WorldWideScience

Sample records for cell fatty acid

  1. Nature of the elements transporting long-chain fatty acids through the red cell membrane

    DEFF Research Database (Denmark)

    Bojesen, Inge Norby; Bojesen, Eigil

    1998-01-01

    Docosahexaenoic acid, linoleic acid, red cell membrane, transporting elements, transport kinetics, fatty acid transport......Docosahexaenoic acid, linoleic acid, red cell membrane, transporting elements, transport kinetics, fatty acid transport...

  2. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  3. Differentiation of Bacillus anthracis from Bacillus cereus by gas chromatographic whole-cell fatty acid analysis.

    OpenAIRE

    Lawrence, D; Heitefuss, S; Seifert, H S

    1991-01-01

    Three strains of Bacillus anthracis and seven strains of Bacillus cereus were grown on complex medium and on synthetic medium. Gas chromatographic analysis of whole-cell fatty acids of strains grown on complex medium gave nearly identical fatty acid patterns. Fatty acid patterns of strains grown on synthetic medium showed a high content of branched-chain fatty acids. Significant differences between the fatty acid patterns of the two species were found. Odd iso/anteiso fatty acid ratios were a...

  4. Cryptococcal 3-Hydroxy Fatty Acids Protect Cells Against Amoebal Phagocytosis.

    Science.gov (United States)

    Madu, Uju L; Ogundeji, Adepemi O; Mochochoko, Bonang M; Pohl, Carolina H; Albertyn, Jacobus; Swart, Chantel W; Allwood, J William; Southam, Andrew D; Dunn, Warwick B; May, Robin C; Sebolai, Olihile M

    2015-01-01

    We previously reported on a 3-hydroxy fatty acid that is secreted via cryptococcal capsular protuberances - possibly to promote pathogenesis and survival. Thus, we investigated the role of this molecule in mediating the fate of Cryptococcus (C.) neoformans and the related species C. gattii when predated upon by amoebae. We show that this molecule protects cells against the phagocytic effects of amoebae. C. neoformans UOFS Y-1378 (which produces 3-hydroxy fatty acids) was less sensitive toward amoebae compared to C. neoformans LMPE 046 and C. gattii R265 (both do not produce 3-hydroxy fatty acids) and addition of 3-hydroxy fatty acids to C. neoformans LMPE 046 and C. gattii R265 culture media, causes these strains to become more resistant to amoebal predation. Conversely, addition of aspirin (a 3-hydroxy fatty acid inhibitor) to C. neoformans UOFS Y-1378 culture media made cells more susceptible to amoebae. Our data suggest that this molecule is secreted at a high enough concentration to effect intracellular signaling within amoeba, which in turn, promotes fungal survival.

  5. Cryptococcal 3-hydroxy fatty acids protect cells against amoebal phagocytosis

    Directory of Open Access Journals (Sweden)

    Uju Lynda Madu

    2015-12-01

    Full Text Available We previously reported on a 3-hydroxy fatty acid that is secreted via cryptococcal capsular protuberances - possibly to promote pathogenesis and survival. Thus, we investigated the role of this molecule in mediating the fate of Cryptococcus (C. neoformans and the related species C. gattii when predated upon by amoebae. We show that this molecule protects cells against the phagocytic effects of amoebae. C. neoformans UOFS Y-1378 (which produces 3-hydroxy fatty acids was less sensitive towards amoebae compared to C. neoformans LMPE 046 and C. gattii R265 (both do not produce 3-hydroxy fatty acids and addition of 3-hydroxy fatty acids to C. neoformans LMPE 046 and C. gattii R265 culture media, causes these strains to become more resistant to amoebal predation. Conversely, addition of aspirin (a 3-hydroxy fatty acid inhibitor to C. neoformans UOFS Y-1378 culture media made cells more susceptible to amoebae. Our data suggest that this molecule is secreted at a high enough concentration to effect intracellular signalling within amoeba, which in turn, promotes fungal survival.

  6. Metabolically engineered cells for the production of polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    2005-01-01

    The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves improvem......The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves...... improvement of the PUFA content in the host organism through fermentation optimization, e.g. decreasing the temperature and/or designing an optimal medium, or through improving the flux towards fatty acids by metabolic engineering, e.g. through over-expression of fatty acid synthases, over-expression of other...... enzymes involved in biosynthesis of the precursor for PUFAs, or codon optimization of the heterologous genes, or expression of heterologous enzymes involved in the biosynthesis of the precursor for PUFAs....

  7. Furan fatty acids efficiently rescue brain cells from cell death induced by oxidative stress

    NARCIS (Netherlands)

    Teixeira, A.; Cox, R.C.; Egmond, M.R.

