of linoleic acid desaturation to gamma-linolenic acid, but did not modify the approximate Km of the reaction. 3. The inactivation of the delta6-desaturase of microsomes separated from fish kept at 29-30 degrees C and 14-15 degrees C was the same when heated at 40 degrees C. However, the enzyme was deactivated faster when heated at 29-30 degrees C than at 14-15 degrees C. 4. The increase of the delta6-desaturation activity of the microsomes evoked by the decrease of the temperature of the aquarium was mostly compensated for by the correlative decrease of the specific reaction rate of the reaction. For this reason it is assumed that the adaptive change of the desaturation activity of the microsomes with the environmental temperature does not greatly modify the fatty acid composition of the fish. PMID:1252479

  8. Supercritical carbon dioxide extraction of seed oil from winter melon (Benincasa hispida) and its antioxidant activity and fatty acid composition.

    PubMed

    Bimakr, Mandana; Rahman, Russly Abdul; Taip, Farah Saleena; Adzahan, Noranizan Mohd; Sarker, Md Zaidul Islam; Ganjloo, Ali

    2013-01-01

    In the present study, supercritical carbon dioxide (SC-CO(2)) extraction of seed oil from winter melon (Benincasa hispida) was investigated. The effects of process variables namely pressure (150-300 bar), temperature (40-50 °C) and dynamic extraction time (60-120 min) on crude extraction yield (CEY) were studied through response surface methodology (RSM). The SC-CO(2) extraction process was modified using ethanol (99.9%) as co-solvent. Perturbation plot revealed the significant effect of all process variables on the CEY. A central composite design (CCD) was used to optimize the process conditions to achieve maximum CEY. The optimum conditions were 244 bar pressure, 46 °C temperature and 97 min dynamic extraction time. Under these optimal conditions, the CEY was predicted to be 176.30 mg-extract/g-dried sample. The validation experiment results agreed with the predicted value. The antioxidant activity and fatty acid composition of crude oil obtained under optimized conditions were determined and compared with published results using Soxhlet extraction (SE) and ultrasound assisted extraction (UAE). It was found that the antioxidant activity of the extract obtained by SC-CO(2) extraction was strongly higher than those obtained by SE and UAE. Identification of fatty acid composition using gas chromatography (GC) showed that all the extracts were rich in unsaturated fatty acids with the most being linoleic acid. In contrast, the amount of saturated fatty acids extracted by SE was higher than that extracted under optimized SC-CO(2) extraction conditions. PMID:23322066

  9. Long chain polyunsaturated fatty acid synthesis in a marine vertebrate: ontogenetic and nutritional regulation of a fatty acyl desaturase with ?4 activity.

    PubMed

    Morais, Sofia; Castanheira, Filipa; Martinez-Rubio, Laura; Conceio, Luis E C; Tocher, Douglas R

    2012-04-01

    Solea senegalensis is an unusual marine teleost as it has very low dietary requirement for long-chain polyunsaturated fatty acids (LC-PUFA) during early development. Aquaculture is rapidly becoming the main source of health-beneficial fish products for human consumption. This, associated with limited supply of LC-PUFA-rich ingredients for fish feeds, render S. senegalensis a highly interesting species in which to study the LC-PUFA biosynthesis pathway. We have cloned and functionally characterized fatty acyl desaturase and elongase cDNAs corresponding to ?4fad (with some ?5 activity for the n-3 series) and elovl5 with the potential to catalyze docosahexaenoic acid (DHA) biosynthesis from eicosapentaenoic acid (EPA). Changes in expression of both transcripts were determined during embryonic and early larval development, and transcriptional regulation in response to higher or lower dietary n-3 LC-PUFA was assessed during larval and post-larval stages. There was a marked pattern of regulation during early ontogenesis, with both transcripts showing peak expression coinciding with the start of exogenous feeding. Although elovl5 transcripts were present in fertilized eggs, ?4fad only appeared at hatching. However, eggs have high proportions of DHA (~20%) and high DHA/EPA ratio (~11) to meet the high demands for early embryonic development. The fatty acid profile of larvae after the start of exogenous feeding closely reflected dietary composition. Nonetheless, ?4fad was significantly up-regulated in response to LC-PUFA-poor diets, which may suggest biological relevance of this pathway in reducing LC-PUFA dietary requirements in this species, compared to other marine teleosts. These results indicate that sole is capable of synthesizing DHA from EPA through a Sprecher-independent pathway. PMID:22245719

  10. Synthesis, and Surface-Active Properties of Palm Fatty Acid and 1(2-HYDROXYETHYL - Esteramide Quat

    NASA Astrophysics Data System (ADS)

    Mishra, Shilpi; Tyagi, V. K.

    In this study, an attempt has been made to synthesize esteramide quat by esterification of palm fatty acids with 1(2-hydroxyethyl piperazine) followed by quaternization with dimethyl sulphate (DMS). The optimum reaction conditions for esterification of palm fatty acids and 1(2-hydroxyethyl piperazine) were found to be 170°C reaction temperature and 150 mmHg pressure. The obtained esteramide was subjected to quaternization with different molar ratios of DMS. The consequences revealed that esteramide to DMS ratio of 1 : 0.95 and duration of quaternization for 2 h yielded esteramide quat of maximum cationic content, i.e., 64.9%. The instrumental analysis, viz. FT-IR, 1H NMR, 13C NMR verified the esterification and subsequent quaternization of the obtained esteramide quat. Furthermore, the surface-active and performance properties of synthesized esteramide quat were also evaluated.

  11. Fatty Acid Synthesis and Pyruvate Metabolism Pathways Remain Active in Dihydroartemisinin-Induced Dormant Ring Stages of Plasmodium falciparum

    PubMed Central

    Chen, Nanhua; LaCrue, Alexis N.; Teuscher, Franka; Waters, Norman C.; Gatton, Michelle L.; Kyle, Dennis E.

    2014-01-01

    Artemisinin (ART)-based combination therapy (ACT) is used as the first-line treatment of uncomplicated falciparum malaria worldwide. However, despite high potency and rapid action, there is a high rate of recrudescence associated with ART monotherapy or ACT long before the recent emergence of ART resistance. ART-induced ring-stage dormancy and recovery have been implicated as possible causes of recrudescence; however, little is known about the characteristics of dormant parasites, including whether dormant parasites are metabolically active. We investigated the transcription of 12 genes encoding key enzymes in various metabolic pathways in P. falciparum during dihydroartemisinin (DHA)-induced dormancy and recovery. Transcription analysis showed an immediate downregulation for 10 genes following exposure to DHA but continued transcription of 2 genes encoding apicoplast and mitochondrial proteins. Transcription of several additional genes encoding apicoplast and mitochondrial proteins, particularly of genes encoding enzymes in pyruvate metabolism and fatty acid synthesis pathways, was also maintained. Additions of inhibitors for biotin acetyl-coenzyme A (CoA) carboxylase and enoyl-acyl carrier reductase of the fatty acid synthesis pathways delayed the recovery of dormant parasites by 6 and 4 days, respectively, following DHA treatment. Our results demonstrate that most metabolic pathways are downregulated in DHA-induced dormant parasites. In contrast, fatty acid and pyruvate metabolic pathways remain active. These findings highlight new targets to interrupt recovery of parasites from ART-induced dormancy and to reduce the rate of recrudescence following ART treatment. PMID:24913167

  12. Biodegradation of C5-C 8 fatty acids and production of aroma volatiles by Myroides sp. ZB35 isolated from activated sludge.

    PubMed

    Xiao, Zijun; Zhu, Xiankun; Xi, Lijun; Hou, Xiaoyuan; Fang, Li; Lu, Jian R

    2014-05-01

    In the effluents of a biologically treated wastewater from a heavy oil-refining plant, C5-C8 fatty acids including pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, and 2-methylbutanoic acid are often detected. As these residual fatty acids can cause further air and water pollution, a new Myroides isolate ZB35 from activated sludge was explored to degrade these C5-C8 fatty acids in this study. It was found that the biodegradation process involved a lag phase that became prolonged with increasing acyl chain length when the fatty acids were individually fed to this strain. However, when fed as a mixture, the ones with longer acyl chains were found to become more quickly assimilated. The branched 2-methylbutanoic acid was always the last one to be depleted among the five fatty acids under both conditions. Metabolite analysis revealed one possible origin of short chain fatty acids in the biologically treated wastewater. Aroma volatiles including 2-methylbutyl isovalerate, isoamyl 2-methylbutanoate, isoamyl isovalerate, and 2-methylbutyl 2-methylbutanoate were subsequently identified from ZB35 extracts, linking the source of the fruity odor to these esters excreted by Myroides species. To our best knowledge, this is the first finding of these aroma esters in bacteria. From a biotechnological viewpoint, this study has revealed the potential of Myroides species as a promising source of aroma esters attractive for food and fragrance industries. PMID:24810320

  13. Link between light and fatty acid synthesis: Thioredoxin-linked reductive activation of plastidic acetyl-CoA carboxylase

    PubMed Central

    Sasaki, Yukiko; Kozaki, Akiko; Hatano, Mika

    1997-01-01

    Fatty acid synthesis in chloroplasts is regulated by light. The synthesis of malonyl-CoA, which is catalyzed by acetyl-CoA carboxylase (ACCase) and is the first committed step, is modulated by light/dark. Plants have ACCase in plastids and the cytosol. To determine the possible involvement of a redox cascade in light/dark modulation of ACCase, the effect of DTT, a known reductant of S-S bonds, was examined in vitro for the partially purified ACCase from pea plant. Only the plastidic ACCase was activated by DTT. This enzyme was activated in vitro more efficiently by reduced thioredoxin, which is a transducer of redox potential during illumination, than by DTT alone. Chloroplast thioredoxin-f activated the enzyme more efficiently than thioredoxin-m. The ACCase also was activated by thioredoxin reduced enzymatically with NADPH and NADP-thioredoxin reductase. These findings suggest that the reduction of ACCase is needed for activation of the enzyme, and a redox potential generated by photosynthesis is involved in its activation through thioredoxin as for enzymes of the reductive pentose phosphate cycle. The catalytic activity of ACCase was maximum at pH 8 and 2–5 mM Mg2+, indicating that light-produced changes in stromal pH and Mg2+ concentration modulate ACCase activity. These results suggest that light directly modulates a regulatory site of plastidic prokaryotic form of ACCase via a signal transduction pathway of a redox cascade and indirectly modulates its catalytic activity via stromal pH and Mg2+ concentration. A redox cascade is likely to link between light and fatty acid synthesis, resulting in coordination of fatty acid synthesis with photosynthesis. PMID:9380765

  14. Accumulation fatty acids of in Chlorella vulgaris under heterotrophic conditions in relation to activity of acetyl-CoA carboxylase, temperature, and co-immobilization with Azospirillum brasilense

    NASA Astrophysics Data System (ADS)

    Leyva, Luis A.; Bashan, Yoav; Mendoza, Alberto; de-Bashan, Luz E.

    2014-10-01

    The relation between fatty acid accumulation, activity of acetyl-CoA carboxylase (ACC), and consequently lipid accumulation was studied in the microalgae Chlorella vulgaris co-immobilized with the plant growth-promoting bacterium Azospirillum brasilense under dark heterotrophic conditions with Na acetate as a carbon source. In C. vulgaris immobilized alone, cultivation experiments for 6 days showed that ACC activity is directly related to fatty acid accumulation, especially in the last 3 days. In co-immobilization experiments, A. brasilense exerted a significant positive effect over ACC activity, increased the quantity in all nine main fatty acids, increased total lipid accumulation in C. vulgaris, and mitigated negative effects of nonoptimal temperature for growth. No correlation between ACC activity and lipid accumulation in the cells was established for three different temperatures. This study demonstrated that the interaction between A. brasilense and C. vulgaris has a significant effect on fatty acid and lipid accumulation in the microalgae.

  15. Accumulation of fatty acids in Chlorella vulgaris under heterotrophic conditions in relation to activity of acetyl-CoAcarboxylase, temperature, and co-immobilization with Azospirillum brasilense [corrected].

    PubMed

    Leyva, Luis A; Bashan, Yoav; Mendoza, Alberto; de-Bashan, Luz E

    2014-10-01

    The relation between fatty acid accumulation, activity of acetyl-CoA carboxylase (ACC), and consequently lipid accumulation was studied in the microalgae Chlorella vulgaris co-immobilized with the plant growth-promoting bacterium Azospirillum brasilense under dark heterotrophic conditions with Na acetate as a carbon source. In C. vulgaris immobilized alone, cultivation experiments for 6 days showed that ACC activity is directly related to fatty acid accumulation, especially in the last 3 days. In co-immobilization experiments, A. brasilense exerted a significant positive effect over ACC activity, increased the quantity in all nine main fatty acids, increased total lipid accumulation in C. vulgaris, and mitigated negative effects of nonoptimal temperature for growth. No correlation between ACC activity and lipid accumulation in the cells was established for three different temperatures. This study demonstrated that the interaction between A. brasilense and C. vulgaris has a significant effect on fatty acid and lipid accumulation in the microalgae. PMID:25129521

  16. Identification of a two-component fatty acid kinase responsible for host fatty acid incorporation by Staphylococcus aureus

    PubMed Central

    Parsons, Joshua B.; Broussard, Tyler C.; Bose, Jeffrey L.; Rosch, Jason W.; Jackson, Pamela; Subramanian, Chitra; Rock, Charles O.

    2014-01-01

    Extracellular fatty acid incorporation into the phospholipids of Staphylococcus aureus occurs via fatty acid phosphorylation. We show that fatty acid kinase (Fak) is composed of two dissociable protein subunits encoded by separate genes. FakA provides the ATP binding domain and interacts with two distinct FakB proteins to produce acyl-phosphate. The FakBs are fatty acid binding proteins that exchange bound fatty acid/acyl-phosphate with fatty acid/acyl-phosphate presented in detergent micelles or liposomes. The ΔfakA and ΔfakB1 ΔfakB2 strains were unable to incorporate extracellular fatty acids into phospholipid. FakB1 selectively bound saturated fatty acids whereas FakB2 preferred unsaturated fatty acids. Affymetrix array showed a global perturbation in the expression of virulence genes in the ΔfakA strain. The severe deficiency in α-hemolysin protein secretion in ΔfakA and ΔfakB1 ΔfakB2 mutants coupled with quantitative mRNA measurements showed that fatty acid kinase activity was required to support virulence factor transcription. These data reveal the function of two conserved gene families, their essential role in the incorporation of host fatty acids by Gram-positive pathogens, and connects fatty acid kinase to the regulation of virulence factor transcription in S. aureus. PMID:25002480

  17. Angiotensin (1-7)/Mas receptor axis activation ameliorates the changes in fatty acid composition in diabetic rats with nephropathy

    PubMed Central

    Singh, Kulwinder; Singh, Tajinder; Sharma, PL

    2010-01-01

    Diabetes mellitus is often associated with altered fatty acids composition. This study was designed to investigate the role of angiotensin (Ang) (1-7)/Mas receptor in improving fatty acids composition in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats. Rats treated with STZ (50 mg/kg, i.p. once) developed DN after 8 weeks. Fatty acid composition was estimated in renal cortical tissue by gas chromatography. Treatment with Ang (1-7), A-779, and Ang (1-7) plus A-779 was given from week 4 to week 8. Diabetic rats exhibited a significant increase in levels of saturated fatty acids and a significant decrease in levels of polyunsaturated fatty acids (PUFAs). Treatment with Ang (1-7) significantly attenuated these diabetes-induced changes. In diabetic rats, prior administration of A-779 significantly attenuated the increase in PUFAs produced by Ang (1-7); however, for saturated fatty acids, A-779 significantly blocked the decrease in palmitic acid only. Our study, for the first time, documented that endogenous Ang (1-7) modulates fatty acid composition in rats. Further, treatment with Ang (1-7) significantly attenuated diabetes-induced changes in fatty acids composition. This may be an additional mechanism implying the renoprotective role of Ang (1-7) in diabetic rats.

  18. Fatty acid biosynthesis in actinomycetes

    PubMed Central

    Gago, Gabriela; Diacovich, Lautaro; Arabolaza, Ana; Tsai, Shiou-Chuan; Gramajo, Hugo

    2011-01-01

    All organisms that produce fatty acids do so via a repeated cycle of reactions. In mammals and other animals, these reactions are catalyzed by a type I fatty acid synthase (FAS), a large multifunctional protein to which the growing chain is covalently attached. In contrast, most bacteria (and plants) contain a type II system in which each reaction is catalyzed by a discrete protein. The pathway of fatty acid biosynthesis in Escherichia coli is well established and has provided a foundation for elucidating the type II FAS pathways in other bacteria (White et al., 2005). However, fatty acid biosynthesis is more diverse in the phylum Actinobacteria: Mycobacterium, possess both FAS systems while Streptomyces species have only the multi-enzyme FAS II system and Corynebacterium species exclusively FAS I. In this review we present an overview of the genome organization, biochemical properties and physiological relevance of the two FAS systems in the three genera of actinomycetes mentioned above. We also address in detail the biochemical and structural properties of the acyl-CoA carboxylases (ACCases) that catalyzes the first committed step of fatty acid synthesis in actinomycetes, and discuss the molecular bases of their substrate specificity and the structure-based identification of new ACCase inhibitors with anti-mycobacterial properties. PMID:21204864

  19. Activation of phospholipase A2 in human neutrophils by polyunsaturated fatty acids and its role in stimulation of superoxide production.

    PubMed Central

    Robinson, B S; Hii, C S; Ferrante, A

    1998-01-01

    Although polyunsaturated fatty acids (PUFA) have been shown to stimulate neutrophil responses such as the oxygen-dependent respiratory burst (superoxide production), the mechanisms involved still remain undefined. Here we investigate the effect of PUFA on the phospholipase A2 (PLA2)-signal transduction process in human neutrophils. Exogenous eicosatetraenoic acid [arachidonic acid; C20:4(n-6)] or docosahexaenoic acid [C22:6(n-3)] promoted the release of [3H]C20:4(n-6) from prelabelled neutrophils in a time- and dose-dependent manner, which is indicative of PLA2 activation. The release of [3H]C20:4(n-6) from the cells by C20:4(n-6) and C22:6(n-3) was suppressed by PLA2 inhibitors. Other PUFA ¿eicosapentaenoic [C20:5(n-3)], octadecatrienoic [gamma-linolenic; C18:3(n-6)] and octadecadienoic [linoleic; C18:2(n-6)] acids¿ also had the ability to release [3H]C20:4(n-6); however, certain C20:4(n-6) derivatives [15-hydroperoxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid and C20:4(n-6) methyl ester] and saturated fatty acids [octadecanoic (stearic; C18:0) and eicosanoic (arachidic; C20:0) acids] had no significant effect. Treatment of the neutrophils with exogenous C22:6(n-3) caused the mass of endogenous unesterified C20:4(n-6) to increase. Incubation of the leucocytes with C20:4(n-6) or C22:6(n-3) evoked activation of the 85 kDa cytosolic PLA2 (cPLA2) and the 14 kDa secretory PLA2 (sPLA2), but not the cytosolic Ca2+-independent PLA2. In contrast, C20:0 did not activate any of the PLA2 isoforms. Activation of cPLA2 by PUFA was found to precede that of sPLA2. C22:6(n-3), C20:4(n-6) and other PUFA induced punctate localization of cPLA2 in the cells, which was not observed with saturated fatty acids. Pretreatment of the leucocytes with PLA2 inhibitors markedly decreased superoxide production induced by C20:4(n-6). These results show that PUFA activate PLA2 in neutrophils, which might have a mandatory role in biological responses. PMID:9841872

  20. Abnormal n-6 fatty acid metabolism in cystic fibrosis is caused by activation of AMP-activated protein kinase

    PubMed Central

    Umunakwe, Obi C.; Seegmiller, Adam C.

    2014-01-01

    Cystic fibrosis (CF) patients and model systems exhibit consistent abnormalities in PUFA metabolism, including increased metabolism of linoleate to arachidonate. Recent studies have connected these abnormalities to increased expression and activity of the Δ6- and Δ5-desaturase enzymes. However, the mechanism connecting these changes to the CF transmembrane conductance regulator (CFTR) mutations responsible for CF is unknown. This study tests the hypothesis that increased activity of AMP-activated protein kinase (AMPK), previously described in CF bronchial epithelial cells, causes these changes in fatty acid metabolism by driving desaturase expression. Using CF bronchial epithelial cell culture models, we confirm elevated activity of AMPK in CF cells and show that it is due to increased phosphorylation of AMPK by Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ). We also show that inhibition of AMPK or CaMKKβ reduces desaturase expression and reverses the metabolic alterations seen in CF cells. These results signify a novel AMPK-dependent mechanism linking the genetic defect in CF to alterations in PUFA metabolism. PMID:24859760

  1. Variation of Photosynthesis, Fatty Acid Composition, ATPase and Acid Phosphatase Activities, and Anatomical Structure of Two Tea (Camellia sinensis (L.) O. Kuntze) Cultivars in Response to Fluoride

    PubMed Central

    Wang, L. X.; Tang, J. H.; Xiao, B.; Yang, Y. J.; Liu, J.

    2013-01-01

    The changes of photosynthetic parameters, water use efficiency (WUE), fatty acid composition, chlorophyll (Chl) content, malondialdehyde (MDA) content, ATPase and acid phosphatase activities, fluoride (F) content, and leaf anatomical structure of two tea cultivars, “Pingyangtezao” (PY) and “Fudingdabai” (FD), after F treatments were investigated. The results show that net photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (E) significantly decreased in both cultivars after 0.3 mM F treatment, but FD had higher Pn, gs, and WUE and lower E than PY. Chl content in PY significantly decreased after 0.2 and 0.3 mM F treatments, while no significant changes were observed in FD. The proportions of shorter chain and saturated fatty acids increased and those of longer chain and unsaturated fatty acids decreased in both cultivars under F treatments. The contents of MDA increased after F treatments but were higher in PY than in FD. In addition, F treatments decreased the activities of ATPase and acid phosphatase and increased F content in both cultivars; however, compared with PY, FD showed higher enzymatic activities and lower F content in roots and leaves. Leaf anatomical structure in FD indicated that cells in leaf midrib region were less injured by F than in PY. PMID:24023526

  2. Abundance and distribution of fatty acids within the walls of an active deep-sea sulfide chimney

    NASA Astrophysics Data System (ADS)

    Li, Jiwei; Zhou, Huaiyang; Peng, Xiaotong; Fu, Meiyan; Chen, Zhiqiang; Yao, Huiqiang

    2011-04-01

    Abundance and distribution of total fatty acids (TFAs) were examined along the physicochemical gradient within an active hydrothermal chimney collected from the Main Endeavour segment of Juan de Fuca Ridge. Approximately 27 fatty acids are identified with a chain-length ranging from C12 to C22. From the exterior to the interior of the chimney walls, the total concentrations of TFAs (∑ TFAs) show a trend of evident decrease. The observed compositions of TFAs are rich in bacterial biomarkers especially monounsaturated fatty acids (MUFAs) and minor branched and cyclopropyl FAs. On the basis of the species-specific FAs and bacterial 16SrRNA gene analysis (Li et al., unpublished data), sulfur-based metabolism appears to be the essential metabolic process in the chimney. Furthermore, the sulfur oxidizing bacteria (SOB) are identified as a basic component of microbial communities at the exterior of the hydrothermal chimney, and its proportion shows an inward decrease while the sulfate reducing bacteria (SRB) have an inverse distribution.

  3. [Omega-3 fatty acids in psychiatry].

    PubMed

    Bourre, Jean-Marie

    2005-02-01

    The brain is one of the organs with the highest level of lipids (fats). Brain lipids, formed of fatty acids, participate in the structure of membranes, for instance 50 % fatty acids are polyunsaturated in the gray matter, 1/3 are of the omega-3 family, and are thus of dietary origin. The omega-3 fatty acids (mainly alpha-linolenic acid, ALA) participated in one of the first experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out on ex vivo cultured brain cells, then on in vivo brain cells (neurons, astrocytes and oligodendrocytes) from animals fed ALA deficient diet, finally on physicochemical (membrane fluidity), biochemical, physiological, neurosensory (vision an auditory responses), and behavioural or learning parameters. These findings indicated that the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for human infants determines to a certain extend the visual, neurological, and intellectual abilities. Thus, in view of these results and of the high polyunsaturated fatty acid content of the brain, it is normal to consider that they could be involved in psychiatric diseases and in the cognitive decline of ageing. Omega-3 fatty acids appear effective in the prevention of stress, however their role as regulator of mood is a matter for discussion. Indeed, they play a role in the prevention of some disorders including depression (especially post partum), as well as in dementia, particularly Alzheimer's disease. Their role in major depression and bipolar disorder (manic-depressive disease), only poorly documented, is not clearly demonstrated. The intervention of omega-3 in dyslexia, autism, and schizophrenia has been suggested, but it does not necessarily infer a nutritional problems. The respective importance of the vascular system (where the omega-3 are actually active) and the cerebral parenchyma itself, remain to be resolved. However, the insufficient supply of omega-3 fatty acids in today diet in occidental (less than 50 % of the recommended dietary intakes values for ALA) raises the problem of how to correct inadequate dietary habits, by prescribing mainly rapeseed (canola) and walnut oils on the one hand, fatty fish (wild, or farmed, but the nature of fatty acids present in fish flesh is the direct consequence of the nature of fats with which they have been fed), and eggs from laying hens fed omega-3 fatty acids. PMID:15691497

  4. ON EXTRACELLULAR AND INTRACELLULAR VENOM ACTIVATORS OF THE BLOOD, WITH ESPECIAL REFERENCE TO LECITHIN AND FATTY ACIDS AND THEIR COMPOUNDS.

    PubMed

    Noguchi, H

    1907-07-17

    In normal serums of the majority of mammalian and avian blood there exists certain substances capable of activating venom haemolysin. They are extractable from serum by means of ether, and are capable of conferring upon the originally non-activating serum a power to activate venom, when mixed with the latter. The ethereal extract consists of fatty acids, neutral fats and possibly also some ether soluble organic soaps. The fatty acids and soaps, especially of the oleinic series, acquire certain characteristics of complements in general, when they are mixed with serum. They are inactive without the venom in the mixture; they are inactivable with calcium chloride; they exhibit a tendency to go off in activity with age; they are inactive or only weakly active at 0 degrees C., and they are extractable by ether. In testing the serum from which the ether soluble substances are removed, it is found that no venom activating property is left. Warm alcoholic extraction of such serum yields, however, a large quantity of lecithin. In the case of non-activating serums no venom activating fats appear in the ethereal extract. Lecithin exists in such serum in no less quantity than in the activating kind. The addition of oleinic acid or its soluble soaps to a non-activating serum, in a ratio which corresponds to the percentage of fatty acids or soaps contained in some of the easily activating serums, will make the serum highly active in regard to venom. In normal serum of dog there exists, besides the group of activators already mentioned, another kind of venom activators which has been identified as a lecithin compound acting in the manner of free lecithin. A very sharp differentiation of the haemolysis produced by this activator and by the other groups of activators is obtained by means of calcium chloride, which is powerless against lecithin or lecithin compounds, but effective in removing the action of the latter. This lecithin containing proteid can be precipitated by half saturation with ammonium sulphate, but is perfectly soluble in water, and is not coagulated in neutral alkaline salt solutions upon boiling. Alcohol precipitates a proteid-like coagulum and extracts lecithin from it; ether does not extract lecithin from this compound. Non-activating serums do not contain any such lecithin compound. Lecithin contained in other serum proteids, mainly as lecithalbumin, and perhaps as contained in globulin, is not able to activate venom. This is true of all the serums with which I worked; it matters not whether these fractions (obtained with ammonium sulphate) belong to the most activating serum (dog) or to the non-activating serum (ox). The non-coagulable portion of all heated serum contains a venom activator of the nature of lecithin. This activator is contained in a non-coagulable proteid described by Howell which is identical with Chabrie's albumon. As there is no ether-extractable lecithin in this portion of the serum, the activating property of heated serum must be due to this proteid compound of lecithin. That this lecithin proteid does not pre-exist in normal serum but is produced by the action of high temperature is true of all serums except that of the dog. In venom activation we know now that lecithin becomes reactive with venom when it is transformed from other proteid compounds into the non-coagulable form, the albumon. Howell's view of the non-existence of the non-coagulable proteid in normal serum seems to receive a biological support from venom haemolysis. Ovovitellin derived from hen's egg is one of the best venom activators of the lecithin proteid type. The cause of venom susceptibility of various kinds of blood corpuscles does not depend upon the existence of lecithin in the corpuscles, but solely upon the amount of fatty acids, and perhaps, also, soaps and fats, contained in the corpuscles. The protection which calcium chloride gives against venom haemolysis is proof of the absence of lecithin activation. From the stroma of susceptible corpuscles fatty acids or some fats can be extracted with ether. After ethereal extraction the stroma becomes non-activating, while the extract contains fatty acids and some soaps or fats, which when added to venom-resistant corpuscles render the latter vulnerable to venom. The corpuscular solution of non-activating corpuscles does not contain enough fatty acids. The larger the amount of fatty acids and soaps in the corpuscles, the easier the cells undergo venom haemolysis. Lecithin exists in the strorna of all kinds of corpuscles, but in a form unavailable for venom activation. The somatic cytolytic processes caused by venom requires intracellular complements. The experiments performed on the cells of liver, kidney, testis and brain of the guinea-pig and rat indicate that the substances which act as complements are inactivable by calcium chloride. PMID:19867102

  5. Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria.

    PubMed

    Fischer, Carol L; Drake, David R; Dawson, Deborah V; Blanchette, Derek R; Brogden, Kim A; Wertz, Philip W

    2012-03-01

    There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity--the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid--against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. D-sphingosine (MBC range, 0.3 to 19.6 μg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 μg/ml), and phytosphingosine (MBC range, 3.3 to 62.5 μg/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection. PMID:22155833

  6. Delta 6-desaturase activity in liver microsomes of rats fed diets enriched with cholesterol and/or omega 3 fatty acids.

    PubMed Central

    Garg, M L; Sebokova, E; Thomson, A B; Clandinin, M T

    1988-01-01

    The effect of feeding semipurified diets enriched in linseed (rich in C18:3, omega 3 fatty acid) or fish (rich in C20:5, omega 3 and C22:6, omega 3 fatty acid) oil with and without cholesterol supplementation on the desaturation of linoleic acid (C18:2, omega 6) by rat liver microsomal fractions was investigated. Animals fed diets supplemented with beef tallow were used as equal-energy controls. Both linseed-oil and fish-oil diets, without added cholesterol, decrease conversion of C18:2, omega 6 fatty acid to gamma-linolenic acid (C18:3, omega 6). Reduction in delta 6-desaturation was significantly greater for animals fed the diet containing fish oil than with animals fed the linseed-oil diet. The major effect of cholesterol supplementation was to decrease the rate of desaturation of C18:2, omega 6, when fed in combination with the beef-tallow diet, whereas delta 6-desaturation was unaffected when cholesterol was fed along with diets high in omega 3 fatty acids (linseed oil or fish oil). The activity of the delta 6-desaturase in vitro is consistent with the fatty acid composition observed for the microsomal membranes on which this enzyme is localized. Dietary linseed oil and fish oil lowered the arachidonic (C20:4, omega 6) acid content of rat liver microsomes, with an accompanying increase in membrane eicosapentaenoic (C20:5, omega 3) and docosahexaenoic (C22:6, omega 3) acid content, in comparison with the group fed beef tallow. Inclusion of cholesterol into the beef-tallow or linseed-oil diets resulted in decreased membrane C20:4, omega 6-fatty-acid content, with concomitant increase in C18:2, omega 6-fatty-acid content. However, addition of cholesterol to the fish-oil diet did not alter the microsomal membrane content of C20:4, omega 6 fatty acid. Thus it is suggested that (1) the decrease in prostaglandin E2, thromboxane and prostacyclin levels generally observed after fish-oil consumption may be at least partly due to inhibition of C20:4, omega 6-fatty-acid synthesis from C18:2, omega 6 fatty acid; and (2) consumption of fish oil prevents the further decrease in C20:4, omega 6-fatty-acid levels by dietary cholesterol that is apparent when cholesterol is fed in combination with diets high in saturated fat or C18:3, omega 3 fatty acid. PMID:3342019

  7. Dietary fatty acids influence the activity and metabolic control of mitochondrial carnitine palmitoyltransferase I in rat heart and skeletal muscle.

    PubMed

    Power, G W; Newsholme, E A

    1997-11-01

    The fatty acid composition of the diet has been found to influence the activity and sensitivity of mitochondrial carnitine palmitoyltransferase I (CPT I; EC 2.3.1.21) to inhibition by malonyl CoA in rat heart and skeletal muscle. The nutritional state of rats has been shown to have less influence on the activity and metabolic control of mitochondrial CPT I in heart and skeletal muscle tissue than in the liver, a tissue in which CPT I activity and sensitivity to inhibition by malonyl CoA can be shown to be regulated acutely under different nutritional conditions. However, because manipulation of the nutritional state in these previous studies was restricted mainly to examining the effect of starvation, this study was undertaken to determine whether, as in liver, the fatty acid content and composition of the diet can regulate the activity and metabolic control of CPT I in heart and skeletal muscle. Rats were fed for up to 10 wk either a nonpurified low fat diet (30 g fat/kg) or a high fat diet (200 g fat/kg) containing one of the following five oil types: hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or menhaden (fish) oil (MO). Feeding a diet enriched in MO had the most pronounced effect. Rats fed MO had a significantly greater skeletal muscle CPT I specific activity and tissue capacity, and a lower sensitivity of CPT I to malonyl CoA inhibition compared with rats fed a low fat diet, but the duration of feeding required to modulate this sensitivity was longer than that observed previously for the liver enzyme. Progressively greater sensitivity of heart CPT I to malonyl CoA occurred with feeding duration in all groups. These studies indicate that the fatty acid composition of the diet is involved in the regulation of mitochondrial CPT I activity in heart and skeletal muscle. PMID:9349840

  8. Isolation and chemical analysis of a fatty acid fraction of Kalanchoe pinnata with a potent lymphocyte suppressive activity.

    PubMed

    Almeida, A P; Da Silva, S A; Souza, M L; Lima, L M; Rossi-Bergmann, B; de Moraes, V L; Costa, S S

    2000-03-01

    Previously we demonstrated that Kalanchoe pinnata (KP) leaf extracts inhibited in vitro lymphocyte proliferation and showed in vivo immunosuppressive activity. Here we attempt to identify the immunosuppressive substances present in KP guided by the lymphoproliferative assays. From the ethanolic extract was purified a fraction (KP12SA) twenty-fold more potent to block murine lymphocyte proliferation than the crude extract. Chemical analysis by 1H- and 13C-NMR, IR and GC-MS of KP12SA (methylated sample) showed 89.3% of palmitic acid (C16), 10.7% of stearic acid (C18) and traces of arachidic (C20) and behenic acids (C22). This study provides evidence that fatty acids present in Kalanchoe pinnata may be responsible, at least in part, for its immunosuppressive effect in vivo. PMID:10763586

  9. Biocatalytic acylation of carbohydrates with fatty acids from palm fatty acid distillates.

    PubMed

    Chaiyaso, Thanongsak; H-Kittikun, Aran; Zimmermann, Wolfgang

    2006-05-01

    Palm fatty acid distillates (PFAD) are by-products of the palm oil refining process. Their use as the source of fatty acids, mainly palmitate, for the biocatalytic synthesis of carbohydrate fatty acid esters was investigated. Esters could be prepared in high yields from unmodified acyl donors and non-activated free fatty acids obtained from PFAD with an immobilized Candida antarctica lipase preparation. Acetone was found as a compatible non-toxic solvent, which gave the highest conversion yields in a heterogeneous reaction system without the complete solubilization of the sugars. Glucose, fructose, and other acyl acceptors could be employed for an ester synthesis with PFAD. The synthesis of glucose palmitate was optimized with regard to the water activity of the reaction mixture, the reaction temperature, and the enzyme concentration. The ester was obtained with 76% yield from glucose and PFAD after reaction for 74 h with 150 U ml(-1) immobilized lipase at 40 degrees C in acetone. PMID:16402249

  10. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats

    PubMed Central

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-01-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  11. A potential plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses...

  12. Fatty Acid and Essential Oil Compositions of Trifolium angustifolium var. angustifolium with Antioxidant, Anticholinesterase and Antimicrobial Activities.

    PubMed

    Ertaş, Abdulselam; Boğa, Mehmet; Haşimi, Nesrin; Yılmaz, Mustafa Abdullah

    2015-01-01

    This study represents the first report on the chemical composition and biological activity of Trifolium angustifolium var. angustifolium. The major components of the essential oil were identified as hexatriacontene (23.0%), arachidic acid (15.5%) and α-selinene (10.0%). The main constituents of the fatty acid obtained from the petroleum ether extract were identified as palmitic acid (29.8%), linoleic acid (18.6%) and oleic acid (10.5%). In particular, the water extract exhibited higher activity than α-tocopherol and BHT, which were used as standards in the ABTS cation radical scavenging assay and indicated higher inhibitory effect against acetylcholinesterase enzyme than the reference compound, galanthamine but exhibited weak activity in β-carotene bleaching, DPPH-free radical scavenging, and cupric-reducing antioxidant capacity assays. The petroleum ether extract exhibited higher activity than α-tocopherol which was used as standard in the β-carotene bleaching method at concentration 100 μg/mL. The acetone extract exhibited higher activity than α-tocopherol which was used as standard cupric reducing antioxidant capacity (CUPRAC) method at 100 μg/mL concentration. The acetone and methanol extracts were active on all microorganisms tested with a small zone diameter indicating weak activity. PMID:25561929

  13. Fatty Acid and Essential Oil Compositions of Trifolium angustifolium var. angustifolium with Antioxidant, Anticholinesterase and Antimicrobial Activities

    PubMed Central

    Ertaş, Abdulselam; Boğa, Mehmet; Haşimi, Nesrin; Yılmaz, Mustafa Abdullah

    2015-01-01

    This study represents the first report on the chemical composition and biological activity of Trifolium angustifolium var. angustifolium. The major components of the essential oil were identified as hexatriacontene (23.0%), arachidic acid (15.5%) and α-selinene (10.0%). The main constituents of the fatty acid obtained from the petroleum ether extract were identified as palmitic acid (29.8%), linoleic acid (18.6%) and oleic acid (10.5%). In particular, the water extract exhibited higher activity than α-tocopherol and BHT, which were used as standards in the ABTS cation radical scavenging assay and indicated higher inhibitory effect against acetylcholinesterase enzyme than the reference compound, galanthamine but exhibited weak activity in β-carotene bleaching, DPPH-free radical scavenging, and cupric-reducing antioxidant capacity assays. The petroleum ether extract exhibited higher activity than α-tocopherol which was used as standard in the β-carotene bleaching method at concentration 100 μg/mL. The acetone extract exhibited higher activity than α-tocopherol which was used as standard cupric reducing antioxidant capacity (CUPRAC) method at 100 μg/mL concentration. The acetone and methanol extracts were active on all microorganisms tested with a small zone diameter indicating weak activity. PMID:25561929

  14. Dietary fatty acids and arthritis.

    PubMed

    Hurst, S; Zainal, Z; Caterson, B; Hughes, C E; Harwood, J L

    2010-01-01

    Musculoskeletal complaints are the second most frequent reason for medical treatments. Within these diseases rheumatoid arthritis (RA) and, especially, osteoarthritis (OA) are common. Although the causes of arthritis are multifactorial and not fully understood, clinical trials have generally shown benefit from dietary n-3 polyunsaturated fatty acids. This has usually been attributed to their anti-inflammatory properties. Recently we have used in vitro model systems to study the molecular mechanism(s) by which n-3 PUFAs may act to alleviate the symptoms of arthritis. These experiments showed that n-3 PUFAs reduce expression of cartilage-degrading proteinases, cyclooxygenase-2 and inflammatory cytokines. Eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) or alpha-linolenic acid. The data provide a scientific rationale for the consumption of n-3 fatty acids as part of a healthy diet and perhaps in treating arthritis. PMID:20189789

  15. Use of agar diffusion assay to measure bactericidal activity of alkaline salts of fatty acids against bacteria associated with poultry processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The agar diffusion assay was used to examine antibacterial activity of alkaline salts of caproic, caprylic, capric, lauric, and myristic acids. A 0.5M concentration of each fatty acid was dissolved in 1.0 M potassium hydroxide (KOH), and pH of the mixtures was adjusted to 10.5 with citric acid. Solu...

  16. Medium chain fatty acids are selective peroxisome proliferator activated receptor (PPAR) γ activators and pan-PPAR partial agonists.