    2013-01-01

    Treatment of rat brain C6 astroglioma cells with furan fatty acid F6 prior to exposure to hydrogen peroxide shows a strong protective effect of F6 against cell death resulting from oxidative stress. This protective effect is obtained only for F6 administered as a free fatty acid and with an intact f

  8. Gene transfer of Chlorella vulgaris n-3 fatty acid desaturase optimizes the fatty acid composition of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Meilan Xue

    2012-12-01

    Full Text Available Chlorella vulgaris has the gene of n-3 fatty acid desaturase (CvFad3, which can synthesize the precursor of n-3 polyunsaturated fatty acids (PUFAs or convert n-6 to n-3 PUFAs. The objective of the present study was to examine whether the CvFad3 gene from C. vulgaris can be functionally and efficiently expressed in human breast cancer cells and whether its expression can exert a significant effect on cell fatty acid composition. We inserted the CvFad3 gene into the plasmid pEGFP-C3 to construct the eukaryotic expression vector pEGFP-C3-n-3 and to express the n-3 Fad gene in human breast cancer cells (MCF-7 cells. Transfection of MCF-7 cells with the recombinant vector resulted in a high expression of n-3 fatty acid desaturase. Lipid analysis indicated that the ratio of n-6/n-3 PUFAs was decreased from 6:1 in the control cells to about 1:1 in the cells expressing the n-3 fatty acid desaturase. Accordingly, the CvFad3 gene significantly decreased the ratio of n-6/n-3 PUFAs of the MCF-7 cell membrane. The expression of the CvFad3 gene can decrease cell proliferation and promote cell apoptosis. This study demonstrates that the CvFad3 gene can dramatically balance the ratio of n-6/n-3 PUFAs and may provide an effective approach to the modification of the fatty acid composition of mammalian cells, also providing a basis for potential applications of its transfer in experimental and clinical settings.

  9. Gene transfer of Chlorella vulgaris n-3 fatty acid desaturase optimizes the fatty acid composition of human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Meilan; Ge, Yinlin; Zhang, Jinyu [Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao Shandong (China); Wang, Qing [Affiliated Hospital of Qingdao University, Qingdao Shandong (China); Hou, Lin [Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao Shandong (China)

    2012-09-14

    Chlorella vulgaris has the gene of n-3 fatty acid desaturase (CvFad3), which can synthesize the precursor of n-3 polyunsaturated fatty acids (PUFAs) or convert n-6 to n-3 PUFAs. The objective of the present study was to examine whether the CvFad3 gene from C. vulgaris can be functionally and efficiently expressed in human breast cancer cells and whether its expression can exert a significant effect on cell fatty acid composition. We inserted the CvFad3 gene into the plasmid pEGFP-C3 to construct the eukaryotic expression vector pEGFP-C3-n-3 and to express the n-3 Fad gene in human breast cancer cells (MCF-7 cells). Transfection of MCF-7 cells with the recombinant vector resulted in a high expression of n-3 fatty acid desaturase. Lipid analysis indicated that the ratio of n-6/n-3 PUFAs was decreased from 6:1 in the control cells to about 1:1 in the cells expressing the n-3 fatty acid desaturase. Accordingly, the CvFad3 gene significantly decreased the ratio of n-6/n-3 PUFAs of the MCF-7 cell membrane. The expression of the CvFad3 gene can decrease cell proliferation and promote cell apoptosis. This study demonstrates that the CvFad3 gene can dramatically balance the ratio of n-6/n-3 PUFAs and may provide an effective approach to the modification of the fatty acid composition of mammalian cells, also providing a basis for potential applications of its transfer in experimental and clinical settings.

  10. The Role of Fatty Acids and Caveolin-1 in TNF-α-Induced Endothelial Cell Activation

    OpenAIRE

    Wang, Lei; Lim, Eun-Jin; Toborek, Michal; Hennig, Bernhard

    2008-01-01

    Hypertriglyceridemia and associated high circulating free fatty acids are important risk factors of atherosclerosis. In contrast to omega-3 fatty acids, linoleic acid, the major omega-6 unsaturated fatty acid in the American diet, may be atherogenic by amplifying an endothelial inflammatory response. We hypothesize that omega-6 and omega-3 fatty acids can differentially modulate TNF-α-induced endothelial cell activation and that functional plasma membrane microdomains called caveolae are requ...

  11. Smoking and red blood cell phospholipid membrane fatty acids.

    Science.gov (United States)

    Murff, H J; Tindle, H A; Shrubsole, M J; Cai, Q; Smalley, W; Milne, G L; Swift, L L; Ness, R M; Zheng, W

    2016-09-01

    Smoking is associated with lower n-3 long chain polyunsaturated fatty acids (LCPUFA) concentrations; however, limited studies have accounted for dietary PUFA intake or whether tobacco dose or smoking duration influences this association. We measured red blood cell phospholipid (RBC) membrane concentrations of fatty acids in 126 current smokers, 311 former smokers, and 461 never smokers using gas liquid chromatography and tandem mass spectrometry. Smokers had lower RBC membrane percentages of total n-3 LCPUFAs compared to former smokers or never smokers (median percent: 5.46, [interquartile range (IQR) 4.52, 6.28] versus 6.39; [IQR: 5.18, 7.85] versus 6.59; [IQR 5.34, 8.01]) (psmoking and cigarettes per day were not associated with RBC membrane n-3 LCPUFA differences. Smoking is associated with lower n-3 LCPUFA RBC membrane percentages and this association was not influenced by diet or smoking dose or duration. PMID:27637337

  12. Stimulation of proliferation of an essential fatty acid-deficient fish cell line by C20 and C22 polyunsaturated fatty acids and effects on fatty acid composition.

    Science.gov (United States)

    Tocher, D R; Dick, J R; Sargent, J R

    1996-11-01

    Recently we reported the development of a fish cell line, EPC-EFAD, derived from the carp (Cyprinus carpio) epithelial papilloma line, EPC, that could survive and proliferate in essential fatty acid-deficient (EFAD) medium. The EPC-EFAD cell line may be a useful model system in which to study the cellular biochemical effects of EFA deficiency and has advantages in studies of polyunsaturated fatty acid (PUFA) and eicosanoid metabolism in fish in that the complications introduced by culture in relatively n-6 PUFA-rich mammalian sera are removed. In the present study, the effects on cell proliferation rate of supplementing EPC-EFAD cells with various n-3 and n-6 PUFA were investigated to determine the possible role(s) of PUFA in cell growth and division. The selectivity of incorporation of specific PUFA into individual glycerophospholipid classes and the feasibility of reproducing in vivo fatty acid compositions in vitro were also investigated. Proliferation of the EPC-EFAD cell line was stimulated by arachidonic (20:4 n-6), eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) fatty acids but not by 18:2 n-6 or 18:3 n-3. The differential effects of PUFA on cellular proliferation may be related to the lack of significant delta 5 desaturase activity in the cells at 22 degrees C and may implicate a role for eicosanoids in the mechanism of stimulation of proliferation. PUFA supplementation increased the cytotoxic effects of longer term culture, an effect that was partly alleviated by inclusion of vitamin E in the culture medium. The cells could generally be supplemented with PUFA to produce cellular fatty acid compositions in vitro that were similar to in vivo compositions. PMID:8981632

  13. Omega-3 fatty acids, lipid rafts, and T cell signaling.

    Science.gov (United States)

    Hou, Tim Y; McMurray, David N; Chapkin, Robert S

    2016-08-15

    n-3 polyunsaturated fatty acids (PUFA) have been shown in many clinical studies to attenuate inflammatory responses. Although inflammatory responses are orchestrated by a wide spectrum of cells, CD4(+) T cells play an important role in the etiology of many chronic inflammatory diseases such as inflammatory bowel disease and obesity. In light of recent concerns over the safety profiles of non-steroidal anti-inflammatory drugs (NSAIDs), alternatives such as bioactive nutraceuticals are becoming more attractive. In order for these agents to be accepted into mainstream medicine, however, the mechanisms by which nutraceuticals such as n-3 PUFA exert their anti-inflammatory effects must be fully elucidated. Lipid rafts are nanoscale, dynamic domains in the plasma membrane that are formed through favorable lipid-lipid (cholesterol, sphingolipids, and saturated fatty acids) and lipid-protein (membrane-actin cytoskeleton) interactions. These domains optimize the clustering of signaling proteins at the membrane to facilitate efficient cell signaling which is required for CD4(+) T cell activation and differentiation. This review summarizes novel emerging data documenting the ability of n-3 PUFA to perturb membrane-cytoskeletal structure and function in CD4(+) T cells. An understanding of these underlying mechanisms will provide a rationale for the use of n-3 PUFA in the treatment of chronic inflammation.

  14. p63 promotes cell survival through fatty acid synthase.

    Directory of Open Access Journals (Sweden)

    Venkata Sabbisetti

    Full Text Available There is increasing evidence that p63, and specifically DeltaNp63, plays a central role in both development and tumorigenesis by promoting epithelial cell survival. However, few studies have addressed the molecular mechanisms through which such important function is exerted. Fatty acid synthase (FASN, a key enzyme that synthesizes long-chain fatty acids and is involved in both embryogenesis and cancer, has been recently proposed as a direct target of p53 family members, including p63 and p73. Here we show that knockdown of either total or DeltaN-specific p63 isoforms in squamous cell carcinoma (SCC9 or immortalized prostate epithelial (iPrEC cells caused a decrease in cell viability by inducing apoptosis without affecting the cell cycle. p63 silencing significantly reduced both the expression and the activity of FASN. Importantly, stable overexpression of either FASN or myristoylated AKT (myr-AKT was able to partially rescue cells from cell death induced by p63 silencing. FASN induced AKT phosphorylation and a significant reduction in cell viability was observed when FASN-overexpressing SCC9 cells were treated with an AKT inhibitor after p63 knockdown, indicating that AKT plays a major role in FASN-mediated survival. Activated AKT did not cause any alteration in the FASN protein levels but induced its activity, suggesting that the rescue from apoptosis documented in the p63-silenced cells expressing myr-AKT cells may be partially mediated by FASN. Finally, we demonstrated that p63 and FASN expression are positively associated in clinical squamous cell carcinoma samples as well as in the developing prostate. Taken together, our findings demonstrate that FASN is a functionally relevant target of p63 and is required for mediating its pro-survival effects.