    PubMed

    Liberato, Marcelo Vizoná; Nascimento, Alessandro S; Ayers, Steven D; Lin, Jean Z; Cvoro, Aleksandra; Silveira, Rodrigo L; Martínez, Leandro; Souza, Paulo C T; Saidemberg, Daniel; Deng, Tuo; Amato, Angela Angelica; Togashi, Marie; Hsueh, Willa A; Phillips, Kevin; Palma, Mário Sérgio; Neves, Francisco A R; Skaf, Munir S; Webb, Paul; Polikarpov, Igor

    2012-01-01

    Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) γ to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPARγ ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8-C10) bind the PPARγ LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPARγ LBD, stronger partial agonists with full length PPARγ and exhibit full blockade of PPARγ phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPARγ also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/β-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARγ modulators with useful clinical profiles among natural products. PMID:22649490

  17. Brain Lipotoxicity of Phytanic Acid and Very Long-chain Fatty Acids. Harmful Cellular/Mitochondrial Activities in Refsum Disease and X-Linked Adrenoleukodystrophy

    PubMed Central

    Schönfeld, Peter; Reiser, Georg

    2016-01-01

    It is increasingly understood that in the aging brain, especially in the case of patients suffering from neurodegenerative diseases, some fatty acids at pathologically high concentrations exert detrimental activities. To study such activities, we here analyze genetic diseases, which are due to compromised metabolism of specific fatty acids, either the branched-chain phytanic acid or very long-chain fatty acids (VLCFAs). Micromolar concentrations of phytanic acid or of VLCFAs disturb the integrity of neural cells by impairing Ca2+ homeostasis, enhancing oxidative stress or de-energizing mitochondria. Finally, these combined harmful activities accelerate cell death. Mitochondria are more severely targeted by phytanic acid than by VLCFAs. The insertion of VLCFAs into the inner membrane distorts the arrangement of membrane constituents and their functional interactions. Phytanic acid exerts specific protonophoric activity, induces reactive oxygen species (ROS) generation, and reduces ATP generation. A clear inhibition of the Na+, K+-ATPase activity by phytanic acid has also been reported. In addition to the instantaneous effects, a chronic exposure of brain cells to low micromolar concentrations of phytanic acid may produce neuronal damage in Refsum disease by altering epigenetic transcriptional regulation. Myelin-producing oligodendrocytes respond with particular sensitivity to VLCFAs. Deleterious activity of VLCFAs on energy-dependent mitochondrial functions declines with increasing the hydrocarbon chain length (C22:0 > C24:0 > C26:0). In contrast, the reverse sequence holds true for cell death induction by VLCFAs (C22:0 < C24:0 < C26:0). In adrenoleukodystrophy, the uptake of VLCFAs by peroxisomes is impaired by defects of the ABCD1 transporter. Studying mitochondria from ABCD1-deficient and wild-type mice proves that the energy-dependent functions are not altered in the disease model. Thus, a defective ABCD1 apparently exerts no obvious adaptive pressure on mitochondria. Further research has to elucidate the detailed mechanistic basis for the failures causing fatty acid-mediated neurodegeneration and should help to provide possible therapeutic interventions. PMID:27114847

  18. Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice

    PubMed Central

    Zeng, Hong-liang; Huang, Su-ling; Xie, Fu-chun; Zeng, Li-min; Hu, You-hong; Leng, Ying

    2015-01-01

    Aim: Defects in fatty acid metabolism contribute to the pathogenesis of insulin resistance and obesity. In this study, we investigated the effects of a novel compound yhhu981 on fatty acid metabolism in vitro and in vivo. Methods: The capacity to stimulate fatty acid oxidation was assessed in C2C12 myotubes. The fatty acid synthesis was studied in HepG2 cells using isotope tracing. The phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) was examined with Western blot analysis. For in vivo experiments, ob/ob mice were orally treated with yhhu981 acutely (300 mg/kg) or chronically (150 or 300 mg·kg−1·d−1 for 22 d). On the last day of treatment, serum and tissue samples were collected for analysis. Results: Yhhu981 (12.5–25 μmol/L) significantly increased fatty acid oxidation and the expression of related genes (Sirt1, Pgc1α and Mcad) in C2C12 myotubes, and inhibited fatty acid synthesis in HepG2 cells. Furthermore, yhhu981 dose-dependently increased the phosphorylation of AMPK and ACC in both C2C12 myotubes and HepG2 cells. Compound C, an AMPK inhibitor, blocked fatty acid oxidation in yhhu981-treated C2C12 myotubes and fatty acid synthesis decrease in yhhu981-treated HepG2 cells. Acute administration of yhhu981 decreased the respiratory exchange ratio in ob/ob mice, whereas chronic treatment with yhhu981 ameliorated the lipid abnormalities and ectopic lipid deposition in skeletal muscle and liver of ob/ob mice. Conclusion: Yhhu981 is a potent compound that stimulates fatty acid oxidation, and exerts pleiotropic effects on lipid metabolism by activating AMPK. PMID:25732571

  19. Suicide Deaths of Active Duty U.S. Military and Omega-3 Fatty Acid Status: A Case Control Comparison

    PubMed Central

    Lewis, Michael D.; Hibbeln, Joseph R.; Johnson, Jeremiah E.; Lin, Yu Hong; Hyun, Duk Y.; Loewke, James D.

    2011-01-01

    Background The recent escalation of US Military suicide deaths to record numbers has been an sentinel for impaired force efficacy and has accelerated the search for reversible risk factors. Objective Determine if deficiencies of neuroactive highly unsaturated omega-3 essential fatty acids (n-3 HUFA), in particular docosahexaenoic acid (DHA), are associated with increased risk of suicide death among a large random sample of active duty US military. Methods Serum fatty acids were quantified as % of total fatty acids, among US military suicide deaths (n= 800) and controls (n=800) matched for age, date of collection, sex, rank and year of incident. Participants were Active Duty US Military personnel (2002–2008). Outcome measures, included death by suicide, post deployment health assessment questionnaire and ICD-9 mental health diagnosis data. Results Risks of suicide death was 14% higher, per standard deviation [SD] lower DHA % (OR =1.14, 95% CI; 1.02–1.27, p<0.03), in adjusted logistic regressions. Among men risk of suicide death was 62% greater with low serum DHA status (adjusted Odds Ratio [OR] =1.62, 95% CI 1.12–2.34, p<0.01, comparing DHA below 1.75% [n=1,389] to above [n=141]). Risk of suicide death was 54% greater in those who reported having seen wounded, dead or killed coalition personnel (OR = 1.54, 95% CI; 1.12–2.12, p< 0.007.) Conclusion This US military population had a very low and narrow range of n-3 HUFA status. Although these data suggest that low serum DHA may be a risk factor for suicides, well designed intervention trials are needed to evaluate causality. PMID:21903029

  20. Activation of long chain fatty acids with acyl carrier protein: demonstration of a new enzyme, acyl-acyl carrier protein synthetase, in Escherichia coli.

    PubMed Central

    Ray, T K; Cronan, J E

    1976-01-01

    A soluble enzyme activity which catalyzes the synthesis of acyl-acyl carrier protein from acyl carrier proteins, a long chain fatty acid, and ATP has been demonstrated in E. coli. The reaction requires high concentrations of both Ca++ and Mg++ for activity, and cleaves ATP to AMP and PPi. The fatty acyl product has been identified as acyl-acyl carrier protein by its solubility, thioester linkage, molecular weight, charge, and biological activity. Several criteria indicate the enzyme is distinct from acyl-CoA synthetase. The fatty acid specificity of the enzyme suggests a role of acyl-acyl carrier protein synthetase in the incorporation of fatty acids into phospholipid. PMID:794875

  1. Structural Basis for Ligand Regulation of the Fatty Acid-binding Protein 5, Peroxisome Proliferator-activated Receptor β/δ (FABP5-PPARβ/δ) Signaling Pathway*

    PubMed Central

    Armstrong, Eric H.; Goswami, Devrishi; Griffin, Patrick R.; Noy, Noa; Ortlund, Eric A.

    2014-01-01

    Fatty acid-binding proteins (FABPs) are a widely expressed group of calycins that play a well established role in solubilizing cellular fatty acids. Recent studies, however, have recast FABPs as active participants in vital lipid-signaling pathways. FABP5, like its family members, displays a promiscuous ligand binding profile, capable of interacting with numerous long chain fatty acids of varying degrees of saturation. Certain “activating” fatty acids induce the protein's cytoplasmic to nuclear translocation, stimulating PPARβ/δ transactivation; however, the rules that govern this process remain unknown. Using a range of structural and biochemical techniques, we show that both linoleic and arachidonic acid elicit FABP5's translocation by permitting allosteric communication between the ligand-sensing β2 loop and a tertiary nuclear localization signal within the α-helical cap of the protein. Furthermore, we show that more saturated, nonactivating fatty acids inhibit nuclear localization signal formation by destabilizing this activation loop, thus implicating FABP5 specifically in cis-bonded, polyunsaturated fatty acid signaling. PMID:24692551

  2. Bioluminescent determination of free fatty acids.

    PubMed

    Kather, H; Wieland, E

    1984-08-01

    A simple, highly specific, and sensitive bioluminescent method for determination of free fatty acids in unextracted plasma or serum has been developed. The method is based on the activation of free fatty acids by acyl-CoA synthetase (EC 6.2.1.3). The pyrophosphate formed is used to phosphorylate fructose 6-phosphate in a reaction catalyzed by the enzyme pyrophosphate-fructose-6-phosphate phosphotransferase (EC 4.1.2.13). The triosephosphates produced from fructose 1,6-bisphosphate by aldolase are oxidized by NAD in the presence of arsenate to 3-phosphoglycerate. The NADH is detected via the bacterial NADH-linked luciferase system. Excellent agreement has been obtained by comparison with accepted methods. In addition, for the determination of serum free fatty acids, the method is particularly applicable for following lipolysis of isolated adipocytes. PMID:6486422

  3. Fenofibrate, a PPARα agonist, protect proximal tubular cells from albumin-bound fatty acids induced apoptosis via the activation of NF-kB

    PubMed Central

    Zuo, Nan; Zheng, Xiaoyu; Liu, Hanzhe; Ma, Xiaoli

    2015-01-01

    Albumin-bound fatty acids is the main cause of renal damage, PPARα is responsible in the metabolism of fatty acids. Previous study found that PPARα played a protective role in fatty acids overload associated tubular injury. The aim of the present study is to investigate whether fenofibrate, a PPARα ligands, could contribute to the renoprotective action in fatty acids overload proximal tubule epithelial cells. We observed in HK-2 cells that fenofibrate significantly inhibited fatty acids bound albumin (FA-BSA) induced up-regulation of MCP-1 and IL-8. Treatment with fenofibrate attenuated renal oxidative stress induced by FA-BSA as evidenced by decreased MDA level, increased SOD activity and catalase, GPx-1 expression. FA-BSA induced apoptosis of HK-2 cells were also obviously prevented by fenofibrate. Furthermore, fenofibrate significantly increased the expression of PPARα mRNA and protein in FA-BSA treated cells. Finally, the activation of NF-kB induced by FA-BSA was markedly suppressed by fenofibrate. Taken together, our study describes a renoprotective role of fenofibrate in fatty acids associated tubular toxicity, and the transcriptional activation of PPARα and suppression of NF-kB were at least partially involved. PMID:26617775

  4. Fenofibrate, a PPARα agonist, protect proximal tubular cells from albumin-bound fatty acids induced apoptosis via the activation of NF-kB.

    PubMed

    Zuo, Nan; Zheng, Xiaoyu; Liu, Hanzhe; Ma, Xiaoli

    2015-01-01

    Albumin-bound fatty acids is the main cause of renal damage, PPARα is responsible in the metabolism of fatty acids. Previous study found that PPARα played a protective role in fatty acids overload associated tubular injury. The aim of the present study is to investigate whether fenofibrate, a PPARα ligands, could contribute to the renoprotective action in fatty acids overload proximal tubule epithelial cells. We observed in HK-2 cells that fenofibrate significantly inhibited fatty acids bound albumin (FA-BSA) induced up-regulation of MCP-1 and IL-8. Treatment with fenofibrate attenuated renal oxidative stress induced by FA-BSA as evidenced by decreased MDA level, increased SOD activity and catalase, GPx-1 expression. FA-BSA induced apoptosis of HK-2 cells were also obviously prevented by fenofibrate. Furthermore, fenofibrate significantly increased the expression of PPARα mRNA and protein in FA-BSA treated cells. Finally, the activation of NF-kB induced by FA-BSA was markedly suppressed by fenofibrate. Taken together, our study describes a renoprotective role of fenofibrate in fatty acids associated tubular toxicity, and the transcriptional activation of PPARα and suppression of NF-kB were at least partially involved. PMID:26617775

  5. Dietary fatty acids and minerals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulating evidence in animals and humans shows that dietary fatty acids influence the absorption and utilization of certain mineral elements. Fat intake exceeding 10% of energy intake reduces calcium uptake and use by the body, and this effect is more pronounced with saturated compared to unsatu...

  6. Oxidative stability of fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of polyunsaturated fatty acids in poultry feeds follows the recent trend in the food industry to fortify processed foods with health promoting supplements. The chemical structure of these compounds presents a challenge to the feed formulator and producer that must contend with such unstable ...

  7. Phosphorus-based fatty acid methyl esters.

    PubMed

    Katir, Nadia; El Kadib, Abdelkrim; Castel, Annie

    2013-09-01

    With the aim of designing novel transformable fatty acid diesters, various strategies for introducing phosphorus arms to the fatty backbone have been examined. While lithiated phosphine reacts classically to brominated fatty esters to afford the mono-addition product, the synthesis of phosphorylated diesters was found to be difficult, a fact related to the bulkiness of fatty acids and phosphine reagents. A base-induced dehydrochlorination reaction using ArPCl2 and hydroxy-terminated fatty esters resulted in metastable diester for which hydrolytic cleavage undergo phosphine oxidation and expulsion of one fatty chain. Alternatively, ArPOCl2 alleviates this drawback and provides stable, phosphorylated fatty acid diesters. PMID:23845998

  8. Conjugated Fatty Acid Synthesis

    PubMed Central

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-01-01

    Conjugated linolenic acids (CLNs), 18:3 ?9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 ?9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 ?9cis,11trans,13cis) or ?-eleostearic acid (18:3 ?9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly ?-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of ?-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

  9. Fatty Acid Transduction of Nitric Oxide Signaling

    PubMed Central

    Baker, Paul R. S.; Lin, Yiming; Schopfer, Francisco J.; Woodcock, Steven R.; Groeger, Alison L.; Batthyany, Carlos; Sweeney, Scott; Long, Marshall H.; Iles, Karen E.; Baker, Laura M. S.; Branchaud, Bruce P.; Chen, Yuqing E.; Freeman, Bruce A.

    2007-01-01

    Mass spectrometric analysis of human plasma and urine revealed abundant nitrated derivatives of all principal unsaturated fatty acids. Nitrated palmitoleic, oleic, linoleic, linolenic, arachidonic and eicosapentaenoic acids were detected in concert with their nitrohydroxy derivatives. Two nitroalkene derivatives of the most prevalent fatty acid, oleic acid, were synthesized (9- and 10-nitro-9-cis-octadecenoic acid; OA-NO2), structurally characterized and determined to be identical to OA-NO2 found in plasma, red cells, and urine of healthy humans. These regioisomers of OA-NO2 were quantified in clinical samples using 13C isotope dilution. Plasma free and esterified OA-NO2 concentrations were 619 ± 52 and 302 ± 369 nM, respectively, and packed red blood cell free and esterified OA-NO2 was 59 ± 11 and 155 ± 65 nM. The OA-NO2 concentration of blood is ~50% greater than that of nitrated linoleic acid, with the combined free and esterified blood levels of these two fatty acid derivatives exceeding 1 μM. OA-NO2 is a potent ligand for peroxisome proliferator activated receptors at physiological concentrations. CV-1 cells co-transfected with the luciferase gene under peroxisome proliferator-activated receptor (PPAR) response element regulation, in concert with PPARγ, PPARα, or PPARδ expression plasmids, showed dose-dependent activation of all PPARs by OA-NO2. PPARγ showed the greatest response, with significant activation at 100 nM, while PPARα and PPARδ were activated at ~300 nM OA-NO2. OA-NO2 also induced PPARγ-dependent adipogenesis and deoxyglucose uptake in 3T3-L1 preadipocytes at a potency exceeding nitrolinoleic acid and rivaling synthetic thiazo-lidinediones. These data reveal that nitrated fatty acids comprise a class of nitric oxide-derived, receptor-dependent, cell signaling mediators that act within physiological concentration ranges. PMID:16227625

  10. Synthesis and evaluation of odour-active methionyl esters of fatty acids via esterification and transesterification of butter oil.

    PubMed

    Li, Cheng; Sun, Jingcan; Fu, Caili; Yu, Bin; Liu, Shao Quan; Li, Tianhu; Huang, Dejian

    2014-02-15

    Methionol-derived fatty acid esters were synthesised by both chemical and lipase catalysed esterification between fatty acids and methionol. Beneficial effects of both methods were compared qualitatively and quantitatively by GC-MS/GC-FID results. And the high acid and heat stability of our designed methionyl esters meet the requirement of the food industry. Most importantly, the sensory test showed that fatty acid carbon-chain length had an important effect on the flavour attributes of methionyl esters. Moreover, through Lipozyme TL IM-mediated transesterification, valuable methionol-derived esters were synthesised from the readily available natural material butter oil as the fatty acid source. The conversion of methionol and yield of each methionyl ester were also elucidated by GC-MS-FID. PMID:24128547

  11. AMP-Activated Protein Kinase Interacts with the Peroxisome Proliferator-Activated Receptor Delta to Induce Genes Affecting Fatty Acid Oxidation in Human Macrophages

    PubMed Central

    Kemmerer, Marina; Finkernagel, Florian; Cavalcante, Marcela Frota; Abdalla, Dulcineia Saes Parra; Müller, Rolf; Brüne, Bernhard; Namgaladze, Dmitry

    2015-01-01

    AMP-activated protein kinase (AMPK) maintains energy homeostasis by suppressing cellular ATP-consuming processes and activating catabolic, ATP-producing pathways such as fatty acid oxidation (FAO). The transcription factor peroxisome proliferator-activated receptor δ (PPARδ) also affects fatty acid metabolism, stimulating the expression of genes involved in FAO. To question the interplay of AMPK and PPARδ in human macrophages we transduced primary human macrophages with lentiviral particles encoding for the constitutively active AMPKα1 catalytic subunit, followed by microarray expression analysis after treatment with the PPARδ agonist GW501516. Microarray analysis showed that co-activation of AMPK and PPARδ increased expression of FAO genes, which were validated by quantitative PCR. Induction of these FAO-associated genes was also observed upon infecting macrophages with an adenovirus coding for AMPKγ1 regulatory subunit carrying an activating R70Q mutation. The pharmacological AMPK activator A-769662 increased expression of several FAO genes in a PPARδ- and AMPK-dependent manner. Although GW501516 significantly increased FAO and reduced the triglyceride amount in very low density lipoproteins (VLDL)-loaded foam cells, AMPK activation failed to potentiate this effect, suggesting that increased expression of fatty acid catabolic genes alone may be not sufficient to prevent macrophage lipid overload. PMID:26098914

  12. Fatty acid, carotenoid and tocopherol compositions of 20 Canadian lentil cultivars and synergistic contribution to antioxidant activities.

    PubMed

    Zhang, Bing; Deng, Zeyuan; Tang, Yao; Chen, Peter; Liu, Ronghua; Ramdath, D Dan; Liu, Qiang; Hernandez, Marta; Tsao, Rong

    2014-10-15

    Understanding the profile of lipophilic phytochemicals in lentils is necessary to better understand the health benefits of lentils. The fatty acid, carotenoid and tocopherol compositions and antioxidant activities of the lipophilic extracts of 20 lentil cultivars (10 red and 10 green) were therefore examined. Lentils contained 1.52-2.95% lipids, of which 77.5-81.7% were unsaturated essential fatty acids. Total tocopherols ranged from 37 to 64μg/g DW, predominantly γ-tocopherol (96-98% of the tocopherol content), followed by δ- and α-tocopherol. trans-Lutein was the primary and major carotenoid (64-78%) followed by trans-zeaxanthin (5-13%). Carotenoids and tocopherols showed weak correlation with 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity (r=0.4893 and 0.3259, respectively), but good correlation when combined (r=0.6688), suggesting they may act synergistically. Carotenoids were found to contribute the most to the strong antioxidant activity measured by photochemiluminescence (PCL) assay. Results from this study contribute to the development of lentil cultivars and related functional foods with increased health benefits. PMID:24837953

  13. Structure-activity analysis of harmful algae inhibition by congeneric compounds: case studies of fatty acids and thiazolidinediones.

    PubMed

    Huang, Haomin; Xiao, Xi; Shi, Jiyan; Chen, Yingxu

    2014-01-01

    The occurrence of harmful algal blooms has been increasing significantly around the world. In order to ensure the safety of drinking water, procedures to screen potential materials as effective algicides are needed, and predictive methods which save both the labor and time compared with traditional experimental approaches, are particularly desirable. In this study, data from previous studies on the algal-growth inhibitory action of two kinds of compounds, namely, the action of fatty acids and thiazolidinediones on the harmful algae Heterosigma akashiwo and Chattonella marina, were modeled using multiple linear regression (MLR) based on quantitative structure-activity relationships (QSAR). The models were shown to have highly predictive ability and stability, and provided insight into the inhibitory mechanisms of congeneric compounds. The main descriptors in the fatty-acid models were the Connolly accessible area and the number of rotatable bonds, illustrating that molecular surface area and shape are important in their algicidal actions. In the thiazolidinedione models, the critical volume, octanol-water partition coefficient (LogP), and Connolly solvent-excluded volume were found to be significant, indicating that hydrophobicity, substituent group size, and mode of action are mechanistically important. Our results showed the algicidal activity of a series of compounds on different algae could be modeled, and each model is efficacious for compounds that fall into the application domain of the QSAR model. This work demonstrates how reliable predictions of the algicidal activity of novel compounds and explanations of their inhibitory mechanisms can be obtained. PMID:24562453

  14. In vitro antibacterial activities and mechanism of sugar fatty acid esters against five food-related bacteria.

    PubMed

    Zhao, Lei; Zhang, Heyan; Hao, Tianyang; Li, Siran

    2015-11-15

    The objective of this study was to evaluate the antibacterial activities of sugar fatty acid esters, with different fatty acid and saccharide moieties, against five food-related bacteria including Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium. Sucrose monocaprate showed the strongest antibacterial activity against all tested bacteria, especially Gram-positive bacteria. The minimum inhibitory concentrations (MICs) for Gram-positive bacteria and Gram-negative bacteria were 2.5 and 10 mM, respectively. The minimum bactericidal concentrations (MBCs) for Gram-positive bacteria were 10 mM. Time-kill assay also showed that sucrose monocaprate significantly inhibit the growth of tested bacteria. The permeability of the cell membrane and intracellular proteins were both changed by sucrose monocaprate according to cell constituents' leakage, SDS-PAGE and scanning electron microscope assays. It is suggested that sucrose monocaprate, with both emulsifying and antibacterial activities, have a potential to serve as a safe multifunctional food additive in food industries. PMID:25977039

  15. Studies on the biological effects of deuteriated organic compounds. III. Antifungal activity of perdeuteriated fatty acids on dermatophytes in vivo experimental microsporie in guinea pigs.

    PubMed

    Dinh-Nguyên, N; Hellgren, L; Vincent, J

    1976-07-16

    Investigations on the antimycotic properties of perdeuteriated fatty acids were carried out on Microsporum cains infections in vivo. The study was performed on experimental microsporie in guinea pigs using four different methods, all based on the ability of M. canis to cause alopecia. Perdeuteriated n-hendecanoic acid showed in vivo a statistically significant enhanced antimycotic effect compared to its unlabelled analogue. This is in accordance with our previous observations in vitro conditions. The remaining perdeuteriated fatty acids (C12--C18) showed no statistically significant growth retarding effect on M. canis infections in guinea pigs when compared with their unlabelled analogues. The present study attempts to ascertain if some perdeuteriated fatty acids have any antifungal activity in vivo conditions. Our previous papers (3,4) concerning the evaluation of the antifungal activity of some perdeuteriated fatty acids on dermatophytes in vitro, demonstrated that the perdeuteriation of n-hendecanoic acid, lead to a pronounced antimycotic effect on common dermatophytes as e.g. E. floccosum, T. rubrum, M. canis and T. mentagrophytes. As our previous results indicate a decreasing of fungistasis with an increasing carbon-chain length of the perdeuteriated fatty acids, we have attempted to verify this observation in vivo conditions. A special interest was, of course, focused on the most promising compound, the perdeuteriated n-hendecanoic acid. PMID:967225

  16. Plant fatty acid hydroxylase

    SciTech Connect

    Somerville, C.; Loo, F. van de

    2000-02-22

    The present invention relates to the identification of nucleic acid sequences and constructs, and methods related to the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.

  17. Plant fatty acid hydroxylase

    DOEpatents

    Somerville, Chris; van de Loo, Frank

    2000-01-01

    The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.

  18. Expression and characterization of an epoxide hydrolase from Anopheles gambiae with high activity on epoxy fatty acids

    PubMed Central

    Xu, Jiawen; Morisseau, Christophe; Hammock, Bruce D.

    2014-01-01

    In insects, epoxide hydrolases (EHs) play critical roles in the metabolism of xenobiotic epoxides from the food resources and in the regulation of endogenous chemical mediators, such as juvenile hormones. Using the baculovirus expression system, we expressed and characterized an epoxide hydrolase from Anopheles gambiae (AgEH) that is distinct in evolutionary history from insect juvenile hormone epoxide hydrolases (JHEHs). We partially purified the enzyme by ion exchange chromatography and isoelectric focusing. The experimentally determined molecular weight and pI were estimated to be 35kD and 6.3 respectively, different than the theoretical ones. The AgEH had the greatest activity on long chain epoxy fatty acids such as 14,15-epoxyeicosatrienoic acids (14,15-EET) and 9,10-epoxy-12Z-octadecenoic acids (9,10-EpOME or leukotoxin) among the substrates evaluated. Juvenile hormone III, a terpenoid insect growth regulator, was the next best substrate tested. The AgEH showed kinetics comparable to the mammalian soluble epoxide hydrolases, and the activity could be inhibited by AUDA [12-(3-adamantan-1-yl-ureido) dodecanoic acid], a urea-based inhibitor designed to inhibit the mammalian soluble epoxide hydrolases. The rabbit serum generated against the soluble epoxide hydrolase of Mus musculus can both cross-react with natural and denatured forms of the AgEH, suggesting immunologically they are similar. The study suggests there are mammalian sEH homologs in insects, and epoxy fatty acids may be important chemical mediators in insects. PMID:25173592

  19. Expression and characterization of an epoxide hydrolase from Anopheles gambiae with high activity on epoxy fatty acids.

    PubMed

    Xu, Jiawen; Morisseau, Christophe; Hammock, Bruce D

    2014-11-01

    In insects, epoxide hydrolases (EHs) play critical roles in the metabolism of xenobiotic epoxides from the food resources and in the regulation of endogenous chemical mediators, such as juvenile hormones. Using the baculovirus expression system, we expressed and characterized an epoxide hydrolase from Anopheles gambiae (AgEH) that is distinct in evolutionary history from insect juvenile hormone epoxide hydrolases (JHEHs). We partially purified the enzyme by ion exchange chromatography and isoelectric focusing. The experimentally determined molecular weight and pI were estimated to be 35 kD and 6.3 respectively, different than the theoretical ones. The AgEH had the greatest activity on long chain epoxy fatty acids such as 14,15-epoxyeicosatrienoic acids (14,15-EET) and 9,10-epoxy-12Z-octadecenoic acids (9,10-EpOME or leukotoxin) among the substrates evaluated. Juvenile hormone III, a terpenoid insect growth regulator, was the next best substrate tested. The AgEH showed kinetics comparable to the mammalian soluble epoxide hydrolases, and the activity could be inhibited by AUDA [12-(3-adamantan-1-yl-ureido) dodecanoic acid], a urea-based inhibitor designed to inhibit the mammalian soluble epoxide hydrolases. The rabbit serum generated against the soluble epoxide hydrolase of Mus musculus can both cross-react with natural and denatured forms of the AgEH, suggesting immunologically they are similar. The study suggests there are mammalian sEH homologs in insects, and epoxy fatty acids may be important chemical mediators in insects. PMID:25173592

  20. Regulation of Thrombospondin-1 expression in alternatively activated macrophages and adipocytes: role of cellular crosstalk and omega-3 fatty acids

    PubMed Central

    Finlin, Brian S.; Zhu, Beibei; Starnes, Catherine P.; McGehee, Robert E.; Peterson, Charlotte A.; Kern, Philip A.

    2013-01-01

    Thrombospondin-1 (TSP-1) expression in human adipose positively correlates with body mass index and may contribute to adipose dysfunction by activating TGF-β and/or inhibiting angiogenesis. Our objective was to determine how TSP-1 is regulated in adipocytes and polarized macrophages using a coculture system and to determine whether fatty acids, including the ω-3 fatty acid DHA, regulate TSP-1 expression. Coculture of M1, M2a, or M2c macrophages with adipocytes induced TSP-1 gene expression in adipocytes (from 2.4 to 4.2-fold, P<0.05), and adipocyte coculture induced TSP-1 gene expression in M1 and M2c macrophages (M1:8.6-fold; M2c 26-fold, P<0.05). TSP-1 protein levels in the shared media of adipocytes and M2c cells was also strongly induced by coculture (>10 fold, P<0.05). DHA treatment during the coculture of adipocytes and M2c macrophages potently inhibited theM2c macrophage TSP-1 mRNA level (97% inhibition, P<0.05). Adipocyte coculture induced IL-10 expression in M2c macrophages (10.1-fold, P<0.05), and this increase in IL-10 mRNA expression was almost completely blocked with DHA treatment (96% inhibition, P<0.05); thus, IL-10 expression closely paralleled TSP-1 expression. Since IL-10 has been shown to regulate TSP-1 in other cell types, we reduced IL-10 expression with siRNA in the M2c cells and found that this caused TSP-1 to be reduced in response to adipocyte coculture by 60% (P<0.05), suggesting that IL-10 regulates TSP-1 expression in M2c macrophages. These results suggest that supplementation with dietary ω-3 fatty acids could potentially be beneficial to adipose tissue in obesity by reducing TSP-1 and fibrosis. PMID:23528972

  1. Effect of dietary fats on some membrane-bound enzyme activities, membrane lipid composition and fatty acid profiles of rat heart sarcolemma.

    PubMed

    Vajreswari, A; Narayanareddy, K

    1992-05-01

    The effect of various dietary fats on membrane lipid composition, fatty acid profiles and membrane-bound enzyme activities of rat cardiac sarcolemma was assessed. Four groups of male weanling Charles Foster Young rats were fed diets containing 20% of groundnut, coconut, safflower or mustard oil for 16 weeks. Cardiac sarcolemma was prepared from each group and the activities of Na+, K(+)-ATPase, 5'-nucleotidase, Ca(2+)-ATPase and acetylcholinesterase were examined. ATPase activities were similar in all groups except the one fed coconut oil, which had the highest activities. Acetylcholinesterase activity was also similar in all the groups, however, it was significantly higher in the group fed mustard oil. No significant changes were observed among the groups in 5'-nucleotidase activity, in the cholesterol-to-phospholipid molar ratio and in sialic acid content. The coconut, safflower and mustard oil diets significantly increased cholesterol and phospholipid contents and the lipid-to-protein ratio of cardiac sarcolemma as compared to feeding the groundnut oil diet. The fatty acid composition of membrane lipids was quite different among the various groups, reflecting the type of dietary fat given. The total unsaturated-to-saturated fatty acid ratio was not different among the various groups; however, the levels of some major fatty acids such as palmitic (16:0), oleic (18:1) and linoleic (18:2) acids were significantly different. Cardiac sarcolemma of the group fed safflower oil had the highest polyunsaturated fatty acid content. The results suggest that dietary fats induce changes not only in the fatty acid composition of the component lipids but also in the activities of sarcolemmal enzymes involved in the regulation of cardiac function. PMID:1406062

  2. Omega-3 Fatty Acids Protect the Brain against Ischemic Injury by Activating Nrf2 and Upregulating Heme Oxygenase 1

    PubMed Central

    Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K.; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun

    2014-01-01

    Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies. PMID:24478369

  3. Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

    PubMed

    Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun; Chen, Jun; Zhang, Feng

    2014-01-29

    Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies. PMID:24478369

  4. Fatty Acid Composition and Antioxidant Activity of Tea (Camellia sinensis L.) Seed Oil Extracted by Optimized Supercritical Carbon Dioxide

    PubMed Central

    Wang, Yuefei; Sun, Da; Chen, Hao; Qian, Lisheng; Xu, Ping

    2011-01-01

    Seeds are another product in addition to leaves (raw materials for teas) of tea (Camellia sinensis L.) plant. The great increase of tea consumption in recent years raises the challenge of finding commercial applications for tea seeds. In the present study, supercritical carbon dioxide (SC-CO2) extraction edible oil from tea seed was carried out, response surface methodology (RSM) was used to optimize processing parameters including time (2090 min), temperature (3545 C) and pressure (5090 MPa). The fatty acid composition and antioxidant activity of the extracted oil was also investigated. The highest yield of oil (29.2 0.6%) was obtained under optimal SC-CO2 extraction conditions (45 C, 89.7 min and 32 MPa, respectively), which was significantly higher (p < 0.05) than that (25.3 1.0%) given by Soxhlet extraction. Meanwhile, tea seed oil extracted by SC-CO2 contained approximately 80% unsaturated fatty acids and showed a much stronger scavenging ability on the DPPH radical than that extracted by Soxhlet. SC-CO2 is a promising alternative for efficient extraction of edible oil from tea seed. Moreover, tea seed oil extracted by SC-CO2 is highly edible and has good antioxidant activity, and therefore may play a potential role as a health-promoting food resource in human diets. PMID:22174626

  5. Central administration of oleate or octanoate activates hypothalamic fatty acid sensing and inhibits food intake in rainbow trout.

    PubMed

    Librán-Pérez, Marta; Otero-Rodiño, Cristina; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2014-04-22

    If levels of fatty acids like oleate and octanoate are directly sensed through different fatty acid (FA) sensing systems in hypothalamus of rainbow trout, intracerebroventricular (ICV) administration of FA should elicit effects similar to those previously observed after intraperitoneal (IP) treatment. Accordingly, we observed after ICV treatment with oleate or octanoate decreased food intake accompanied in hypothalamus by reduced potential of lipogenesis and FA oxidation, and decreased potential of ATP-dependent inward rectifier potassium channel (K(+)ATP). Those changes support direct FA sensing through mechanisms related to FA metabolism and mitochondrial activity. The FA sensing through binding to FAT/CD36 and subsequent expression of transcription factors appears to be also direct but an interaction with peripheral hormones cannot be rejected. Moreover, decreased expression of NPY and increased expression of POMC were observed in parallel with the activation of FA sensing systems and decreased food intake. These results allow us to suggest the involvement of at least these peptides in controlling the decreased food intake noted after oleate and octanoate treatment in rainbow trout. PMID:24631300

  6. n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner.

    PubMed

    Neschen, Susanne; Morino, Katsutaro; Dong, Jianying; Wang-Fischer, Yanlin; Cline, Gary W; Romanelli, Anthony J; Rossbacher, Jörg C; Moore, Irene K; Regittnig, Werner; Munoz, David S; Kim, Jung H; Shulman, Gerald I

    2007-04-01

    Recent studies have suggested that n-3 fatty acids, abundant in fish oil, protect against high-fat diet-induced insulin resistance through peroxisome proliferator-activated receptor (PPAR)-alpha activation and a subsequent decrease in intracellular lipid abundance. To directly test this hypothesis, we fed PPAR-alpha null and wild-type mice for 2 weeks with isocaloric high-fat diets containing 27% fat from either safflower oil or safflower oil with an 8% fish oil replacement (fish oil diet). In both genotypes the safflower oil diet blunted insulin-mediated suppression of hepatic glucose production (P < 0.02 vs. genotype control) and PEPCK gene expression. Feeding wild-type mice a fish oil diet restored hepatic insulin sensitivity (hepatic glucose production [HGP], P < 0.002 vs. wild-type mice fed safflower oil), whereas in contrast, in PPAR-alpha null mice failed to counteract hepatic insulin resistance (HGP, P = NS vs. PPAR-alpha null safflower oil-fed mice). In PPAR-alpha null mice fed the fish oil diet, safflower oil plus fish oil, hepatic insulin resistance was dissociated from increases in hepatic triacylglycerol and acyl-CoA but accompanied by a more than threefold increase in hepatic diacylglycerol concentration (P < 0.0001 vs. genotype control). These data support the hypothesis that n-3 fatty acids protect from high-fat diet-induced hepatic insulin resistance in a PPAR-alpha-and diacylglycerol-dependent manner. PMID:17251275

  7. Nitrated fatty acids: Synthesis and measurement

    PubMed Central

    Woodcock, Steven R.; Bonacci, Gustavo; Gelhaus, Stacy L.; Schopfer, Francisco J.

    2012-01-01

    Nitrated fatty acids are the product of nitrogen dioxide reaction with unsaturated fatty acids. The discovery of peroxynitrite and peroxidase-induced nitration of biomolecules led to the initial reports of endogenous nitrated fatty acids. These species increase during ischemia reperfusion, but concentrations are often at or near the limits of detection. Here, we describe multiple methods for nitrated fatty acid synthesis, sample extraction from complex biological matrices, and a rigorous method of qualitative and quantitative detection of nitrated fatty acids by LC-MS. In addition, optimized instrument conditions and caveats regarding data interpretation are discussed. PMID:23200809

  8. Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation

    SciTech Connect

    Kajimoto, Masaki; Ledee, Dolena R.; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G.; Portman, Michael A.

    2014-01-01

    Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. We previously showed that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study was focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 hours) and wean: normal circulation (Group-C);transient coronary occlusion (10 minutes) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon labeled lactate, medium-chain and long-chain FAs were infused as oxidative substrates. Substrate fractional contribution to the citric acid cycle (FC) was analyzed by 13-Carbon nuclear magnetic resonance. Results: ECMO depressed circulating T3 levels to 40% baseline at 4 hours and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [ATP]/[ADP] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions: T3 releases inhibition of lactate oxidation following ischemia-reperfusion injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

  9. Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease.

    PubMed

    Ma, Liang; Li, Shilin; Zheng, Hao; Chen, Jinying; Lin, Lin; Ye, Xia; Chen, Zhizhi; Xu, Qinyuan; Chen, Tao; Yang, Jincheng; Qiu, Neng; Wang, Guangcheng; Peng, Aihua; Ding, Yi; Wei, Yuquan; Chen, Lijuan

    2011-06-01

    Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease. PMID:21429633

  10. Activation of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

    SciTech Connect

    Kimura, Rino; Takahashi, Nobuyuki; Murota, Kaeko; Yamada, Yuko; Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko; Moriyama, Tatsuya; Goto, Tsuyoshi; Kawada, Teruo

    2011-06-24

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO{sub 2} and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPAR{alpha} activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPAR{alpha} activity is a novel target of PPAR{alpha} agonist for decreasing circulating levels of lipids under postprandial conditions.

  11. PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid ω-Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

    PubMed Central

    Hardwick, James P.; Osei-Hyiaman, Douglas; Wiland, Homer; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2009-01-01

    Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondria β-oxidation with an increase in both peroxisomal β-oxidation, and microsomal ω-oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPARα activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid β-oxidation and ω-oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4α with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the ω-oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPARα. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid ω-hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA) CYP4A and long-chain fatty acid (LCFA) CYP4Fω-hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to steatohepatitis. PMID:20300478

  12. The effect of the paraoxonase 1 (PON1) T(-107)C polymorphism on serum PON1 activity in women is dependent on fatty acid intake.

    PubMed

    Santos, Fabiola G; Becker, Maitê K; Corrêa, Vanessa S; Garcia, Driele N; Vale, Sandra C; Crespo-Ribeiro, José A; Barros, Carlos C; Schneider, Augusto

    2016-01-01

    Paraoxonase 1 (PON1) is an enzyme that prevents the peroxidation of lipoprotein and cell membranes. Our hypothesis is that the effect of the PON1 T(-107)C polymorphism on serum PON1 activity in healthy adult women is dependent on their fatty acid intake profile. This study included women (n = 39) who completed a food frequency questionnaire. Fatty acid intake was estimated based on the interview and a nutrient reference table. Blood samples were collected for genotyping and to measure serum PON1 activity. Serum PON1 activity was different among genotypes and was higher for women of the CC genotype (P < .001). Women in the study were categorized in 2 groups according to the median nutrient intake. Overall, there was a difference (P < .05) in serum PON1 activity between the CC and TT genotypes in women ingesting either above or below the median total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, omega 3 (n-3) and omega 6 (n-6; P < .05). However, genotype effects on serum PON1 activity were not observed in women ingesting below the median (15:1) ratio of n-6/n-3 (P > .05) but were observed in women ingesting above the ratio of n-6/n-3 (P < .05). This is partly because women of the CC genotype had decreased PON1 activity when ingesting a lower ratio of n-6/n-3 diet (P < .05), while women of the TT genotype had increased PON1 activity (P < .05). In conclusion, the overall presence of the C allele was associated with increased serum PON1 activity, although a diet with high saturated fatty acid or a low ratio of n-6/n-3 reduced PON1 activity in women with the CC genotype. PMID:26773776

  13. New radiohalogenated alkenyl tellurium fatty acids

    SciTech Connect

    Srivastava, P.C.; Knapp, F.F. Jr.; Kabalka, G.W.

    1987-01-01

    Radiolabeled long-chain fatty acids have diagnostic value as radiopharmaceutical tools in myocardial imaging. Some applications of these fatty acids are limited due to their natural metabolic degradation in vivo with subsequent washout of the radioactivity from the myocardium. The identification of structural features that will increase the myocardial residence time without decreasing the heart uptake of long-chain fatty acids is of interest. Fatty acids containing the tellurium heteroatom were the first modified fatty acids developed that show unique prolonged myocardial retention and low blood levels. Our detailed studies with radioiodinated vinyliodide substituted tellurium fatty acids demonstrate that heart uptake is a function of the tellurium position. New techniques of tellurium and organoborane chemistry have been developed for the synthesis of a variety of radioiodinated iodoalkenyl tellurium fatty acids. 9 refs., 3 figs., 2 tabs.

  14. Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells.

    PubMed

    Fazio, Chiara; Piazzi, Giulia; Vitaglione, Paola; Fogliano, Vincenzo; Munarini, Alessandra; Prossomariti, Anna; Milazzo, Maddalena; D'Angelo, Leonarda; Napolitano, Manuela; Chieco, Pasquale; Belluzzi, Andrea; Bazzoli, Franco; Ricciardiello, Luigi

    2016-01-01

    Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fatty acid, was shown to prevent colonic tumors in different settings. We recently found that an extra-pure formulation of EPA as Free Fatty Acid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA-FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA. PMID:26864323

  15. Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells

    PubMed Central

    Fazio, Chiara; Piazzi, Giulia; Vitaglione, Paola; Fogliano, Vincenzo; Munarini, Alessandra; Prossomariti, Anna; Milazzo, Maddalena; D’Angelo, Leonarda; Napolitano, Manuela; Chieco, Pasquale; Belluzzi, Andrea; Bazzoli, Franco; Ricciardiello, Luigi

    2016-01-01

    Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fatty acid, was shown to prevent colonic tumors in different settings. We recently found that an extra-pure formulation of EPA as Free Fatty Acid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA-FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA. PMID:26864323

  16. Fatty acid biosynthesis in pea root plastids

    SciTech Connect

    Stahl, R.J.; Sparace, S.A. )

    1989-04-01

    Fatty acid biosynthesis from (1-{sup 14}C)acetate was optimized in plastids isolated from primary root tips of 7-day-old germinating pea seeds. Fatty acid synthesis was maximum at approximately 80 nmoles/hr/mg protein in the presence of 200 {mu}M acetate, 0.5 mM each of NADH, NADPH and CoA, 6 mM each of ATP and MgCl{sub 2}, 1 mM each of the MnCl{sub 2} and glycerol-3-phosphate, 15 mM KHCO{sub 3}, and 0.1M Bis-tris-propane, pH 8.0 incubated at 35C. At the standard incubation temperature of 25C, fatty acid synthesis was linear from up to 6 hours with 80 to 100 {mu}g/mL plastid protein. ATP and CoA were absolute requirements, whereas KHCO{sub 3}, divalent cations and reduced nucleotides all improved activity by 80 to 85%. Mg{sup 2+} and NADH were the preferred cation and nucleotide, respectively. Dithiothreitol and detergents were generally inhibitory. The radioactive products of fatty acid biosynthesis were approximately 33% 16:0, 10% 18:0 and 56% 18:1 and generally did not vary with increasing concentrations of each cofactor.