  15. Liver Fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet induced nonalcoholic fatty liver disease

    OpenAIRE

    Chen, Anping; Tang, Youcai; Davis, Victoria; Hsu, Fong-Fu; Kennedy, Susan M; Song, Haowei; Turk, John; Brunt, Elizabeth M.; Newberry, Elizabeth P.; Davidson, Nicholas O.

    2013-01-01

    Activation of hepatic stellate cells (HSCs) is crucial to the development of fibrosis in nonalcoholic fatty liver disease. Quiescent HSCs contain lipid droplets (LDs), whose depletion upon activation induces a fibrogenic gene program. Here we show that liver fatty acid-binding protein (L-Fabp), an abundant cytosolic protein that modulates fatty acid (FA) metabolism in enterocytes and hepatocytes also modulates HSC FA utilization and in turn regulates the fibrogenic program. L-Fabp expression ...

  16. The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

    Science.gov (United States)

    Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

    2014-01-01

    Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. PMID:24240104

  17. Modulation of the chicken immune cell function by dietary polyunsaturated fatty acids

    NARCIS (Netherlands)

    Sijben, J.W.C.

    2002-01-01

    Polyunsaturated fatty acids (PUFA) possess a wide range of biological properties, including immunomodulation. The amount, type, and ratio of dietary PUFA determine the types of fatty acids that are incorporated into immune cell membranes. Consequently, the physiological properties of immune cells an

  18. Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate.

    Science.gov (United States)

    Dueregger, Andrea; Schöpf, Bernd; Eder, Theresa; Höfer, Julia; Gnaiger, Erich; Aufinger, Astrid; Kenner, Lukas; Perktold, Bernhard; Ramoner, Reinhold; Klocker, Helmut; Eder, Iris E

    2015-01-01

    Tumor cells adapt via metabolic reprogramming to meet elevated energy demands due to continuous proliferation, for example by switching to alternative energy sources. Nutrients such as glucose, fatty acids, ketone bodies and amino acids may be utilized as preferred substrates to fulfill increased energy requirements. In this study we investigated the metabolic characteristics of benign and cancer cells of the prostate with respect to their utilization of medium chain (MCTs) and long chain triglycerides (LCTs) under standard and glucose-starved culture conditions by assessing cell viability, glycolytic activity, mitochondrial respiration, the expression of genes encoding key metabolic enzymes as well as mitochondrial mass and mtDNA content. We report that BE prostate cells (RWPE-1) have a higher competence to utilize fatty acids as energy source than PCa cells (LNCaP, ABL, PC3) as shown not only by increased cell viability upon fatty acid supplementation but also by an increased ß-oxidation of fatty acids, although the base-line respiration was 2-fold higher in prostate cancer cells. Moreover, BE RWPE-1 cells were found to compensate for glucose starvation in the presence of fatty acids. Of notice, these findings were confirmed in vivo by showing that PCa tissue has a lower capacity in oxidizing fatty acids than benign prostate. Collectively, these metabolic differences between benign and prostate cancer cells and especially their differential utilization of fatty acids could be exploited to establish novel diagnostic and therapeutic strategies. PMID:26285134

  19. Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate.

    Directory of Open Access Journals (Sweden)

    Andrea Dueregger

    Full Text Available Tumor cells adapt via metabolic reprogramming to meet elevated energy demands due to continuous proliferation, for example by switching to alternative energy sources. Nutrients such as glucose, fatty acids, ketone bodies and amino acids may be utilized as preferred substrates to fulfill increased energy requirements. In this study we investigated the metabolic characteristics of benign and cancer cells of the prostate with respect to their utilization of medium chain (MCTs and long chain triglycerides (LCTs under standard and glucose-starved culture conditions by assessing cell viability, glycolytic activity, mitochondrial respiration, the expression of genes encoding key metabolic enzymes as well as mitochondrial mass and mtDNA content. We report that BE prostate cells (RWPE-1 have a higher competence to utilize fatty acids as energy source than PCa cells (LNCaP, ABL, PC3 as shown not only by increased cell viability upon fatty acid supplementation but also by an increased ß-oxidation of fatty acids, although the base-line respiration was 2-fold higher in prostate cancer cells. Moreover, BE RWPE-1 cells were found to compensate for glucose starvation in the presence of fatty acids. Of notice, these findings were confirmed in vivo by showing that PCa tissue has a lower capacity in oxidizing fatty acids than benign prostate. Collectively, these metabolic differences between benign and prostate cancer cells and especially their differential utilization of fatty acids could be exploited to establish novel diagnostic and therapeutic strategies.