  17. Effect of liver fatty acid binding protein on fatty acid movement between liposomes and rat liver microsomes.

    PubMed Central

    McCormack, M; Brecher, P

    1987-01-01

    Although movement of fatty acids between bilayers can occur spontaneously, it has been postulated that intracellular movement is facilitated by a class of proteins named fatty acid binding proteins (FABP). In this study we have incorporated long chain fatty acids into multilamellar liposomes made of phosphatidylcholine, incubated them with rat liver microsomes containing an active acyl-CoA synthetase, and measured formation of acyl-CoA in the absence or presence of FABP purified from rat liver. FABP increased about 2-fold the accumulation of acyl-CoA when liposomes were the fatty acid donor. Using fatty acid incorporated into liposomes made either of egg yolk lecithin or of dipalmitoylphosphatidylcholine, it was found that the temperature dependence of acyl-CoA accumulation in the presence of FABP correlated with both the physical state of phospholipid molecules in the liposomes and the binding of fatty acid to FABP, suggesting that fatty acid must first desorb from the liposomes before FABP can have an effect. An FABP-fatty acid complex incubated with microsomes, in the absence of liposomes, resulted in greater acyl-CoA formation than when liposomes were present, suggesting that desorption of fatty acid from the membrane is rate-limiting in the accumulation of acyl-CoA by this system. Finally, an equilibrium dialysis cell separating liposomes from microsomes on opposite sides of a Nuclepore filter was used to show that liver FABP was required for the movement and activation of fatty acid between the compartments. These studies show that liver FABP interacts with fatty acid that desorbs from phospholipid bilayers, and promotes movement to a membrane-bound enzyme, suggesting that FABP may act intracellularly by increasing net desorption of fatty acid from cell membranes. PMID:3446187

  18. Protective Effect of Unsaturated Fatty Acids on Palmitic Acid-Induced Toxicity in Skeletal Muscle Cells is not Mediated by PPARδ Activation.

    PubMed

    Tumova, Jana; Malisova, Lucia; Andel, Michal; Trnka, Jan

    2015-10-01

    Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect. PMID:26255030

  19. Fatty acid hydration activity of a recombinant Escherichia coli-based biocatalyst is improved through targeting the oleate hydratase into the periplasm.

    PubMed

    Jung, Sang-Min; Seo, Joo-Hyun; Lee, Jung-Hoo; Park, Jin-Byung; Seo, Jin-Ho

    2015-12-01

    Whole-cell biotransformation of fatty acids can be influenced by the activities of catalytic enzymes and by the efficiency of substrate transport into host cells. Here, we improved fatty acid hydration activity of the recombinant Escherichia coli expressing an oleate hydratase of Stenotrophomonas maltophilia by targeting the catalytic enzyme into the periplasm instead of the cytoplasm. Recombinant E. coli producing OhyA in the periplasm under guidance of the PelB signal sequence (E. coli OhyA_PP) exhibited significantly greater hydration activity with oleic acid and linoleic acid compared to a recombinant E. coli producing OhyA in the cytoplasm (E. coli OhyA_CS). For example, the oleate double bond hydration rate of E. coli OhyA_PP was >400 μmol/g dry cells/min (400 U/g dry cells), which is >10-fold higher than that of E. coli OhyA_CS. As the specific activities of the enzymes targeted into the cytoplasm and periplasm were comparable, we assumed that targeting OhyA into the periplasm could accelerate fatty acid transport to the catalytic enzymes by skipping the major mass transport barrier of the cytoplasmic membrane. Our results will contribute to the development of whole-cell biocatalysts for fatty acid biotransformation. PMID:26429801

  20. Increased long chain acyl-Coa synthetase activity and fatty acid import is linked to membrane synthesis for development of picornavirus replication organelles.

    PubMed

    Nchoutmboube, Jules A; Viktorova, Ekaterina G; Scott, Alison J; Ford, Lauren A; Pei, Zhengtong; Watkins, Paul A; Ernst, Robert K; Belov, George A

    2013-01-01

    All positive strand (+RNA) viruses of eukaryotes replicate their genomes in association with membranes. The mechanisms of membrane remodeling in infected cells represent attractive targets for designing future therapeutics, but our understanding of this process is very limited. Elements of autophagy and/or the secretory pathway were proposed to be hijacked for building of picornavirus replication organelles. However, even closely related viruses differ significantly in their requirements for components of these pathways. We demonstrate here that infection with diverse picornaviruses rapidly activates import of long chain fatty acids. While in non-infected cells the imported fatty acids are channeled to lipid droplets, in infected cells the synthesis of neutral lipids is shut down and the fatty acids are utilized in highly up-regulated phosphatidylcholine synthesis. Thus the replication organelles are likely built from de novo synthesized membrane material, rather than from the remodeled pre-existing membranes. We show that activation of fatty acid import is linked to the up-regulation of cellular long chain acyl-CoA synthetase activity and identify the long chain acyl-CoA syntheatse3 (Acsl3) as a novel host factor required for polio replication. Poliovirus protein 2A is required to trigger the activation of import of fatty acids independent of its protease activity. Shift in fatty acid import preferences by infected cells results in synthesis of phosphatidylcholines different from those in uninfected cells, arguing that the viral replication organelles possess unique properties compared to the pre-existing membranes. Our data show how poliovirus can change the overall cellular membrane homeostasis by targeting one critical process. They explain earlier observations of increased phospholipid synthesis in infected cells and suggest a simple model of the structural development of the membranous scaffold of replication complexes of picorna-like viruses, that may be relevant for other (+)RNA viruses as well. PMID:23762027

  1. [Changes in amino acid and fatty acid contents as well as activity of some related enzymes in apple fruit during aroma production].

    PubMed

    Nie, Lan-Chun; Sun, Jian-She; Di, Bao

    2005-12-01

    Aroma volatiles from apple (Malus domestica Borkh. var. Starkrimson) fruit at different stages of maturity were collected by solid adsorbent-Tenax-GC and determined by thermodesorption and GC-MS. Production of propyl acetate, butyl acetate, ethyl 2-methyl-butanoate and total ester volatiles and changes in concentration of the precursors of aroma biosynthsis--free amino acids and fatty acids and activities of lipoxygenases (LOX) and alcohol acetyltransferase (AAT) in apple fruits during ripening were studied. The results showed that propyl acetate and total esters were very low when the endogenous ethylene formation of the fruit was very low. At the stage of the increase in ethylene production, the rate of formation of propyl acetate and total esters increased. Butyl acetate appeared at the beginning of ethylene rise and increased thereafter. Ethyl 2-methyl-butanoate was produced at the beginning of climacteric stage and then increased sharply (Figs.1). These facts suggest that the aroma production is closely related to ethylene production. Among the 14 free amino acids detected in fruit, isoleucine which is considered to be the biosynthetic precursor of some branched chain esters showed a great increase during fruit ripening while the others decreased or remained stable (Table 1). The accumulation of isoleucine suggested that isoleucine supply in fruit may not limit the biosynthesis of esters with branched chain alkyl groups. Concentrations of free fatty acids such as palmitic, linolenic, oleic, linoleic, stearic acids increased before the increase of aroma production, decreased with the increase of aroma production and showed an increase at postclimacteric stages (Fig.2). LOX activity increased at climacteric stages and declined rapidly thereafter. AAT activity increased sharply at the early stage of fruit maturity when the aroma was very low and remained at a stable high level during fruit ripening (Fig.3) indicating that the AAT activity is not the limiting factor for aroma formation in apple fruit. PMID:16361796

  2. Dietary trans fatty acids and their impact on plasma lipoproteins.

    PubMed

    Katan, M B; Mensink, R; Van Tol, A; Zock, P L

    1995-10-01

    Foods contain isomers of unsaturated fatty acids that have double bonds in unusual configurations (trans instead of cis) or unusual positions, or both. Such fatty acids arise through biohydrogenation in the rumen of cows and sheep or catalytic hydrogenation in industrial hardening of oils. The effects of transmonounsaturates on lipoproteins in man are opposite to those of their cis-isomer, oleic acid: trans fatty acids raise low density lipoprotein (LDL) cholesterol and lipoprotein Lp(a) and lower high density lipoprotein (HDL) cholesterol, all in a dose-dependent fashion. Trans fatty acids raised serum cholesteryl ester transfer activity in 52 of 55 volunteers (mean change 18%, P < 0.02), and lowered the ratio of cholesteryl esters to triglycerides in HDL. Lecithin cholesterol acyl transferase was unchanged. The effects of trans fatty acids on HDL and LDL may thus be mediated through cholesterol ester transfer protein. PMID:7585291

  3. Mechanism for Inhibition of Vibrio cholerae ToxT Activity by the Unsaturated Fatty Acid Components of Bile

    PubMed Central

    Plecha, Sarah C.

    2015-01-01

    ABSTRACT The Gram-negative curved bacillus Vibrio cholerae causes the severe diarrheal illness cholera. During host infection, a complex regulatory cascade results in production of ToxT, a DNA-binding protein that activates the transcription of major virulence genes that encode cholera toxin (CT) and toxin-coregulated pilus (TCP). Previous studies have shown that bile and its unsaturated fatty acid (UFA) components reduce virulence gene expression and therefore are likely important signals upon entering the host. However, the mechanism for the bile-mediated reduction of TCP and CT expression has not been clearly defined. There are two likely hypotheses to explain this reduction: (i) UFAs decrease DNA binding by ToxT, or (ii) UFAs decrease dimerization of ToxT. The work presented here elucidates that bile or UFAs directly affect DNA binding by ToxT. UFAs, specifically linoleic acid, can enter V. cholerae when added exogenously and are present in the cytoplasm, where they can then interact with ToxT. Electrophoretic mobility shift assays (EMSAs) with ToxT and various virulence promoters in the presence or absence of UFAs showed a direct reduction in ToxT binding to DNA, even in promoters with only one ToxT binding site. Virstatin, a synthetic ToxT inhibitor, was previously shown to reduce ToxT dimerization. Here we show that virstatin affects DNA binding only at ToxT promoters with two binding sites, unlike linoleic acid, which affects ToxT binding promoters having either one or two ToxT binding sites. This suggests a mechanism in which UFAs, unlike virstatin, do not affect dimerization but affect monomeric ToxT binding to DNA. IMPORTANCE Vibrio cholerae must produce the major virulence factors cholera toxin (CT) and toxin-coregulated pilus (TCP) to cause cholera. CT and TCP production depends on ToxT, the major virulence transcription activator. ToxT activity is negatively regulated by unsaturated fatty acids (UFAs) present in the lumen of the upper small intestine. This study investigated the mechanism for inhibition of ToxT activity by UFAs and found that UFAs directly reduce specific ToxT binding to DNA at virulence promoters and subsequently reduce virulence gene expression. UFAs inhibit ToxT monomers from binding DNA. This differs from the inhibitory mechanism of a synthetic ToxT inhibitor, virstatin, which inhibits ToxT dimerization. Understanding the mechanisms for inhibition of virulence could lead to better cholera therapeutics. PMID:25733618

  4. Cross-sectional associations of food consumption with plasma fatty acid composition and estimated desaturase activities in Finnish children.

    PubMed

    Venäläinen, Taisa; Schwab, Ursula; Ågren, Jyrki; de Mello, Vanessa; Lindi, Virpi; Eloranta, Aino-Maija; Kiiskinen, Sanna; Laaksonen, David; Lakka, Timo A

    2014-05-01

    Plasma fatty acid (FA) composition is known to be an indicator of dietary fat quality, but the associations of other dietary factors with plasma FA composition remain unknown in children. We investigated the cross-sectional associations of food consumption with the proportions of FA and estimated desaturase activities in plasma cholesteryl esters (CE) and phospholipids (PL) among children. The subjects were a population sample of 423 children aged 6–8 years examined at baseline of The Physical Activity and Nutrition in Children (PANIC) Study. We assessed food consumption by food records and plasma FA composition by gas chromatography. We used linear regression models adjusted for age, sex, physical activity and total energy intake to analyze the associations. A higher consumption of vegetable oil-based margarine (fat 60–80 %) was associated with a higher proportion of linoleic and α-linolenic acids in plasma CE and PL. A higher consumption of high-fiber grain products was related to a lower proportion of oleic acid in CE and PL. The consumption of candy was directly associated with the proportion of palmitoleic and oleic acid in plasma CE. The consumption of vegetable oil-based margarine was inversely associated with estimated stearoyl-CoA-desaturase activity in plasma CE and PL and the consumption of candy was directly related to it in plasma CE. The results of our study suggest that plasma FA composition is not only a biomarker for dietary fat quality but also reflects the consumption of high-fiber grain products and foods high in sugar among children. PMID:24659110

  5. Relationship between Single Nucleotide Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Gene and Fatty Acid Composition in Korean Native Cattle.

    PubMed

    Lee, Jea-Young; Ha, Jae-Jung; Park, Yong-Soo; Yi, Jun-Koo; Lee, Seunguk; Mun, Seyoung; Han, Kyudong; Kim, J-J; Kim, Hyun-Ji; Oh, Dong-Yep

    2016-02-01

    The peroxisome proliferator-activated receptor gamma (PPARγ) gene plays an important role in the biosynthesis process controlled by a number of fatty acid transcription factors. This study investigates the relationships between 130 single-nucleotide polymorphisms (SNPs) in the PPARγ gene and the fatty acid composition of muscle fat in the commercial population of Korean native cattle. We identified 38 SNPs and verified relationships between 3 SNPs (g.1159-71208 A>G, g.42555-29812 G>A, and g.72362 G>T) and the fatty acid composition of commercial Korean native cattle (n = 513). Cattle with the AA genotype of g.1159-71208 A>G and the GG genotype of g.42555-29812 G>A and g.72362 G>T had higher levels of monounsaturated fatty acids and carcass traits (p<0.05). The results revealed that the 3 identified SNPs in the PPARγ gene affected fatty acid composition and carcass traits, suggesting that these 3 SNPs may improve the flavor and quality of beef in commercial Korean native cattle. PMID:26732443

  6. Relationship between Single Nucleotide Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Gene and Fatty Acid Composition in Korean Native Cattle

    PubMed Central

    Lee, Jea-young; Ha, Jae-jung; Park, Yong-soo; Yi, Jun-koo; Lee, Seunguk; Mun, Seyoung; Han, Kyudong; Kim, J.-J.; Kim, Hyun-Ji; Oh, Dong-yep

    2016-01-01

    The peroxisome proliferator-activated receptor gamma (PPARγ) gene plays an important role in the biosynthesis process controlled by a number of fatty acid transcription factors. This study investigates the relationships between 130 single-nucleotide polymorphisms (SNPs) in the PPARγ gene and the fatty acid composition of muscle fat in the commercial population of Korean native cattle. We identified 38 SNPs and verified relationships between 3 SNPs (g.1159-71208 A>G, g.42555-29812 G>A, and g.72362 G>T) and the fatty acid composition of commercial Korean native cattle (n = 513). Cattle with the AA genotype of g.1159-71208 A>G and the GG genotype of g.42555-29812 G>A and g.72362 G>T had higher levels of monounsaturated fatty acids and carcass traits (p<0.05). The results revealed that the 3 identified SNPs in the PPARγ gene affected fatty acid composition and carcass traits, suggesting that these 3 SNPs may improve the flavor and quality of beef in commercial Korean native cattle. PMID:26732443

  7. Modulation of Nitro-fatty Acid Signaling

    PubMed Central

    Vitturi, Dario A.; Chen, Chen-Shan; Woodcock, Steven R.; Salvatore, Sonia R.; Bonacci, Gustavo; Koenitzer, Jeffrey R.; Stewart, Nicolas A.; Wakabayashi, Nobunao; Kensler, Thomas W.; Freeman, Bruce A.; Schopfer, Francisco J.

    2013-01-01

    Inflammation, characterized by the activation of both resident and infiltrated immune cells, is accompanied by increased production of oxidizing and nitrating species. Nitrogen dioxide, the proximal nitrating species formed under these conditions, reacts with unsaturated fatty acids to yield nitroalkene derivatives. These electrophilic products modulate protein function via post-translational modification of susceptible nucleophilic amino acids. Nitroalkenes react with Keap1 to instigate Nrf2 signaling, activate heat shock response gene expression, and inhibit NF-κB-mediated signaling, inducing net anti-inflammatory and tissue-protective metabolic responses. We report the purification and characterization of a NADPH-dependent liver enzyme that reduces the nitroalkene moiety of nitro-oleic acid, yielding the inactive product nitro-stearic acid. Prostaglandin reductase-1 (PtGR-1) was identified as a nitroalkene reductase by protein purification and proteomic studies. Kinetic measurements, inhibition studies, immunological and molecular biology approaches as well as clinical analyses confirmed this identification. Overexpression of PtGR-1 in HEK293T cells promoted nitroalkene metabolism to inactive nitroalkanes, an effect that abrogated the Nrf2-dependent induction of heme oxygenase-1 expression by nitro-oleic acid. These results situate PtGR-1 as a critical modulator of both the steady state levels and signaling activities of fatty acid nitroalkenes in vivo. PMID:23878198

  8. Molecular recognition of nitrated fatty acids by PPAR[gamma

    SciTech Connect

    Li, Yong; Zhang, Jifeng; Schopfer, Francisco J.; Martynowski, Dariusz; Garcia-Barrio, Minerva T.; Kovach, Amanda; Suino-Powell, Kelly; Baker, Paul R.S.; Freeman, Bruce A.; Chen, Y. Eugene; Xu, H. Eric

    2010-03-08

    Peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR{gamma} ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR{gamma}. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR{gamma} discrimination of various naturally occurring fatty acid derivatives.

  9. Fatty acids of Pinus elliottii tissues.

    NASA Technical Reports Server (NTRS)

    Laseter, J. L.; Lawler, G. C.; Walkinshaw, C. H.; Weete, J. D.

    1973-01-01

    The total fatty constituents of slash pine (Pinus elliottii) tissue cultures, seeds, and seedlings were examined by GLC and MS. Qualitatively, the fatty acid composition of these tissues was found to be very similar to that reported for other pine species. The fatty acid contents of the tissue cultures resembled that of the seedling tissues. The branched-chain C(sub 17) acid reported for several other Pinus species was confirmed as the anteiso isomer.

  10. Fatty acid content of selected seed oils.

    PubMed

    Orhan, Ilkay; Sener, Bilge

    2002-01-01

    Fatty acid content of selected seed oils from world-wide edible fruits, Ceratonia ciliqua (carob) from Caesalpiniaceae family, Diospyros kaki (persimmon) from Ebenaceae family, Zizyphus jujuba (jujube) from Rhamnaceae family, and Persea gratissima (avocado pear) from Lauraceae family, were determined by capillary gas chromatography- mass spectrometry (GC-MS) to find new natural sources for essential fatty acids. Among the seed oils analyzed, Ceratonia ciliqua has been found to have the highest essential fatty acid content. PMID:15277087

  11. Fatty acid profile of kenaf seed oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fatty acid profile of kenaf (Hibiscus cannabinus L.) seed oil has been the subject of several previous reports in the literature. These reports vary considerably regarding the presence and amounts of specific fatty acids, notably epoxyoleic acid but also cyclic (cyclopropene and cyclopropane) fa...

  12. Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs

    PubMed Central

    Zhou, Lufang; Cabrera, Marco E; Huang, Hazel; Yuan, Celvie L; Monika, Duda K; Sharma, Naveen; Bian, Fang; Stanley, William C

    2007-01-01

    Steady state concentrations of ATP and ADP in vivo are similar at low and high cardiac workloads; however, the mechanisms that regulate the activation of substrate metabolism and oxidative phosphorylation that supports this stability are poorly understood. We tested the hypotheses that (1) there is parallel activation of mitochondrial and cytosolic dehydrogenases in the transition from low to high workload, which increases NADH/NAD+ ratio in both compartments, and (2) this response does not require an increase in fatty acid oxidation (FAO). Anaesthetized pigs were subjected to either sham treatment, or an abrupt increase in cardiac workload for 5 min with dobutamine infusion and aortic constriction. Myocardial oxygen consumption and FAO were increased 3- and 2-fold, respectively, but ATP and ADP concentrations did not change. NADH-generating pathways were rapidly activated in both the cytosol and mitochondria, as seen in a 40% depletion in glycogen stores, a 3.6-fold activation of pyruvate dehydrogenase, and a 50% increase in tissue NADH/NAD+. Simulations from a multicompartmental computational model of cardiac energy metabolism predicted that parallel activation of glycolysis and mitochondrial metabolism results in an increase in the NADH/NAD+ ratio in both cytosol and mitochondria. FAO was blocked by 75% in a third group of pigs, and a similar increase in and the NAHD/NAD+ ratio was observed. In conclusion, in the transition to a high cardiac workload there is rapid parallel activation of substrate oxidation that results in an increase in the NADH/NAD+ ratio. PMID:17185335

  13. Trans fatty acids, lipoproteins, and coronary risk.

    PubMed

    Zock, P L; Katan, M B

    1997-03-01

    Most dietary fatty acids contain at least one double bond, which is usually in the cis configuration. However, biohydrogenation in the rumen of cows and sheep, or catalytic hydrogenation of vegetable oils in the food industries, will convert some of the cis double bonds to the trans configuration. Trans fatty acid intake in western Europe and North America probably ranges from 5 to 15 g/day. Major dietary sources are frying fats used in industrial food preparation, margarines, and other spreads. In the past, margarines contained up to 50% trans fatty acids; however, these are now being phased out. Trans fatty acids raise serum low density lipoprotein (LDL) cholesterol and lower high density lipoprotein (HDL) cholesterol in humans when substituted for cis unsaturated fatty acids in the diet. These effects may be mediated by the cholesteryl ester transfer protein. Trans fatty acids also increase lipoprotein (a) levels relative to other fatty acids. The effects of trans fatty acids on the risk profile for coronary heart disease are thus unfavorable, and labels of food products should state the trans fatty acid content. PMID:9164704

  14. Fatty acid supplementation and skin disease.

    PubMed

    Campbell, K L

    1990-11-01

    The importance of dietary fatty acids to the health of the skin was recognized more than 60 years ago. Fatty acids are important in providing membrane fluidity and maintaining the cutaneous water permeability barrier. Fatty acids function as precursors of eicosanoids. Eicosanoids, which include prostaglandins and leukotrienes, influence cellular interactions, cellular proliferation, and inflammation. Certain diseases, such as atopy and hypothyroidism, are characterized by abnormalities in fatty acid metabolism. Dietary manipulations may be useful in the treatment of diseases mediated by eicosanoids. PMID:2251737

  15. Ultrasonic-Assisted Extraction of Raspberry Seed Oil and Evaluation of Its Physicochemical Properties, Fatty Acid Compositions and Antioxidant Activities

    PubMed Central

    Huang, Qun; Wang, Jinli; Lin, Qiyang; Liu, Mingxin; Lee, Won Young; Song, Hongbo

    2016-01-01

    Ultrasonic-assisted extraction was employed for highly efficient separation of aroma oil from raspberry seeds. A central composite design with two variables and five levels was employed and effects of process variables of sonication time and extraction temperature on oil recovery and quality were investigated. Optimal conditions predicted by response surface methodology were sonication time of 37 min and extraction temperature of 54°C. Specifically, ultrasonic-assisted extraction (UAE) was able to provide a higher content of beneficial unsaturated fatty acids, whereas conventional Soxhlet extraction (SE) resulted in a higher amount of saturated fatty acids. Moreover, raspberry seed oil contained abundant amounts of edible linoleic acid and linolenic acid, which suggest raspberry seeds could be valuable edible sources of natural γ-linolenic acid products. In comparison with SE, UAE exerted higher free radical scavenging capacities. In addition, UAE significantly blocked H2O2-induced intracellular reactive oxygen species (ROS) generation. PMID:27120053

  16. De novo fatty acid synthesis and elongation of fatty acids by subcellular fractions of lung.

    PubMed

    Schiller, H; Bensch, K

    1971-03-01

    Fatty acid synthesis by subcellular fractions of rabbit lung was studied by measuring the incorporation of either radioactive acetyl coenzyme A or malonyl coenzyme A into long-chain fatty acids. Evidence is presented to support the conclusions that the 95,000 g-supernatant fraction contains the enzymes, i.e., fatty acid synthetase and acetyl coenzyme A carboxylase, necessary for de novo fatty acid synthesis and is capable of synthesizing long-chain fatty acids, probably palmitic acid, under the appropriate conditions. The mitochondrial fraction incorporates the short-chain coenzyme A derivatives into fatty acids predominantly by the elongation pathway. It is suggested that the palmitic acid synthesized in vivo by the de novo fatty acid synthetic pathway, demonstrated in vitro in rabbit lung, may be a source of the lecithin palmitic acid utilized in the synthesis of pulmonary surfactant. PMID:4396563

  17. The Fatty Acid Signaling Molecule cis-2-Decenoic Acid Increases Metabolic Activity and Reverts Persister Cells to an Antimicrobial-Susceptible State

    PubMed Central

    Morozov, Aleksey; Planzos, Penny; Zelaya, Hector M.

    2014-01-01

    Persister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is believed to significantly improve efforts in eradicating biofilm-related, chronic infections. While much research has focused on elucidating the mechanism(s) by which persister cells form, little is known about the mechanism or factors that enable persister cells to revert to an active and susceptible state. Here, we demonstrate that cis-2-decenoic acid (cis-DA), a fatty acid signaling molecule, is able to change the status of Pseudomonas aeruginosa and Escherichia coli persister cells from a dormant to a metabolically active state without an increase in cell number. This cell awakening is supported by an increase of the persister cells' respiratory activity together with changes in protein abundance and increases of the transcript expression levels of several metabolic markers, including acpP, 16S rRNA, atpH, and ppx. Given that most antimicrobials target actively growing cells, we also explored the effect of cis-DA on enhancing antibiotic efficacy in killing persister cells due to their inability to keep a persister cell state. Compared to antimicrobial treatment alone, combinational treatments of persister cell subpopulations with antimicrobials and cis-DA resulted in a significantly greater decrease in cell viability. In addition, the presence of cis-DA led to a decrease in the number of persister cells isolated. We thus demonstrate the ability of a fatty acid signaling molecule to revert bacterial cells from a tolerant phenotype to a metabolically active, antimicrobial-sensitive state. PMID:25192989

  18. Fatty acid oxidation and epilepsy.

    PubMed

    Auvin, Stphane

    2012-07-01

    The ketogenic diet (KD) is a high-fat and low carbohydrate diet with an established efficacy to treat refractory epilepsy. Lipids, particularly fatty acids, are nutrients which provide the most important part of the caloric intake under the KD. It has been suggested that the 'high-fat' component of the KD plays a role in its anticonvulsant properties. It has been shown experimentally that polyunsaturated fatty acids alone (PUFA) exhibit anticonvulsant properties. But clinical trials in epilepsy using PUFA have failed to show any effect. This discrepancy can be explained by recent experimental data. Several experimental studies have suggested that PUFA may support the efficacy of the KD. PUFA may exhibit anticonvulsant properties via various mechanisms such as a modification of the composition of the CNS cell membranes, stimulation of nuclear receptor such as PPAR and by attenuating inflammation. Most of these hypotheses have evolved from experimental studies. However, it remains necessary to prove the role of PUFA in the KD, and therefore, further studies on this subject are needed. A better understanding of the underlying mechanisms may lead to the design new dietary treatment such as more liberal rules for KD or KD formula with a higher efficacy. PMID:21856124

  19. Polyunsaturated fatty acid metabolism in prostate cancer

    PubMed Central

    Berquin, Isabelle M.; Edwards, Iris J.; Kridel, Steven J.

    2013-01-01

    Polyunsaturated fatty acids (PUFA) play important roles in the normal physiology and in pathological states including inflammation and cancer. While much is known about the biosynthesis and biological activities of eicosanoids derived from ?6 PUFA, our understanding of the corresponding ?3 series lipid mediators is still rudimentary. The purpose of this review is not to offer a comprehensive summary of the literature on fatty acids in prostate cancer but rather to highlight some of the areas where key questions remain to be addressed. These include substrate preference and polymorphic variants of enzymes involved in the metabolism of PUFA, the relationship between de novo lipid synthesis and dietary lipid metabolism pathways, the contribution of cyclooxygenases and lipoxygenases as well as terminal synthases and prostanoid receptors in prostate cancer, and the potential role of PUFA in angiogenesis and cell surface receptor signaling. PMID:22015690

  20. Non-Alcoholic Fatty Liver Disease: The Bile Acid-Activated Farnesoid X Receptor as an Emerging Treatment Target

    PubMed Central

    Fuchs, Michael

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. It may progress to liver cirrhosis and liver cancer and is poised to represent the most common indication for liver transplantation in the near future. The pathogenesis of NAFLD is multifactorial and not fully understood, but it represents an insulin resistance state characterized by a cluster of cardiovascular risk factors including obesity, dyslipidemia, hyperglycemia, and hypertension. Importantly, NAFLD also has evolved as independent risk factor for cardiovascular disease. Unfortunately thus far no established treatment does exist for NAFLD. The bile acid-activated nuclear farnesoid X receptor (FXR) has been shown to play a role not only in bile acid but also in lipid and glucose homeostasis. Specific targeting of FXR may be an elegant and very effective way to readjust dysregulated nuclear receptor-mediated metabolic pathways. This review discusses the body's complex response to the activation of FXR with its beneficial actions but also potential undesirable side effects. PMID:22187656

  1. Addition of an N-terminal epitope tag significantly increases the activity of plant fatty acid desaturases expressed in yeast cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Saccharomyces cerevisiae shows great potential for development of bioreactor systems geared towards the production of high-value lipids such as polyunsaturated omega-3 fatty acids, the yields of which are largely dependent on the activity of ectopically-expressed enzymes. Here we show that the addit...

  2. Use of agar diffusion assay to evaluate bactericidal activity of formulations of alkaline salts of fatty acids against bacteria associated with poultry processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The agar diffusion assay was used to examine antibacterial activity of alkaline salts of fatty acids (FA). Wells in agar media seeded with bacteria were filled with FA-potassium hydroxide (KOH) solutions, plates were incubated, and zones of inhibition were measured. The relationship between bacteric...

  3. Applying a Multitarget Rational Drug Design Strategy: a First Set of Modulators with Potent and Balanced Activity toward Dopamine D3 Receptor and Fatty Acid Amide Hydrolase

    PubMed Central

    De Simone, Alessio; Filippo, Gian; Albani, Clara; Tarozzo, Glauco; Bandiera, Tiziano; Piomelli, Daniele; Cavalli, Andrea; Bottegoni, Giovanni

    2014-01-01

    Combining computer-assisted drug design and synthetic efforts, we generated compounds with potent and balanced activities toward both D3 dopamine receptor and fatty acid amide hydrolase (FAAH) enzyme. Concurrently modulating these targets, our compounds hold a great potential toward exerting a disease-modifying effect on nicotine addiction and other forms of compulsive behavior. PMID:24691497

  4. First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus.

    PubMed

    Carballeira, Néstor M; Montano, Nashbly; Balaña-Fouce, Rafael; Prada, Christopher Fernández

    2009-09-01

    The first total synthesis for the (Z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 12-bromo-1-dodecanol followed by a second acetylide coupling to the short-chain 3-methyl-1-bromobutane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fatty acid. The title compound displayed antiprotozoal activity against Leishmania donovani (EC(50) = 19.8 microg/ml) and inhibited the leishmania DNA topoisomerase IB at concentrations of 50 microM. PMID:19527698

  5. Dietary Fatty Acids and the Aging Brain

    PubMed Central

    Cole, Greg M.; Ma, Qiu-Lan; Frautschy, Sally A.

    2014-01-01

    Summary Aging contributes to physiological decline and vulnerability to disease. In the brain, even with minimal neuron loss, aging increases oxidative damage, inflammation, demyelination, impaired processing and metabolic deficits, particularly during pathological brain aging. We discuss the possible role of docosahexaenoic acid (DHA) in prevention of age related disruption of brain function. High-fat diabetogenic diets, cholesterol and the omega-6 fatty acid arachidonate and its prostaglandin metabolites have all been implicated in promoting AD pathogenesis. We argue that DHA acts to oppose this pathogenesis, exerting a plethora of pleiotropic activities to protect against AD pathogenesis. PMID:21091943

  6. Fatty Acids, Lipid Mediators, and T-Cell Function

    PubMed Central

    de Jong, Anja J.; Kloppenburg, Margreet; Toes, René E. M.; Ioan-Facsinay, Andreea

    2014-01-01

    Research toward the mechanisms underlying obesity-linked complications has intensified during the last years. As a consequence, it has become clear that metabolism and immunity are intimately linked. Free fatty acids and other lipids acquired in excess by current feeding patterns have been proposed to mediate this link due to their immune modulatory capacity. The functional differences between saturated and unsaturated fatty acids, in combination with their dietary intake are believed to modulate the outcome of immune responses. Moreover, unsaturated fatty acids can be oxidized in a tightly regulated and specific manner to generate either potent pro-inflammatory or pro-resolving lipid mediators. These oxidative derivatives of fatty acids have received detailed attention during the last years, as they have proven to have strong immune modulatory capacity, even in pM ranges. Both fatty acids and oxidized fatty acids have been studied especially in relation to macrophage and T-cells functions. In this review, we propose to focus on the effect of fatty acids and their oxidative derivatives on T-cells, as it is an active area of research during the past 5 years. The effect of fatty acids and their derivatives on activation and proliferation of T-cells, as well as the delicate balance between stimulation and lipotoxicity will be discussed. Moreover, the receptors involved in the interaction between free fatty acids and their derivatives with T-cells will be summarized. Finally, the mechanisms involved in modulation of T-cells by fatty acids will be addressed, including cellular signaling and metabolism of T-cells. The in vitro results will be placed in context of in vivo studies both in humans and mice. In this review, we summarize the latest findings on the immune modulatory function of lipids on T-cells and will point out novel directions for future research. PMID:25352844

  7. Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells.

    PubMed

    Robblee, Megan M; Kim, Charles C; Porter Abate, Jess; Valdearcos, Martin; Sandlund, Karin L M; Shenoy, Meera K; Volmer, Romain; Iwawaki, Takao; Koliwad, Suneil K

    2016-03-22

    Diets rich in saturated fatty acids (SFAs) produce a form of tissue inflammation driven by "metabolically activated" macrophages. We show that SFAs, when in excess, induce a unique transcriptional signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, particularly IRE1α and many adaptive downstream target genes. SFAs also activate the NLRP3 inflammasome in macrophages, resulting in IL-1β secretion. We found that IRE1α mediates SFA-induced IL-1β secretion by macrophages and that its activation by SFAs does not rely on unfolded protein sensing. We show instead that the ability of SFAs to stimulate either IRE1α activation or IL-1β secretion can be specifically reduced by preventing their flux into phosphatidylcholine (PC) or by increasing unsaturated PC levels. Thus, IRE1α is an unrecognized intracellular PC sensor critical to the process by which SFAs stimulate macrophages to secrete IL-1β, a driver of diet-induced tissue inflammation. PMID:26971994

  8. [The fatty acid composition of ordinary flax seed oil (Linum usitatissimum L.) cultivated in Georgia and its byological activity].

    PubMed

    Kakilashvili, B Iu; Zurabashvili, D Z; Turabelidze, D G; Shanidze, L A; Parulava, G K

    2014-02-01

    The aim of the study was individual quantitatively and qualitatively determination of fatty acids in ordinary flax seed oil (Linum usitatissimum L.), cultivated in Georgia. The neutral lipids extracts were fractionated and analyzed by high performance liquid chromatography (PTC-1, Waters) with refractory detector R-401. Analitical column (150,0x3,0 mm) was filled with reversphase Bondopak C18). Software OASIS-740 is used. The correction retention times of each fatty acids is compared with comformity standard. The investigation showed that in flax seed oil linoleic (31,3±2,1 mg%) and linolenic (40,2±2,9 mg%) acids were predominant and together constitute principal basic of research composition. The flax seed oil contained also palmitic and stearic acids in less quantitaty. PMID:24632654

  9. [Essential fatty acids and lipid mediators. Endocannabinoids].

    PubMed

    Caramia, G

    2012-01-01

    In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in polyunsaturated fatty acids (PUFA) as precursors of "lipid mediator" molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines, maresins that regulate immunity, platelet aggregation, inflammation, etc. They showed that the balance between omega-3 and omega-6 acids has a profound influence on all the body's inflammatory responses and a raised level of PUFA omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer's. The CYP-catalyzed epoxidation and hydroxylation of arachidonic acid (AA) were established recently as the so-called third branch of AGE cascade. Cytochrome P450 (CYP) epoxygenases convert AA to four epoxyeicosatrienoic acid (EET) regioisomers, that produce vascular relaxation anti-inflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and brain. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are accessible to CYP enzymes in the same way as AA. Metabolites derived from EPA include epoxye-icosatetraenoic acids (EETR) and hydroxyeicosapentaenoic acids (19- and 20-HEPE), whereas DHA include epoxydocosapentaenoic acids (EDPs) hydroxydocosahexaenoic acids (21- and 22-HDoHE). For many of the CYP isoforms, the n-3 PUFAs are the preferred substrates and the available data suggest that some of the vasculo- and cardioprotective effects attributed to dietary n-3 PUFAs may be mediated by CYP-dependent metabolites of EPA and DHA. From AA derives also endocannabinoids like anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol, capable of mimicking the pharmacological actions of the active principle of Cannabis sativa preparations such as hashish and marijuana (-)-Delta9-tetrahydrocannabinol. They act as true 'endogenous cannabinoids' by binding and functionally activating one or both cannabinoid receptor present on nervous and peripheral cell membranes. Enzymes that carry out anandamide oxidation are the same fatty acid oxygenases that are known to act on endogenous arachidonic acid namely, the members of the COX, LOX, and P450 families of enzymes. Recent advances in the biochemistry and pharmacology of the endocannabinoid system, also for its central and peripheral roles in regulating food intake, will offer the development of novel therapeutic agents. PMID:22730630

  10. Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway

    SciTech Connect

    Zheng, Xuqin; Sun, Tao; Wang, Xiaodong

    2013-07-05

    Highlights: •TC, a CB2R specific agonist, stimulates SIRT1 activity by PKA/CREB pathway. •TC promotes PGC-1α transcriptional activity by increasing its deacetylation. •TC increases the expression of genes linked to FAO and promotes the rate of FAO. •The effects of TC in FAO are dependent on CB2R. •Suggesting CB2R as a target to treat diseases with lipid dysregulation. -- Abstract: Abnormal fatty acid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcription of fatty acid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fatty acid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.

  11. Desaturation of fatty acids in Trypanosoma cruzi

    SciTech Connect

    de Lema, M.G.; Aeberhard, E.E.

    1986-11-01

    Uptake and metabolism of saturated (16:0, 18:0) and unsaturated (18:1(n-9), 18:2(n-6), 18:3(n-3)) fatty acids by cultured epimastigotes of Trypanosoma cruzi were studied. Between 17.5 and 33.5% of the total radioactivity of (1-/sup 14/C)labeled fatty acids initially added to the culture medium was incorporated into the lipids of T. cruzi and mostly choline and ethanolamine phospholipids. As demonstrated by argentation thin layer chromatography, gas liquid chromatography and ozonolysis of the fatty acids synthesized, exogenous palmitic acid was elongated to stearic acid, and the latter was desaturated to oleic acid and 18:2 fatty acid. The 18:2 fatty acid was tentatively identified as linoleic acid with the first bond in the delta 9 position and the second bond toward the terminal methyl end. Exogenous stearic acid was also desaturated to oleic and 18:2 fatty acid, while oleic acid was only converted into 18:2. All of the saturated and unsaturated fatty acids investigated were also converted to a small extent (2-4%) into polyunsaturated fatty acids. No radioactive aldehyde methyl ester fragments of less than nine carbon atoms were detected after ozonolysis of any of the fatty acids studied. These results demonstrate the existence of delta 9 and either delta 12 or delta 15 desaturases, or both, in T. cruzi and suggest that delta 6 desaturase or other desaturases of the animal type are likely absent in cultured forms of this organism.

  12. Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids.

    PubMed

    Frémont, L; Belguendouz, L; Delpal, S

    1999-01-01

    Wine polyphenols were examined for their capacity to protect the lipid and protein moieties of porcine low density lipoproteins (LDL) during oxidation. The efficiency of resveratrol (3, 4', 5, trihydroxystilbene) and defined flavonoids was compared to that of a wine extract (WE) containing 0.5 g/g proanthocyanidols. The efficiency of resveratrol for protecting polyunsaturated fatty acids (PUFA) was higher than that of flavonoids in copper-induced oxidation and lower in AAPH (radical initiator)-induced oxidation. The LDL receptor activity was evaluated by flow cytometry using LDL labeled with fluorescein isothiocyanate (FITC) and Chinese hamster ovary cells (CHO-K1). The incubation of CHO-K1 with FITC-LDL oxidized for 16 h reduced the proportion of fluorescent cells from 97% to 4%. At a concentration of 40 microM, resveratrol and flavonoids completely restored the uptake of copper-oxidized LDL and AAPH-oxidized LDL respectively. Total fluorescence could also be obtained with 20 mg/L of WE with both oxidation systems. These data are consistent with previous findings relative to the formation of degradative products from PUFA. They confirm that resveratrol was more effective than flavonoids as a chelator of copper and less effective as a free-radical scavenger. Moreover, they show that WE, which contained monomeric and oligomeric forms of flavonoids and phenolic acids, protected LDL by both mechanisms. PMID:10403511

  13. Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

    SciTech Connect

    Lee, Myoung-Su; Kim, Daeyoung; Jo, Keunae; Hwang, Jae-Kwan; Translational Research Center for Protein Function Control, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749

    2010-10-08

    Research highlights: {yields} NDGA decreases high-fat diet-induced body weight gain and adiposity. {yields} NDGA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} NDGA improves lipid storage in vitro through altering lipid regulatory proteins. {yields} Inhibition of lipid storage in vivo and in vitro is mediated by AMPK activation. -- Abstract: Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. We evaluated body weight, adiposity, liver histology, and hepatic triglyceride content in high-fat diet (HFD)-fed C57BL/6J mice treated with NDGA. In addition, we characterized the underlying mechanism of NDGA's effects in HepG2 hepatocytes by Western blot and RT-PCR analysis. NDGA (100 or 200 mg/kg/day) reduced weight gain, fat pad mass, and hepatic triglyceride accumulation, and improved serum lipid parameters in mice fed a HFD for 8 weeks. NDGA significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the liver and in HepG2 hepatocytes. NDGA downregulated the level of mature SREBP-1 and its target genes (acetyl-CoA carboxylase and fatty acid synthase), but, it upregulated expression of genes involved in fatty acid oxidation, such as peroxisome proliferator-activated receptor (PPAR){alpha}, PPAR{gamma} coactivator-1, carnitine palmitoyl transferase-1, and uncoupling protein-2. The specific AMPK inhibitor compound C attenuated the effects of NDGA on expression of lipid metabolism-related proteins in HepG2 hepatocytes. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.