  20. Polyunsaturated fatty acids and inflammation

    OpenAIRE

    Calder Philip C

    2004-01-01

    The n-6 polyunsaturated fatty acid arachidonic acid gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites) and through these regulates the activities of inflammatory cells, the production of cytokines and the various balances within the immune system. Fish oil and oily fish are good sources of long chain n-3 polyunsaturated fatty acids. Consumption of these fatty acids decreases the amount of arachidonic acid in cell membranes and ...

  1. Metabolically Engineered Fungal Cells With Increased Content Of Polyunsaturated Fatty Acids

    DEFF Research Database (Denmark)

    2008-01-01

    This invention relates to the production of fatty acids and particularly to the production of the polyunsaturated fatty acids (PUFAs) arachidonic acid (ARA) and eicosapentaenoic acid (EPA) in genetically engineered fungal cells, in particular, to metabolically engineered Saccharomyces cerevisiae...... cells with increased content of ARA and EPA. The invention especially involves improvement of the PUFA content in the host organism through various over-expression of e.g. cytochrome b5 and cytochrome b5 reductase involved in fatty acid desaturation, and heterologous expression of cytochrome b5...

  2. Polyunsaturated fatty acid supplementation stimulates differentiation of oligodendroglia cells

    NARCIS (Netherlands)

    van Meeteren, ME; Baron, W; Beermann, C; van Tol, EAF

    2006-01-01

    Dietary polyunsaturated fatty acids (PUFAs) have been postulated as alternative supportive treatment for multiple sclerosis, since they may promote myelin repair. We set out to study the effect of supplementation with n-3 and n-6 PUFAs on OLN-93 oligodendroglia and rat primary oligodendrocyte differ

  3. Cell membrane fatty acid composition differs between normal and malignant cell lines.

    Science.gov (United States)

    Meng, Xialong; Riordan, Neil H; Riordan, Hugh D; Mikirova, Nina; Jackson, James; González, Michael J; Miranda-Massari, Jorge R; Mora, Edna; Trinidad Castillo, Waleska

    2004-06-01

    Twenty-eight fatty acids (C8:0 to C24:l n-9) were measured by gas chromatography in four normal cell lines (C3H / 10T1 / 2, CCD-18Co, CCD-25SK and CCD-37Lu) and seven cancer cell lines (C-41, Caov-3, LS-180, PC-3, SK-MEL-28, SK-MES-1 and U-87 MG). Results show differences in the content and proportions of fatty acids when comparing cancer cell lines with their normal counterparts. Cancer cell lines showed lower C20: 4 n-6, C24:1 n-9, polyunsaturated fatty acids (PUFA's) and ratios of C20:4 n-6 to C20:5 n-3 and C16:0 to C18:1 n-9 and stearic to oleic (SA/OA) than their normal counterparts. All cancer cell lines had SA/OA ratios lower than 7.0 while normal cell lines had ratios greater than 0.7 (p<0.05). In addition, the ratios of total saturated fatty acids (SFA) to PUFA'S and the concentration of C18:1 n-9, C18:2 n-6, C20:5 n-3 were higher in cancer cell lines as compared to normal cell lines. A positive correlation was detected between C16:0 and longer SFA'S (r = +0.511, p<0.05) in normal cell lines whereas a negative correlation (r=0.608, p<0.05) was obtained for malignant cell lines. Moreover, cancerous cell lines exhibited a particular desaturation defect and an abnormal incorporation of C18:2 n-6 and C20-4 n-6 fatty acids. PMID:15377057

  4. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories

    DEFF Research Database (Denmark)

    Zhou, Yongjin J.; Buijs, Nicolaas A; Zhu, Zhiwei;

    2016-01-01

    -level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l−1 of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous...... alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l−1) and fatty alcohols (1.5 g l−1), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories...

  5. Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells

    OpenAIRE

    E. P. da Silva; Nachbar, R. T.; Levada-Pires, A. C.; Hirabara, S. M.; Lambertucci, R. H.

    2015-01-01

    During physical activity, increased reactive oxygen species production occurs, which can lead to cell damage and in a decline of individual’s performance and health. The use of omega-3 polyunsaturated fatty acids as a supplement to protect the immune system has been increasing; however, their possible benefit to the anti-oxidant system is not well described. Thus, the aim of this study was to evaluate whether the omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) can be bene...