  14. Phylogenomic reconstruction of archaeal fatty acid metabolism

    PubMed Central

    Dibrova, Daria V.; Galperin, Michael Y.; Mulkidjanian, Armen Y.

    2014-01-01

    While certain archaea appear to synthesize and/or metabolize fatty acids, the respective pathways still remain obscure. By analyzing the genomic distribution of the key lipid-related enzymes, we were able to identify the likely components of the archaeal pathway of fatty acid metabolism, namely, a combination of the enzymes of bacterial-type β-oxidation of fatty acids (acyl-CoA-dehydrogenase, enoyl-CoA hydratase, and 3-hydroxyacyl-CoA dehydrogenase) with paralogs of the archaeal acetyl-CoA C-acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three β-oxidation enzymes working in the reverse direction could potentially catalyze biosynthesis of fatty acids, with paralogs of acetyl-CoA C-acetyltransferase performing addition of C2 fragments. The presence in archaea of the genes for energy-transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase, and diverse rhodopsins, was found to correlate with the presence of the proposed system of fatty acid biosynthesis. We speculate that because these membrane complexes functionally depend on fatty acid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fatty acid biosynthesis. The proposed pathway of archaeal fatty acid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications. PMID:24818264

  15. 21 CFR 172.860 - Fatty acids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Fatty acids. 172.860 Section 172.860 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.860 Fatty acids....

  16. Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2

    PubMed Central

    Parkinson, Eric Kenneth

    2013-01-01

    The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603

  17. Comparison of Bacillus monooxygenase genes for unique fatty acid production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper reviews Bacillus genes encoding monooxygenase enzymes producing unique fatty acid metabolites. Specifically, it examines standard monooxygenase electron transfer schemes and related domain structures of these fused domain enzymes on route to understanding the observed oxygenase activiti...

  18. Alkyl polyglucose enhancing propionic acid enriched short-chain fatty acids production during anaerobic treatment of waste activated sludge and mechanisms.

    PubMed

    Luo, Jingyang; Feng, Leiyu; Chen, Yinguang; Sun, Han; Shen, Qiuting; Li, Xiang; Chen, Hong

    2015-04-15

    Adding alkyl polyglucose (APG) into an anaerobic treatment system of waste activated sludge (WAS) was reported to remarkably improve the production of short-chain fatty acids (SCFAs), especially propionic acid via simultaneously accelerating solubilization and hydrolysis, enhancing acidification, inhibiting methanogenesis and balancing carbon to nitrogen (C/N) ratio of substrate. Not only the production of SCFAs, especially propionic acid, was significantly improved by APG, but also the feasible operation time was shortened. The SCFAs yield at 0.3 g APG per gram of total suspended solids (TSS) within 4 d was 2988 ± 60 mg chemical oxygen demand (COD) per liter, much higher than that those from sole WAS or sole WAS plus sole APG. The corresponding yield of propionic acid was 1312 ± 25 mg COD/L, 7.9-fold of sole WAS. Mechanism investigation showed that during anaerobic treatment of WAS in the presence of APG both the solubilization and hydrolysis were accelerated and the acidification was enhanced, while the methanogenesis was inhibited. Moreover, the activities of key enzymes involved in WAS hydrolysis and acidification were improved through the adjustment of C/N ratio of substrates with APG. The abundance of microorganisms responsible for organic compounds hydrolysis and SCFAs production was also observed to be greatly enhanced with APG via 454 high-throughput pyrosequencing analysis. PMID:25697695

  19. Regulating effect of β-ketoacyl synthase domain of fatty acid synthase on fatty acyl chain length in de novo fatty acid synthesis.

    PubMed

    Cui, Wei; Liang, Yan; Tian, Weixi; Ji, Mingjuan; Ma, Xiaofeng

    2016-03-01

    Fatty acid synthase (FAS) is a multifunctional homodimeric protein, and is the key enzyme required for the anabolic conversion of dietary carbohydrates to fatty acids. FAS synthesizes long-chain fatty acids from three substrates: acetyl-CoA as a primer, malonyl-CoA as a 2 carbon donor, and NADPH for reduction. The entire reaction is composed of numerous sequential steps, each catalyzed by a specific functional domain of the enzyme. FAS comprises seven different functional domains, among which the β-ketoacyl synthase (KS) domain carries out the key condensation reaction to elongate the length of fatty acid chain. Acyl tail length controlled fatty acid synthesis in eukaryotes is a classic example of how a chain building multienzyme works. Different hypotheses have been put forward to explain how those sub-units of FAS are orchestrated to produce fatty acids with proper molecular weight. In the present study, molecular dynamic simulation based binding free energy calculation and access tunnels analysis showed that the C16 acyl tail fatty acid, the major product of FAS, fits to the active site on KS domain better than any other substrates. These simulations supported a new hypothesis about the mechanism of fatty acid production ratio: the geometric shape of active site on KS domain might play a determinate role. PMID:26680361

  20. Volatile Fatty Acid Requirement of a Strain of Listeria monocytogenes

    PubMed Central

    Larson, A. D.; Hattier, L. V.; McCleskey, C. S.

    1965-01-01

    Larson, A. D. (Louisiana State University, Baton Rouge), L. V. Hattier, and C. S. McCleskey. Volatile fatty acid requirement of a strain of Listeria monocytogenes. J. Bacteriol. 89:819–824. 1965.—Listeria monocytogenes strain 2 requires either isobutyric or 2-methylbutyric acid for growth. Elucidation of this requirement began with characterization of the growth-enhancing substance in culture filtrates of Aerobacter aerogenes. A. aerogenes required tryptose, glucose, and aerobic conditions for excretion of active fatty acids into the medium. Commercial preparations of isobutyric, 2-methylbutyric, isovaleric, 3-methylvaleric, and n-valeric acid supported the growth of strain 2. Purification of these fatty acids by gas chromatography demonstrated that strain 2 responded significantly only to isobutyric and 2-methylbutyric acid. Amines, alcohols, and hydroxy fatty acids, which were structurally related to the active acids, did not satisfy the fatty acid requirement of L. monocytogenes strain 2. Only one isolate (strain 2) of 128 cultures of L. monocytogenes required volatile fatty acid for growth. Images PMID:14273667

  1. In vitro percutaneous absorption studies and in vivo evaluation of anti-inflammatory activity of essential fatty acids (EFA) from fish oil extracts.

    PubMed

    Puglia, Carmelo; Tropea, Salvatore; Rizza, Luisa; Santagati, Natale Alfredo; Bonina, Francesco

    2005-08-11

    The aim of the present study was to evaluate the in vitro percutaneous absorption and the in vivo anti-inflammatory activity of EPA and DHA fatty acids from three oily extracts, obtained by acetonic extractions from the entrails of different varieties of Mediterranean fishes such as mackerel (Scomber scombrus), sardine (Sardina pilchardus) and horse mackerel (Trachurus mediterraneus). In the first part of our research, we focused our attention on the characterization of the oily extracts to determine their omega-3 polyunsaturated fatty acid content, then, we evaluated the in vitro percutaneous absorption through excised human skin (stratum corneum/epidermis membranes; SCE) of EPA and DHA contained in the extracts. In the second part, the fish oil which guaranteed the best in vitro permeation profile of these omega-3 fatty acids was studied in order to evaluate its inhibiting ability towards the in vivo UVB-induced skin erythema. From the results obtained, all the fish oils tested in this study presented significant amounts of omega-3 fatty acids EPA and DHA, and particularly sardine oil extract showed higher concentrations of these substances compared to the other two fish oils. The in vitro experiments revealed interesting fluxes of these compounds from sardine extract through the stratum corneum/epidermis membranes and an appreciable anti-inflammatory activity against UVB-induced erythema in human volunteers was also observed. PMID:15979259

  2. Consequences of Essential Fatty Acids

    PubMed Central

    Lands, Bill

    2012-01-01

    Essential fatty acids (EFA) are nutrients that form an amazingly large array of bioactive mediators that act on a large family of selective receptors. Nearly every cell and tissue in the human body expresses at least one of these receptors, allowing EFA-based signaling to influence nearly every aspect of human physiology. In this way, the health consequences of specific gene-environment interactions with these nutrients are more extensive than often recognized. The metabolic transformations have similar competitive dynamics for the n-3 and n-6 homologs when converting dietary EFA from the external environment of foods into the highly unsaturated fatty acid (HUFA) esters that accumulate in the internal environment of cells and tissues. In contrast, the formation and action of bioactive mediators during tissue responses to stimuli tend to selectively create more intense consequences for n-6 than n-3 homologs. Both n-3 and n-6 nutrients have beneficial actions, but many common health disorders are undesired consequences of excessive actions of tissue n-6 HUFA which are preventable. This review considers the possibility of preventing imbalances in dietary n-3 and n-6 nutrients with informed voluntary food choices. That action may prevent the unintended consequences that come from eating imbalanced diets which support excessive chronic actions of n-6 mediators that harm human health. The consequences from preventing n-3 and n-6 nutrient imbalances on a nationwide scale may be very large, and they need careful evaluation and implementation to avoid further harmful consequences for the national economy. PMID:23112921

  3. Radioiodinated fatty acid analogs for myocardial imaging

    SciTech Connect

    Ruyan, M.K.

    1993-01-01

    Fatty acids are the preferred substrate for the normoxic heart. About sixty percent of the energy required by the myocardium is provided by fatty acid [beta]-oxidation. Many scientists have focused on the alterations in fatty acid metabolism in the ischemic heart for the development of radiolabelled fatty acids for functional imaging of the heart. Three main categories of compounds were synthesized: tetrazoles (1 and 2), glycidic and [alpha]-methylene acids (3-5), and analogs of oleic acid (6,7 and 7A). The tetrazole group has a similar pKa and size to that of a carboxyl group; however, such fatty acid analogs cannot undergo normal fatty acid metabolism. Glycidic and [alpha]-methylene analogs are potential irreversible inhibitors of fatty acid metabolism. Oleic acid analogs were investigated to assess the affect of stereochemical consequences on biodistribution. The key intermediates in the synthesis of the target compounds were [omega]-nitrophenyl alkylcarboxylic acids and alcohols, which were made using a variety of cross-coupling reactions. The Wittig reaction, which was used in the synthesis of tetrazole 1 and glycidic acid 3, gave low yields of the cross-coupled products. The remaining target compounds were synthesized by condensation of appropriate RCu (CN) ZnI and substituted benzyl bromides or by Pd[sup II] catalyzed cross-coupling of substituted arylhalides with suitable alkynes. The latter two reactions produced much higher yields of the desired products. All of the target compounds were radiolabeled with [sup 125]I by various Cu(I) catalyzed radioiodine exchange procedures and were then subjected to tissue biodistribution (TD) studies in rats. Except for the 15-(4-iodophenyl)-2-methylene-pentadecanoic acid (5), all of the fatty acid analogs failed to surpass clinically-used 15-(4-iodophenyl)pentadecanoic acid (IPPA) in their ability to be taken up and retained by the rat myocardium.

  4. Tissue fatty acid composition and estimated ∆ desaturase activity after castration in chicken broilers fed with linseed or sunflower oil.

    PubMed

    Mašek, T; Starčević, K; Filipović, N; Stojević, Z; Brozić, D; Gottstein, Z; Severin, K

    2014-04-01

    The aims of this study were to investigate the influence of the short-term addition of sunflower and linseed oil and castration on fatty acid composition and desaturation indexes in chicken broilers. Forty-eight male Ross 308 chicken broilers were supplemented with 5% of sunflower or linseed oil. The four experimental groups were linseed oil supplementation and castration (LC), linseed oil without castration (LN), sunflower oil and castration (SC) and sunflower oil without castration (SN). There was no significant influence of castration or oil supplement on live weights, weight gain, feed intake or feed conversion. Castration resulted in an increase in polyunsaturated fatty acids (PUFA), total n3, n6, measured desaturation indexes and a decrease in the saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) content of abdominal fat. In breast muscle, castration increased PUFA and 18:3n3 values, while in the liver tissue, castration did not influence the parameters measured. Linseed oil supplementation significantly increased 18:3n3, n3 long chain polyunsaturated fatty acids (LC PUFA), total n3 and decreased total n6, n6/n3 ratio, and 20:4n6 content. Values for 20:4n6 were the highest in SC and the lowest in the LC group. Linseed oil also significantly decreased ∆5 and ∆4 desaturation indexes in the thighs and ∆5 and ∆5, 6 in abdominal fat and the liver. These results suggest that short-term supplementation of basal diet with 5% of linseed oil could significantly increase n3 LC PUFA and decrease n6/n3 ratio content in the edible tissues of chicken broilers, without adverse effects on growth performance. Meanwhile, castration only improved fatty acid profile in abdominal fat, which is not nutritionally important. The interactions observed between basal diet, supplemented oil, sex hormones and other non-nutritional factors must be elucidated in future trials in order to correctly predict the nutritional value of linseed-fed poultry. PMID:23905627

  5. Fatty acids on continental sulfate aerosol particles

    NASA Astrophysics Data System (ADS)

    Tervahattu, H.; Juhanoja, J.; Vaida, V.; Tuck, A. F.; Niemi, J. V.; Kupiainen, K.; Kulmala, M.; VehkamäKi, H.

    2005-03-01

    Surface analyses of atmospheric aerosols from different continental sources, such as forest fires and coal and straw burning, show that organic surfactants are found on such aerosols. The predominant organic species detected by time-of-flight secondary ion mass spectrometry on the sulfate aerosols are fatty acids of different carbon chain length up to the C32 acid. These observations are consistent with literature accounts of functional group analysis of bulk samples, but this is the first direct evidence of fatty acid films on the surface of sulfate aerosols. Surface analysis leads to the conclusion that fatty acid films on continental aerosols may be more common than has been previously suggested.

  6. Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer

    PubMed Central

    Zhang, Guodong; Kodani, Sean; Hammock, Bruce D.

    2014-01-01

    Epoxygenated fatty acids (EpFAs), which are lipid mediators produced by cytochrome P450 epoxygenases from polyunsaturated fatty acids, are important signaling molecules known to regulate various biological processes including inflammation, pain and angiogenesis. The EpFAs are further metabolized by soluble epoxide hydrolase (sEH) to form fatty acid diols which are usually less-active. Pharmacological inhibitors of sEH that stabilize endogenous EpFAs are being considered for human clinical uses. Here we review the biology of ω-3 and ω-6 EpFAs on inflammation, pain, angiogenesis and tumorigenesis. PMID:24345640

  7. Which polyunsaturated fatty acids are active in children with attention-deficit hyperactivity disorder receiving PUFA supplementation? A fatty acid validated meta-regression analysis of randomized controlled trials.

    PubMed

    Puri, Basant K; Martins, Julian G

    2014-05-01

    Concerns about growth retardation and unknown effects on long-term brain development with stimulants have prompted interest in polyunsaturated fatty acid supplementation (PUFA) as an alternative treatment. However, randomized controlled trials (RCTs) and meta-analyses of PUFA supplementation in ADHD have shown marginal benefit, and uncertainty exists as to which, if any, PUFA might be effective in alleviating symptoms of ADHD. We conducted an updated meta-analysis of RCTs in ADHD together with multivariable meta-regression analyses using data on PUFA content obtained from independent fatty acid methyl ester analyses of each study PUFA regimen. The PubMed, Embase and PsycINFO databases were searched with no start date and up to 28th July 2013. Study inclusion criteria were: randomized design, placebo controlled, PUFA preparation as active intervention, reporting change scores on ADHD rating-scale measures. Rating-scale measures of inattention and hyperactive-impulsive symptoms were extracted, study authors were contacted to obtain missing data, studies not reporting negative findings had these data imputed, and study quality was assessed using the Jadad system plus other indicators. Random-effects models were used for pooled effects and for meta-regression analyses. Standardized mean differences (SMD) in inattention, hyperactive-impulsive and combined symptoms were assessed as rated by parents, teachers or all raters. The influence of study characteristics and PUFA regimen content was explored in multivariable meta-regression analyses. The overall pooled estimate from 18 studies showed that combined ADHD symptoms rated by all raters decreased with PUFA supplementation; SMD -0.192 (95% CI: -0.297, -0.086; P<0.001). However, when analyzed by rater, only parent-rated symptoms decreased significantly. Multivariable meta-regression showed that longer study duration, γ-linolenic acid (GLA), and the interaction between GLA and eicosapentaenoic acid (EPA) were associated with significant decreases in inattention; however, PUFA regimen content was unrelated to changes in hyperactive-impulsive symptoms. Certain fatty acids present in placebo preparations may potentially have been psychoactive. This meta-analysis provides modest evidence of PUFA effectiveness in ADHD, especially GLA and EPA for inattention symptoms; however, evidence of reporting bias, publication bias, variable methodological quality, and use of potentially psychoactive placebos limit the generalizability of these findings. PMID:24560325

  8. Identification of novel protein domains required for the expression of an active dehydratase fragment from a polyunsaturated fatty acid synthase

    PubMed Central

    Oyola-Robles, Delise; Gay, Darren C; Trujillo, Uldaeliz; Sánchez-Parés, John M; Bermúdez, Mei-Ling; Rivera-Díaz, Mónica; Carballeira, Néstor M; Baerga-Ortiz, Abel

    2013-01-01

    Polyunsaturated fatty acids (PUFAs) are made in some strains of deep-sea bacteria by multidomain proteins that catalyze condensation, ketoreduction, dehydration, and enoyl-reduction. In this work, we have used the Udwary-Merski Algorithm sequence analysis tool to define the boundaries that enclose the dehydratase (DH) domains in a PUFA multienzyme. Sequence analysis revealed the presence of four areas of high structure in a region that was previously thought to contain only two DH domains as defined by FabA-homology. The expression of the protein fragment containing all four protein domains resulted in an active enzyme, while shorter protein fragments were not soluble. The tetradomain fragment was capable of catalyzing the conversion of crotonyl-CoA to β-hydroxybutyryl-CoA efficiently, as shown by UV absorbance change as well as by chromatographic retention of reaction products. Sequence alignments showed that the two novel domains contain as much sequence conservation as the FabA-homology domains, suggesting that they too may play a functional role in the overall reaction. Structure predictions revealed that all domains belong to the hotdog protein family: two of them contain the active site His70 residue present in FabA-like DHs, while the remaining two do not. Replacing the active site His residues in both FabA domains for Ala abolished the activity of the tetradomain fragment, indicating that the DH activity is contained within the FabA-homology regions. Taken together, these results provide a first glimpse into a rare arrangement of DH domains which constitute a defining feature of the PUFA synthases. PMID:23696301

  9. Cellular fatty acid profile and H(+)-ATPase activity to assess acid tolerance of Bacillus sp. for potential probiotic functional attributes.

    PubMed

    Shobharani, P; Halami, Prakash M

    2014-11-01

    The present study has been focused widely on comparative account of probiotic qualities of Bacillus spp. for safer usage. Initially, 170 heat resistant flora were isolated and selected for non-pathogenic cultures devoid of cytK, hblD, and nhe1 virulence genes. Subsequently, through biochemical tests along with 16S rRNA gene sequencing and fatty acid profiling, the cultures were identified as Bacillus megaterium (AR-S4), Bacillus subtilis (HR-S1), Bacillus licheniformis (Csm1-1a and HN-S1), and Bacillus flexus (CDM4-3c and CDM3-1). The selected cultures showed 70-80 % survival under simulated gastrointestinal condition which was also confirmed through H(+)-ATPase production. The amount of H(+)-ATPase increased by more than 2-fold when grown at pH 2 which support for the acid tolerance ability of Bacillus isolates. The study also examined the influence of acidic pH on cellular fatty acid composition of Bacillus spp. A remarkable shift in the fatty acid profile was observed at acidic pH through an increased amount of even numbered fatty acid (C16 and C18) in comparison with odd numbered (C15 and C17). Additionally, the cultures exhibited various probiotic functional properties. Overall, the study increases our understanding of Bacillus spp. and will allow both industries and consumers to choose for well-defined probiotic with possible health benefits. PMID:25125040

  10. Δ6-fatty acid desaturase and fatty acid elongase mRNA expression, phagocytic activity and weight-to-length relationships in channel catfish (Ictalurus punctatus) fed alternative diets with soy oil and a probiotic.

    PubMed

    Santerre, A; Téllez-Bañuelos, M C; Casas-Solís, J; Castro-Félix, P; Huízar-López, M R; Zaitseva, G P; Horta-Fernández, J L; Trujillo-García, E A; de la Mora-Sherer, D; Palafox-Luna, J A; Juárez-Carrillo, E

    2015-01-01

    A time-course feeding trial was conducted for 120 days on juvenile channel catfish (Ictalurus punctatus) to study the effects of diets differing in oil source (fish oil or soy oil) and supplementation with a commercial probiotic. Relative levels of Δ6-fatty acid desaturase (Δ6-FAD) and fatty acid elongase (FAE) expression were assessed in brain and liver tissues. Both genes showed similar expression levels in all groups studied. Fish weight-to-length relationships were evaluated using polynomial regression analyses, which identified a burst in weight and length in the channel catfish on day 105 of treatment; this increase was related to an increase in gene expression. Mid-intestinal lactic acid bacterium (LAB) count was determined according to morphological and biochemical criteria using API strips. There was no indication that intestinal LAB count was affected by the modified diets. The Cunningham glass adherence method was applied to evaluate phagocytic cell activity in peripheral blood. Reactive oxygen species (ROS) generation was assessed through the respiratory burst activity of spleen macrophages by the NBT reduction test. Probiotic-supplemented diets provided a good substrate for innate immune system function; the phagocytic index was significantly enhanced in fish fed soy oil and the probiotic, and at the end of the experimental period, ROS production increased in fish fed soy oil. The substitution of fish oil by soy oil is recommended for food formulation and will contribute to promoting sustainable aquaculture. Probiotics are also recommended for channel catfish farming as they may act as immunonutrients. PMID:26400353

  11. Concurrent Physical Activity Modifies the Association between n3 Long-Chain Fatty Acids and Cardiometabolic Risk in Midlife Adults12

    PubMed Central

    Muldoon, Matthew F.; Erickson, Kirk I.; Goodpaster, Bret H.; Jakicic, John M.; Conklin, Sarah M.; Sekikawa, Akira; Yao, Jeffrey K.; Manuck, Stephen B.

    2013-01-01

    Greater consumption of n3 (ω3) polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce risk for cardiovascular disease events, yet their effects on metabolic risk factors and diabetes remain unclear. This cross-sectional study used a community volunteer sample to test whether the associations between n3 fatty acids and cardiometabolic risk vary as a function of physical activity. Participants were 344 generally healthy adults, 30–54 y of age, not taking fish oil supplements or confounding medications. Serum phospholipid EPA and DHA were used together (EPA+DHA) as a biomarker of n3 fatty acid exposure. Cardiometabolic risk was calculated as a continuous measure based on standardized distributions of blood pressure, waist circumference, HDL cholesterol, triglycerides, glucose, and a simple count of risk factors. Insulin resistance was estimated from the homeostatic model assessment. Physical activity was found to predict cardiometabolic risk (P ≤ 0.02) and insulin resistance (P ≤ 0.02) and to moderate the association between EPA+DHA and both cardiometabolic risk (P-interaction ≤ 0.02) and insulin resistance (P-interaction ≤ 0.02). Specifically, higher EPA+DHA was associated with lower cardiometabolic risk and insulin resistance in persons engaged in regular physical activity but not in relatively inactive individuals. These findings were noted in several components of cardiometabolic risk, in men and women separately, and in models adjusted for overall diet quality. In midlife adults, habitual physical activity may be necessary to unmask the salutary effects of n3 fatty acids on cardiometabolic risk and insulin resistance. PMID:23884386

  12. Fatty acid and phytosterol content of commercial saw palmetto supplements.

    PubMed

    Penugonda, Kavitha; Lindshield, Brian L

    2013-09-01

    Saw palmetto supplements are one of the most commonly consumed supplements by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH and lower urinary tract symptoms (LUTS) with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fatty acids and phytosterols, of the saw palmetto supplements. To this end, we quantified the major fatty acids (laurate, myristate, palmitate, stearate, oleate, linoleate) and phytosterols (campesterol, stigmasterol, β-sitosterol) in 20 commercially available saw palmetto supplements using GC-FID and GC-MS, respectively. Samples were classified into liquids, powders, dried berries, and tinctures. Liquid saw palmetto supplements contained significantly higher (p < 0.05) concentrations of total fatty acids (908.5 mg/g), individual fatty acids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Powders contained significantly higher (p < 0.05) concentrations of total fatty acids than tinctures, which contain negligible amounts of fatty acids (46.3 mg/g) and phytosterols (0.10 mg/g). Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement with the highest concentrations of both fatty acids and phytosterols. PMID:24067389

  13. Effect of manipulation of incubation temperature on fatty acid profiles and antioxidant enzyme activities in meat-type chicken embryos.

    PubMed

    Yalçin, S; Bağdatlioğlu, N; Yenisey, Ç; Siegel, P B; Özkan, S; Akşit, M

    2012-12-01

    Eggs (n = 1,800) obtained from Ross broiler breeders at 32 and 48 wk of age were incubated at either a constant temperature of 37.6°C throughout (T1), or the temperature was reduced for 6 h to 36.6°C each day during embryonic age (EA) 10 to 18 (T2). Yolk sac, liver, and brain fatty acid profiles and oxidant and antioxidant status of liver and brain were measured at EA 14, 19, and day of hatch (DOH). Fatty acid profiles of yolk sac, liver, and brain were influenced by age of breeder with significant breeder hen age × incubation temperature interactions. At EA 14, higher levels of 20:4n-6 and 22:6n-3 had been transferred from the yolk sac to T2 embryos from younger than older breeders, whereas for T1 and T2 embryos, yolk sac 20:4n-6 and 22.6n-3 values were similar for older breeders. Accumulation of 20:4n-6 and 22:6n-3 fatty acids in the liver of T1 and T2 embryos from younger breeders was similar; however, T2 embryos from older breeders had higher liver levels of 20:4n-6 and 22:6n-3 than T1 embryos. At EA 19, liver nitric oxide levels were higher for T2 embryos from younger breeders than those from breeders incubated at T1. Brain catalase levels of T2 embryos from younger breeders were higher than those from older breeders at DOH. Thus, changes in fatty acid profiles and catalase and nitric oxide production of brain and liver tissues resulting from 1°C lower incubation temperature from EA 10 to 18 reflect adaptive changes. PMID:23155039

  14. Efficient production of fatty acid methyl ester from waste activated bleaching earth using diesel oil as organic solvent.

    PubMed

    Kojima, Seiji; Du, Dongning; Sato, Masayasu; Park, Enoch Y

    2004-01-01

    Fatty acid methyl ester (FAME) production from waste activated bleaching earth (ABE) discarded by the crude oil refining industry was investigated using fossil fuel as a solvent in the esterification of triglycerides. Lipase from Candida cylindracea showed the highest stability in diesel oil. Using diesel oil as a solvent, 3 h was sufficient to obtain a yield of approximately 100% of FAME in the presence of 10% lipase from waste ABE. Kerosene was also a good solvent in the esterification of triglycerides embedded in the waste ABE. Fuel analysis showed that the FAME produced using diesel oil as a solvent complied with the Japanese diesel standard and the 10% residual carbon amount was lower than that of FAME produced using other solvents. Use of diesel oil as solvent in the FAME production from the waste ABE simplified the process, because there was no need to separate the organic solvent from the FAME-solvent mixture. These results demonstrate a promising reutilization method for the production of FAME, for use as a biodiesel, from industrial waste resources containing waste vegetable oils. PMID:16233730

  15. Resistance of callose synthase activity to free fatty acid inhibition as an indicator of Fusarium head blight resistance in wheat

    PubMed Central

    Ellinger, Dorothea; Sode, Björn; Falter, Christian; Voigt, Christian A

    2014-01-01

    The fungal pathogen Fusarium graminearum is the causal agent of Fusarium head blight (FHB); a devastating crop disease resulting in heavy yield losses and grain contamination with mycotoxins. We recently showed that the secreted lipase FGL1, a virulence factor of F. graminearum, targets plant defense-related callose biosynthesis during wheat head infection. This effector-like function is based on a FGL1-mediated release of polyunsaturated free fatty acids (FFA) that can inhibit callose synthase activity. The importance of FGL1 in successful wheat head colonization was demonstrated in FGL1 disruption mutants (Δfgl1), where infection was restricted to directly inoculated spikelets and accompanied by strong callose deposition in the spikelet’s phloem. The application of polyunsaturated FFA to Δfgl1-infected spikelets prevented callose deposition in the phloem and partially restored wheat head colonization.   The comparative analysis of 3 wheat cultivars revealed that the level of resistance to FHB correlated with resistance to FFA-dependent inhibition of callose biosynthesis. Therefore, resistance of callose biosynthesis to FFA inhibition might be used as marker and/or direct target in the breeding of FHB-resistant wheat cultivars. PMID:25763484

  16. Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes*

    PubMed Central

    Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

    2013-01-01

    Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID:24240094

  17. Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer

    SciTech Connect

    Bian, Yong; Yu, Yun; Wang, Shanshan; Li, Lin

    2015-08-07

    Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan–Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDAC patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. - Highlights: • Increased expression of FASN indicates a poor prognosis in PDAC. • Elevated FASN favors tumor growth in PDAC in vitro. • Activation of EGFR signaling contributes to elevated FASN expression.

  18. Inhibition of fatty acid amide hydrolase activates Nrf2 signalling and induces heme oxygenase 1 transcription in breast cancer cells

    PubMed Central

    Li, H; Wood, J T; Whitten, K M; Vadivel, S K; Seng, S; Makriyannis, A; Avraham, H K

    2013-01-01

    BACKGROUND AND PURPOSE Endocannabinoids such as anandamide (AEA) are important lipid ligands regulating cell proliferation, differentiation and apoptosis. Their levels are regulated by hydrolase enzymes, the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). Here, we investigated whether FAAH or AEA are involved in NF (erythroid-derived 2)-like 2 (Nrf2)/antioxidant responsive element (ARE) pathway. EXPERIMENTAL APPROACH The aim of this study was to analyse the effects of AEA or FAAH inhibition by the URB597 inhibitor or FAAH/siRNA on the activation of Nrf2-ARE signalling pathway and heme oxygenase-1 (HO-1) induction and transcription. KEY RESULTS Endogenous AEA was detected in the immortalized human mammary epithelial MCF-10A cells (0.034 ng per 106 cells) but not in MCF-7 or MDA-MB-231 breast cancer cells. Because breast tumour cells express FAAH abundantly, we examined the effects of FAAH on Nrf2/antioxidant pathway. We found that inhibition of FAAH by the URB597 inhibitor induced antioxidant HO-1 in breast cancer cells and MCF-10A cells. RNAi-mediated knockdown of FAAH or treatment with AEA-activated ARE-containing reporter induced HO-1 mRNA and protein expression, independent of the cannabinoid receptors, CB1, CB2 or TRPV1. Furthermore, URB597, AEA and siRNA-FAAH treatments induced the nuclear translocation of Nrf2, while siRNA-Nrf2 treatment and Keap1 expression blocked AEA, URB597 and si-FAAH from activation of ARE reporter and HO-1 induction. siRNA-HO-1 treatment decreased the viability of breast cancer cells and MCF-10A cells. CONCLUSIONS AND IMPLICATIONS These data uncovered a novel mechanism by which inhibition of FAAH or exposure to AEA induced HO-1 transcripts and implicating AEA and FAAH as direct modifiers in signalling mediated activation of Nrf2-HO-1 pathway, independent of cannabinoid receptors. PMID:23347118

  19. Effect of a seaweed extract on fatty acid accumulation and glycerol-3-phosphate dehydrogenase activity in 3T3-L1 adipocytes.

    PubMed

    He, M L; Wang, Y; You, J S; Mir, P S; McAllister, T A

    2009-02-01

    This study was to determine the effect of a seaweed Ascophyllum nodosum extract (SE) containing 220 mg g(-1) phlorotannins on differentiation and fatty acid accumulation in differentiating 3T3-L1 adipocytes. 3T3-L1 cells (2 x 10(4) mL(-1)) were seeded to 24-well plates and proliferated to reach confluence and then were treated with media containing 0, 12.5, 25, 50, 75 and 100 mug mL(-1) SE for 8 days. Dexamethasone, methyl-isobutylxanthine and insulin (DMI) were added to the media in the first 2 days to induce cell differentiation. On day 8 the adipocytes were harvested for measuring cellular fatty acid concentration and the activity of glycerol-3-phosphate dehydrogenase (GPDH). It was found that treatment with SE increased (P < 0.01, n = 6) cellular myristoleic acid (C14:1), palmitoleic acid (C16:1) and oleic acid (C18:1) and total monounsaturated fatty acids (MUFA) without significantly affecting the cell number and saturated fatty acid (SFA). Ratios of MUFA/SFA, C14:1/C14:0, C16:1/C16:0 and C18:1/C18:0 in cellular lipids increased (P < 0.05, n = 6) with the SE treatment in a dose dependent manner (P < 0.001). Treatment with 75 microg mL(-1) SE depressed (P < 0.05) cellular GPDH activity. The results indicate that the biological factors in the SE may be involved in differentiation and MUFA accumulation in adipocytes. PMID:18982374

  20. Alterations of N-3 Polyunsaturated Fatty Acid-Activated K2P Channels in Hypoxia-Induced Pulmonary Hypertension

    PubMed Central

    Nielsen, Gorm; Wandall-Frostholm, Christine; Sadda, Veeranjaneyulu; Oliván-Viguera, Aida; Lloyd, Eric E.; Bryan, Robert M.; Simonsen, Ulf; Köhler, Ralf

    2013-01-01

    Polyunsaturated fatty acid (PUFA)-activated two-pore domain potassium channels (K2P) have been proposed to be expressed in the pulmonary vasculature. However, their physiological or pathophysiological roles are poorly defined. Here we tested the hypothesis that PUFA-activated K2P are involved in pulmonary vasorelaxation and that alterations of channel expression are pathophysiologically linked to pulmonary hypertension. Expression of PUFA-activated K2P in the murine lung was investigated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), by patch clamp (PC), and myography. K2P-gene expression was examined in chronic hypoxic mice. QRT-PCR showed that the K2P2.1 and K2P6.1 were the predominantly expressed K2P in the murine lung. IHC revealed protein expression of K2P2.1 and K2P6.1 in the endothelium of pulmonary arteries and of K2P6.1 in bronchial epithelium. PC showed pimozide-sensitive K2P-like K+-current activated by docosahexaenoic acid (DHA) in freshly isolated endothelial cells as well as DHA-induced membrane hyperpolarization. Myography on pulmonary arteries showed that DHA-induced concentration-dependent and instantaneous relaxations that were resistant to endothelial removal and inhibition of NO and prostacyclin synthesis and to a cocktail of blockers of calcium-activated K+ channels but were abolished by high extracellular (30 mM) K+-concentration. Gene expression and protein of K2P2.1 were not altered in chronic hypoxic mice while K2P6.1 was up-regulated by fourfold. In conclusion, the PUFA-activated K2P2.1 and K2P6.1 are expressed in murine lung and functional K2P-like channels contribute to endothelium-hyperpolarization and pulmonary artery relaxation. The increased K2P6.1-gene expression may represent a novel counter-regulatory mechanism in pulmonary hypertension, and suggest that arterial K2P2.1 and K2P6.1 could be novel therapeutic targets. PMID:23724868

  1. Omega-3 fatty acids and cardiovascular disease.

    PubMed

    Jain, A P; Aggarwal, K K; Zhang, P-Y

    2015-01-01

    Cardioceuticals are nutritional supplements that contain all the essential nutrients including vitamins, minerals, omega-3-fatty acids and other antioxidants like a-lipoic acid and coenzyme Q10 in the right proportion that provide all round protection to the heart by reducing the most common risks associated with the cardiovascular disease including high low-density lipoprotein cholesterol and triglyceride levels and factors that contribute to coagulation of blood. Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Omega-3 fatty acids are also used to treat hyperlipidemia and hypertension. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g/day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardio protection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2-4 g/day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids. PMID:25720716

  2. An efficient and green pretreatment to stimulate short-chain fatty acids production from waste activated sludge anaerobic fermentation using free nitrous acid.

    PubMed

    Li, Xiaoming; Zhao, Jianwei; Wang, Dongbo; Yang, Qi; Xu, Qiuxiang; Deng, Yongchao; Yang, Weiqiang; Zeng, Guangming

    2016-02-01

    Short-chain fatty acid (SCFA) production from waste activated sludge (WAS) anaerobic fermentation is often limited by the slow hydrolysis rate and poor substrate availability, thus a long fermentation time is required. This paper reports a new pretreatment approach, i.e., using free nitrous acid (FNA) to pretreat sludge, for significantly enhanced SCFA production. Experimental results showed the highest SCFA production occurred at 1.8 mg FNA/L with time of day 6, which was 3.7-fold of the blank at fermentation time of day 12. Mechanism studies revealed that FNA pretreatment accelerated disruption of both extracellular polymeric substances and cell envelope. It was also found that FNA pretreatment benefited hydrolysis and acidification processes but inhibited the activities of methanogens, thereby promoting the yield of SCFA. In addition, the FNA pretreatment substantially stimulated the activities of key enzymes responsible for hydrolysis and acidification, which were consistent with the improvement of solubilization, hydrolysis and acidification of WAS anaerobic fermentation. PMID:26363316

  3. Anticandidal activity of cell extracts from 13 probiotic Lactobacillus strains and characterisation of lactic acid and a novel fatty acid derivative from one strain.

    PubMed

    Nyanzi, Richard; Awouafack, Maurice D; Steenkamp, Paul; Jooste, Piet J; Eloff, Jacobus N

    2014-12-01

    This study investigated the anti-Candida activity of methanol extracts from freeze-dried probiotic cells and the isolation of some constituents in the extracts. The MIC values of the probiotic methanol cell extracts against Candida albicans ranged between 1.25 and 5mg/ml after 48 h of incubation. However, Lactococcus latics subsp. lactis strain X and Lactobacillus casei strain B extracts had an MIC of 10mg/ml after 48 h of incubation. The extracts had fungistatic rather than fungicidal activity. These extracts had a much higher antifungal activity than antifungal compounds isolated from the growth medium by many other authors. This indicates that probiotics may also release antifungal compounds in their cells that could contribute to a therapeutic effect. Lactic acid (1) and 6-O-(α-D-glucopyranosyl)-1,6-di-O-pentadecanoyl-α-D-glucopyranose a novel fatty acid derivative (2) were isolated from methanol probiotic extracts and the structure of these compounds were elucidated using NMR (1 and 2D) and mass spectrometry (MS). PMID:24996359

  4. Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins.

    PubMed Central

    Belisle, J T; Brandt, M E; Radolf, J D; Norgard, M V

    1994-01-01

    A fundamental ultrastructural feature shared by the spirochetal pathogens Treponema pallidum subsp. pallidum (T. pallidum) and Borrelia burgdorferi, the etiological agents of venereal syphilis and Lyme disease, respectively, is that their most abundant membrane proteins contain covalently attached fatty acids. In this study, we identified the fatty acids covalently bound to lipoproteins of B. burgdorferi and T. pallidum and examined potential acyl donors to these molecules. Palmitate was the predominant fatty acid of both B. burgdorferi and T. pallidum lipoproteins. T. pallidum lipoproteins also contained substantial amounts of stearate, a fatty acid not typically prevalent in prokaryotic lipoproteins. In both spirochetes, the fatty acids of cellular lipids differed from those of their respective lipoproteins. To characterize phospholipids in these organisms, spirochetes were metabolically labeled with [3H]palmitate or [3H]oleate; B. burgdorferi contained only phosphatidylglycerol and phosphatidylcholine, while T. pallidum contained phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Although palmitate predominated in the lipoproteins, there were no apparent differences in the incorporation of these two fatty acids into phospholipids (putative acyl donors). Phospholipase A1 and A2 digestion of phosphatidylcholine from B. burgdorferi and T. pallidum labeled with either [3H]palmitate or [3H]oleate also revealed that neither fatty acid was incorporated preferentially into the 1 and 2 positions (potential acyl donor sites) of the glycerol backbone. The combined findings suggest that fatty acid utilization during lipoprotein synthesis is determined largely by the fatty acid specificities of the lipoprotein acyl transferases. These findings also provide the basis for ongoing efforts to elucidate the relationship between lipoprotein acylation and the physiological functions and inflammatory activities of these molecules. Images PMID:8157583

  5. Enzymatic acylation of isoorientin and isovitexin from bamboo-leaf extracts with fatty acids and antiradical activity of the acylated derivatives.