  6. Isolation of fatty acids and aromatics from cell suspension cultures of Lavandula angustifolia.

    Science.gov (United States)

    Topçu, Gülaçti; Herrmann, Gabriele; Kolak, Ufuk; Gören, C; Porzel, Andrea; Kutchan, Toni M

    2007-02-01

    Cell suspension cultures of Lavandula angustifolia Mill. ssp. angustifolia (syn.: L. officinalis Chaix.) afforded a fatty acid composition, cis and trans p-coumaric acids (=p-hydroxy cinnamic acids), and beta-sitosterol. The fatty acid composition was analyzed by GC-MS, and the structures of the isolated three compounds were determined by 1H- and 13C-NMR, and MS spectroscopic techniques.

  7. Potential Role of Omega-3 Fatty Acids on the Myogenic Program of Satellite Cells.

    Science.gov (United States)

    Bhullar, Amritpal S; Putman, Charles T; Mazurak, Vera C

    2016-01-01

    Skeletal muscle loss is associated with aging as well as pathological conditions. Satellite cells (SCs) play an important role in muscle regeneration. Omega-3 fatty acids are widely studied in a variety of muscle wasting diseases; however, little is known about their impact on skeletal muscle regeneration. The aim of this review is to evaluate studies examining the effect of omega-3 fatty acids, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on the regulation of SC proliferation and differentiation. This review highlights mechanisms by which omega-3 fatty acids may modulate the myogenic program of the stem cell population within skeletal muscles and identifies considerations for future studies. It is proposed that minimally three myogenic transcriptional regulatory factors, paired box 7 (Pax7), myogenic differentiation 1 protein, and myogenin, should be measured to confirm the stage of SCs within the myogenic program affected by omega-3 fatty acids.

  8. Effect of fatty acids on human bone marrow mesenchymal stem cell energy metabolism and survival.

    Science.gov (United States)

    Fillmore, Natasha; Huqi, Alda; Jaswal, Jagdip S; Mori, Jun; Paulin, Roxane; Haromy, Alois; Onay-Besikci, Arzu; Ionescu, Lavinia; Thébaud, Bernard; Michelakis, Evangelos; Lopaschuk, Gary D

    2015-01-01

    Successful stem cell therapy requires the optimal proliferation, engraftment, and differentiation of stem cells into the desired cell lineage of tissues. However, stem cell therapy clinical trials to date have had limited success, suggesting that a better understanding of stem cell biology is needed. This includes a better understanding of stem cell energy metabolism because of the importance of energy metabolism in stem cell proliferation and differentiation. We report here the first direct evidence that human bone marrow mesenchymal stem cell (BMMSC) energy metabolism is highly glycolytic with low rates of mitochondrial oxidative metabolism. The contribution of glycolysis to ATP production is greater than 97% in undifferentiated BMMSCs, while glucose and fatty acid oxidation combined only contribute 3% of ATP production. We also assessed the effect of physiological levels of fatty acids on human BMMSC survival and energy metabolism. We found that the saturated fatty acid palmitate induces BMMSC apoptosis and decreases proliferation, an effect prevented by the unsaturated fatty acid oleate. Interestingly, chronic exposure of human BMMSCs to physiological levels of palmitate (for 24 hr) reduces palmitate oxidation rates. This decrease in palmitate oxidation is prevented by chronic exposure of the BMMSCs to oleate. These results suggest that reducing saturated fatty acid oxidation can decrease human BMMSC proliferation and cause cell death. These results also suggest that saturated fatty acids may be involved in the long-term impairment of BMMSC survival in vivo.

  9. Estimating Fatty Acid Composition of Infant Buccal Mucosal Cells by Capillary Gas Chromatography

    Institute of Scientific and Technical Information of China (English)

    CHEN Fei; ZHANG Wei-li; LI Fang; ZHU Xiao-dong; ZHU Jian-xing

    2008-01-01

    Long chain polyunsaturated fatty adds, i. e., docosahexaenoic acid (DHA or C22 : 6n -3), arachidonic acid (AA or C20 : 4n - 6) have been identified as essential fatty acids and play an important role in growth and development of infants. Mensurement of fatty acid composition is usually by collection of blood, but to obtain blood in infants is difficult. Nowadays, the fatty acid composition can be estimated by collecting buccal mucosal cells, which can avoid repeated blood sampling. The purpose of this paper is to compare the fatty acid composition of cheek calls with that of plasma and red blood cells (RBCs). In this study, twenty-seven infants were enrolled, and buccal mucosal cells and blood samples were obtained from these infants of the same time. Fatty acid composition of buccal mucesal cells, plasma and RBCs were measured by capillary gas chromatography. The results show that the contents of AA and DHA in the buccal mucosal cells are correlated well with that in the plasma [r=0.36 (P=0.042) and r=0.38 (P=0.033), respectively]. The ratio of AA to DHA is 1.32% in buccal mucosal cells, 1.60% in plasma and 1.55% in RBCs and there are no significant differences among groups (P = 0.134). It shows that the fatty acid composition in buccal mucosal cells can reflect the fat nutrition status in infants and can be detected by capillary gas chromatography. Estimating fatty acid composition of buccal mucosal cells in infants by capillary gas chromatography is feasible, and because of its noninvasiveness, it can be suitable for nutrition research in infants.