    PubMed

    Ma, Xiang; Yan, Rian; Yu, Shuqi; Lu, Yuyun; Li, Zhuo; Lu, Haohao

    2012-10-31

    This study enzymatically acrylates two flavonoids from bamboo-leaf extracts, isoorientin and isovitexin, with different fatty acids as acyl donors using Candida antarctica lipase B (CALB). The conversion yield ranged from 35 to 80% for fatty acids with different chain lengths. Higher isoorientin and isovitexin conversion yields (>75%) were obtained using lauric acid in tert-amyl-alcohol as the reaction medium. (1)H and (13)C nuclear magnetic resonance spectroscopy analysis showed that, in the presence of CALB, acylation occurred at the isoorientin and isovitexin primary hydroxyl group of glucose moiety and only monoesters were detected. Introducing an acyl group into isoorientin and isovitexin significantly improved their lipophilicity but reduced their antiradical activity. PMID:23057589

  6. Proto-oncogene FBI-1 (Pokemon) and SREBP-1 synergistically activate transcription of fatty-acid synthase gene (FASN).

    PubMed

    Choi, Won-Il; Jeon, Bu-Nam; Park, Hyejin; Yoo, Jung-Yoon; Kim, Yeon-Sook; Koh, Dong-In; Kim, Myung-Hwa; Kim, Yu-Ri; Lee, Choong-Eun; Kim, Kyung-Sup; Osborne, Timothy F; Hur, Man-Wook

    2008-10-24

    FBI-1 (Pokemon/ZBTB7A) is a proto-oncogenic transcription factor of the BTB/POZ (bric-à-brac, tramtrack, and broad complex and pox virus zinc finger) domain family. Recent evidence suggested that FBI-1 might be involved in adipogenic gene expression. Coincidentally, expression of FBI-1 and fatty-acid synthase (FASN) genes are often increased in cancer and immortalized cells. Both FBI-1 and FASN are important in cancer cell proliferation. SREBP-1 is a major regulator of many adipogenic genes, and FBI-1 and SREBP-1 (sterol-responsive element (SRE)-binding protein 1) interact with each other directly via their DNA binding domains. FBI-1 enhanced the transcriptional activation of SREBP-1 on responsive promoters, pGL2-6x(SRE)-Luc and FASN gene. FBI-1 and SREBP-1 synergistically activate transcription of the FASN gene by acting on the proximal GC-box and SRE/E-box. FBI-1, Sp1, and SREBP-1 can bind to all three SRE, GC-box, and SRE/E-box. Binding competition among the three transcription factors on the GC-box and SRE/E-box appears important in the transcription regulation. FBI-1 is apparently changing the binding pattern of Sp1 and SREBP-1 on the two elements in the presence of induced SREBP-1 and drives more Sp1 binding to the proximal promoter with less of an effect on SREBP-1 binding. The changes induced by FBI-1 appear critical in the synergistic transcription activation. The molecular mechanism revealed provides insight into how proto-oncogene FBI-1 may attack the cellular regulatory mechanism of FASN gene expression to provide more phospholipid membrane components needed for rapid cancer cell proliferation. PMID:18682402

  7. CYP4 Enzymes as potential drug targets: focus on enzyme multiplicity, inducers and inhibitors, and therapeutic modulation of 20-hydroxyeicosatetraenoic acid (20-HETE) synthase and fatty acid ω-hydroxylase activities

    PubMed Central

    Edson, Katheryne Z.; Rettie, Allan E.

    2014-01-01

    The Cytochrome P450 4 (CYP4) family of enzymes in humans is comprised of thirteen isozymes that typically catalyze the ω-oxidation of endogenous fatty acids and eicosanoids. Several CYP4 enzymes can biosynthesize 20-hydroxyeicosatetraenoic acid or 20-HETE, an important signaling eicosanoid involved in regulation of vascular tone and kidney reabsorption. Additionally, accumulation of certain fatty acids is a hallmark of the rare genetic disorders, Refsum disease and X-ALD. Therefore, modulation of CYP4 enzyme activity, either by inhibition or induction, is a potential strategy for drug discovery. Here we review the substrate specificities, sites of expression, genetic regulation, and inhibition by exogenous chemicals of the human CYP4 enzymes, and discuss the targeting of CYP4 enzymes in the development of new treatments for hypertension, stroke, certain cancers and the fatty acid-linked orphan diseases. PMID:23688133

  8. 21 CFR 172.860 - Fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Fatty acids. 172.860 Section 172.860 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.860 Fatty...

  9. [Dietary fatty acids and experimental carcinogenesis].

    PubMed

    Bougnoux, Philippe; Menanteau, Jean

    2005-07-01

    Experiments in animal models of mammary carcinogenesis suggest that fatty acids promote mammary tumors development. This effect depends first on the amount then on the type of fatty acids available. n-6 fatty acids such as linoleic acid generally stimulates mammary tumor growth, while n-3 fatty acids oppose this effect. Conjugated diene fatty acids (CLA) inhibit mammary carcinogenesis when brought at elevated amount. There are limitations in using an animal model in the analysis between nutrition and colorectal cancers. This is ascribable to the following: firstly, the digestive tract of rodents if different from that of humans and secondly, the induction of colon cancer in these animals (chemical carcinogenesis, injection of cancerous cells or transgenesis) does not mimic human colon carcinogenesis. However, on the basis of numerous published data, some important correlations have arisen that could generate hypotheses and guide new epidemiological/interventional and experimental studies. In these animal models it appears that an adequate supply of n-3 PUFAs and oleic acid in food may exert a protective effect at all stages of colon carcinogenesis. On the other hand, an excessive consumption of n-6 PUFAs and of saturated fatty acids could promote colon cancers. PMID:16123007

  10. Maternal micronutrients, omega-3 fatty acids, and placental PPARγ expression.

    PubMed

    Meher, Akshaya P; Joshi, Asmita A; Joshi, Sadhana R

    2014-07-01

    An altered one-carbon cycle is known to influence placental and fetal development. We hypothesize that deficiency of maternal micronutrients such as folic acid and vitamin B12 will lead to increased oxidative stress, reduced long-chain polyunsaturated fatty acids, and altered expression of peroxisome proliferator activated receptor (PPARγ) in the placenta, and omega-3 fatty acid supplementation to these diets will increase the expression of PPARγ. Female rats were divided into 5 groups: control, folic acid deficient, vitamin B12 deficient, folic acid deficient + omega-3 fatty acid supplemented, and vitamin B12 deficient + omega-3 fatty acid supplemented. Dams were dissected on gestational day 20. Maternal micronutrient deficiency leads to lower (p < 0.05) levels of placental docosahexaenoic acid, arachidonic acid, PPARγ expression and higher (p < 0.05) levels of plasma malonidialdehyde, placental IL-6, and TNF-α. Omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalized the expression of PPARγ and lowered the levels of placental TNF-α. In the case of supplementation to a folic acid deficient diet it lowered the levels of malonidialdehyde and placental IL-6 and TNF-α. This study has implications for fetal growth as oxidative stress, inflammation, and PPARγ are known to play a key role in the placental development. PMID:24749811

  11. Fatty Acids Inhibit Apical Membrane Chloride Channels in Airway Epithelia

    NASA Astrophysics Data System (ADS)

    Anderson, Matthew P.; Welsh, Michael J.

    1990-09-01

    Apical membrane Cl^- channels control the rate of transepithelial Cl^- secretion in airway epithelia. cAMP-dependent protein kinase and protein kinase C regulate Cl^- channels by phosphorylation; in cystic fibrosis cells, phosphorylation-dependent activation of Cl^- channels is defective. Another important signaling system involves arachidonic acid, which is released from cell membranes during receptor-mediated stimulation. Here we report that arachidonic acid reversibly inhibited apical membrane Cl^- channels in cell-free patches of membrane. Arachidonic acid itself inhibited the channel and not a cyclooxygenase or lipoxygenase metabolite because (i) inhibitors of these enzymes did not block the response, (ii) fatty acids that are not substrates for the enzymes had the same effect as arachidonic acid, and (iii) metabolites of arachidonic acid did not inhibit the channel. Inhibition occurred only when fatty acids were added to the cytosolic surface of the membrane patch. Unsaturated fatty acids were more potent than saturated fatty acids. Arachidonic acid inhibited Cl^- channels from both normal and cystic fibrosis cells. These results suggest that fatty acids directly inhibit apical membrane Cl^- channels in airway epithelial cells.

  12. [Metabolism of fatty acids in the healthy myocardium and in ischemia].

    PubMed

    Matiushin, I F; Boiarinov, G A; Bogdarin, Iu A

    1984-01-01

    Data on absorption and consumption in heart tissue of free and ester-bound fatty acids from blood lipids are discussed. Preferential utilization of individual fatty acids in heart tissue from blood lipids is considered. Dependence of fatty acid metabolism on the activity of tricarboxylic acid cycle, interrelationship between metabolism of endogenous and exogenous fatty acids in heart muscle are considered. The data are analyzed on pathways of exogenous fatty acids turnover in tissues, their conversion into endogenous fatty acids, specific for individual tissue, cells and their organelles. Development of syndrome of unsaturated fatty acids deficiency, induced by incomplete fatty diet, is discussed. Metabolism of fatty acids in heart under conditions of oxygen deficiency is considered. The data are reviewed on the effects of hypoxia on metabolism of fatty acids in myocardium. Carbohydrate and fatty acid consumption in heart muscle, typical alterations in fatty acid incorporation into heart lipids, effect of fatty acids excess on functioning of sarcoplasmic reticulum and mitochondrial membranes are discussed. PMID:6396941

  13. Plasma fatty acid profile and alternative nutrition.

    PubMed

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Klvanová, J

    1997-01-01

    Plasma profile of fatty acids was examined in a group of children consisting of 7 vegans, 15 lactoovovegetarians and 10 semivegetarians. The children were 11-15 years old and the average period of alternative nutrition was 3.4 years. The results were compared with a group of 19 omnivores that constituted an average sample with respect to biochemical and hematological parameters from a larger study of health and nutritional status of children in Slovakia. Alternative nutrition groups had significantly lower values of saturated fatty acids. The content of oleic acid was identical to omnivores. A significant increase was observed for linoleic and alpha-linolenic (n-3) acids. The dihomo-gamma-linolenic (n-6) acid and arachidonic (n-6) acid values were comparable to omnivores for all alternative nutrition groups. Values of n-3 polyunsaturated fatty acids in lactoovovegetarians were identical to those of omnivores whereas they were significantly increased in semivegetarians consuming fish twice a week. Due to the total exclusion of animal fats from the diet, vegans had significantly reduced values of palmitoleic acid as well as eicosapentaenoic (n-3) acid and docosahexaenoic (n-3) acid resulting in an increased n-6/n-3 ratio. Values of plasma fatty acids found in alternative nutrition groups can be explained by the higher intake of common vegetable oils (high content of linoleic acid), oils rich in alpha-linolenic acid (cereal germs, soybean oil, walnuts), as well as in n-3 polyunsaturated fatty acids (fish). The results of fatty acids (except n-3 in vegans) and other lipid parameters confirm the beneficial effect of vegetarian nutrition in the prevention of cardiovascular diseases. PMID:9491192

  14. Enhancement of lipase catalyzed-fatty acid methyl esters production from waste activated bleaching earth by nullification of lipase inhibitors.

    PubMed

    Dwiarti, Lies; Ali, Ehsan; Park, Enoch Y

    2010-01-01

    This study sought to identify inhibitory factors of lipase catalyzed-fatty acid methyl esters (FAME) production from waste activated bleaching earth (wABE). During the vegetable oil refinery process, activated bleaching earth (ABE) is used for removing the impure compounds, but adsorbs vegetable oil up to 35-40% as on a weight basis, and then the wABE is discarded as waste material. The impurities were extracted from the wABE with methanol and evaluated by infra-red (IR) spectroscopy, which revealed that some were chlorophyll-plant pigments. The chlorophylls inhibited the lipase during FAME conversion from wABE. The inhibition by a mixture of chlorophyll a and b was found to be competitive. The inhibition of the enzymatic hydrolysis of waste vegetable oil contained in wABE by chlorophyll a alone was competitive, while the inhibition by chlorophyll b alone was non-competitive. Furthermore, the addition of a small amount of alkali nullified this inhibitory effect and accelerated the FAME production rate. When 0.9% KOH (w/w wABE) was added to the transesterification reaction with only 0.05% lipase (w/w wABE), the maximum FAME production rate improved 120-fold, as compared to that without the addition of KOH. The alkali-combined lipase significantly enhanced the FAME production rate from wABE, in spite of the presence of the plant pigments, and even when a lower amount of lipase was used as a catalyst. PMID:19726181

  15. Activity and Viability of Methanogens in Anaerobic Digestion of Unsaturated and Saturated Long-Chain Fatty Acids

    PubMed Central

    Sousa, Diana Z.; Salvador, Andreia F.; Ramos, Juliana; Guedes, Ana P.; Barbosa, Sónia; Stams, Alfons J. M.; Alves, M. Madalena

    2013-01-01

    Lipids can be anaerobically digested to methane, but methanogens are often considered to be highly sensitive to the long-chain fatty acids (LCFA) deriving from lipids hydrolysis. In this study, the effect of unsaturated (oleate [C18:1]) and saturated (stearate [C18:0] and palmitate [C16:0]) LCFA toward methanogenic archaea was studied in batch enrichments and in pure cultures. Overall, oleate had a more stringent effect on methanogens than saturated LCFA, and the degree of tolerance to LCFA was different among distinct species of methanogens. Methanobacterium formicicum was able to grow in both oleate- and palmitate-degrading enrichments (OM and PM cultures, respectively), whereas Methanospirillum hungatei only survived in a PM culture. The two acetoclastic methanogens tested, Methanosarcina mazei and Methanosaeta concilii, could be detected in both enrichment cultures, with better survival in PM cultures than in OM cultures. Viability tests using live/dead staining further confirmed that exponential growth-phase cultures of M. hungatei are more sensitive to oleate than are M. formicicum cultures; exposure to 0.5 mM oleate damaged 99% ± 1% of the cell membranes of M. hungatei and 53% ± 10% of the cell membranes of M. formicicum. In terms of methanogenic activity, M. hungatei was inhibited for 50% by 0.3, 0.4, and 1 mM oleate, stearate, and palmitate, respectively. M. formicicum was more resilient, since 1 mM oleate and >4 mM stearate or palmitate was needed to cause 50% inhibition on methanogenic activity. PMID:23645196

  16. Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

    PubMed Central

    2012-01-01

    Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC) patients. The mechanism of response to interferon-alpha (IFN-α) therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV) replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP) and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP) cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER) stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN-α response in CHC. PMID:22863531

  17. PPARα (Peroxisome Proliferator-activated Receptor α) Activation Reduces Hepatic CEACAM1 Protein Expression to Regulate Fatty Acid Oxidation during Fasting-refeeding Transition.

    PubMed

    Ramakrishnan, Sadeesh K; Khuder, Saja S; Al-Share, Qusai Y; Russo, Lucia; Abdallah, Simon L; Patel, Payal R; Heinrich, Garrett; Muturi, Harrison T; Mopidevi, Brahma R; Oyarce, Ana Maria; Shah, Yatrik M; Sanchez, Edwin R; Najjar, Sonia M

    2016-04-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed at high levels in the hepatocyte, consistent with its role in promoting insulin clearance in liver. CEACAM1 also mediates a negative acute effect of insulin on fatty acid synthase activity. Western blot analysis reveals lower hepatic CEACAM1 expression during fasting. Treating of rat hepatoma FAO cells with Wy14,643, an agonist of peroxisome proliferator-activated receptor α (PPARα), rapidly reduces Ceacam1 mRNA and CEACAM1 protein levels within 1 and 2 h, respectively. Luciferase reporter assay shows a decrease in the promoter activity of both rat and mouse genes by Pparα activation, and 5'-deletion and block substitution analyses reveal that the Pparα response element between nucleotides -557 and -543 is required for regulation of the mouse promoter activity. Chromatin immunoprecipitation analysis demonstrates binding of liganded Pparα toCeacam1promoter in liver lysates ofPparα(+/+), but notPparα(-/-)mice fed a Wy14,643-supplemented chow diet. Consequently, Wy14,643 feeding reduces hepatic Ceacam1 mRNA and CEACAM1 protein levels, thus decreasing insulin clearance to compensate for compromised insulin secretion and maintain glucose homeostasis and insulin sensitivity in wild-type mice. Together, the data show that the low hepatic CEACAM1 expression at fasting is mediated by Pparα-dependent mechanisms. Changes in CEACAM1 expression contribute to the coordination of fatty acid oxidation and insulin action in the fasting-refeeding transition. PMID:26846848

  18. Influence of selenium supplementation on fatty acids profile and biological activity of four edible amaranth sprouts as new kind of functional food.

    PubMed

    Pasko, Pawel; Gdula-Argasinska, Joanna; Podporska-Carroll, Joanna; Quilty, Brid; Wietecha-Posluszny, Renata; Tyszka-Czochara, Malgorzata; Zagrodzki, Pawel

    2015-08-01

    Suitability assessment of amaranth sprouts as a new functional food was carried out. The optimisation of sprouting process and the influence of selenium supplementation, in doses 10, 15, and 30 mg/l of selenium as sodium selenite, on amaranth growth and fatty acid profile were examined. Methods such as FRAP, DPPH, polyphenols content and GPX activity were applied to characterize antioxidant potential of seeds and sprouts of four different edible amaranth genera. E. coli, S. aureus, C. albicans were used to evaluate amaranth sprouts antimicrobial properties. Interaction between amaranth sprouts and biological systems was assessed by analysing antibacterial and antifungal properties with a disc diffusion test. The studies proved amaranth sprouts to be potentially attractive as functional food. As confirmed by all the data amaranth sprouts are suitable as a moderate selenium accumulator and are rich in essential fatty acids, especially linoleic and alpha-linolenic acids, which are precursors of long chain polyunsaturated fatty acids. Thus, it opens dietary opportunities for amaranth sprouts. They can also serve as a moderate source of antioxidant compounds. Nevertheless, the experiments revealed neither antibacterial, nor antifungal properties of sprouts. In general, amaranth sprouts biological activity under evaluation has failed to prove to be significantly impacted by selenium fertilization. PMID:26243894

  19. Non-esterified fatty acids activate the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    PubMed

    Li, Xinwei; Li, Xiaobing; Chen, Hui; Lei, Liancheng; Liu, Juxiong; Guan, Yuan; Liu, Zhaoxi; Zhang, Liang; Yang, Wentao; Zhao, Chenxu; Fu, Shixin; Li, Peng; Liu, Guowen; Wang, Zhe

    2013-01-01

    Non-esterified fatty acids (NEFAs) act as signaling molecules involved in regulating genes expression to modulate lipid metabolism. However, the regulation mechanism of NEFAs on lipid metabolism in dairy cows is unclear. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of NEFAs and AMPKα inhibitors (BML-275). NEFAs increased AMPKα phosphorylation through up-regulating the protein levels of liver kinase B1. Activated AMPKα increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α (PPARα). NEFAs also directly activate the PPARα independent of AMPKα. Activated PPARα increased the lipolytic genes expression to increase lipid oxidation. Furthermore, activated AMPKα inhibited the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid synthesis. Activated AMPKα phosphorylated and inhibited acetyl-CoA carboxylase and increased carnitine palmitoyltransferase-1 activity, which increased lipid oxidation. Consequently, the triglyceride content in the NEFAs-treated hepatocytes was significantly decreased. These results indicate that NEFAs activate the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in hepatocytes, which in turn, generates more ATP to relieve the negative energy balance in transition dairy cows. PMID:23690240

  20. Oxygenases for aliphatic hydrocarbons and fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxygenases catalyzing the insertion of oxygen into either aliphatic hydrocarbons or fatty acids have great similarity. There are two classes of oxygenases: monooxygenases and dioxygenases. Dioxygenase inserts both atoms of molecular oxygen into a substrate, whereas monooxygenase incorporates one a...

  1. [The n-3 fatty acid/dopamine hypothesis in schizophrenia].

    PubMed

    Ohara, Koichi

    2006-08-01

    The dopamine hypothesis of schizophrenia has been most influential since the 1970s. Normally, the prefrontal dopamine system suppressively controls the limbic dopamine system. Since the activities of prefrontal dopaminergic neurons are reduced in schizophrenia, the suppressive effect of the prefrontal area on the limbic system is reduced, and activities of the limbic dopamine system are enhanced. Reduced activities of the prefrontal dopamine system cause negative symptoms and cognitive disorders, and the increased activity of the limbic dopamine system induces positive symptoms. While the dopamine hypothesis explains the relationship between intracranial dopamine kinetics and psychiatric symptoms in schizophrenia, it is not a direct explanation of its etiology. The cause of the activities of dopaminergic neurons in schizophrenia and the resultant symptoms are unknown. n-3 Fatty acids are not synthesized in the human body and are called "essential fatty acids". Since the late 1980s, it has been revealed that the n-3 fatty acid concentration is reduced in the plasma and erythrocyte membranes of schizophrenic patients, and that the administration of n-3 fatty acids is effective for the treatment of schizophrenia. However, how n-3 fatty acid deficiency induces psychiatric symptoms remains unclear, and the mechanism of the therapeutic effect of n-3 fatty acids has not been clarified. Recently, the dopamine hypothesis and n-3 fatty acid hypothesis have been suggested to represent different aspects of the same pathology of schizophrenia. In schizophrenia, the inactivation of phospholipase A2 causes an excessive depletion of essential fatty acids from the Sn2 position of cell membrane phospholipids, and the brain concentrations of essential fatty acids decrease. This causes decreases in dopamine vesicles, dopamine concentration, and D2-receptors at prefrontal presynaptic terminals. The reduced activity of dopaminergic neurons in the prefrontal area induce negative symptoms and cognitive disorders. Furthermore, as the suppression of activities in the limbic dopamine system by the prefrontal area is reduced, the dopamine concentration and D2-receptors increase in the striate body. As a result, the hyperactivity of the limbic dopamine system induces positive symptoms. The administration of antipsychotics and n-3 fatty acids act on different points in this etiological cascade. PMID:17020131

  2. Hypolipidemic Activity of Peony Seed Oil Rich in α-Linolenic, is Mediated Through Inhibition of Lipogenesis and Upregulation of Fatty Acid β-Oxidation.

    PubMed

    Su, Jianhui; Ma, Chaoyang; Liu, Chengxiang; Gao, Chuanzhong; Nie, Rongjing; Wang, Hongxin

    2016-04-01

    Peony seed oil (PSO) is a new resource food rich in α-Linolenic Acid(ALA) (38.66%). The objective of this study was to assess the modulatory effect of PSO on lipid metabolism. Lard oil, safflower oil (SFO), and PSO were fed to wistar rats with 1% cholesterol in the diet for 60 d. Serum and liver lipids showed significant decrease in total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) levels in PSO fed rats compared to lard oil and SFO fed rats. ALA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), contents were significantly increased, whereas linoleic acid (LA), arachidonic acid (AA) levels decreased in serum and liver of PSO fed rats. Feeding PSO increased ALA level and decreased n-6 to n-3 polyunsaturated fatty acid (PUFA) ratio. The hypolipidemic result of PSO indicated that PSO participated in the regulation of plasma lipid concentration and cholesterol metabolism in liver. The decreased expression of sterol regulatory element-binding proteins 1C (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS)-reduced lipid synthesis; Activation of peroxisome proliferator-activator receptor (PPARα) accompanied by increase of uncoupling protein2 (UP2) and acyl-CoA oxidase (AOX) stimulated lipid metabolism and exerted an antiobesity effect via increasing energy expenditure for prevention of obesity. PMID:26930155

  3. Enhanced cellular uptake and in vitro antitumor activity of short-chain fatty acid acylated daunorubicin-GnRH-III bioconjugates.

    PubMed

    Hegedüs, Rózsa; Manea, Marilena; Orbán, Erika; Szabó, Ildikó; Kiss, Eva; Sipos, Eva; Halmos, Gábor; Mező, Gábor

    2012-10-01

    Here we report on the synthesis and biochemical characterization (enzymatic stability, cellular uptake, in vitro antitumor activity, membrane interaction and GnRH-receptor binding affinity) of novel short-chain fatty acid (SCFA) acylated daunorubicin-GnRH-III bioconjugates, which may serve as drug delivery systems for targeted cancer chemotherapy. Ser in position 4 of GnRH-III was replaced by Lys, followed by the acylation of its ε-amino group with various fatty acids. SCFAs are potentially chemoprotective agents by suppressing the growth of cancer cells and therefore may enhance the antitumor activity of the bioconjugates. We found that all synthesized bioconjugates had high cytostatic effect in vitro, were stable in cell culture medium for 6 h and degraded in the presence of rat liver lysosomal homogenate leading to the formation of an oxime bond-linked daunorubicin-Lys as the smallest active metabolite. In the presence of α-chymotrypsin, all compounds were digested, the degradation rate strongly depending on the type of fatty acid. The bioconjugate containing Lys(nBu) in position 4 was taken up most efficiently by the cancer cells and exerted higher in vitro cytostatic effect than the previously developed GnRH-III((4)Lys(Ac), (8)Lys(Dau = Aoa)) or the parent GnRH-III(Dau = Aoa) bioconjugate. Our results could be explained by the increased binding affinity of the newly developed compound containing Lys(nBu) to the GnRH receptors. PMID:22967796

  4. [Fatty acid composition of the lipids in human blood plasma and erythrocyte membranes during simulation of extravehicular activities of cosmonauts].

    PubMed

    Skedina, M A; Katuntsev, V P; Buravkova, L B; Na?dina, V P

    1998-01-01

    Dynamics of the lipoacidic content of total plasma lipids and erythtocyte membranes was studied in 32 experiments with ten apparently healthy male subjects aged 27 to 41 years who were exposed to repeated decompression from the normal ground down to 40-35 kPa. For two hours of exposure to lowered pressure the subjects were breathing pure oxygen in mask and performing incremental physical work mimicking loading of the upper extremities of cosmonauts doing extravehicular activities (EVA) at the energy cost of 3 kcal/min. Decompression sessions were repeated with intervals from 3 to 5 days. In seven experiments, the subjects developed symptoms of the decompression sickness (DCS). Penetration of gas bubbles (GB) into the pulmonary artery was registered in 27 cases (84.4%). In 24 cases maximal intensity of the US signals from GB reached 3 to 4 Spencer's points. No changes in the lipidoacidic content of blood plasma or erythrocyte membranes were determined following the first exposure to decompression. BY the onset of repeated decompression, total number of lipids in erythrocyte membranes decreased from 54.6 to 40.4 mg% in the group of subjects who had not displayed DCS symptoms (n = 5) and from 51.2 to 35.2 mg% (p < 0.05) in the group of subjects with DCS symptoms (n = 5). In the subjects with DCS, polyunsaturated linoleic acid (18:2) tended to decrease against the upward trend of saturated fatty acids (16:0, 18:0). In these subjects, arachidonic acid in erythrocyte membranes (20:4) decreased following each decompression exposure and significantly increased (p < 0.05) in-between. In both groups, blood plasma showed slight fluctuations in the lipoacidic contents. These data suggest that exposure to the variety of the EVA-simulating factors may entail quite distinct but reversible modifications in the lipid metabolism in blood and the structural/functional state of erythrocyte membranes. The most marked alterations were observed in the subjects with the DCS symptoms during high intensity of US signals from GB in the venous blood flow. PMID:9883330

  5. Methods to monitor Fatty Acid transport proceeding through vectorial acylation.

    PubMed

    Arias-Barrau, Elsa; Dirusso, Concetta C; Black, Paul N

    2009-01-01

    The process of fatty acid transport across the plasma membrane occurs by several mechanisms that involve distinct membrane-bound and membrane-associated proteins and enzymes. Among these are the fatty acid transport proteins (FATP) and long-chain acyl CoA synthetases (Acsl). Previous studies in yeast and adipocytes have shown FATP and Acsl form a physical complex at the plasma membrane and are required for fatty acid transport, which proceeds through a coupled process-linking transport with metabolic activation termed vectorial acylation. At present, six isoforms of FATP and five isoforms of ACSL have been identified in mice and man. In addition, there are a number of splice variants of different FATP and Acsl isoforms. The different FATP and Acsl isoforms have distinct tissue expression profiles and different cellular locations suggesting they function in the channeling of fatty acids into discrete metabolic pools. The concerted activity of these proteins is proposed to allow cells to discriminate different classes of fatty acids and provides the mechanistic basis underpinning the selectivity and specificity of the fatty acid transport process. PMID:19784603

  6. Polyhydroxy Fatty Acids Derived from Sophorolipids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starting from 17-hydroxyoleic acid, which is readily available from acid alcoholysis of sophorolipids, several new polyhydroxy fatty acids have been synthesized. These compounds contain from 2 to 5 hydroxy groups, in some instances combined with other functional groups. The added hydroxy groups ca...

  7. Dietary omega-3 fatty acids for women.

    PubMed

    Bourre, Jean-Marie

    2007-01-01

    This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs. PMID:17254747

  8. The Effects of Dietary Fatty Acids on Lipid Metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Depending on their degree of unsaturation and chain length, dietary fatty acids can affect blood lipids and lipoprotein levels. Both saturated fatty acids (12:0-16:0) and dietary cholesterol increase blood cholesterol and polyunsaturated fatty acids reduce it. Trans fatty acids, even though are pol...

  9. Kefir Grains Change Fatty Acid Profile of Milk during Fermentation and Storage

    PubMed Central

    Vieira, C. P.; Álvares, T. S.; Gomes, L. S.; Torres, A. G.; Paschoalin, V. M. F.; Conte-Junior, C. A.

    2015-01-01

    Several studies have reported that lactic acid bacteria may increase the production of free fatty acids by lipolysis of milk fat, though no studies have been found in the literature showing the effect of kefir grains on the composition of fatty acids in milk. In this study the influence of kefir grains from different origins [Rio de Janeiro (AR), Viçosa (AV) e Lavras (AD)], different time of storage, and different fat content on the fatty acid content of cow milk after fermentation was investigated. Fatty acid composition was determined by gas chromatography. Values were considered significantly different when p<0.05. The highest palmitic acid content, which is antimutagenic compost, was seen in AV grain (36.6g/100g fatty acids), which may have contributed to increasing the antimutagenic potential in fermented milk. Higher monounsaturated fatty acid (25.8g/100g fatty acids) and lower saturated fatty acid (72.7g/100g fatty acids) contents were observed in AV, when compared to other grains, due to higher Δ9-desaturase activity (0.31) that improves the nutritional quality of lipids. Higher oleic acid (25.0g/100g fatty acids) and monounsaturated fatty acid (28.2g/100g fatty acids) and lower saturated fatty acid (67.2g/100g fatty acids) contents were found in stored kefir relatively to fermented kefir leading to possible increase of antimutagenic and anticarcinogenic potential and improvement of nutritional quality of lipids in storage milk. Only high-lipidic matrix displayed increase polyunsaturated fatty acids after fermentation. These findings open up new areas of study related to optimizing desaturase activity during fermentation in order to obtaining a fermented product with higher nutritional lipid quality. PMID:26444286

  10. Effect of the anorectic fatty acid synthase inhibitor C75 on neuronal activity in the hypothalamus and brainstem

    PubMed Central

    Gao, Su; Lane, M. Daniel

    2003-01-01

    Intraperitoneal (i.p.) injection of C75, a fatty acid synthase inhibitor, causes a rapid (≤2-h) and persistent (to at least 24-h) ≈95% decrease in food intake. The persistent effect seems to be due to inhibition of the fasting-induced up-regulation of expression of hypothalamic orexigenic neuropeptides neuropeptide Y and agouti-related protein and down-regulation of expression of anorexigenic neuropeptides pro-opiomelanocortin/α-melanocyte-stimulating hormone and cocaine-amphetamine-related transcript. The effect of C75 on neuronal activity in the hypothalamus and brainstem was assessed by c-Fos expression. Consistent with its effect on neuropeptide expression, C75 blocked fasting-induced c-Fos expression in the arcuate nucleus (Arc), lateral hypothalamic area (LHA), and paraventricular nucleus (PVN) 10–24 h after i.p. injection. However, i.p. C75 induced a rapid (≤2-h) c-Fos expression in the nucleus of the solitary tract (NTS) and area postrema of the brainstem but not in the Arc or LHA. Intracerebroventricular administration of C75 rapidly induced c-Fos expression in the Arc, PVN, and NTS, supporting a central role of C75 in the regulation of food intake. Thus, suppression of food intake by C75 administered i.p. seems to be mediated in two phases, a rapid initial phase via the NTS/area postrema of the brainstem and a delayed phase via the Arc, LHA, and PVN of the hypothalamus. The delayed effect of C75 on the Arc, LHA, and PVN correlates well with its ability to interfere with the fasting-induced effects on the expression of key orexigenic (neuropeptide Y and agouti-related protein) and anorexigenic (pro-opiomelanocortin/α-melanocyte-stimulating hormone and cocaine-amphetamine-related transcript) messages in the hypothalamus. PMID:12724522

  11. Fatty acids, inflammation and immune responses.

    PubMed

    Zurier, R B

    1993-01-01

    Evidence obtained from experiments in vitro and in vivo suggests that certain unsaturated fatty acids (FA) may be safe and effective antiinflammatory and immunomodulatory agents. Generation of a unique eicosanoid profile with different biological effects by administration of FA precursors other than arachidonic acid is one approach under investigation. In addition to their role as eicosanoid precursors, FA are of major importance in maintaining cell membrane structure, are key determinants of membrane bound enzyme activity and receptor expression. FA can exert these functions directly and therefore may themselves be important regulators of immune responses. For example, certain FA influence cytokine production and proliferation of human T lymphocytes in a manner that is direct and not due to their conversion to eicosanoids. The observations indicate that FA can modulate immune responses by acting directly on T-cells and suggest that alteration of cellular FA may be a worthwhile approach to control of inflammation. PMID:8424124

  12. Mitochondrial fatty acid synthesis in Trypanosoma brucei.

    PubMed

    Stephens, Jennifer L; Lee, Soo Hee; Paul, Kimberly S; Englund, Paul T

    2007-02-16

    Whereas other organisms utilize type I or type II synthases to make fatty acids, trypanosomatid parasites such as Trypanosoma brucei are unique in their use of a microsomal elongase pathway (ELO) for de novo fatty acid synthesis (FAS). Because of the unusual lipid metabolism of the trypanosome, it was important to study a second FAS pathway predicted by the genome to be a type II synthase. We localized this pathway to the mitochondrion, and RNA interference (RNAi) or genomic deletion of acyl carrier protein (ACP) and beta-ketoacyl-ACP synthase indicated that this pathway is likely essential for bloodstream and procyclic life cycle stages of the parasite. In vitro assays show that the largest major fatty acid product of the pathway is C16, whereas the ELO pathway, utilizing ELOs 1, 2, and 3, synthesizes up to C18. To demonstrate mitochondrial FAS in vivo, we radio-labeled fatty acids in cultured procyclic parasites with [(14)C]pyruvate or [(14)C]threonine, either of which is catabolized to [(14)C]acetyl-CoA in the mitochondrion. Although some of the [(14)C]acetyl-CoA may be utilized by the ELO pathway, a striking reduction in radiolabeled fatty acids following ACP RNAi confirmed that it is also consumed by mitochondrial FAS. ACP depletion by RNAi or gene knockout also reduces lipoic acid levels and drastically decreases protein lipoylation. Thus, octanoate (C8), the precursor for lipoic acid synthesis, must also be a product of mitochondrial FAS. Trypanosomes employ two FAS systems: the unconventional ELO pathway that synthesizes bulk fatty acids and a mitochondrial pathway that synthesizes specialized fatty acids that are likely utilized intramitochondrially. PMID:17166831

  13. Stereoselective oxidation of regioisomeric octadecenoic acids by fatty acid dioxygenases

    PubMed Central

    Oliw, Ernst H.; Wennman, Anneli; Hoffmann, Inga; Garscha, Ulrike; Hamberg, Mats; Jernern, Fredrik

    2011-01-01

    Seven Z-octadecenoic acids having the double bond located in positions 6Z to 13Z were photooxidized. The resulting hydroperoxy-E-octadecenoic acids [HpOME(E)] were resolved by chiral phase-HPLC-MS, and the absolute configurations of the enantiomers were determined by gas chromatographic analysis of diastereoisomeric derivatives. The MS/MS/MS spectra showed characteristic fragments, which were influenced by the distance between the hydroperoxide and carboxyl groups. These fatty acids were then investigated as substrates of cyclooxygenase-1 (COX-1), manganese lipoxygenase (MnLOX), and the (8R)-dioxygenase (8R-DOX) activities of two linoleate diol synthases (LDS) and 10R-DOX. COX-1 and MnLOX abstracted hydrogen at C-11 of (12Z)-18:1 and C-12 of (13Z)-18:1. (11Z)-18:1 was subject to hydrogen abstraction at C-10 by MnLOX and at both allylic positions by COX-1. Both allylic hydrogens of (8Z)-18:1 were also abstracted by 8R-DOX activities of LDS and 10R-DOX, but only the allylic hydrogens close to the carboxyl groups of (11Z)-18:1 and (12Z)-18:1. 8R-DOX also oxidized monoenoic C14-C20 fatty acids with double bonds at the (9Z) position, suggesting that the length of the omega end has little influence on positioning for oxygenation. We conclude that COX-1 and MnLOX can readily abstract allylic hydrogens of octadecenoic fatty acids from C-10 to C-12 and 8R-DOX from C-7 and C-12. PMID:21852690

  14. Effect of n-3 and n-6 Polyunsaturated Fatty Acids on Microsomal P450 Steroidogenic Enzyme Activities and In Vitro Cortisol Production in Adrenal Tissue From Yorkshire Boars.

    PubMed

    Xie, Xuemei; Wang, Xudong; Mick, Gail J; Kabarowski, Janusz H; Wilson, Landon Shay; Barnes, Stephen; Walcott, Gregory P; Luo, Xiaoping; McCormick, Kenneth

    2016-04-01

    Dysregulation of adrenal glucocorticoid production is increasingly recognized to play a supportive role in the metabolic syndrome although the mechanism is ill defined. The adrenal cytochrome P450 (CYP) enzymes, CYP17 and CYP21, are essential for glucocorticoid synthesis. The omega-3 and omega-6 polyunsaturated fatty acids (PUFA) may ameliorate metabolic syndrome, but it is unknown whether they have direct actions on adrenal CYP steroidogenic enzymes. The aim of this study was to determine whether PUFA modify adrenal glucocorticoid synthesis using isolated porcine microsomes. The enzyme activities of CYP17, CYP21, 11β-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase (H6PDH), and CYP2E1 were measured in intact microsomes treated with fatty acids of disparate saturated bonds. Cortisol production was measured in a cell-free in vitro model. Microsomal lipid composition after arachidonic acid (AA) exposure was determined by sequential window acquisition of all theoretical spectra-mass spectrometry. Results showed that adrenal microsomal CYP21 activity was decreased by docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid, α-linolenic acid, AA, and linoleic acid, and CYP17 activity was inhibited by DPA, DHA, eicosapentaenoic acid, and AA. Inhibition was associated with the number of the PUFA double bonds. Similarly, cortisol production in vitro was decreased by DPA, DHA, and AA. Endoplasmic enzymes with intraluminal activity were unaffected by PUFA. In microsomes exposed to AA, the level of AA or oxidative metabolites of AA in the membrane was not altered. In conclusion, these observations suggest that omega-3 and omega-6 PUFA, especially those with 2 or more double bonds (DPA, DHA, and AA), impede adrenal glucocorticoid production. PMID:26889941

  15. Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPAR α/γ activity in microvascular endothelial cells.

    PubMed

    Madonna, Rosalinda; Salerni, Sara; Schiavone, Deborah; Glatz, Jan F; Geng, Yong-Jian; De Caterina, Raffaele

    2011-09-01

    Microvascular dysfunction occurs in insulin resistance and/or hyperinsulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPARα/γ-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), ± different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10(-8) and 10(-7) M) time-dependently increased DiI-oxLDL uptake and CD36 surface expression (by 30 ± 13%, p<0.05 vs. untreated control after 24 hours incubation), as assessed by ELISA and flow cytometry, an effect that was potentiated by the PI3-kinase inhibitor wortmannin and reverted by the ERK1/2 inhibitor PD98059 and the PPARα/γ antagonist GW9662. A ≥ 24 hour exposure to 50 μM DHA or EPA, but not other FA, blunted both the constitutive (by 23 ± 3% and 29 ± 2%, respectively, p<0.05 for both) and insulin-induced CD36 expressions (by 45 ± 27 % and 12 ± 3 %, respectively, p<0.05 for both), along with insulin-induced uptake of DiI-oxLDL and the downregulation of phosphorylated endothelial nitric oxide synthase (P-eNOS). At gel shift assays, DHA reverted insulin-induced basal and oxLDL-stimulated transactivation of PPRE and DNA binding of PPARα/γ and NF-κB. In conclusion, omega-3 fatty acids blunt the increased CD36 expression and activity promoted by high concentrations of insulin. Such mechanisms may be the basis for the use of omega-3 fatty acids in diabetic microvasculopathy. PMID:21727988

  16. Oxidation of fatty aldehydes to fatty acids by Escherichia coli cells expressing the Vibrio harveyi fatty aldehyde dehydrogenase (FALDH).

    PubMed

    Buchhaupt, Markus; Guder, Jan; Sporleder, Fenja; Paetzold, Melanie; Schrader, Jens

    2013-03-01

    Fatty acids represent an important renewable feedstock for the chemical industry. To enable biotechnological one carbon truncations of fatty acids, the enzymes α-dioxygenase and fatty aldehyde dehydrogenase (FALDH) have to be combined in a two-step process. We expressed an FALDH from V. harveyi in E. coli and characterized its substrate spectrum with a focus on the number and position of double bonds in the fatty aldehyde molecules. Synthesis of the expected fatty acid products was proven by analysis of whole cell biotransformation products. Coexpression of a H(2)O-forming NADPH oxidase (NOX) from Lactobacillus sanfranciscensis led to the implementation of a cofactor regeneration cycle in in vitro oxidation experiments. The presence of NOX in whole cell biotransformations improved reaction velocity but did not result in higher product yields. We could further demonstrate that at least part of the endogenous NAD(P)(+) regeneration capacity in the resting cells results from the respiratory chain. The whole cell catalyst with the high broad range FALDH activity described here is an important biotechnological module for lipid biotransformation processes, especially the shortening of fatty acids. PMID:23180547

  17. Omega-3 fatty acids and athletics.

    PubMed

    Simopoulos, Artemis P

    2007-07-01

    Human beings evolved consuming a diet that contained about equal amounts of y-6 and y-3 essential fatty acids. Today, in Western diets, the ratio of y-6 to y-3 fatty acids ranges from approximately 10:1 to 20:1 instead of the traditional range of 1:1 to 2:1. Studies indicate that a high intake of y-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction, and decreases in bleeding time. y-3 fatty acids, however, have anti-inflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. Excessive radical formation and trauma during high-intensity exercise leads to an inflammatory state that is made worse by the increased amount of y-6 fatty acids in Western diets, although this can be counteracted by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For the majority of athletes, especially those at the leisure level, general guidelines should include EPA and DHA of about 1 to 2 g/d at a ratio of EPA:DHA of 2:1. PMID:17617998

  18. Control of bovine hepatic fatty acid oxidation

    SciTech Connect

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-09-01

    Fatty acid oxidation by bovine liver slices and mitochondria was examined to determine potential regulatory sites of fatty acid oxidation. Conversion of 1-(/sup 14/C)palmitate to /sup 14/CO/sub 2/ and total (/sup 14/C)acid-soluble metabolites was used to measure fatty acid oxidation. Oxidation of palmitate (1 mM) was linear in both liver slice weight and incubation time. Carnitine stimulated palmitate oxidation; 2 mM dl-carnitine produced maximal stimulation of palmitate oxidation to both CO/sup 2/ and acid-soluble metabolites. Propionate (10 mM) inhibited palmitate oxidation by bovine liver slices. Propionate (.5 to 10 mM) had no effect on palmitate oxidation by mitochondria, but malonyl Coenzyme A, the first committed intermediate of fatty acid synthesis, inhibited mitochondrial palmitate oxidation (inhibition constant = .3 ..mu..M). Liver mitochonndrial carnitine palmitoyltransferase exhibited Michaelis constants for palmitoyl Coenzyme A and l-carnitine of 11.5 ..mu..M and .59 mM, respectively. Long-chain fatty acid oxidation in bovine liver is regulated by mechanisms similar to those in rats but adapted to the unique digestive physiology of the bovine.