  10. Influence of free fatty acids on glucose uptake in prostate cancer cells

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Divilov, Vadim; Sevak, Kuntalkumar;

    2014-01-01

    The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate.......The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate....

  11. Fluorescent n-3 and n-6 Very Long Chain Polyunsaturated Fatty Acids: THREE-PHOTON IMAGING IN LIVING CELLS EXPRESSING LIVER FATTY ACID-BINDING PROTEIN*

    OpenAIRE

    McIntosh, Avery L.; Huang, Huan; Atshaves, Barbara P.; Wellberg, Elizabeth; Kuklev, Dmitry V.; Smith, William L.; Kier, Ann B.; Schroeder, Friedhelm

    2010-01-01

    Despite the considerable beneficial effects of n-3 and n-6 very long chain polyunsaturated fatty acids (VLC-PUFAs), very little is known about the factors that regulate their uptake and intracellular distribution in living cells. This issue was addressed in cells expressing liver-type fatty acid-binding protein (L-FABP) by real time multiphoton laser scanning microscopy of novel fluorescent VLC-PUFAs containing a conjugated tetraene fluorophore near the carboxyl group and natural methylene-in...

  12. Kinase Signaling in Apoptosis Induced by Saturated Fatty Acids in Pancreatic β-Cells.

    Science.gov (United States)

    Šrámek, Jan; Němcová-Fürstová, Vlasta; Kovář, Jan

    2016-01-01

    Pancreatic β-cell failure and death is considered to be one of the main factors responsible for type 2 diabetes. It is caused by, in addition to hyperglycemia, chronic exposure to increased concentrations of fatty acids, mainly saturated fatty acids. Molecular mechanisms of apoptosis induction by saturated fatty acids in β-cells are not completely clear. It has been proposed that kinase signaling could be involved, particularly, c-Jun N-terminal kinase (JNK), protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and Akt kinases and their pathways. In this review, we discuss these kinases and their signaling pathways with respect to their possible role in apoptosis induction by saturated fatty acids in pancreatic β-cells. PMID:27626409

  13. Kinase Signaling in Apoptosis Induced by Saturated Fatty Acids in Pancreatic β-Cells

    Directory of Open Access Journals (Sweden)

    Jan Šrámek

    2016-09-01

    Full Text Available Pancreatic β-cell failure and death is considered to be one of the main factors responsible for type 2 diabetes. It is caused by, in addition to hyperglycemia, chronic exposure to increased concentrations of fatty acids, mainly saturated fatty acids. Molecular mechanisms of apoptosis induction by saturated fatty acids in β-cells are not completely clear. It has been proposed that kinase signaling could be involved, particularly, c-Jun N-terminal kinase (JNK, protein kinase C (PKC, p38 mitogen-activated protein kinase (p38 MAPK, extracellular signal-regulated kinase (ERK, and Akt kinases and their pathways. In this review, we discuss these kinases and their signaling pathways with respect to their possible role in apoptosis induction by saturated fatty acids in pancreatic β-cells.

  14. Inhibitor of fatty acid synthase induced apoptosis in human colonic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Pei Lin Huang; Zhen Sheng Dai; Yue Lin Jin; Shi Neng Zhu; Shi Lun Lu

    2000-01-01

    @@INTRODUCTION The treatment of human epithelial malignancies is limited by drug resistance and toxic and side effects,which results in the failure in the treatment of majority of advanced cancer victims. To seek for a new, and specific antineoplastic therapy will provide hope for tumor treatment. Although disordered intermediary metabolism in cancer cells has been known for many years, much of the work focused on abnormal glucose catabolism. At the same time, little attention has been paid to fatty acid synthasis in tumor tissues, dispite of the significance of fatty acid synthase (FAS) in some clinical human ovarian[1], breast[2], colorectal[3],and prostatic cancers[4,5]. Tumor cells which express high levels of fatty acid synthesizing enzymes use endogeneously synthesized fatty acids for membrance biosynthesis and appear to export large amounts of lipid. In contrast, normal cells preferentially utilize diary lipid.

  15. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    McMahan, Rachel H.; Porsche, Cara E.; Edwards, Michael G.; Rosen, Hugo R.

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease. PMID:27454769

  16. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  17. Immunoglobulin and fatty acids

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...