  19. Lipid metabolism. Evidence of a ?-oxidation pathway for saturated fatty acids

    PubMed Central

    Dimick, P. S.; Walker, N. J.; Patton, Stuart

    1969-01-01

    1. Specific radioactivities of milk triglyceride fatty acids and ?- and ?-hydroxy fatty acids were measured after the intramammary infusion of [1-14C]acetate, ?-hydroxy[1-14C]laurate and [1-14C]laurate as their sodium salts into fed lactating goats. 2. Net incorporations of the radioactive tracer into the total milk lipids were comparable, being 16, 17 and 21% of the label infused respectively. 3. The specific radioactivities of the C4C8 fatty acids after [1-14C]acetate infusion were lower than those of the C10C14 fatty acids. 4. After ?-hydroxy[1-14C]laurate administration the milk triglyceride fatty acids were labelled and their specific radioactivities were characterized by decreasing values with increasing chain length of the fatty acids, implicating C4 unit incorporation. 5. The ?- and ?-hydroxy fatty acids isolated after [1-14C]laurate infusion were highly labelled and the milk triglyceride fatty acids, other than laurate, exhibited a labelling pattern similar to that of the fatty acids derived from the radioactive ?-hydroxy fatty acid. 6. Evidence is presented for the existence of saturated fatty acid ?-oxidation in the mammary gland, in which the ?- and ?-hydroxy fatty acids are active intermediates. PMID:5774468

  20. Importance of fatty acids in the perinatal period.

    PubMed

    Demmelmair, Hans; Koletzko, Berthold

    2015-01-01

    Long-chain polyunsaturated fatty acids (LC-PUFAs) influence a variety of cellular and physiological processes during the perinatal period by serving as membrane components, precursors of eicosanoids and docosanoids, and nuclear receptor activators. These processes include the growth of neural cells and signal transduction, the growth and differentiation of adipocytes, and the function of regulatory T cells. LC-PUFA levels depend on these fatty acids' dietary availability and their endogenous synthesis from essential fatty acids, which is known to differ among subjects according to fatty acid desaturase genotype. Intrauterine placental mechanisms support the preferential transfer of LC-PUFAs from the mother to the foetus. After birth, breast milk provides arachidonic acid and docosahexaenoic acid, although not in amounts that can prevent lower percentages in infant plasma than in umbilical cord blood plasma. The available epidemiological data suggest associations of perinatal LC-PUFAs with later body weight, the risk of allergic diseases and cognitive performance. Randomised clinical trials that compare different maternal or infant intakes of n-3 LC-PUFAs or combinations of n-3 and n-6 fatty acids so far have not led to firm conclusions about the optimal LC-PUFA status of pregnant women or infants, but there are good indications of beneficial effects of a higher pre- or postnatal docosahexaenoic acid status on visual function and asthma risk. PMID:25471800

  1. Effect of media compositions on α-glucosidase inhibitory activity, growth and fatty acid content in mycelium extracts of Colletotrichum sp. TSC13 from Taxus Sumatrana (Miq.) de Laub.

    PubMed

    Artanti, Nina; Tachibana, Sanro; Kardono, Leonardus B S

    2014-07-01

    The active α-glucosidase inhibitor compounds in the endophytic fungus Colletotrichum sp. TSC13 were found to be the unsaturated fatty acids (oleic, linoleic and linolenic acids). These compounds have potential as antidiabetic agents. The aim of the present study is to investigate the effects of various media composition on growth (mycelium dry weight) and the fatty acids content (μg mg(-1) mycelium DW) of Colletotrichum sp. TSC13 in relation to its α-glucosidase inhibitory activity. For that purpose, the experiments were set up by varying the carbon and nitrogen sources, metal ions and desaturase and fatty acid synthase inhibitors in the media. Colletotrichum sp. TSC13 grown on potato dextrose broth (PDB) was used as control. The α-glucosidase inhibitory activities were (range from 43.9 ± 2.5 to 88.6 ± 5.2%) at 10 μg mL(-1). This activity seemed to correlate with the unsaturated fatty acids content of the samples. Different sugars as carbon source experiment showed that xylose gave the highest growth (938.7 ± 141.6 mg). However, the highest fatty acids content was obtained from fructose medium which containing linoleic acid (38.8 ± 4.9 μ g mg(-1) DW). Soluble starch gave better growth (672.5 ± 62.3 mg) but very low fatty acids content (2.8 ± 0.1 μg mg(-1) DW) was obtained. Yeast extract was the best nitrogen source. Fatty acids production was better as compared to beef extract and soytone. This is the first report of various media compositions on fatty acids content in Colletotrichum sp. TSC13 in relation to its α-glucosidase inhibitory activity. PMID:26035936

  2. The relationship between fatty acid profiles in milk identified by Fourier transform infrared spectroscopy and onset of luteal activity in Norwegian dairy cattle.

    PubMed

    Martin, A D; Afseth, N K; Kohler, A; Randby, Å; Eknæs, M; Waldmann, A; Dørum, G; Måge, I; Reksen, O

    2015-08-01

    To investigate the feasibility of milk fatty acids as predictors of onset of luteal activity (OLA), 87 lactations taken from 73 healthy Norwegian Red cattle were surveyed over 2 winter housing seasons. The feasibility of using frozen milk samples for dry-film Fourier transform infrared (FTIR) determination of milk samples was also tested. Morning milk samples were collected thrice weekly (Monday, Wednesday, Friday) for the first 10 wk in milk (WIM). These samples had bronopol (2-bromo-2-nitropropane-1,3-diol) added to them before being frozen at -20°C, thawed, and analyzed by ELISA to determine progesterone concentration and the concentrations of the milk fatty acids C4:0, C14:0, C16:0, C18:0, and cis-9 C18:1 as a proportion of total milk fatty acid content using dry-film FTIR, and averaged by WIM. Onset of luteal activity was defined as the first day that milk progesterone concentrations were >3 ng/mL for 2 successive measurements; the study population was categorized as early (n=47) or late (n=40) OLA, using the median value of 21 DIM as the cutoff. Further milk samples were collected 6 times weekly, from morning and afternoon milkings, these were pooled by WIM, and one proportional sample was analyzed fresh for fat, protein, and lactose content by the dairy company Tine SA, using traditional FTIR spectrography in the wet phase of milk. Daily energy-balance calculations were performed in 42 lactations and averaged by WIM. Animals experiencing late OLA had a more negative energy balance in WIM 1, 3, 4, and 5, with the greatest differences been seen in WIM 3 and 4. A higher proportion of the fatty acids were medium chained, C14:0 and C16:0, in the early than in the late OLA group from WIM 1. In WIM 4, the proportion of total fatty acid content that was C16:0 predicted late OLA, with 74% sensitivity and 80% specificity. The long-chain proportion of the fatty acids C18:0 and cis-9 C18:1 were lower in the early than in the late OLA group. Differences were greatest in WIM 4 and 5. Differences in concentrations of cis-9 C18:1 were seen between the groups from WIM 1. No relationship was seen between OLA and milk concentrations of either protein or fat, or between OLA and the milk fat:protein ratio. The differences in milk fatty acid proportions between the 2 groups are most likely related to differences in energy balance. The study shows that frozen milk samples can be tested for fatty acids by FTIR spectroscopy and that FTIR spectroscopy of milk can be used to provide real-time information about cow reproductive function. PMID:26004832

  3. Acute regulation of 5?-AMP-activated protein kinase by long-chain fatty acid, glucose and insulin in rat primary adipocytes

    PubMed Central

    Hebbachi, Abdel; Saggerson, David

    2012-01-01

    Palmitate increased AMPK (5?-AMP-activated protein kinase) activity, glucose utilization and 2-DOG (2-deoxyglucose) transport in rat adipocytes. All three effects were blocked by the AMPK inhibitor Compound C, leading to the conclusion that in response to an increase in long-chain NEFA (non-esterified fatty acid) concentration AMPK mediated an enhancement of adipocyte glucose transport, thereby providing increased glycerol 3-phosphate for FA (fatty acid) esterification to TAG (triacylglycerol). Activation of AMPK in response to palmitate was not due to an increase in the adipocyte AMP:ATP ratio. Glucose decreased AMPK activity and effects of palmitate and glucose on AMPK activity were antagonistic. While insulin had no effect on basal AMPK activity insulin did decrease AMPK activity in the presence of palmitate and also decreased the percentage effectiveness of palmitate to increase the transport of 2-DOG. It is suggested that activation of adipocyte AMPK by NEFA, as well as decreasing the activity of hormone-sensitive lipase, could modulate adipose tissue dynamics by increasing FA esterification and, under certain circumstances, FA synthesis. PMID:23095119

  4. Synergistic effect of natural compounds on the fatty acid-induced autophagy of activated hepatic stellate cells.

    PubMed

    Lee, Kuan-Wei; Thiyagarajan, Varadharajan; Sie, Huei-Wun; Cheng, Ming-Fan; Tsai, May-Jywan; Chia, Yi-Chen; Weng, Ching-Feng

    2014-09-01

    Autophagy, a lysosomal pathway to maintain cellular homeostasis, is mediated via the mammalian target of rapamycin (mTOR)-dependent pathways. Hepatic stellate cells (HSCs), previously termed fat- or vitamin A-storing cells, can transdifferentiate into myofibroblast-like cells and are the most relevant cell type for overproduction of extracellular matrix (ECM) and development of liver fibrosis during injury. However, the role of autophagy in fat metabolism of HSCs remains unclear. This study investigates the regulatory effect of natural compounds on fatty acid-induced autophagy pathways of nonchemical-induced HSC (NHSC) and thioacetamide-induced HSC. Oleic acid (OA) and palmitic acid (PA) have shown a significant effect on cell proliferation with oil red O staining and Western blot confirming that OA and PA induce fat storage ability and autophagy protein expression in NHSC. Natural compounds rutin, curcumin, antroquinonol and benzyl cinnamate treatment have shown no effect on the autophagy protein expression. Nevertheless, cells pretreated with OA and PA then treated with rutin, curcumin, antroquinonol and benzyl cinnamate could significantly induce the light chain I/II (LC3 I/II) protein expression. In mTOR-dependent pathway, the PI3K-Class I, Akt, and p-mTOR proteins were decreased with PA treatment. However, there were no significant changes in PI3K-Class III and Beclin-1 protein expressions found to imply that this autophagy is unrelated to the mTOR-independent pathway. Taken together, the present study unveils rutin and curcumin as a possible effective stimulation for fatty acid-induced autophagy via mTOR-dependent pathways in NHSC. We further suggest the benefits of these natural compounds for alleviating liver fibrosis. PMID:24857031

  5. Evaluation of chemical constitute, fatty acids and antioxidant activity of the fruit and seed of sea buckthorn (Hippophae rhamnoides L.) grown wild in Iran.

    PubMed

    Saeidi, Keramatollah; Alirezalu, Abolfazl; Akbari, Zahra

    2016-02-01

    In this investigation, the chemical compositions of berries from sea buckthorn were studied. The amount of ascorbic acid and ?-carotene determined by HPLC was 170mg/100g FW and 0.20mg/g FW, respectively. Total phenols, anthocyanins, acidity and total soluble solids (TSS) contents were 247mgGAE/100gFW, 3mg/L (cyanidin-3-glucoside), 5.32% and 13.8%, respectively. Fruit antioxidant activity determined by the ferric reducing ability of plasma (FRAP) method was 24.85mMFe/100gFW. Results confirmed the presence of six dominant fatty acids (determined by GC) in fruit including linoleic (34.2%), palmitoleic (21.37%), palmitic (17.2%), oleic (12.8%), linolenic (5.37%) and stearic acid (1.67%). Five dominant fatty acids of the seeds were linoleic (42.36%), linolenic (21.27%), oleic (21.34%), palmitic (6.54%) and stearic acid (2.54%). The nitrogen content was 3.96%. The P, K, Ca, Mg, Fe, Zn, Mn, Cu, Cd and Cl contents of fruit were 491, 1674, 1290, 990, 291, 29.77, 108.37, 17.87, 0.021 and 2.18mg/kgDW, respectively. PMID:26214249

  6. Amino and fatty acids in carbonaceous meteorites

    NASA Technical Reports Server (NTRS)

    Kvenvolden, K. A.

    1974-01-01

    Analyses of two carbonaceous meteorites have provided much of the latest evidence which seems to support Oparin's theory on the origin of life. The meteorites involved are the Murray meteorite, which fell in 1950, and the Murchison meteorite, which fell in 1969. The amino acids in the two meteorites are similar in composition. Eight of the twenty amino acids found belong to amino acids present in proteins. A number of monocarboxylic and dicarboxylic fatty acids were also found in the meteorites.

  7. Hypothalamic-pituitary-adrenal axis activation and immune regulation in heat-stressed sheep after supplementation with polyunsaturated fatty acids.

    PubMed

    Caroprese, M; Ciliberti, M G; Annicchiarico, G; Albenzio, M; Muscio, A; Sevi, A

    2014-07-01

    The aim of this study was to assess the effects of supplementation with polyunsaturated fatty acids from different sources on immune regulation and hypothalamic-pituitary-adrenal (HPA) axis activation in heat-stressed sheep. The experiment was carried out during the summer 2012. Thirty-two Comisana ewes were divided into 4 groups (8 sheep/group): (1) supplemented with whole flaxseed (FS); (2) supplemented with Ascophyllum nodosum (AG); (3) supplemented with a combination of flaxseed and A. nodosum (FS+AG); and (4) control (C; no supplementation). On d 22 of the experiment, cortisol concentrations in sheep blood were measured after an injection of ACTH. Cellular immune response was evaluated by intradermic injection of phytohemagglutinin (PHA) at 0, 15, and 30 d of the trial. Humoral response to ovalbumin (OVA) was measured at 0, 15, and 30 d. At 0, 15, and 30 d of the experiment, blood samples were collected from each ewe to determine production of T-helper (Th)1 cytokines (IL-12 and IFN-γ), and Th2 cytokines (IL-10, IL-4, IL-13), and concentrations of heat shock proteins (HSP) 70 and 90. Ewes supplemented with flaxseed alone had greater cortisol concentrations and a longer-lasting cell-mediated immune response compared with ewes in the control and other groups. Anti-OVA IgG concentrations increased in all groups throughout the trial, even though ewes in the FS+AG group had the lowest anti-OVA IgG concentrations at 15 d. The level of IL-10 increased in all groups throughout the experiment; the FS+AG group had the lowest IL-13 concentration at 15 and 30 d. The concentration of HSP 70 increased in AG ewes at the end of the experiment and decreased in FS ewes, whereas that of HSP 90 increased in FS ewes compared with FS+AG ewes. Flaxseed supplementation was found to influence in vivo HPA activation in heat-stressed sheep, resulting in increased cortisol concentrations, probably to meet increased energy demand for thermoregulation. Flaxseed supplementation also supported Th1 response via a complex cross-talk between IL-10, IL-12, and IFN-γ production. PMID:24792803

  8. Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2ARE pathway

    PubMed Central

    Wang, Rui; Paul, Valerie J.; Luesch, Hendrik

    2013-01-01

    Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an ?,?-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by AREluciferase reporter assay. We isolated three monounsaturated fatty acid (MUFA) derivatives as active components, including a new keto-type C18 fatty acid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamatecysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched with 1, which showed ARE-activating effects similar to those observed in vitro. This could be owing to this fraction's ability to stabilize Nrf2 through inhibition of Keap1-mediated Nrf2 ubiquitination and the subsequent accumulation and nuclear translocation of Nrf2. The induction of many ARE-driven antioxidant genes in vivo and most prominently in the heart agreed with the commonly recognized cardioprotective properties of MUFAs. A significant increase in Nqo1 transcript levels was also found in other mouse tissues such as the brain, lung, and stomach. Collectively, this study provides new insight into why consumption of dietary seaweed may have health benefits, and the identified compounds add to the list of chemopreventive dietary unsaturated fatty acids. PMID:23291594

  9. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ.

    PubMed

    Alex, Sheril; Lange, Katja; Amolo, Tom; Grinstead, Jeffrey S; Haakonsson, Anders K; Szalowska, Ewa; Koppen, Arjen; Mudde, Karin; Haenen, Daniëlle; Al-Lahham, Sa'ad; Roelofsen, Han; Houtman, René; van der Burg, Bart; Mandrup, Susanne; Bonvin, Alexandre M J J; Kalkhoven, Eric; Müller, Michael; Hooiveld, Guido J; Kersten, Sander

    2013-04-01

    Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as a circulating mediator between the gut microbiota and fat storage. Here, we show that transcription and secretion of ANGPTL4 in human T84 and HT29 colon adenocarcinoma cells is highly induced by physiological concentrations of short-chain fatty acids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor peroxisome proliferator activated receptor γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, and transactivation assays, which show activation of PPARγ but not PPARα and PPARδ by SCFA. At concentrations required for PPARγ activation and ANGPTL4 induction in colon adenocarcinoma cells, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modeling. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPARγ. Our data point to activation of PPARs as a novel mechanism of gene regulation by SCFA in the colon, in addition to other mechanisms of action of SCFA. PMID:23339868

  10. Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ

    PubMed Central

    Alex, Sheril; Lange, Katja; Amolo, Tom; Grinstead, Jeffrey S.; Haakonsson, Anders K.; Szalowska, Ewa; Koppen, Arjen; Mudde, Karin; Haenen, Daniëlle; Al-Lahham, Sa'ad; Roelofsen, Han; Houtman, René; van der Burg, Bart; Mandrup, Susanne; Bonvin, Alexandre M. J. J.; Kalkhoven, Eric; Müller, Michael; Hooiveld, Guido J.

    2013-01-01

    Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as a circulating mediator between the gut microbiota and fat storage. Here, we show that transcription and secretion of ANGPTL4 in human T84 and HT29 colon adenocarcinoma cells is highly induced by physiological concentrations of short-chain fatty acids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor peroxisome proliferator activated receptor γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, and transactivation assays, which show activation of PPARγ but not PPARα and PPARδ by SCFA. At concentrations required for PPARγ activation and ANGPTL4 induction in colon adenocarcinoma cells, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modeling. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPARγ. Our data point to activation of PPARs as a novel mechanism of gene regulation by SCFA in the colon, in addition to other mechanisms of action of SCFA. PMID:23339868

  11. PlsX deletion impacts fatty acid synthesis and acid adaptation in Streptococcus mutans.

    PubMed

    Cross, Benjamin; Garcia, Ariana; Faustoferri, Roberta; Quivey, Robert G

    2016-04-01

    Streptococcus mutans, one of the primary causative agents of dental caries in humans, ferments dietary sugars in the mouth to produce organic acids. These acids lower local pH values, resulting in demineralization of the tooth enamel, leading to caries. To survive acidic environments, Strep. mutans employs several adaptive mechanisms, including a shift from saturated to unsaturated fatty acids in membrane phospholipids. PlsX is an acyl-ACP : phosphate transacylase that links the fatty acid synthase II (FASII) pathway to the phospholipid synthesis pathway, and is therefore central to the movement of unsaturated fatty acids into the membrane. Recently, we discovered that plsX is not essential in Strep. mutans. A plsX deletion mutant was not a fatty acid or phospholipid auxotroph. Gas chromatography of fatty acid methyl esters indicated that membrane fatty acid chain length in the plsX deletion strain differed from those detected in the parent strain, UA159. The deletion strain displayed a fatty acid shift similar to WT, but had a higher percentage of unsaturated fatty acids at low pH. The deletion strain survived significantly longer than the parent strain when cultures were subjected to an acid challenge of pH 2.5.The ΔplsX strain also exhibited elevated F-ATPase activity at pH 5.2, compared with the parent. These results indicate that the loss of plsX affects both the fatty acid synthesis pathway and the acid-adaptive response of Strep. mutans. PMID:26850107

  12. Free nitrous acid serving as a pretreatment method for alkaline fermentation to enhance short-chain fatty acid production from waste activated sludge.

    PubMed

    Zhao, Jianwei; Wang, Dongbo; Li, Xiaoming; Yang, Qi; Chen, Hongbo; Zhong, Yu; Zeng, Guangming

    2015-07-01

    Alkaline condition (especially pH 10) has been demonstrated to be a promising method for short-chain fatty acid (SCFA) production from waste activated sludge anaerobic fermentation, because it can effectively inhibit the activities of methanogens. However, due to the limit of sludge solubilization rate, long fermentation time is required but SCFA yield is still limited. This paper reports a new pretreatment method for alkaline fermentation, i.e., using free nitrous acid (FNA) to pretreat sludge for 2 d, by which the fermentation time is remarkably shortened and meanwhile the SCFA production is significantly enhanced. Experimental results showed the highest SCFA production of 370.1 mg COD/g VSS (volatile suspended solids) was achieved at 1.54 mg FNA/L pretreatment integration with 2 d of pH 10 fermentation, which was 4.7- and 1.5-fold of that in the blank (uncontrolled) and sole pH 10 systems, respectively. The total time of this integration system was only 4 d, whereas the corresponding time was 15 d in the blank and 8 d in the sole pH 10 systems. The mechanism study showed that compared with pH 10, FNA pretreatment accelerated disruption of both extracellular polymeric substances and cell envelope. After FNA pretreatment, pH 10 treatment (1 d) caused 38.0% higher substrate solubilization than the sole FNA, which indicated that FNA integration with pH 10 could cause positive synergy on sludge solubilization. It was also observed that this integration method benefited hydrolysis and acidification processes. Therefore, more SCFA was produced, but less fermentation time was required in the integrated system. PMID:25935366

  13. Fatty acid metabolism and thyroid hormones

    PubMed Central

    Sayre, Naomi L.; Lechleiter, James D.

    2013-01-01

    The importance of thyroid hormone signaling in the acute regulation of metabolic activity has been recognized for decades. Slowly, the underlying mechanisms responsible for this activity are being elucidated. A prominent characteristic of thyroid signaling is rapid increases in oxygen consumption and ATP production. This discovery implicated a non-genomic regulation of mitochondrial metabolism by thyroid hormones. Another important clue came from the discovery that thyroid hormones stimulated fatty acid oxidation (FAO) in a variety of tissues in a receptor-dependent, but transcriptional-independent manner. Recently, key linkages between thyroid hormone signaling and specific mitochondrial-targeted pathways have been discovered. This review focuses on the molecular mechanisms by which mitochondrial FAO can be increased through thyroid hormone signaling. The roles of both the full-length and shortened mitochondrial isoforms of thyroid hormone receptor will be discussed. Additionally, the impact of thyroid hormone signaling on dyslipidemias such as obesity, type II diabetes, and fatty liver disease will be considered. PMID:24436572

  14. Methoxylated fatty acids in Blumeria graminis conidia.

    PubMed

    Muchembled, Jérôme; Sahraoui, Anissa Lounès-Hadj; Laruelle, Frédéric; Palhol, Fabien; Couturier, Daniel; Grandmougin-Ferjani, Anne; Sancholle, Michel

    2005-04-01

    The total fatty acids (FA) composition of Blumeria graminis f.sp. tritici conidia, the causal agent of wheat powdery mildew, was analyzed as a function of their age. A total of 19 FA (C12-C24 saturated and unsaturated) and unusual methoxylated fatty acids (mFA) were detected in young, intermediate and old conidia. Two very long chain methoxylated FA were identified by GC-MS as 3-methoxydocosanoic and 3-methoxytetracosanoic acids. Medium chain FA were predominant in young conidia (75%, including 13% of mFA) while very long chain fatty acids constituted the major compounds in old conidia (74%, including 30% of mFA). We have shown for the first time that the total FA composition is strongly correlated with the age of B. graminis f.sp. tritici (Bgt) conidia. PMID:15797605

  15. 21 CFR 172.860 - Fatty acids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... food additive consists of one or any mixture of the following straight-chain monobasic carboxylic acids... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Fatty acids. 172.860 Section 172.860 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR...

  16. Effects of conjugated linoleic acid. 1. Fatty acid modification of yolks and neonatal fatty acid metabolism.

    PubMed

    Latour, M A; Devitt, A A; Meunier, R A; Stewart, J J; Watkins, B A

    2000-06-01

    The purpose of this study was to evaluate the effects of conjugated linoleic acids (CLA) on neonatal fatty acid metabolism. In this study, layer hens (n = 40) were divided into four equal groups and subjected to the following treatments. Group A served as the control group, Group B received 1 g CLA every other day, Group C received 1 g CLA every 4th d, and Group D was sham-supplemented with 1 g safflower oil every other day. After 4 mo of feeding, Group B hens exhibited an increase in BW and egg size; however, there were no differences noted in feed consumption among the various treatment groups. At the same time, hens were inseminated with a constant dose of pooled rooster semen to evaluate changes in chick liver and yolk fatty acid metabolism during neonatal growth. At hatch and through 6 d of age, there were no significant differences in breakout data (fertility and numbers of early-, mid-, or late-dead chicks) or chick BW, respectively. However, Group B chicks exhibited an increase in liver 18:3n3 and 22:1n9 and a decrease in 20:3n6 and 22:5n3 fatty acids when compared with chicks from Groups A and D. Also noted for Group B chicks, yolk 18:0 fatty acid was higher than that for Group A and D chicks. These results suggest that CLA alters lipid metabolism in growing chicks. PMID:10875761

  17. 2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani.

    PubMed

    Carballeira, Nstor M; Cartagena, Michelle; Sanabria, David; Tasdemir, Deniz; Prada, Christopher F; Reguera, Rosa M; Balaa-Fouce, Rafael

    2012-10-01

    2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC(50)=5.30.7?M. The potency of LdTopIB inhibition follows the trend 2-ODA>2-HDA>2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC(50)=11.0?M), but it was less effective against other protozoa, Trypanosoma cruzi (IC(50)=48.1?M) and Trypanosoma brucei rhodesiense (IC(50)=64.5?M). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA>2-HDA>2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. PMID:22932312

  18. Modulation of fatty acid oxidation alters contact hypersensitivity to urushiols: role of aliphatic chain beta-oxidation in processing and activation of urushiols.

    PubMed

    Kalergis, A M; López, C B; Becker, M I; Díaz, M I; Sein, J; Garbarino, J A; De Ioannes, A E

    1997-01-01

    Lithraea caustica, or litre, a tree of the Anacardiaceae family that is endemic to the central region of Chile, induces a severe contact dermatitis in susceptible human beings. The allergen was previously isolated and characterized as a 3-(pentadecyl-10-enyl) catechol, a molecule belonging to the urushiol group of allergens isolated from poison ivy and poison oak plants. Because urushiols are pro-electrophilic haptens, it is believed that the reactive species are generated intracellularly by skin keratinocytes and Langerhans cells. The active species are presumed to modify self proteins which, after proteolytic processing, would generate immunogenic peptides carrying the hapten. The presence of a 15-carbon-length hydrophobic chain should impair antigen presentation of self-modified peptides by class I MHC molecules, either by steric hindrance or by limiting their sorting to the ER lumen. We have proposed that the shortening of the aliphatic chain by beta-oxidation within peroxisomes and/or mitochondria should be a requirement for the antigen presentation process. To test this hypothesis we investigated the effect of drugs that modify the fatty acid metabolism on urushiol-induced contact dermatitis in mice. Clofibrate, a peroxisomal proliferator in mice, increased the immune response to the urushiols from litre by 50%. Conversely, tetradecyl glycidic acid, an inhibitor of the uptake of fatty acids by mitochondria, decreased the hypersensitivity to the hapten. An increase in the level in glutathione by treatment of the animals with 2-oxotiazolidin-4-carboxilic acid lowered the response. Those findings strongly support a role for the fatty acid oxidative metabolism in the processing and activation of urushiols in vivo. PMID:8980288

  19. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

    PubMed

    Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

    2016-06-01

    Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH. PMID:27000704

  20. Production of hydroxylated fatty acids in genetically modified plants

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank; Boddupalli, Sekhar S.

    2011-08-23

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  1. Production of hydroxylated fatty acids in genetically modified plants

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank; Boddupalli, Sekhar S.

    2005-08-30

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  2. Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance

    PubMed Central

    Warensjö, Eva; Rosell, Magdalena; Hellenius, Mai-Lis; Vessby, Bengt; De Faire, Ulf; Risérus, Ulf

    2009-01-01

    Fatty acid composition of serum lipids and adipose tissue triacylglycerols (AT-TAG) partly reflect dietary fatty acid intake. The fatty acid composition is, besides the diet, also influenced by desaturating enzymes that can be estimated using product-to-precursor fatty acid ratios. The interrelationships between desaturase indices derived from different serum lipid fractions and adipose tissue are unclear, as well as their associations with obesity and insulin resistance. We aimed to investigate cross-sectional correlations between desaturase indices as measured in serum lipid fractions (phospholipids; PL and free fatty acids; FFA) and in adipose tissue (AT-TAG). In a population-based sample of 301 healthy 60-year-old men various desaturase indices were assessed: stearoyl-CoA-desaturase (16:1n-7/16:0; SCD-16 and 18:1n-9/18:0; SCD-18, respectively), delta-6-desaturase (20:3n-6/18:2n-6; D6D) and delta-5-desaturase (20:4n-6/20:3n-6; D5D). Correlations with BMI and insulin resistance (HOMA-IR) were also examined. SCD-16 and D5D were significantly correlated between fractions and tissues (all r > 0.30), whereas SCD-18 and D6D were not. Desaturase indices in serum FFA and AT-TAG were significantly correlated; SCD-16 (r = 0.63), SCD-18 (r = 0.37), and D5D (r = 0.43). In phospholipids, SCD-16 was positively correlated to BMI (r = 0.15), while D5D negatively to both BMI (r = -0.30) and HOMA-IR (r = -0.31), all p < 0.01. D6D in both phospholipids and AT-TAG was positively correlated to HOMA-IR and BMI (all p < 0.01). In conclusion, SCD-1 and D5D activity indices showed overall strong correlations between lipid pools. SCD-1 activity index in adipose tissue is best reflected by 16:1/16:0-ratio in serum FFA, but associations with obesity and insulin resistance differ between these pools. D5D in PL was inversely related to obesity and insulin resistance, whereas D6D index showed positive associations. PMID:19712485

  3. Association of serum fatty acid and estimated desaturase activity with hypertension in middle-aged and elderly Chinese population

    PubMed Central

    Yang, Bo; Ding, Fang; Wang, Feng-Lei; Yan, Jing; Ye, Xiong-Wei; Yu, Wei; Li, Duo

    2016-01-01

    We aimed to investigate the cross-sectional associations of serum fatty acid (FA) and related Δ-desaturase with hypertension among 2,447 community-dwellers aged 35–79 years living in Zhejiang Province, China. Individual FA was determined in serum, Δ5-desaturase (D5D) and Δ6-desaturase (D6D) activities were indirectly estimated by FA product/precursor ratios. Participants in the highest quartile of D5D component scores (20:4n–6, 20:5n–3, 22:6n–3 and D5D) have significantly lower odds of hypertension compared with individuals in the lowest (multivariate-adjusted odds ratio (OR) = 0.68, 95% CI: 0.46–0.98). When further stratified by gender, high D5D component scores were significantly associated with lower odds of hypertension in women (OR = 0.53, 95% CI: 0.35–0.80), but not in men (OR = 0.78, 95% CI: 0.52-1.18). Multivariate-adjusted prevalent OR for an interquartile increment of individual FA and estimated desaturase was 1.27 (95% CI: 1.08–1.50) for 16:0, 1.15 (95% CI: 1.01–1.30) for 16:1n–7, 0.89 (95% CI: 0.80–0.99) for 22:6n–3, 1.32 (95% CI: 1.01–1.72) for D6D (18:3n–6/18:2n–6), and 0.74 (95% CI: 0.56, 0.98) for D5D (20:4n–6/20:3n–6). Present findings suggested that high serum 22:6n–3 and D5D as well as low 16:0, 16:1n–7 and D6D were associated with a low prevalence of hypertension in this Chinese population. PMID:27006169

  4. Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates

    PubMed Central

    Zarei, Mahnaz; Fakher, Shima; Tabei, Seyed Mohammad Bagher; Javanbakht, Mohammad Hassan; Derakhshanian, Hoda; Farahbakhsh-Farsi, Payam; Sadeghi, Mohammad Reza; Mostafavi, Ebrahim; Djalali, Mahmoud

    2016-01-01

    INTRODUCTION This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications. PMID:26996784

  5. Antioxidant activity of phenolic compounds added to a functional emulsion containing omega-3 fatty acids and plant sterol esters.

    PubMed

    Espinosa, Raquel Rainho; Inchingolo, Raffaella; Alencar, Severino Matias; Rodriguez-Estrada, Maria Teresa; Castro, Inar Alves

    2015-09-01

    The effect of eleven compounds extracted from red propolis on the oxidative stability of a functional emulsion was evaluated. Emulsions prepared with Echium oil as omega 3 (ω-3 FA) source, containing 1.63 g/100mL of α-linolenic acid (ALA), 0.73 g/100 mL of stearidonic acid (SDA) and 0.65 g/100mL of plant sterol esters (PSE) were prepared without or with phenolic compounds (vanillic acid, caffeic acid, trans-cinnamic acid, 2,4-dihydroxycinnamic acid, p-coumaric acid, quercetin, trans-ferulic acid, trans,trans-farnesol, rutin, gallic acid or sinapic acid). tert-Butylhydroquinone and a mixture containing ascorbic acid and FeSO4 were applied as negative and positive controls of the oxidation. Hydroperoxide, thiobarbituric acid reactive substances (TBARS), malondialdehyde and phytosterol oxidation products (POPs) were evaluated as oxidative markers. Based on hydroperoxide and TBARS analysis, sinapic acid and rutin (200 ppm) showed the same antioxidant activity than TBHQ, representing a potential alternative as natural antioxidant to be applied in a functional emulsion containing ω-3 FA and PSE. PMID:25842314

  6. Development of Escherichia coli MG1655 strains to produce long chain fatty acids by engineering fatty acid synthesis (FAS) metabolism.

    PubMed

    Jeon, Eunyoung; Lee, Sunhee; Won, Jong-In; Han, Sung Ok; Kim, Jihyeon; Lee, Jinwon

    2011-06-10

    The goal of this research was to develop recombinant Escherichia coli to improve fatty acid synthesis (FAS). Genes encoding acetyl-CoA carboxylase (accA, accB, accC), malonyl-CoA-[acyl-carrier-protein] transacylase (fabD), and acyl-acyl carrier protein thioesterase (EC 3.1.2.14 gene), which are all enzymes that catalyze key steps in the synthesis of fatty acids, were cloned and over-expressed in E. coli MG1655. The acetyl-CoA carboxylase (ACC) enzyme catalyzes the addition of CO(2) to acetyl-CoA to generate malonyl-CoA. The enzyme encoded by the fabD gene converts malonyl-CoA to malonyl-[acp], and the EC 3.1.2.14 gene converts fatty acyl-ACP chains to long chain fatty acids. All the genes except for the EC 3.1.2.14 gene were homologous to E. coli genes and were used to improve the enzymatic activities to over-express components of the FAS pathway through metabolic engineering. All recombinant E. coli MG1655 strains containing various gene combinations were developed using the pTrc99A expression vector. To observe changes in metabolism, the in vitro metabolites and fatty acids produced by the recombinants were analyzed. The fatty acids (C16) from recombinant strains were produced 1.23-2.41 times higher than that from the wild type. PMID:22112270

  7. The nitrite-oxidizing community in activated sludge from a municipal wastewater treatment plant determined by fatty acid methyl ester-stable isotope probing.

    PubMed

    Kruse, Myriam; Zumbrägel, Sabine; Bakker, Evert; Spieck, Eva; Eggers, Till; Lipski, André

    2013-10-01

    Metabolically-active autotrophic nitrite oxidizers from activated sludge were labeled with (13)C-bicarbonate under exposure to different temperatures and nitrite concentrations. The labeled samples were characterized by FAME-SIP (fatty acid methyl ester-stable isotope probing). The compound cis-11-palmitoleic acid, which is the major lipid of the most abundant nitrite oxidizer in activated sludge, Candidatus Nitrospira defluvii, showed (13)C-incorporation in all samples exposed to 3 mM nitrite. Subsequently, the lipid cis-7-palmitoleic acid was labeled, and it indicated the activity of a nitrite oxidizer that was different from the known Nitrospira taxa in activated sludge. The highest incorporation of cis-7-palmitoleic acid label was found after incubation with a nitrite concentration of 0.3 mM at 17 and 22°C. While activity of Nitrobacter populations could not be detected by the FAME-SIP approach, an unknown nitrite oxidizer with the major lipid cis-9 isomer of palmitoleic acid exhibited (13)C-incorporation at 28°C with 30 mM nitrite. These results indicated flexibility of nitrite-oxidizing guilds in a complex community responding to different conditions. Labeled lipids so far not described for activated sludge-associated nitrifiers indicated the presence of unknown nitrite oxidizers in this habitat. The FAME-SIP-based information can be used to define appropriate conditions for the enrichment of nitrite-oxidizing guilds from complex samples. PMID:23921154

  8. Fatty acid compositions of six wild edible mushroom species.

    PubMed

    Günç Ergönül, Pelin; Akata, Ilgaz; Kalyoncu, Fatih; Ergönül, Bülent

    2013-01-01

    The fatty acids of six wild edible mushroom species (Boletus reticulatus, Flammulina velutipes var. velutipes, Lactarius salmonicolor, Pleurotus ostreatus, Polyporus squamosus, and Russula anthracina) collected from different regions from Anatolia were determined. The fatty acids were identified and quantified by gas chromatography and studied using fruit bodies. Fatty acid composition varied among species. The dominant fatty acid in fruit bodies of all mushrooms was cis-linoleic acid (18 : 2). Percentage of cis-linoleic acid in species varied from 22.39% to 65.29%. The other major fatty acids were, respectively, cis-oleic, palmitic, and stearic acids. Fatty acids analysis of the mushrooms showed that the unsaturated fatty acids were at higher concentrations than saturated fatty acids. PMID:23844377

  9. Fatty Acid Compositions of Six Wild Edible Mushroom Species

    PubMed Central

    Gn Ergnl, Pelin; Akata, Ilgaz; Kalyoncu, Fatih; Ergnl, Blent

    2013-01-01

    The fatty acids of six wild edible mushroom species (Boletus reticulatus, Flammulina velutipes var. velutipes, Lactarius salmonicolor, Pleurotus ostreatus, Polyporus squamosus, and Russula anthracina) collected from different regions from Anatolia were determined. The fatty acids were identified and quantified by gas chromatography and studied using fruit bodies. Fatty acid composition varied among species. The dominant fatty acid in fruit bodies of all mushrooms was cis-linoleic acid (18?:?2). Percentage of cis-linoleic acid in species varied from 22.39% to 65.29%. The other major fatty acids were, respectively, cis-oleic, palmitic, and stearic acids. Fatty acids analysis of the mushrooms showed that the unsaturated fatty acids were at higher concentrations than saturated fatty acids. PMID:23844377

  10. Fatty acid production in genetically modified cyanobacteria

    PubMed Central

    Liu, Xinyao; Sheng, Jie; Curtiss III, Roy

    2011-01-01

    To avoid costly biomass recovery in photosynthetic microbial biofuel production, we genetically modified cyanobacteria to produce and secrete fatty acids. Starting with introducing an acyl–acyl carrier protein thioesterase gene, we made six successive generations of genetic modifications of cyanobacterium Synechocystis sp. PCC6803 wild type (SD100). The fatty acid secretion yield was increased to 197 ± 14 mg/L of culture in one improved strain at a cell density of 1.0 × 109 cells/mL by adding codon-optimized thioesterase genes and weakening polar cell wall layers. Although these strains exhibited damaged cell membranes at low cell densities, they grew more rapidly at high cell densities in late exponential and stationary phase and exhibited less cell damage than cells in wild-type cultures. Our results suggest that fatty acid secreting cyanobacteria are a promising technology for renewable biofuel production. PMID:21482809

  11. Is There a Fatty Acid Taste?

    PubMed Central

    Mattes, Richard D.

    2010-01-01

    Taste is a chemical sense that aids in the detection of nutrients and guides food choice. A limited number of primary qualities comprise taste. Accumulating evidence has raised a question about whether fat should be among them. Most evidence indicates triacylglycerol is not an effective taste stimulus, though it clearly contributes sensory properties to foods by carrying flavor compounds and altering texture. However, there is increasing anatomical, electrophysiological, animal behavior, imaging, metabolic, and psychophysical evidence that free fatty acids are detectable when non-taste cues are minimized. Free fatty acids varying in saturation and chain length are detectable, suggesting the presence of multiple transduction mechanisms and/or a nonspecific mechanism in the oral cavity. However, confirmation of “fatty” as a taste primary will require additional studies that verify these observations are taste specific. Oral exposure to free fatty acids likely serves as a warning signal to discourage intake and influences lipid metabolism. PMID:19400700

  12. Soybean Aphid Infestation Induces Changes in Fatty Acid Metabolism in Soybean

    PubMed Central

    Kanobe, Charles; McCarville, Michael T.; O’Neal, Matthew E.; Tylka, Gregory L.; MacIntosh, Gustavo C.

    2015-01-01

    The soybean aphid (Aphis glycines Matsumura) is one of the most important insect pests of soybeans in the North-central region of the US. It has been hypothesized that aphids avoid effective defenses by inhibition of jasmonate-regulated plant responses. Given the role fatty acids play in jasmonate-induced plant defenses, we analyzed the fatty acid profile of soybean leaves and seeds from aphid-infested plants. Aphid infestation reduced levels of polyunsaturated fatty acids in leaves with a concomitant increase in palmitic acid. In seeds, a reduction in polyunsaturated fatty acids was associated with an increase in stearic acid and oleic acid. Soybean plants challenged with the brown stem rot fungus or with soybean cyst nematodes did not present changes in fatty acid levels in leaves or seeds, indicating that the changes induced by aphids are not a general response to pests. One of the polyunsaturated fatty acids, linolenic acid, is the precursor of jasmonate; thus, these changes in fatty acid metabolism may be examples of “metabolic hijacking” by the aphid to avoid the induction of effective defenses. Based on the changes in fatty acid levels observed in seeds and leaves, we hypothesize that aphids potentially induce interference in the fatty acid desaturation pathway, likely reducing FAD2 and FAD6 activity that leads to a reduction in polyunsaturated fatty acids. Our data support the idea that aphids block jasmonate-dependent defenses by reduction of the hormone precursor. PMID:26684003

  13. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance.

    PubMed

    Jang, Cholsoon; Oh, Sungwhan F; Wada, Shogo; Rowe, Glenn C; Liu, Laura; Chan, Mun Chun; Rhee, James; Hoshino, Atsushi; Kim, Boa; Ibrahim, Ayon; Baca, Luisa G; Kim, Esl; Ghosh, Chandra C; Parikh, Samir M; Jiang, Aihua; Chu, Qingwei; Forman, Daniel E; Lecker, Stewart H; Krishnaiah, Saikumari; Rabinowitz, Joshua D; Weljie, Aalim M; Baur, Joseph A; Kasper, Dennis L; Arany, Zoltan

    2016-04-01

    Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes. PMID:26950361

  14. Role of sphingomyelin and ceramide in the regulation of the activity and fatty acid specificity of group V secretory phospholipase A2

    PubMed Central

    Singh, Dev K.; Gesquiere, Laurence R.; Subbaiah, Papasani V.

    2007-01-01

    We previously showed that group V secretory phospholipase A2 (sPLA2V) is inhibited by sphingomyelin (SM), but activated by ceramide. Here we investigated the effect of sphingolipid structure on the activity and acyl specificity of sPLA2V. Degradation of HDL SM to ceramide, but not to ceramide phosphate, stimulated the activity by 6-fold, with the release of all unsaturated fatty acids being affected equally. Ceramide-enrichment of HDL similarly stimulated the release of unsaturated fatty acids. Incorporation of SM into phosphatidylcholine (PC) liposomes preferentially inhibited the hydrolysis of 16:0–20:4 PC. Conversely, SMase C treatment or ceramide incorporation resulted in preferential stimulation of hydrolysis of 16:0–20:4 PC. The presence of a long chain acyl group in ceramide was essential for the activation, and long chain diacylglycerols were also effective. However, ceramide phosphate was inhibitory. These studies show that SM and ceramide in the membranes and lipoproteins not only regulate the activity of phospholipases, but also the release of arachidonate, the precursor of eicosanoids. PMID:17178097

  15. CD4(+) T-cell activation is differentially modulated by bacteria-primed dendritic cells, but is generally down-regulated by n-3 polyunsaturated fatty acids.

    PubMed

    Brix, Susanne; Lund, Pia; Kjaer, Tanja M R; Straarup, Ellen M; Hellgren, Lars I; Frøkiaer, Hanne

    2010-03-01

    Appropriate activation of CD4(+) T cells is fundamental for efficient initiation and progression of acquired immune responses. Here, we showed that CD4(+) T-cell activation is dependent on changes in membrane n-3 polyunsaturated fatty acids (PUFAs) and is dynamically regulated by the type of signals provided by dendritic cells (DCs). Upon interaction with DCs primed by different concentrations and species of gut bacteria, CD4(+) T cells were activated according to the type of DC stimulus. The levels of CD80 were found to correlate to the levels of expression of CD28 and to the proliferation of CD4(+) T cells, while the presence of CD40 and CD86 on DCs inversely affected inducible costimulator (ICOS) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in CD4(+) T cells. For all DC stimuli, cells high in n-3 PUFAs showed reduced ability to respond to CD28 stimulation, to proliferate, and to express ICOS and CTLA-4. Diminished T-cell receptor (TCR) and CD28 signalling was found to be responsible for n-3 PUFA effects. Thus, the dietary fatty acid composition influences the overall level of CD4(+) T-cell activation induced by DCs, while the priming effect of the DC stimuli modulates CD80, CD86 and CD40 levels, thereby affecting and shaping activation of acquired immunity by differential regulation of proliferation and costimulatory molecule expression in CD4(+) T cells. PMID:19909377

  16. Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mouse model.

    TOXLINE Toxicology Bibliographic Information

    Kabuto H; Yamanushi TT; Janjua N; Takayama F; Mankura M

    2013-01-01

    Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities. We examined the effects of oral administration of squalene or squalane on a PD mouse model, which was developed by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA). Squalene administration 7 days before and 7 days after one 6-OHDA injection prevented a reduction in striatal dopamine (DA) levels, while the same administration of squalane enhanced the levels. Neither squalene nor squalane administration for 7 days changed the levels of catalase, glutathione peroxidase, or superoxide dismutase activities in the striatum. Squalane increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, in the striatum. Both squalane and squalene increased the ratio of linoleic acid/linolenic acid in the striatum. These results suggest that the administration of squalene or squalane induces similar changes in the composition of fatty acids and has no effect on the activities of active oxygen scavenging enzymes in the striatum. However, squalane increases oxidative damage in the striatum and exacerbates the toxicity of 6-OHDA, while squalene prevents it. The effects of squalene or squalane treatment in this model suggest their possible uses and risks in the treatment of PD.

  17. Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mouse model.

    PubMed

    Kabuto, Hideaki; Yamanushi, Tomoko T; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2013-01-01

    Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities. We examined the effects of oral administration of squalene or squalane on a PD mouse model, which was developed by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA). Squalene administration 7 days before and 7 days after one 6-OHDA injection prevented a reduction in striatal dopamine (DA) levels, while the same administration of squalane enhanced the levels. Neither squalene nor squalane administration for 7 days changed the levels of catalase, glutathione peroxidase, or superoxide dismutase activities in the striatum. Squalane increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, in the striatum. Both squalane and squalene increased the ratio of linoleic acid/linolenic acid in the striatum. These results suggest that the administration of squalene or squalane induces similar changes in the composition of fatty acids and has no effect on the activities of active oxygen scavenging enzymes in the striatum. However, squalane increases oxidative damage in the striatum and exacerbates the toxicity of 6-OHDA, while squalene prevents it. The effects of squalene or squalane treatment in this model suggest their possible uses and risks in the treatment of PD. PMID:23357814

  18. Selective Enrichment of Omega-3 Fatty Acids in Oils by Phospholipase A1

    PubMed Central

    Puri, Munish; Barrow, Colin; Rao, Nalam Madhusudhana

    2016-01-01

    Omega fatty acids are recognized as key nutrients for healthier ageing. Lipases are used to release ω-3 fatty acids from oils for preparing enriched ω-3 fatty acid supplements. However, use of lipases in enrichment of ω-3 fatty acids is limited due to their insufficient specificity for ω-3 fatty acids. In this study use of phospholipase A1 (PLA1), which possesses both sn-1 specific activity on phospholipids and lipase activity, was explored for hydrolysis of ω-3 fatty acids from anchovy oil. Substrate specificity of PLA1 from Thermomyces lenuginosus was initially tested with synthetic p-nitrophenyl esters along with a lipase from Bacillus subtilis (BSL), as a lipase control. Gas chromatographic characterization of the hydrolysate obtained upon treatment of anchovy oil with these enzymes indicated a selective retention of ω-3 fatty acids in the triglyceride fraction by PLA1 and not by BSL. 13C NMR spectroscopy based position analysis of fatty acids in enzyme treated and untreated samples indicated that PLA1 preferably retained ω-3 fatty acids in oil, while saturated fatty acids were hydrolysed irrespective of their position. Hydrolysis of structured triglyceride,1,3-dioleoyl-2-palmitoylglycerol, suggested that both the enzymes hydrolyse the fatty acids at both the positions. The observed discrimination against ω-3 fatty acids by PLA1 appears to be due to its fatty acid selectivity rather than positional specificity. These studies suggest that PLA1 could be used as a potential enzyme for selective concentrationof ω-3 fatty acids. PMID:26978518

  19. Selective Enrichment of Omega-3 Fatty Acids in Oils by Phospholipase A1.

    PubMed

    Ranjan Moharana, Tushar; Byreddy, Avinesh R; Puri, Munish; Barrow, Colin; Rao, Nalam Madhusudhana

    2016-01-01

    Omega fatty acids are recognized as key nutrients for healthier ageing. Lipases are used to release ω-3 fatty acids from oils for preparing enriched ω-3 fatty acid supplements. However, use of lipases in enrichment of ω-3 fatty acids is limited due to their insufficient specificity for ω-3 fatty acids. In this study use of phospholipase A1 (PLA1), which possesses both sn-1 specific activity on phospholipids and lipase activity, was explored for hydrolysis of ω-3 fatty acids from anchovy oil. Substrate specificity of PLA1 from Thermomyces lenuginosus was initially tested with synthetic p-nitrophenyl esters along with a lipase from Bacillus subtilis (BSL), as a lipase control. Gas chromatographic characterization of the hydrolysate obtained upon treatment of anchovy oil with these enzymes indicated a selective retention of ω-3 fatty acids in the triglyceride fraction by PLA1 and not by BSL. 13C NMR spectroscopy based position analysis of fatty acids in enzyme treated and untreated samples indicated that PLA1 preferably retained ω-3 fatty acids in oil, while saturated fatty acids were hydrolysed irrespective of their position. Hydrolysis of structured triglyceride,1,3-dioleoyl-2-palmitoylglycerol, suggested that both the enzymes hydrolyse the fatty acids at both the positions. The observed discrimination against ω-3 fatty acids by PLA1 appears to be due to its fatty acid selectivity rather than positional specificity. These studies suggest that PLA1 could be used as a potential enzyme for selective concentrationof ω-3 fatty acids. PMID:26978518

  20. Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-kappaB activation: from cells to bed rest to astronauts.

    PubMed

    Zwart, Sara R; Pierson, Duane; Mehta, Satish; Gonda, Steve; Smith, Scott M

    2010-05-01

    NF-kappaB is a transcriptional activator of many genes, including some that lead to muscle atrophy and bone resorption-significant concerns for astronauts. NF-kappaB activation is inhibited by eicosapentaenoic acid (EPA), but the influence of this omega-3 fatty acid on the effects of weightlessness are unknown. We report here cellular, ground analogue, and spaceflight findings. We investigated the effects of EPA on differentiation of RAW264.7 monocyte/macrophage cells induced by receptor activator of NF-kappaB ligand (RANKL) and on activation of NF-kappaB by tumor necrosis factor alpha (TNF-alpha) or exposure to modeled weightlessness. EPA (50 microM for 24 hours) inhibited RANKL-induced differentiation and decreased activation of NF-kappaB induced by 0.2 microg/mL of TNF-alpha for 30 minutes or by modeled weightlessness for 24 hours (p < .05). In human studies, we evaluated whether NF-kappaB activation was altered after short-duration spaceflight and determined the relationship between intake of omega-3 fatty acids and markers of bone resorption during bed rest and the relationship between fish intake and bone mineral density after long-duration spaceflight. NF-kappaB was elevated in crew members after short-duration spaceflight, and higher consumption of fish (a rich source of omega-3 fatty acids) was associated with reduced loss of bone mineral density after flight (p < .05). Also supporting the cell study findings, a higher intake of omega-3 fatty acids was associated with less N-telopeptide excretion during bed rest (Pearson r = -0.62, p < .05). Together these data provide mechanistic cellular and preliminary human evidence of the potential for EPA to counteract bone loss associated with spaceflight. PMID:19874203

  1. Fatty acid composition of Swedish bakery products, with emphasis on trans-fatty acids.

    PubMed

    Trattner, Sofia; Becker, Wulf; Wretling, Sören; Öhrvik, Veronica; Mattisson, Irene

    2015-05-15

    Trans-fatty acids (TFA) have been associated with increased risk of coronary heart disease, by affecting blood lipids and inflammation factors. Current nutrition recommendations emphasise a limitation of dietary TFA intake. The aim of this study was to investigate fatty acid composition in sweet bakery products, with emphasis on TFA, on the Swedish market and compare fatty acid composition over time. Products were sampled in 2001, 2006 and 2007 and analysed for fatty acid composition by using GC. Mean TFA levels were 0.7% in 2007 and 5.9% in 2001 of total fatty acids. In 1995-97, mean TFA level was 14.3%. In 2007, 3 of 41 products had TFA levels above 2% of total fatty acids. TFA content had decreased in this product category, while the proportion of saturated (SFA) and polyunsaturated (PUFA) fatty acids had increased, mostly through increased levels of 16:0 and 18:2 n-6, respectively. The total fat content remained largely unchanged. PMID:25577101

  2. Effect of long-term administration of arachidonic acid on n-3 fatty acid deficient mice.

    PubMed

    Harauma, Akiko; Tomita, Makiko; Muto, Daiki; Moriguchi, Toru

    2015-04-01

    The effect of long-term oral administration of arachidonic acid (ARA, 240 mg/kg/day) on brain function was assessed for mice maintained on an n-3 fatty acid adequate or deficient diet. The administration of ARA for 13 weeks resulted in an elevation of spontaneous motor activity, or the tendency thereof, in both the n-3 fatty acid adequate and deficient groups. However, the n-3 fatty acid deficient mice that were administered with ARA revealed marked deterioration in motor function in a motor coordination test. In the experiment to investigate changes over time, the motor activity of the ARA-administered group continued to increase mildly in n-3 deficient mice, although that of the control group showed a decrease involving habituation for both diet groups from the second week. The fatty acid composition of the brain at the end of the behavioral experiments indicated an increase in the levels of ARA and other n-6 fatty acids, as well as a decrease in the levels of docosahexaenoic acid. These results suggest that long-term administration of ARA causes an increase of futile spontaneous motor activity and the diminution of motor function by aggravation of n-3 fatty acid deficiency. PMID:25650363

  3. Activation of cytosolic phospholipase A2 and fatty acid transacylase is essential but not sufficient for thrombin-induced smooth muscle cell proliferation.

    PubMed

    Gluck, Nathan; Schwob, Ouri; Krimsky, Miron; Yedgar, Saul

    2008-06-01

    Thrombin is a potent stimulant of smooth muscle cell (SMC) proliferation in inflammatory conditions, leading to pathological thickening of vascular walls in atherosclerosis and airway remodeling in asthma. Cell proliferation requires the formation and remodeling of cell membrane phospholipids (PLs), involving the activation of PL-metabolizing enzymes. Yet, the role of specific PL-metabolizing enzymes in SMC proliferation has hardly been studied. To bridge this gap, in the present study, we investigated the role of key enzymes involved in PL metabolism, the PL-hydrolyzing enzyme phospholipase A2 (PLA2) and the PL-synthesizing enzyme lysophosphatidic acid-fatty acid transacylase (LPAAT), in thrombin-induced proliferation of bovine aortic SMCs (BASMCs). Concomitantly with the induction of BASMC proliferation, thrombin activated cytosolic PLA2 (cPLA2-alpha), expressed by selective release of arachidonic acid and mRNA expression, as well as LPAAT, expressed by nonselective incorporation of fatty acid and mRNA expression. Specific inhibitors of these enzymes, arachidonyl-trifluoromethyl-ketone for cPLA2 and thimerosal for LPAAT, suppressed their activities, concomitantly with suppression of BASMC proliferation, suggesting a mandatory requirement for cPLA2 and LPAAT activation in thrombin-induced SMC proliferation. Thrombin acts through the protease-activated receptor (PAR-1), and, accordingly, we found that thrombin-induced BASMC proliferation was suppressed by the PAR-1 inhibitor SCH-79797. However, the PAR-1 inhibitor did not prevent thrombin-induced mRNA expression of cPLA2 and LPAAT, implying that the activation of cPLA2 and LPAAT is essential but not sufficient for thrombin-induced proliferation of BASMCs. PMID:18385289

  4. The science of fatty acids and inflammation.

    PubMed

    Fritsche, Kevin L

    2015-05-01

    Inflammation is believed to play a central role in many of the chronic diseases that characterize modern society. In the past decade, our understanding of how dietary fats affect our immune system and subsequently our inflammatory status has grown considerably. There are compelling data showing that high-fat meals promote endotoxin [e.g., lipopolysaccharide (LPS)] translocation into the bloodstream, stimulating innate immune cells and leading to a transient postprandial inflammatory response. The nature of this effect is influenced by the amount and type of fat consumed. The role of various dietary constituents, including fats, on gut microflora and subsequent health outcomes in the host is another exciting and novel area of inquiry. The impact of specific fatty acids on inflammation may be central to how dietary fats affect health. Three key fatty acid-inflammation interactions are briefly described. First, the evidence suggests that saturated fatty acids induce inflammation in part by mimicking the actions of LPS. Second, the often-repeated claim that dietary linoleic acid promotes inflammation was not supported in a recent systematic review of the evidence. Third, an explanation is offered for why omega-3 (n-3) polyunsaturated fatty acids are so much less anti-inflammatory in humans than in mice. The article closes with a cautionary tale from the genomic literature that illustrates why extrapolating the results from inflammation studies in mice to humans is problematic. PMID:25979502

  5. Technological Aspects of Chemoenzymatic Epoxidation of Fatty Acids, Fatty Acid Esters and Vegetable Oils: A Review.

    PubMed

    Milchert, Eugeniusz; Malarczyk, Kornelia; Kłos, Marlena

    2015-01-01

    The general subject of the review is analysis of the effect of technological parameters on the chemoenzymatic epoxidation processes of vegetable oils, fatty acids and alkyl esters of fatty acids. The technological parameters considered include temperature, concentration, amount of hydrogen peroxide relative to the number of unsaturated bonds, the amounts of enzyme catalysts, presence of solvent and amount of free fatty acids. Also chemical reactions accompanying the technological processes are discussed together with different technological options and significance of the products obtained. PMID:26633342

  6. Omega-3 Fatty Acids and Skeletal Muscle Health

    PubMed Central

    Jeromson, Stewart; Gallagher, Iain J.; Galloway, Stuart D. R.; Hamilton, D. Lee

    2015-01-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. PMID:26610527

  7. [Supplementation with omega fatty acids in various diseases].

    PubMed

    Sicińska, Paulina; Pytel, Edyta; Kurowska, Joanna; Koter-Michalak, Maria

    2015-01-01

    For some decades, an increase in propagation of coronary heart disease, obesity, diabetes, tumors and mental disorders has been observed. Consequently, new and effective methods of treatment of these diseases using drugs and diet supplements have been developed. A promising solution is the use of polyunsaturated fatty acids in the treatment of some diseases. These compounds have broad application in prevention of many diseases and are used to support standard therapies. Their activity is connected with participation in metabolic processes regulating biochemical transformations in cells and tissues. Omega-3 fatty acids regulate production of cytokines, increased levels of which may contribute to occurrence of chronic inflammatory diseases, autoaggression of the immunological system, arteriosclerosis or tumor development. These substances exert a beneficial effect on the blood system by improvement of blood circulation and nerve signal transmission. Omega-3 fatty acids reduce the risk of irregular heartbeat, stabilize arterial pressure, and restore balance in cholesterol metabolism disorders. They also play a key role in maintaining physical and mental efficiency; thus administration of these compounds for young children is of great importance. Nevertheless, administration of omega-3 fatty acids in the diet seems to be essential. The purpose of this study is to present the structure and sources of omega-3 and - 6 fatty acids and discuss the problems concerning therapeutic use of these compounds in various disorders. PMID:26206997

  8. Fatty acids enhance membrane permeabilization by pro-apoptotic Bax.

    PubMed Central

    Epand, Raquel F; Martinou, Jean-Claude; Montessuit, Sylvie; Epand, Richard M

    2004-01-01

    Fatty acids are known promoters of apoptosis. In the present study, the direct role of fatty acids with regard to their ability to cause membrane permeabilization by Bax was explored. Addition of fatty acids to liposomes in the presence of cations greatly enhanced the permeabilizing activity of Bax, a pro-apoptotic Bcl-2 protein. This provides a putative mechanism for the role of fatty acids in apoptosis. It is not a result of detergent-like properties of fatty acids, since a different micelle-forming amphiphile, dilysocardiolipin, was strongly inhibitory. We also demonstrate that there is a synergistic effect on Bax-induced permeabilization between Ca(2+) and Mg(2+), both on the binding of Bax to liposomes as well as on the induction of the leakage of liposomal contents. Micromolar concentrations of Ca(2+) added externally or submicromolar concentrations of free Ca(2+) present in the medium were sufficient to promote Bax-induced permeabilization synergistically with externally added Mg(2+). These results indicate that Bax can induce leakage from liposomes at ion concentrations resembling those found physiologically. The synergistic effects of Ca(2+) and Mg(2+) were observed with liposomes with different lipid compositions. Thus the action of Bax is strongly modulated by the presence of bivalent cations that can act synergistically, as well as by micelle-forming lipid components that can be either stimulatory or inhibitory. PMID:14535847

  9. Omega-3 Fatty Acids and Skeletal Muscle Health.

    PubMed

    Jeromson, Stewart; Gallagher, Iain J; Galloway, Stuart D R; Hamilton, D Lee

    2015-11-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. PMID:26610527

  10. ACTIVATION OF VASCULAR ENDOTHELIAL NITRIC OXIDE SYNTHASE AND HEME OXYGENASE-1 EXPRESSION BY ELECTROPHILIC NITRO-FATTY ACIDS

    PubMed Central

    Khoo, Nicholas K.H.; Rudolph, Volker; Cole, Marsha P.; Golin-Bisello, Franca; Schopfer, Francisco J.; Woodcock, Steven R.; Batthyany, Carlos; Freeman, Bruce A.

    2010-01-01

    Reactive oxygen species mediate a decrease in nitric oxide (NO) bioavailability and endothelial dysfunction, with secondary oxidized and nitrated byproducts of these reactions contributing to the pathogenesis of numerous vascular diseases. While oxidized lipids and lipoproteins exacerbate inflammatory reactions in the vasculature, in stark contrast the nitration of polyunsaturated fatty acids and complex lipids yield electrophilic products that exhibit pluripotent anti-inflammatory signaling capabilities acting via both cGMP-dependent and -independent mechanisms. Herein we report that nitro-oleic acid (OA-NO2) treatment increases expression of endothelial nitric oxide synthase (eNOS) and heme oxygenase 1 (HO-1) in the vasculature, thus transducing vascular protective effects associated with enhanced NO production. Administration of OA-NO2 via osmotic pump results in a significant increase in eNOS and HO-1 mRNA in mouse aortas. Moreover, HPLC-MS/MS analysis showed that NO2-FAs are rapidly metabolized in cultured endothelial cells (ECs) and treatment with NO2-FAs stimulated the phosphorylation of eNOS at Ser1179. These post-translational modifications of eNOS, in concert with elevated eNOS gene expression, contributed to an increase in endothelial NO production. In aggregate, OA-NO2-induced eNOS and HO-1 expression by vascular cells can induce beneficial effects on endothelial function and provide a new strategy for treating various vascular inflammatory and hypertensive disorders. PMID:19857569

  11. Quantitative proteomics analysis reveals glutamine deprivation activates fatty acid β-oxidation pathway in HepG2 cells.

    PubMed

    Long, Baisheng; Muhamad, Rodiallah; Yan, Guokai; Yu, Jie; Fan, Qiwen; Wang, Zhichang; Li, Xiuzhi; Purnomoadi, Agung; Achmadi, Joelal; Yan, Xianghua

    2016-05-01

    Glutamine, a multifunctional amino acid, functions in nutrient metabolism, energy balance, apoptosis, and cell proliferation. Lipid is an important nutrient and controls a broad range of physiological processes. Previous studies have demonstrated that glutamine can affect lipolysis and lipogenesis, but the effect of glutamine on the detailed lipid metabolism remains incompletely understood. Here, we applied the quantitative proteomics approach to estimate the relative abundance of proteins in HepG2 cells treated by glutamine deprivation. The results showed that there were 212 differentially abundant proteins in response to glutamine deprivation, including 150 significantly increased proteins and 62 significantly decreased proteins. Interestingly, functional classification showed that 43 differentially abundant proteins were related to lipid metabolism. Further bioinformatics analysis and western blotting validation revealed that lipid accumulation may be affected by β-oxidation of fatty acid induced by glutamine deprivation in HepG2 cells. Together, our results may provide the potential for regulating lipid metabolism by glutamine in animal production and human nutrition. The MS data have been deposited to the ProteomeXchange Consortium with identifier PXD003387. PMID:26837383

  12. Fatty Acids as Surfactants on Aerosol Particles

    NASA Astrophysics Data System (ADS)

    Tervahattu, H.; Juhanoja, J.; Niemi, J.

    2003-12-01

    Fatty acids (n-alcanoic acids) are common compounds in numerous anthropogenic and natural emissions. According to Rogge et al. (1993), catalyst-equipped automobiles emitted more than 600 μg km-1 of fatty acids which was over 50% of all identified organics in fine aerosol emissions. Coal burning produces fatty acids ranging from about 1700 mg kg-1 for bituminous coal to over 10000 mg kg-1 for lignite (Oros and Simoneit, 2000). Similarly, biomass burning is an important source for aerosol fatty acids. They are the major identified compound group in deciduous tree smoke, their total emission factor being measured as 1589 mg kg-1 which was 56% of all identified organic compounds (Oros and Simoneit, 2001a). Large amounts of fatty acid are also emitted from burning of conifer trees and grass (Oros and Simoneit, 2001a; Simoneit, 2002). Fatty acids have been reported to be major constituents of marine aerosols in many investigations (Barger and Garrett, 1976; Gagosian et. al, 1981; Sicre et al., 1990; Stephanou, 1992). It has been suggested that as the marine aerosol particles form, they acquire a coating of organic surfactants (Blanchard, 1964; Gill et al., 1983; Middlebrook et al., 1998; Ellison et al., 1999). Amphiphilic molecules, including lipids, can be assembled as monomolecular layers at air/water interfaces as well as transported to a solid support. Recently, we could show by time-of-flight secondary ion mass spectrometry that fatty acids are important ingredients of the outermost surface layer of the sea-salt aerosol particles (Tervahattu et al., 2002). In their TOF-SIMS studies on the surface composition of atmospheric aerosols, Peterson and Tyler (2002) found fatty acids on the surface of Montana forest fire particles. In this work we have studied by TOF-SIMS the surface chemical composition of aerosol particles emitted from field fires in the Baltic and other East European countries and transported to Finland as well as aerosol particles transported from Russian forest and peat fires. Fatty acids were commonly observed on the surface layer of these particles. The chain length composition was characteristic to each emission source. In our previous work (Tervahattu et al., 2002), fatty acids on sea-salt particles were originated from dead sea plankton organisms with major peaks ranging from C14 to C18 and maximum at C16 (palmitic acid). Major peaks on the surface of forest fire particles ranged from C16 to C30 with the maximum at C24. This composition indicates the involvement of the smoke from both conifer trees and peat (Oros and Simoneit, 2000; 2001b). On the other hand, TOF-SIMS analysis of the surface of field fire particles showed major peaks from C14 to C30 with two maximums at C16 (highest intensity) and C22. It was concluded that the results indicate emissions from both grass burning and fossil fuels (Simoneit, 2002; Oros and Simoneit, 2000). The presence of surface film on aerosol particles may have an impact on their chemical, physical and optical properties and change their role in light scattering and as cloud condensation nuclei as well as interactions with human tissue.

  13. Bioactivity-guided isolation of beta-sitosterol and some fatty acids as active compounds in the anxiolytic and sedative effects of Tilia americana var. mexicana.

    PubMed

    Aguirre-Hernández, Eva; Rosas-Acevedo, Hortensia; Soto-Hernández, Marcos; Martínez, Ana Laura; Moreno, Julia; González-Trujano, Ma Eva

    2007-09-01

    Tilia species have been used as anxiolytics for many years. In a previous study anxiolytic-like effects of a hexane extract of Tilia americana var. mexicana inflorescences were observed in experimental models in mice. To get additional insights into the neuroactive actions of this particular Tilia species, in this study we report a bioactivity guided-fractionation of the extract and separation by column chromatographic methods to isolate three fatty acids and a triterpene identified as beta-sitosterol as major constituents. Our results revealed that the crude extract at 10 and 30 mg/kg I. P. and some pooled fractions at the same dosages potentiated sodium pentobarbital-induced sleeping time and caused a significant increase in the time spent at the open-arm sides in the plus-maze test. A reduction in the exploratory behavioral pattern manifested as ambulatory activity, as well as head dipping and rearing tests was also observed. Further fractionation and purification yielded four major fractions containing fatty acids and beta-sitosterol as the active compounds. A dose-response curve of beta-sitosterol in the range 1 to 30 mg/kg doses indicated that this compound produced an anxiolytic-like action from 1 to 10 mg/kg and a sedative response when the dose was increased to 30 mg/kg, these effects resemble those produced by diazepam (0.1 mg/kg). Our results suggest that hexane extract of Tilia americana var. mexicana produces depressant actions on the central nervous system, at least in part, because of the presence of beta-sitosterol and some fatty acids that remain to be identified. PMID:17823876

  14. Serum Polyunsaturated Fatty Acids and Endometriosis.

    PubMed

    Hopeman, Margaret M; Riley, Joan K; Frolova, Antonina I; Jiang, Hui; Jungheim, Emily S

    2015-09-01

    Polyunsaturated fatty acids (PUFAs) are fatty acids containing 2 or more double bonds, and they are classified by the location of the last double bond. Omega 3 (n-3) and omega 6 (n-6) PUFAs are obtained through food sources including fatty fish and seed/vegetable oils, respectively, and they are important to a number of physiologic processes including inflammation. Previous work demonstrates suppressive effects of n-3 PUFAs on endometriotic lesions in animal models and decreased risk of endometriosis among women with high n-3 PUFA intake. Thus, we sought to determine the relationship between circulating levels of PUFAs and endometriosis in women. To do this, we performed a cross-sectional study of serum PUFAs and clinical data from 205 women undergoing in vitro fertilization (IVF). Serum PUFAs were measured using liquid chromatography coupled to tandem mass spectroscopy and included n-3 PUFAs such as α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid and n-6 PUFAs such as linoleic acid and arachidonic acid. Multivariable logistic regression was used to determine relationships between specific and total serum PUFAs and patient history of endometriosis. Women with high serum EPA levels were 82% less likely to have endometriosis compared to women with low EPA levels (odds ratio = 0.18, 95% confidence interval 0.04-0.78). PMID:25539770

  15. THREE MICROSOMAL OMEGA-3 FATTY ACID DESATURASE GENES CONTRIBUTE TO SOYBEAN LINOLENIC ACID LEVELS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three independent genetic loci have been shown to contribute to soybean (Glycine max L.) seed linolenic acid levels, including the well-characterized Fan locus. Linolenic acid is the product of omega-3-fatty acid desaturase enzyme activity. The objective of this study was to identify and character...

  16. Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis

    SciTech Connect

    Yu X. H.; Shanklin J.; Rawat, R.

    2011-05-01

    Cyclopropane fatty acids (CPA) have been found in certain gymnosperms, Malvales, Litchi and other Sapindales. The presence of their unique strained ring structures confers physical and chemical properties characteristic of unsaturated fatty acids with the oxidative stability displayed by saturated fatty acids making them of considerable industrial interest. While cyclopropenoid fatty acids (CPE) are well-known inhibitors of fatty acid desaturation in animals, CPE can also inhibit the stearoyl-CoA desaturase and interfere with the maturation and reproduction of some insect species suggesting that in addition to their traditional role as storage lipids, CPE can contribute to the protection of plants from herbivory. Three genes encoding cyclopropane synthase homologues GhCPS1, GhCPS2 and GhCPS3 were identified in cotton. Determination of gene transcript abundance revealed differences among the expression of GhCPS1, 2 and 3 showing high, intermediate and low levels, respectively, of transcripts in roots and stems; whereas GhCPS1 and 2 are both expressed at low levels in seeds. Analyses of fatty acid composition in different tissues indicate that the expression patterns of GhCPS1 and 2 correlate with cyclic fatty acid (CFA) distribution. Deletion of the N-terminal oxidase domain lowered GhCPS's ability to produce cyclopropane fatty acid by approximately 70%. GhCPS1 and 2, but not 3 resulted in the production of cyclopropane fatty acids upon heterologous expression in yeast, tobacco BY2 cell and Arabidopsis seed. In cotton GhCPS1 and 2 gene expression correlates with the total CFA content in roots, stems and seeds. That GhCPS1 and 2 are expressed at a similar level in seed suggests both of them can be considered potential targets for gene silencing to reduce undesirable seed CPE accumulation. Because GhCPS1 is more active in yeast than the published Sterculia CPS and shows similar activity when expressed in model plant systems, it represents a strong candidate gene for CFA accumulation via heterologous expression in production plants.

  17. Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis

    PubMed Central

    2011-01-01

    Background Cyclopropane fatty acids (CPA) have been found in certain gymnosperms, Malvales, Litchi and other Sapindales. The presence of their unique strained ring structures confers physical and chemical properties characteristic of unsaturated fatty acids with the oxidative stability displayed by saturated fatty acids making them of considerable industrial interest. While cyclopropenoid fatty acids (CPE) are well-known inhibitors of fatty acid desaturation in animals, CPE can also inhibit the stearoyl-CoA desaturase and interfere with the maturation and reproduction of some insect species suggesting that in addition to their traditional role as storage lipids, CPE can contribute to the protection of plants from herbivory. Results Three genes encoding cyclopropane synthase homologues GhCPS1, GhCPS2 and GhCPS3 were identified in cotton. Determination of gene transcript abundance revealed differences among the expression of GhCPS1, 2 and 3 showing high, intermediate and low levels, respectively, of transcripts in roots and stems; whereas GhCPS1 and 2 are both expressed at low levels in seeds. Analyses of fatty acid composition in different tissues indicate that the expression patterns of GhCPS1 and 2 correlate with cyclic fatty acid (CFA) distribution. Deletion of the N-terminal oxidase domain lowered GhCPS's ability to produce cyclopropane fatty acid by approximately 70%. GhCPS1 and 2, but not 3 resulted in the production of cyclopropane fatty acids upon heterologous expression in yeast, tobacco BY2 cell and Arabidopsis seed. Conclusions In cotton GhCPS1 and 2 gene expression correlates with the total CFA content in roots, stems and seeds. That GhCPS1 and 2 are expressed at a similar level in seed suggests both of them can be considered potential targets for gene silencing to reduce undesirable seed CPE accumulation. Because GhCPS1 is more active in yeast than the published Sterculia CPS and shows similar activity when expressed in model plant systems, it represents a strong candidate gene for CFA accumulation via heterologous expression in production plants. PMID:21612656

  18. Three new fatty acid esters from the mushroom Boletus pseudocalopus.

    PubMed

    Kim, Ki Hyun; Choi, Sang Un; Lee, Kang Ro

    2012-06-01

    A bioassay-guided fractionation and chemical investigation of a MeOH extract of the Korean wild mushroom Boletus pseudocalopus resulted in the identification of three new fatty acid esters, named calopusins A-C (1-3), along with two known fatty acid methyl esters (4-5). These new compounds are structurally unique fatty acid esters with a 2,3-butanediol moiety. Their structures were elucidated through 1D- and 2D-NMR spectroscopic data and GC-MS analysis as well as a modified Mosher's method. The new compounds 1-3 showed significant inhibitory activity against the proliferation of the tested cancer cell lines with IC(50) values in the range 2.77-12.51 μM. PMID:22271425

  19. Lipid and fatty acid requirements of tilapias

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tilapia have been shown to have a dietary requirement for linoleic (n-6) series fatty acids (18:2n-6 or 20:4n-6). The optimum dietary levels of n-6 reported were 0.5 and 1% for redbelly tilapia (Tilapia zillii) and Nile tilapia (Oreochromis niloticus), respectively. Tilapia have been suggested to al...

  20. [THE FATTY ACIDS AND RELATIONSHIP WITH HEALTH].

    PubMed

    Sanhueza Catalán, Julio; Durán Agüero, Samuel; Torres García, Jairo

    2015-01-01

    The functionality of the eukaryotic cell depends on the cell membrane, the genetic information and action of different organelles with or without the presence of membranes. The functionality of the cell membrane and organelles containing it depends primarily on the type and location of fatty acids in the phospholipids and the type of enzymes associated with them, this allows the fatty acids to be metabolized to new species that exert various functions. From this perspective, some essential fatty acids (EFAs) that produce metabolites that exert health benefits are identified, (for example antiinflammatory, neuroprotection, etc) and exert negative effects metabolites (eg inflammation, necrosis promoters, atheroma, etc.) are also generated. In general, these adverse or beneficial effects depend on the ratio of omega-6/omega-3 obtained in the diet. Thus, the higher this ratio is more negative effect; therefore the challenge of the current supply is obtained through food consumption, lower ratios in these fatty acids. The present review aims to present recent evidence on the effects of some AGEs, and the role of diet in maintaining health. PMID:26319861

  1. Hydroxyl Fatty Acids and Hydroxyl Oils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean oil is produced domestically in large supply, averaging over 20 billion pounds per year with an annual carryover of more than one billion pounds. It is important to find new uses for this surplus soybean oil. Hydroxyl fatty acids and hydroxyl oils are platform materials for specialty chemi...

  2. Polyunsaturated fatty acids and gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose of review. This review focuses on the effect(s) of n-3 polyunsaturated fatty acids (PUFA) on gene transcription as determined from data generated using cDNA microarrays. Introduced within the past decade, this methodology allows detection of the expression of thousands of genes simultaneo...

  3. Lipid and Fatty Acid Requirements of Tilapia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary lipids are an important source of highly digestible energy and are the only source of essential fatty acids required for normal growth and development. They are also carriers and assist in the absorption of fat-soluble nutrients, such as sterols and fat-soluble vitamins, serve as a source of...

  4. PLANT FATTY ACID (ETHANOL) AMIDE HYDROLASES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid amide hydrolase (FAAH) plays a central role in modulating endogenous N-acylethanolamine (NAE) levels in vertebrates, and, in part, constitutes an “endocannabinoid” signaling pathway that regulates diverse physiological and behavioral processes in animals. Recently, an Arabidopsis FAAH hom...

  5. Changes in the physiological parameters, fatty acid metabolism, and SCD activity and expression in juvenile GIFT tilapia (Oreochromis niloticus) reared at three different temperatures.

    PubMed

    Ma, X Y; Qiang, J; He, J; Gabriel, N N; Xu, P

    2015-08-01

    We evaluated the effects of rearing temperature on the composition of fatty acids and stearoyl-CoA desaturase (SCD) activity and gene expression in GIFT (genetically improved farmed tilapia) tilapia. Three triplicate groups of fish were reared for 40 days at 22, 28, or 34 °C. At the end of the trial, the final body weight of juveniles reared at 28 °C was higher than that of fish reared at 22 or 34 °C. Feed intake, feed efficiency, and the protein efficiency ratio were also higher at 28 °C. The fatty acid composition of muscle tissue differed significantly (P < 0.05) among the treatment groups. The content of SFA decreased with decreasing temperature, whereas the UFA content increased. We observed high levels of PUFA, particularly n-3 PUFAs, in fish reared at the lower temperature. Rearing at low temperature significantly (P < 0.05) increased the expression and activity of the SCD gene. Increased SCD activity and gene expression can increase the biosynthesis of MUFAs in GIFT tilapia muscle. Additionally, cold acclimation can decrease the content of TC and TG in GIFT tilapia, which can help increase cold tolerance. PMID:25939714

  6. The mitochondrial fatty acid synthesis (mtFASII) pathway is capable of mediating nuclear-mitochondrial cross talk through the PPAR system of transcriptional activation

    SciTech Connect

    Parl, Angelika; Mitchell, Sabrina L.; Clay, Hayley B.; Reiss, Sara; Li, Zhen; Murdock, Deborah G.

    2013-11-15

    Highlights: •The function of the mitochondria fatty acid synthesis pathway is partially unknown. •Overexpression of the pathway causes transcriptional activation through PPARs. •Knock down of the pathway attenuates that activation. •The last enzyme in the pathway regulates its own transcription. •Products of the mtFASII pathway are able to drive nuclear transcription. -- Abstract: Mammalian cells contain two fatty acid synthesis pathways, the cytosolic FASI pathway, and the mitochondrial FASII pathway. The selection behind the conservation of the mitochondrial pathway is not completely understood, given the presence of the cytosolic FAS pathway. In this study, we show through heterologous gene reporter systems and PCR-based arrays that overexpression of MECR, the last step in the mtFASII pathway, causes modulation of gene expression through the PPAR pathway. Electromobility shift assays (EMSAs) demonstrate that overexpression of MECR causes increased binding of PPARs to DNA, while cell fractionation and imaging studies show that MECR remains localized to the mitochondria. Interestingly, knock down of the mtFASII pathway lessens the effect of MECR on this transcriptional modulation. Our data are most consistent with MECR-mediated transcriptional activation through products of the mtFASII pathway, although we cannot rule out MECR acting as a coactivator. Further investigation into the physiological relevance of this communication will be necessary to better understand some of the phenotypic consequences of deficits in this pathway observed in animal models and human disease.

  7. Effect of dietary conjugated linoleic acid on the fatty acid composition of egg yolk, plasma and liver as well as hepatic stearoyl-coenzyme A desaturase activity and gene expression in laying hens.

    PubMed

    Shang, X G; Wang, F L; Li, D F; Yin, J D; Li, X J; Yi, G F

    2005-12-01

    A total of 216 Brown Dwarf laying hens (1.62 +/- 0.06 kg BW and 60 wk old) were fed 1 of 3 corn-soybean meal-based diets containing 0, 2.5, or 5.0% conjugated linoleic aicd (CLA) to explore its effects on the fatty acid composition of egg yolk, plasma, and liver as well as hepatic stearoyl-coenzyme A desaturase-1 (SCD-1) activity and its mRNA gene expression. Four hens were placed in wired-floored cages (45 x 40 x 45 cm) and 3 cages were grouped as 1 replicate, resulting in 6 replicates per treatment. The experimental diets were fed for 54 d, and then eggs were collected to determine the fatty acid composition of egg yolk. Four eggs were randomly selected from the total day's production for each replicate, and the contents were pooled prior to analysis. On d 56, one randomly chosen hen from each replicate (6 hens per replicate and a total of 18 hens) was bled via heart puncture and then killed in order to collect liver samples to measure the fatty acid profile of plasma and liver tissue as well as hepatic SCD-1 activity and its mRNA abundance. Dietary supplementation of CLA resulted in a significant deposition of CLA in egg yolk, plasma, and liver lipids (P < 0.01). As the dietary level of CLA increased, the concentration of saturated fatty acids in egg yolk, plasma, and liver also increased (P < 0.05). However, the concentration of monounsaturated fatty acids in these same tissues decreased (P < 0.01). Compared with the control, the activity of SCD-1 was reduced by feeding 2.5% CLA (P < 0.05) without a change in SCD-1 mRNA gene expression. However, feeding 5% CLA reduced both SCD-1 activity and mRNA abundance (P < 0.05). These results indicate that the conversion of saturated to monounsaturated fatty acids in egg yolk, plasma, and liver might be modulated directly at hepatic mRNA gene expression levels, or may be indirectly regulated at the downstream post-transcriptional levels. PMID:16479945

  8. Detection and Quantification of Protein Adduction by Electrophilic Fatty Acids: Mitochondrial Generation of Fatty Acid Nitroalkene Derivatives

    PubMed Central

    Schopfer, F.J.; Batthyany, C.; Baker, P.R.S.; Bonacci, G.; Cole, M.P.; Rudolph, V.; Groeger, A.; Rudolph, T.K.; Nadtochiy, S.; Brookes, P.S.; Freeman, B.A.

    2011-01-01

    Nitroalkene fatty acid derivatives manifest a strong electrophilic nature, are clinically detectable and induce multiple transcriptionally-regulated anti-inflammatory responses. At present, the characterization and quantification of endogenous electrophilic lipids is compromised by their Michael addition with protein and small molecule nucleophilic targets. Herein, we report a trans-nitroalkylation reaction of nitro-fatty acids with β-mercaptoethanol (BME) and apply this reaction to the unbiased identification and quantification of reaction with nucleophilic targets. Trans-nitroalkylation yields are maximal at pH 7 to 8, and occur with physiological concentrations of target nucleophiles. This reaction also amenable to sensitive mass spectrometry-based quantification of electrophilic fatty acid-protein adducts upon electrophoretic resolution of proteins. In-gel trans-nitroalkylation reactions also permit the identification of protein targets without the bias and lack of sensitivity of current proteomic approaches. Using this approach, it was observed that fatty acid nitroalkenes are rapidly metabolized in vivo by a nitroalkene reductase activity and mitochondrial β-oxidation, yielding a variety of electrophilic and non-electrophilic products that could be structurally characterized upon BME-based transnitroalkylation reaction. This strategy was applied to the detection and quantification of fatty acid nitration in mitochondria in response to oxidative inflammatory conditions induced by myocardial ischemia-reoxygenation. PMID:19353781

  9. Long-chain unsaturated fatty acids reduce the transcriptional activity of the rat follicle-stimulating hormone β-subunit gene

    PubMed Central

    MORIYAMA, Ryutaro; YAMAZAKI, Tsubasa; KATO, Takako; KATO, Yukio

    2016-01-01

    Here, we assessed the effects of long-chain fatty acids (LCFAs) and the LCFA receptor agonist GW9508 on the transcription of the gonadotropin subunit genes Cga, Lhb and Fshb because LCFA receptor GPR120 was observed in mouse gonadotropes in our recent study. A transcription assay using LβT2 cells demonstrated that LCFAs, oleic acid, α-linolenic acid, docosahexaenoic acid and palmitate, repressed the expression of Cga, Lhb, and Fshb at concentrations between 50 and 100 µM. On the other hand, treatment with 10 µM unsaturated LCFAs, oleic acid, α-linolenic acid and docosahexaenoic acid, repressed only Fshb expression, while the same dose of a saturated LCFA, palmitate, had no effect on the expression of gonadotropin subunit genes. Furthermore, GW9508 did not affect promoter activity. Next, we examined deletion mutants of the upstream region of Fshb and found that the upstream regulatory region (-2824 to -2343 bp) of Fshb was responsible for the notable repression by 10 µM unsaturated LCFAs. Our results suggest that the upstream region of Fshb is susceptible to unsaturated LCFAs. In addition, unsaturated LCFAs play a role in repressing Fshb expression through the distal -2824 to -2343 bp region, which might be independent of the LCFA receptor GPR120 pathway. PMID:26853521

  10. Identification and structural characterization of two peroxisome proliferator activated receptors and their transcriptional changes at different developmental stages and after feeding with different fatty acids.

    PubMed

    Liang, Xiao; Zhao, Yuntong; Li, Yang; Gao, Jian

    2016-03-01

    Peroxisome proliferator activated receptors beta1 (PPARβ1) and beta2 (PPARβ2) were investigated in loach (Misgurnus anguillicaudatus). The PPARβ1 and PPARβ2 were widely distributed in loach tissues. Multiple alignments of deduced amino acid sequences revealed homologous characteristics of the two subtypes of PPARβ with 88% identity. PPARβ1 was markedly expressed in the liver, about 100-fold higher than liver PPARβ2. The two subtypes in unfertilized ovum (UO) showed the highest transcriptions in early life stages, and there were great divergences in expression between unfertilized and fertilized stages. The regulation of PPARβ1 and PPARβ2 in response to dietary fatty acids was studied in liver of loach fed with diets containing fish oil (FO, rich in n-3 highly unsaturated fatty acid) or soybean oil (SO, rich in 18:2n-6) for 75days. Results showed that hepatic transcription of PPARβ1 in the SO group was higher than in the FO group. However, PPARβ2 expression was similar. The differences of molecular characterization, tissue expressions in early life stages, and transcriptional regulation by lipid resources indicated that PPARβ1 and PPARβ2 were functionally different. This is the first report of differential expression of PPARβ1 and PPARβ2 in various tissues and early life stages of loach are regulated by lipid resources. These results will stimulate further studies to better understand the functional characterization of PPARβ1 and PPARβ2. PMID:26654955

  11. Effects of in vitro UVA irradiation and PUVA treatment on membrane fatty acids and activities of antioxidant enzymes in human keratinocytes

    SciTech Connect

    Punnonen, K.; Jansen, C.T.; Puntala, A.; Ahotupa, M. )

    1991-02-01

    Human Keratinocytes (NCTC 2544) in culture were exposed to either plain ultraviolet A (UVA) irradiation or to 8-methoxypsoralen plus UVA (PUVA) treatment. Lipid peroxidation, activities of antioxidant enzymes, and percentage amounts of 14C-arachidonic acid in various cellular lipid subclasses and in the culture medium were measured. Both UVA irradiation and PUVA treatment induced significant changes in the distribution of arachidonic acid and increased the liberation of arachidonic acid from membrane phospholipids. At 24 h after either UVA irradiation or PUVA treatment the formation of thiobarbituric acid reactive material was significantly increased, whereas the amount of conjugated dienes was unaffected. The activities of the antioxidant enzymes, catalase and superoxide dismutase, were already significantly decreased at 0.5 h after UVA irradiation or PUVA treatment. The enzyme activities were partially restored during the following 24 h incubation. From the present study, we suggest that in keratinocytes both plain UVA irradiation and PUVA treatment induce changes in the distribution of membrane fatty acids and cause an impairment in the enzymic defense system against oxidative stress.

  12. The role of dietary n-6 fatty acids in the prevention of cardiovascular disease.

    PubMed

    Willett, Walter C

    2007-09-01

    n-6 Fatty acids, like n-3 fatty acids, play essential roles in many biological functions. Because n-6 fatty acids are the precursors of proinflammatory eicosanoids, higher intakes have been suggested to be detrimental, and the ratio of n-6 to n-3 fatty acids has been suggested by some to be particularly important. However, this hypothesis is based on minimal evidence, and in humans higher intakes of n-6 fatty acids have not been associated with elevated levels of inflammatory markers. n-6 Fatty acids have long been known to reduce serum total and low-density lipoprotein cholesterol, and increases in polyunsaturated fat intake, mostly as n-6 fatty acids, were a cornerstone of dietary advice during the 1960s and 1970s. In the United States, for example, intake of n-6 fatty acids doubled and coronary heart disease (CHD) mortality fell by 50% over a period of several decades. In a series of relatively small, older randomized trials, in which intakes of polyunsaturated fat were increased (even up to 20% of calories), rates of CHD were generally reduced. In a more recent detailed examination of fatty acid intake within the Nurses' Health Study, greater intake of linoleic acid, up to about 8% of energy, has been strongly related to lower incidence of myocardial infarction or CHD death. Because n-3 fatty acids were also related inversely to risk of CHD, the ratio was unrelated to risk. n-6 Fatty acids reduce insulin resistance, probably by acting as a ligand for peroxisome proliferator-activated receptors-gamma, and intakes have been inversely related to risk of type 2 diabetes. Adequate intakes of both n-6 and n-3 fatty acids are essential for good health and low rates of cardiovascular disease and type 2 diabetes, but the ratio of these fatty acids is not useful. Reductions of linoleic acid to "improve" this ratio would likely increase rates of cardiovascular disease and diabetes. PMID:17876199

  13. Plasma Acylcarnitine Profiles Suggest Incomplete Fatty Acid ß-Oxidation and Altered Tricarboxylic Cycle Activity in Type 2 Diabetic African-American Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inefficient muscle long-chain fatty acid (LCFA) combustion is associated with insulin resistance, but molecular links between mitochondrial fat catabolism and insulin action remain controversial. We hypothesized that plasma acylcarnitine profiling would identify distinct metabolite patterns reflect...

  14. Accumulation of Oxygenated Fatty Acids in Oat Lipids During Storage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxygenated fatty acids were identified in oat grain by gas chromatography - mass spectrometry. We hypothesized that most of these were the results of lipoxygenase activity. This hypothesis was tested by measuring concentrations of these compounds after hydrothermal treatments and storage of oat groa...

  15. Fatty acid composition of chicken breast meat is dependent on genotype-related variation of FADS1 and FADS2 gene expression and desaturating activity.

    PubMed

    Boschetti, E; Bordoni, A; Meluzzi, A; Castellini, C; Dal Bosco, A; Sirri, F

    2016-04-01

    In Western countries the dietary guidance emphasizes the need to decrease the intake of saturated fatty acids and to replace them with polyunsaturated fatty acids (PUFA), particularly long chain n-3 PUFA (LC-PUFA). The production of poultry meat having a lower fat content and healthier fatty acid (FA) profile is a hot topic for the poultry industry, and the possibility to identify genotypes able to produce meat with a higher LC-PUFA content deserves attention. The aims of the present study were to evidence in chicken (i) a genotype-related different expression of the desaturating enzymes delta-6 (Δ6, EC 1.14.99.25), delta-5 (Δ5, EC 1.14.19.) and delta-9 (Δ9, EC 1.14.19.1); (ii) the impact of the hypothesized different expression on the meat FA composition; (iii) the distribution of desaturase products in the different lipid classes. Slow (SG), medium (MG) and fast (FG) growing chickens fed the same diet were evaluated either for the relative expression of FADS1, FADS2 and SCD1 genes in liver (by q-PCR), or for the FA composition of breast meat. MG and particularly SG birds showed a greater expression of FADS2 and FADS1 genes, a higher Δ6 and Δ5 activity (estimated using desaturase indices), and consequently a higher LC-PUFA content in the breast meat than FG birds. The relationship between genotype and desaturating ability was demonstrated, with a significant impact on the PUFA content of breast meat. Due to the high consumption rate of avian meat, the identification of the best genotypes for meat production could represent an important goal not only for the food industry, but also for the improvement of human nutrition. PMID:26670346

  16. Current Progress and Future Research on the Production of Oxygenated Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxygenated (hydroxy-, epoxy-) fatty acids such as ricinoleic, vernolic and /or sebacic acids are high value chemicals and can be used to produce polymers and specialty chemicals. Oxygenated fatty acids also have many bioactive properties, such as antimicrobial activity against Salmonella, Staphyloc...

  17. Biochemical characterization of polyunsaturated fatty acid synthesis in Schizochytrium: release of the products as free fatty acids.

    PubMed

    Metz, James G; Kuner, Jerry; Rosenzweig, Bradley; Lippmeier, James C; Roessler, Paul; Zirkle, Ross

    2009-06-01

    In marine bacteria and some thraustochytrids (marine stramenopiles) long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are produced de novo by PUFA synthases. These large, multi-domain enzymes carry out the multitude of individual reactions required for conversion of malonyl-CoA to the final LC-PUFA products. Here we report on the release of fatty acids from the PUFA synthase found in Schizochytrium, a thraustochytrid that has been developed as a commercial source for DHA-enriched biomass and oil. Data from in vitro activity assays indicate that the PUFAs are released from the enzyme as free fatty acids (FFAs). Addition of ATP and Mg(2+) to in vitro assays facilitates appearance of radiolabel from (14)C-malonyl-CoA in a triacylglycerol fraction, suggesting the involvement of acyl-CoA synthetases (ACS). Furthermore, addition of triascin C, an inhibitor of ACSs, to the assays blocks this conversion. When the Schizochytrium PUFA synthase is expressed in Escherichia coli, the products of the enzyme accumulate as FFAs, suggesting that the thioesterase activity required for fatty acid release is an integral part of the PUFA synthase. PMID:19272783

  18. 40 CFR 721.10463 - Fatty acid amides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amides (generic). 721.10463... Substances § 721.10463 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amides (PMN...

  19. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  20. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide (generic). 721.10320... Substances 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  1. 40 CFR 721.10687 - Fatty acid amide hydrochlorides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide hydrochlorides... Specific Chemical Substances 721.10687 Fatty acid amide hydrochlorides (generic). (a) Chemical substance... fatty acid amide hydrochlorides (PMNs P-13-201, P-13-203, P-13-204, P-13-205, P-13-206, P-13-207,...

  2. 40 CFR 721.10520 - Acetylated fatty acid glycerides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Acetylated fatty acid glycerides... Specific Chemical Substances 721.10520 Acetylated fatty acid glycerides (generic). (a) Chemical substance... acetylated fatty acid glycerides (PMN P-11-160) is subject to reporting under this section for...

  3. 40 CFR 721.10691 - Fatty acid amide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide (generic). 721.10691... Substances 721.10691 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-13-267) is...

  4. 40 CFR 721.3710 - Polyether modified fatty acids (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyether modified fatty acids... Specific Chemical Substances 721.3710 Polyether modified fatty acids (generic). (a) Chemical substance... Polyether modified fatty acids (PMN P-99-0435) is subject to reporting under this section for...

  5. 40 CFR 721.10686 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10686... Substances 721.10686 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as fatty acid amides (PMNs...

  6. 40 CFR 721.3710 - Polyether modified fatty acids (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polyether modified fatty acids... Specific Chemical Substances 721.3710 Polyether modified fatty acids (generic). (a) Chemical substance... Polyether modified fatty acids (PMN P-99-0435) is subject to reporting under this section for...

  7. 40 CFR 721.10520 - Acetylated fatty acid glycerides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Acetylated fatty acid glycerides... Specific Chemical Substances 721.10520 Acetylated fatty acid glycerides (generic). (a) Chemical substance... acetylated fatty acid glycerides (PMN P-11-160) is subject to reporting under this section for...

  8. 40 CFR 721.3710 - Polyether modified fatty acids (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polyether modified fatty acids... Specific Chemical Substances 721.3710 Polyether modified fatty acids (generic). (a) Chemical substance... Polyether modified fatty acids (PMN P-99-0435) is subject to reporting under this section for...

  9. 40 CFR 721.10463 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10463... Substances 721.10463 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amides (PMN...

  10. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Fatty acid amide (generic). 721.10320... Substances 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  11. 40 CFR 721.10680 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10680... Substances 721.10680 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as fatty acid amides (PMNs...

  12. 40 CFR 721.3710 - Polyether modified fatty acids (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polyether modified fatty acids... Specific Chemical Substances 721.3710 Polyether modified fatty acids (generic). (a) Chemical substance... Polyether modified fatty acids (PMN P-99-0435) is subject to reporting under this section for...

  13. 40 CFR 721.3710 - Polyether modified fatty acids (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polyether modified fatty acids... Specific Chemical Substances § 721.3710 Polyether modified fatty acids (generic). (a) Chemical substance... Polyether modified fatty acids (PMN P-99-0435) is subject to reporting under this section for...

  14. Mutant fatty acid desaturase and methods for directed mutagenesis

    DOEpatents

    Shanklin, John; Whittle, Edward J.

    2008-01-29

    The present invention relates to methods for producing fatty acid desaturase mutants having a substantially increased activity towards substrates with fewer than 18 carbon atom chains relative to an unmutagenized precursor desaturase having an 18 carbon chain length specificity, the sequences encoding the desaturases and to the desaturases that are produced by the methods. The present invention further relates to a method for altering a function of a protein, including a fatty acid desaturase, through directed mutagenesis involving identifying candidate amino acid residues, producing a library of mutants of the protein by simultaneously randomizing all amino acid candidates, and selecting for mutants which exhibit the desired alteration of function. Candidate amino acids are identified by a combination of methods. Enzymatic, binding, structural and other functions of proteins can be altered by the method.

  15. The nature of fatty acid modifies the equilibrium position in the esterification catalyzed by lipase.

    PubMed

    Flores, M V; Sewalt, J J; Janssen, A E; van der Padt, A

    2000-02-01

    The equilibrium position in lipase mediated esterification of various fatty acids and butanol was studied. The influence of the chain length and the presence of unsaturations in the fatty acids on the equilibrium position was measured and predicted. To predict equilibrium position the program TREP extended (TREPEX) based on the UNIFAC group contribution method was used. Using an equilibrium constant of 35, calculated on the basis of thermodynamic activities, the equilibrium position between butanol and saturated and/or unsaturated fatty acids with different chain lengths can be predicted. The ester mole fraction at equilibrium increases with the fatty acid chain length, and for fatty acids with the same carbon number, the highest values are found for unsaturated fatty acids. For reaction systems containing two saturated fatty acids, a slightly higher mole fraction is obtained for the fatty acid with the higher chain length, while for mixtures consisting of saturated and unsaturated fatty acids, the mole fractions of the unsaturated esters are lower than those of the saturated ones, regardless the chain length of the fatty acid. These experimental results are in good agreement with the calculations with TREPEX. PMID:10620267

  16. Fatty acid-amino acid conjugates diversification in Lepidopteran caterpillars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid amino acid conjugates (FACs) have been found in Noctuid as well as Sphingid caterpillar oral secretions and especially volicitin [N-(17-hydroxylinolenoyl)-L-Glutamine] and its biochemical precursor, N-linolenoyl-L-glutamine, are known elicitors of induced volatile emissions in corn plants...

  17. Intrinsic acyl-CoA thioesterase activity of a peroxisomal ATP binding cassette transporter is required for transport and metabolism of fatty acids.

    PubMed

    De Marcos Lousa, Carine; van Roermund, Carlo W T; Postis, Vincent L G; Dietrich, Daniela; Kerr, Ian D; Wanders, Ronald J A; Baldwin, Stephen A; Baker, Alison; Theodoulou, Frederica L

    2013-01-22

    Peroxisomes are organelles that perform diverse metabolic functions in different organisms, but a common function is β-oxidation of a variety of long chain aliphatic, branched, and aromatic carboxylic acids. Import of substrates into peroxisomes for β-oxidation is mediated by ATP binding cassette (ABC) transporter proteins of subfamily D, which includes the human adrenoleukodystropy protein (ALDP) defective in X-linked adrenoleukodystrophy (X-ALD). Whether substrates are transported as CoA esters or free acids has been a matter of debate. Using COMATOSE (CTS), a plant representative of the ABCD family, we demonstrate that there is a functional and physical interaction between the ABC transporter and the peroxisomal long chain acyl-CoA synthetases (LACS)6 and -7. We expressed recombinant CTS in insect cells and showed that membranes from infected cells possess fatty acyl-CoA thioesterase activity, which is stimulated by ATP. A mutant, in which Serine 810 is replaced by asparagine (S810N) is defective in fatty acid degradation in vivo, retains ATPase activity but has strongly reduced thioesterase activity, providing strong evidence for the biological relevance of this activity. Thus, CTS, and most likely the other ABCD family members, represent rare examples of polytopic membrane proteins with an intrinsic additional enzymatic function that may regulate the entry of substrates into the β-oxidation pathway. The cleavage of CoA raises questions about the side of the membrane where this occurs and this is discussed in the context of the peroxisomal coenzyme A (CoA) budget. PMID:23288899

  18. Fatty acid composition of brown adipose tissue in genetically heat-tolerant FOK rats

    NASA Astrophysics Data System (ADS)

    Ohno, T.; Furuyama, F.; Kuroshima, A.

    The phospholipid fatty acid composition of brown adipose tissue (BAT) was examined in inbred heat-tolerant FOK rats and compared with that in conventional Wistar rats not previously exposed to heat. The FOK rats showed higher unsaturation states, as indicated by higher levels of polyunsaturated fatty acids and a higher unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio. This higher level of unsaturation was characterized by the higher amount of polyunsaturated fatty acids such as linoleic acid, arachidonic acid and docosahexaenoic acid. It may be concluded that the increased docosahexaenoic acid level in BAT phospholipids brings about the hyperplasia of BAT, causing an enhancement of its in vivo thermogernic activity as well as the systemic non-shivering thermogenesis observed in heat-tolerant FOK rats.

  19. Fatty Acid Composition and Volatile Constituents of Protaetia brevitarsis Larvae

    PubMed Central

    Yeo, Hyelim; Youn, Kumju; Kim, Minji; Yun, Eun-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira

    2013-01-01

    A total of 48 different volatile oils were identified form P. brevitarsis larvae by gas chromatography/mass spectrometry (GC/MS). Acids (48.67%) were detected as the major group in P. brevitarsis larvae comprising the largest proportion of the volatile compounds, followed by esters (19.84%), hydrocarbons (18.90%), alcohols (8.37%), miscellaneous (1.71%), aldehydes (1.35%) and terpenes (1.16%). The major volatile constituents were 9-hexadecenoic acid (16.75%), 6-octadecenoic acid (14.88%) and n-hexadecanoic acid (11.06%). The composition of fatty acid was also determined by GC analysis and 16 fatty acids were identified. The predominant fatty acids were oleic acid (C18:1, 64.24%) followed by palmitic acid (C16:0, 15.89%), palmitoleic acid (C16:1, 10.43%) and linoleic acid (C18:2, 4.69%) constituting more than 95% of total fatty acids. The distinguished characteristic of the fatty acid profile of P. brevitarsis larvae was the high proportion of unsaturated fatty acid (80.54% of total fatty acids) versus saturated fatty acids (19.46% of total fatty acids). Furthermore, small but significant amounts of linoleic, linolenic and ?-linolenic acids bestow P. brevitarsis larvae with considerable nutritional value. The novel findings of the present study provide a scientific basis for the comprehensive utilization of the insect as a nutritionally promising food source and a possibility for more effective utilization. PMID:24471125

  20. 40 CFR 721.10629 - Fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acids, tall-oil, reaction... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10629 Fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (generic)....

  1. 40 CFR 721.10629 - Fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acids, tall-oil, reaction... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10629 Fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (generic)....

  2. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    PubMed

    Awasthi, Neeraj Praphulla; Singh, R P

    2007-01-01

    Ammonolysis of fatty acids to the corresponding fatty acid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %. PMID:17898456

  3. Microbial short-chain fatty acid production and extracellular enzymes activities during in vitro fermentation of polysaccharides from the seeds of Plantago asiatica L. treated with microwave irradiation.

    PubMed

    Hu, Jie-Lun; Nie, Shao-Ping; Li, Chang; Fu, Zhi-Hong; Xie, Ming-Yong

    2013-06-26

    Effects of microwave irradiation on microbial short-chain fatty acid production and the activites of extracellular enzymes during in vitro fermentation of the polysaccharide from Plantago asiatica L. were investigated in this study. It was found that the apparent viscosity, average molecular weight, and particle size of the polysaccharide decreased after microwave irradiation. Reducing sugar amount increased with molecular weight decrease, suggesting the degradation may derive from glycosidic bond rupture. The polysaccharide surface topography was changed from large flakelike structure to smaller chips. FT-IR showed that microwave irradiation did not alter the primary functional groups in the polysaccharide. However, short-chain fatty acid productions of the polysaccharide during in vitro fermentation significantly increased after microwave irradiation. Activities of microbial extracellular enzymes xylanase, arabinofuranosidase, xylosidase, and glucuronidase in fermentation cultures supplemented with microwave irradiation treated polysaccharide were also generally higher than those of untreated polysaccharide. This showed that microwave irradiation could be a promising degradation method for the production of value-added polysaccharides. PMID:23738978

  4. DIFFERENTIAL EFFECTS OF SATURATED AND UNSATURATED FATTY ACID DIETS ON CARDIOMYOCYTE APOPTOSIS, ADIPOSE DISTRIBUTION, AND SERUM LEPTIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acids are the primary fuel for the heart and are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes encoding proteins involved in fatty acid metabolism. Saturated fatty acids, particularly palmitate, can be converted to the proapoptotic lipi...

  5. Heterologous Reconstitution of Omega-3 Polyunsaturated Fatty Acids in Arabidopsis

    PubMed Central

    Kim, Sun Hee; Roh, Kyung Hee; Park, Jong-Sug; Kim, Kwang-Soo; Kim, Hyun Uk; Lee, Kyeong-Ryeol; Kang, Han-Chul; Kim, Jong-Bum

    2015-01-01

    Reconstitution of nonnative, very-long-chain polyunsaturated fatty acid (VLC-PUFA) biosynthetic pathways in Arabidopsis thaliana was undertaken. The introduction of three primary biosynthetic activities to cells requires the stable coexpression of multiple proteins within the same cell. Herein, we report that C22 VLC-PUFAs were synthesized from C18 precursors by reactions catalyzed by Δ6-desaturase, an ELOVL5-like enzyme involved in VLC-PUFA elongation, and Δ5-desaturase. Coexpression of the corresponding genes (McD6DES, AsELOVL5, and PtD5DES) under the control of the seed-specific vicilin promoter resulted in production of docosapentaenoic acid (22:5 n-3) and docosatetraenoic acid (22:4 n-6) as well as eicosapentaenoic acid (20:5 n-3) and arachidonic acid (20:4 n-6) in Arabidopsis seeds. The contributions of the transgenic enzymes and endogenous fatty acid metabolism were determined. Specifically, the reasonable synthesis of omega-3 stearidonic acid (18:4 n-3) could be a useful tool to obtain a sustainable system for the production of omega-3 fatty acids in seeds of a transgenic T3 line 63-1. The results indicated that coexpression of the three proteins was stable. Therefore, this study suggests that metabolic engineering of oilseed crops to produce VLC-PUFAs is feasible. PMID:26339641

  6. Supercritical CO₂ extraction of oil, fatty acids and flavonolignans from milk thistle seeds: Evaluation of their antioxidant and cytotoxic activities in Caco-2 cells.

    PubMed

    Ben Rahal, Naila; Barba, Francisco J; Barth, Danielle; Chevalot, Isabelle

    2015-09-01

    The optimal conditions of supercritical carbon dioxide (SC-CO2) (160-220 bars, 40-80 °C) technology combined with co-solvent (ethanol), to recover oil, flavonolignans (silychristin, silydianin and silybinin) and fatty acids from milk thistle seeds, to be used as food additives and/or nutraceuticals, were studied. Moreover, the antioxidant and cytotoxic activities of the SC-CO2 oil seeds extracts were evaluated in Caco-2 carcinoma cells. Pressure and temperature had a significant effect on oil and flavonolignans recovery, although there was not observed a clear trend. SC-CO2 with co-solvent extraction at 220 bars, 40 °C was the optimum treatment to recover oil (30.8%) and flavonolignans from milk thistle seeds. Moreover, linoleic (47.64-66.70%), and oleic (19.68-24.83%) acids were the predominant fatty acids in the oil extracts recovered from milk thistle under SC-CO2. In addition, SC-CO2 extract showed a high antioxidant activity determined by DPPH and ABTS tests. Cytotoxic activities of silychristin, silydianin and silybinin and the obtained SC-CO2 extract (220 bars, 40 °C) were evaluated against Caco-2 cells. The SC-CO2 extract inhibited the proliferation of Caco-2 cells in a dose-responsive manner and induced the highest percentage of mortality of Caco-2 cells (from 43 to 71% for concentrations from 10 up to 100 μg/ml of SC-CO2 oil seeds). PMID:26172510

  7. Supercritical CO₂ extraction of oil, fatty acids and flavonolignans from milk thistle seeds: Evaluation of their antioxidant and cytotoxic activities in Caco-2 cells.

    TOXLINE Toxicology Bibliographic Information

    Ben Rahal N; Barba FJ; Barth D; Chevalot I

    2015-09-01

    The optimal conditions of supercritical carbon dioxide (SC-CO2) (160-220 bars, 40-80 °C) technology combined with co-solvent (ethanol), to recover oil, flavonolignans (silychristin, silydianin and silybinin) and fatty acids from milk thistle seeds, to be used as food additives and/or nutraceuticals, were studied. Moreover, the antioxidant and cytotoxic activities of the SC-CO2 oil seeds extracts were evaluated in Caco-2 carcinoma cells. Pressure and temperature had a significant effect on oil and flavonolignans recovery, although there was not observed a clear trend. SC-CO2 with co-solvent extraction at 220 bars, 40 °C was the optimum treatment to recover oil (30.8%) and flavonolignans from milk thistle seeds. Moreover, linoleic (47.64-66.70%), and oleic (19.68-24.83%) acids were the predominant fatty acids in the oil extracts recovered from milk thistle under SC-CO2. In addition, SC-CO2 extract showed a high antioxidant activity determined by DPPH and ABTS tests. Cytotoxic activities of silychristin, silydianin and silybinin and the obtained SC-CO2 extract (220 bars, 40 °C) were evaluated against Caco-2 cells. The SC-CO2 extract inhibited the proliferation of Caco-2 cells in a dose-responsive manner and induced the highest percentage of mortality of Caco-2 cells (from 43 to 71% for concentrations from 10 up to 100 μg/ml of SC-CO2 oil seeds).

  8. Cultural Characteristics and Fatty Acid Composition of Corynebacterium acnes

    PubMed Central

    Moss, C. Wayne; Dowell, V. R.; Lewis, V. J.; Schekter, M. A.

    1967-01-01

    A detailed study of the cultural characteristics and cellular fatty acid composition of 27 isolates of Corynebacterium acnes was performed to establish the properties by which this organism may be identified and characterized. The fatty acids were extracted directly from whole cells and examined as methyl esters by gas-liquid chromatography. Each strain possessed a similar fatty acid profile which was characterized by a large percentage of C15 branched-chain acid. Uniformity in certain biochemical reactions and cultural characteristics was also observed. All strains were catalase-positive, nonmotile, and urease-negative, reduced nitrate, liquefied gelatin, failed to hydrolyze esculin and starch, and gave a positive methyl red test. Glucose, fructose, and glycerol were fermented, but not lactose, salicin, sucrose, maltose, xylose, or arabinose. Production of hydrogen sulfide and indole, fermentation of mannitol, and hemolytic activity were variable characteristics. Two species of the genus Propionibacterium were also tested and found to be similar to C. acnes both in cultural characteristics and fatty acid composition. The results strengthen previous suggestions that C. acnes should be classified in the genus Propionibacterium. PMID:6057790

  9. Palladium Catalysts for Fatty Acid Deoxygenation: Influence of the Support and Fatty Acid Chain Length on Decarboxylation Kinetics

    SciTech Connect

    Ford, JP; Immer, JG; Lamb, HH

    2012-03-29

    Supported metal catalysts containing 5 wt% Pd on silica, alumina, and activated carbon were evaluated for liquid-phase deoxygenation of stearic (octadecanoic), lauric (dodecanoic), and capric (decanoic) acids under 5 % H-2 at 300 A degrees C and 15 atm. On-line quadrupole mass spectrometry (QMS) was used to measure CO + CO2 yield, CO2 selectivity, H-2 consumption, and initial decarboxylation rate. Post-reaction analysis of liquid products by gas chromatography was used to determine n-alkane yields. The Pd/C catalyst was highly active and selective for stearic acid (SA) decarboxylation under these conditions. In contrast, SA deoxygenation over Pd/SiO2 occurred primarily via decarbonylation and at a much slower rate. Pd/Al2O3 exhibited high initial SA decarboxylation activity but deactivated under the test conditions. Similar CO2 selectivity patterns among the catalysts were observed for deoxygenation of lauric and capric acids; however, the initial decarboxylation rates tended to be lower for these substrates. The influence of alkyl chain length on deoxygenation kinetics was investigated for a homologous series of C-10-C-18 fatty acids using the Pd/C catalyst. As fatty acid carbon number decreases, reaction time and H-2 consumption increase, and CO2 selectivity and initial decarboxylation rate decrease. The increase in initial decarboxylation rates for longer chain fatty acids is attributed to their greater propensity for adsorption on the activated carbon support.

  10. Properties and biosynthesis of cyclopropane fatty acids in Escherichia coli.

    PubMed Central

    Cronan, J E; Reed, R; Taylor, F R; Jackson, M B

    1979-01-01

    The lipid phase transition of Escherichia coli phospholipids containing cyclopropane fatty acids was compared with the otherwise homologous phospholipids lacking cyclopropane fatty acids. The phase transitions (determined by scanning calorimetry) of the two preparations were essentially identical. Infection of E. coli with phage T3 inhibited cyclopropane fatty acid formation over 98%, whereas infection with mutants which lack the phage coded S-adenosylmethionine cleavage enzyme had no effect on cyclopropane fatty acid synthesis. These data indicate that S-adenosylmethionine is the methylene in cyclopropane fatty acid synthesis. PMID:374358

  11. Genetic Variation of Fatty Acid Oxidation and Obesity, A Literature Review

    PubMed Central

    Freitag Luglio, Harry

    2016-01-01

    Modulation of fat metabolism is an important component of the etiology of obesity as well as individual response to weight loss program. The influence of lipolysis process had receives many attentions in recent decades. Compared to that, fatty acid oxidation which occurred after lipolysis seems to be less exposed. There are limited publications on how fatty acid oxidation influences predisposition to obesity, especially the importance of genetic variations of fatty acid oxidation proteins on development of obesity. The aim of this review is to provide recent knowledge on how polymorphism of genes related fatty acid oxidation is obtained. Studies in human as well as animal model showed that disturbance of genes related fatty acid oxidation process gave impact on body weight and risks to obesity. Several polymorphisms on CD36, CPT, ACS and FABP had been shown to be related to obesity either by regulating enzymatic activity or directly influence fatty acid oxidation process. PMID:27127449

  12. Regulation of Inflammation by Short Chain Fatty Acids

    PubMed Central

    Vinolo, Marco A.R.; Rodrigues, Hosana G.; Nachbar, Renato T.; Curi, Rui

    2011-01-01

    The short chain fatty acids (SCFAs) acetate (C2), propionate (C3) and butyrate (C4) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted. PMID:22254083

  13. 21 CFR 172.854 - Polyglycerol esters of fatty acids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....860(b) and/or oleic acid derived from tall oil fatty acids meeting the requirements of § 172.862. (b... to perform its cloud-inhibiting effect. Oleic acid derived from tall oil fatty acids conforming with § 172.862 may be used as a substitute for or together with the oleic acid permitted by this...

  14. Identification of fatty acids in canine seminal plasma.

    PubMed

    Díaz, R; Inostroza, K; Risopatrón, J; Sanchez, R; Sepúlveda, N

    2014-03-01

    Seminal plasma contains various biochemical components associated with sperm function. However, there is limited information regarding the fatty acid composition of seminal plasma and their effect on sperm. The aim of this study was to identify the fatty acid content in canine seminal plasma using gas chromatography. Twelve ejaculates were studied, the seminal plasma was obtained by centrifugation and then the lipids were extracted, methylated and analysed by chromatography. The total lipids in the seminal plasma were 2.5 ± 0.3%, corresponding to 85% saturated fatty acids (SFA) and 15% unsaturated fatty acids (UFA). The greatest proportions of SFA were palmitic acid (30.4%), stearic acid (23.4%) and myristic acid (5.3%) and of UFA oleic acid (9.0%). Therefore, the protocols and techniques used enabled the identification of 18 different fatty acids in canine seminal plasma, which constitutes a good method to evaluate and quantify the fatty acid profile in this species. PMID:23398451

  15. Dual mechanisms for telomerase inhibition in DLD-1 human colorectal adenocarcinoma cells by polyunsaturated fatty acids.

    PubMed

    Eitsuka, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Teruo

    2004-01-01

    Polyunsaturated fatty acids (PUFAs) have been reported to have antitumor activity. In this study, we have tested whether telomerase might be a target for the antitumor effect of fatty acids using DLD-1 colorectal adenocarcinoma cells. In a cell-free approach, fatty acids were added directly to cell lysates, and we confirmed that increasing fatty acid unsaturation correlates with increased inhibition of telomerase activity. Using a cell culture approach, DLD-1 cells were cultured with fatty acids. In a time and dose dependent manner, EPA and DHA suppressed cellular telomerase activity and the mRNAs encoding hTERT (human telomerase reverse transcriptase) and c-myc. Based on these observations, we suggest that PUFAs inhibit telomerase activity through dual mechanisms: direct inhibition of enzymatic activity and down regulation of hTERT, one of the telomerase components. PMID:15630164

  16. Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition

    PubMed Central

    Kishino, Shigenobu; Takeuchi, Michiki; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kunisawa, Jun; Kiyono, Hiroshi; Iwamoto, Ryo; Isobe, Yosuke; Arita, Makoto; Arai, Hiroyuki; Ueda, Kazumitsu; Shima, Jun; Takahashi, Satomi; Yokozeki, Kenzo; Shimizu, Sakayu; Ogawa, Jun

    2013-01-01

    In the representative gut bacterium Lactobacillus plantarum, we identified genes encoding the enzymes involved in a saturation metabolism of polyunsaturated fatty acids and revealed in detail the metabolic pathway that generates hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and partially saturated trans-fatty acids as intermediates. Furthermore, we observed these intermediates, especially hydroxy fatty acids, in host organs. Levels of hydroxy fatty acids were much higher in specific pathogen-free mice than in germ-free mice, indicating that these fatty acids are generated through polyunsaturated fatty acids metabolism of gastrointestinal microorganisms. These findings suggested that lipid metabolism by gastrointestinal microbes affects the health of the host by modifying fatty acid composition. PMID:24127592

  17. The effect of progesterone on prolactin stimulation of fatty acid synthesis, glycerolipid synthesis and lipogenic-enzyme activities in mammary glands of pseudopregnant rabbits, after explant culture or intraductal injection.

    PubMed Central

    Martyn, P; Falconer, I R

    1985-01-01

    The activities of lipogenic enzymes, such as acetyl-CoA carboxylase, fatty acid synthetase and glucose-6-phosphate dehydrogenase, and glycerolipid synthesis increased significantly in mammary explants of 11-day-pseudopregnant rabbits in response to prolactin, in the presence of near-physiological concentrations of insulin and corticosterone in culture. Increasing the concentration of progesterone in culture resulted in suppression of glycerolipid synthesis and activities of acetyl-CoA carboxylase and fatty acid synthetase, but not the pentose phosphate dehydrogenases. However, at near-physiological concentration of progesterone, only acetyl-CoA carboxylase activity was decreased. Injection of prolactin intraductally into 11-day-pseudopregnant rabbits stimulated glycerolipid synthesis, fatty acid synthesis and enzymes involved in fatty acid synthesis, after 3 days. Intraductal injection of progesterone separately or together with prolactin had no significant effect on basal or stimulated lipogenesis in mammary glands. Intramuscular injection of progesterone at 10 mg/day did not suppress fatty acid synthesis stimulated when prolactin was injected intraductally, but a significant inhibition was observed at a higher dose (80 mg/day). PMID:4062899

  18. [Non-esterified fatty acids of blood serum in type 1 diabetic women during late pregnancy].

    PubMed

    Shablinski?, M A; Milent'ev, A Yu; Lotosh, N Yu; Selishcheva, A A; Badyshtov, B A; Besova, N V; Savel'ev, S V

    2014-01-01

    Using gas chromatography a comparative study of the range and content of individual non-esterified fatty acids in serum of patients with diabetes mellitus type 1 in the third trimester of pregnancy, and healthy pregnant and non-pregnant women has been carried out. In groups of pregnant women there was activation of lipid metabolism, confirmed by corresponding changes in serum biochemical parameters, as well as in the content of non-esterified fatty acids. Intergroup differences in the non-esterified fatty acids were not found. However, there were significant differences between the examined groups in the quantitative content of non-esterified fatty acids. PMID:25552510

  19. Transforming triglycerides and fatty acids into biofuels.

    PubMed

    Lestari, Siswati; Mäki-Arvela, Päivi; Beltramini, Jorge; Lu, G Q Max; Murzin, Dmitry Yu

    2009-01-01

    Fuels derived from biobased materials are attracting attention for their potential in securing the energy supply and protecting the environment. In this Minireview, we evaluate the use of biobased sources, particularly fatty acids and triglycerides from seed oils and animal fats, as fuels. The physical and chemical properties of these fatty acids and triglycerides are discussed, including the link to their sources and current availability to meet fuel demands. The current technologies, also known as the first-generation ones, for converting triglycerides into fuels are covered, including conventional methods such as transesterification, pyrolysis, cracking, and emulsions. Recent, second-generation technological developments that lead to more commercially viable biofuels based on diesel-like hydrocarbons are also discussed. PMID:19862784

  20. Metabolic engineering of Pichia pastoris to produce ricinoleic acid, a hydroxy fatty acid of industrial importance.

    PubMed

    Meesapyodsuk, Dauenpen; Chen, Yan; Ng, Siew Hon; Chen, Jianan; Qiu, Xiao

    2015-11-01

    Ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) has many specialized uses in bioproduct industries, while castor bean is currently the only commercial source for the fatty acid. This report describes metabolic engineering of a microbial system (Pichia pastoris) to produce ricinoleic acid using a "push" (synthesis) and "pull" (assembly) strategy. CpFAH, a fatty acid hydroxylase from Claviceps purpurea, was used for synthesis of ricinoleic acid, and CpDGAT1, a diacylglycerol acyl transferase for the triacylglycerol synthesis from the same species, was used for assembly of the fatty acid. Coexpression of CpFAH and CpDGAT1 produced higher lipid contents and ricinoleic acid levels than expression of CpFAH alone. Coexpression in a mutant haploid strain defective in the Δ12 desaturase activity resulted in a higher level of ricinoleic acid than that in the diploid strain. Intriguingly, the ricinoleic acid prod