  18. Synergistic Effects of Zinc Oxide Nanoparticles and Fatty Acids on Toxicity to Caco-2 Cells

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Kermanizadeh, Ali;

    2015-01-01

    Fatty acids exposure may increase sensitivity of intestinal epithelial cells to cytotoxic effects of zinc oxide (ZnO) nanoparticles (NPs). This study evaluated the synergistic effects of ZnO NPs and palmitic acid (PA) or free fatty acids (FFAs) mixture (oleic/PA 2:1) on toxicity to human colon...... epithelial (Caco-2) cells. The ZnO NPs exposure concentration dependently induced cytotoxicity to Caco-2 cells showing as reduced proliferation and activity measured by 3 different assays. PA exposure induced cytotoxicity, and coexposure to ZnO NPs and PA showed the largest cytotoxic effects. The presence of...

  19. Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Nishi, Koji; Suzuki, Kenta; Sawamoto, Junpei; Tokizawa, Yuma; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko

    2016-09-01

    Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells. PMID:27630308

  20. Polyunsaturated fatty acids and inflammation

    Directory of Open Access Journals (Sweden)

    Calder Philip C.

    2004-01-01

    Full Text Available The n-6 polyunsaturated fatty acid arachidonic acid gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites and through these regulates the activities of inflammatory cells, the production of cytokines and the various balances within the immune system. Fish oil and oily fish are good sources of long chain n-3 polyunsaturated fatty acids. Consumption of these fatty acids decreases the amount of arachidonic acid in cell membranes and so available for eicosanoid production. Thus, n-3 polyunsaturated fatty acids act as arachidonic acid antagonists. Components of both natural and acquired immunity, including the production of key inflammatory cytokines, can be affected by n-3 polyunsaturated fatty acids. Although some of the effects of n-3 fatty acids may be brought about by modulation of the amount and types of eicosanoids made, it is possible that these fatty acids might elicit some of their effects by eicosanoid-independent mechanisms. Such n-3 fatty acid-induced effects may be of use as a therapy for acute and chronic inflammation, and for disorders that involve an inappropriately-activated immune response.

  1. Membrane lipid composition of pancreatic AR42J cells: modification by exposure to different fatty acids.

    Science.gov (United States)

    Audi, Nama'a; Mesa, María D; Martínez, María A; Martínez-Victoria, Emilio; Mañas, Mariano; Yago, María D

    2007-04-01

    Dietary fat type influences fatty acids in rat pancreatic membranes, in association with modulation of secretory activity and cell signalling in viable acini. We aimed to confirm whether AR42J cells are a valid model to study the interactions between lipids and pancreatic acinar cell function. For this purpose we have (i) compared the baseline fatty acid composition of AR42J cells with that of pancreatic membranes from rats fed a standard chow; (ii) investigated if fatty acids in AR42J membranes can be modified in culture; and (iii) studied if similar compositional variations that can be evoked in rats when dietary fat type is altered occur in AR42J cells. Weaning Wistar rats were fed for 8 weeks either a commercial chow (C) or semi-purified diets containing virgin olive oil (VOO) or sunflower oil (SO) as fat source. AR42J cells were incubated for 72 hrs in medium containing unmodified fetal calf serum (FCS, AR42J-C cells), FCS enriched with 18:1 n-9 (AR42J-O cells), or FCS enriched with 18:2 n-6 (AR42J-L cells). Fatty acids in crude membranes from rat pancreas and AR42J cells were determined by gas-liquid chromatography. Differences in membrane fatty acids between C rats and AR42J-C cells can be explained in part by variations in the amount of fatty acids in the extracellular environment. Supplementation of FCS with 18:1 n-9 or 18:2 n-6 changed the fatty acid spectrum of AR42J cells in a manner that resembles the pattern found, respectively, in VOO and SO rats, although AR42J-L cells were unable to accumulate 20:4 n-6. The AR42J cell line can be a useful tool to assess the effect of membrane compositional changes on acinar cell function. However, differences in baseline characteristics, and perhaps fatty acid metabolism, indicate that results obtained in AR42J cells should be confirmed with experiments in the whole animal.

  2. Origin of fatty acids

    International Nuclear Information System (INIS)

    The appearance of fatty acids and membranes is one of the most important events of the prebiotic world because genesis of life required the compartmentalization of molecules. Membranes allowed cells to become enriched with molecules relevant for their evolution and gave rise to gradients convertible into energy. By virtue of their hydrophobic/hydrophilic interface, membranes developed certain enzymatic activities impossible in the aqueous phase. A prebiotic cell is an energy unit but it is also an information unit. It has a past, a present and a future. The biochemistry of fatty acids involves acetylCoA, malonylCoA and an enzyme, acyl synthetase, which joins both molecules. After substitution of the acetyl group in place of the carboxyl group of malonyl derivatives, the chain is reduced and dehydrated to crotonyl derivatives. These molecules can again react with malonylCoA to form unsaturated chain; they can also undergo a new reduction step to form butyryl derivatives which can react with malonylCoA to form a longer aliphatic chain. The formation of malonylCoA consumes ATP. The reduction step needs NADPH and proton. Dehydration requires structural information because the reduction product is chiral (D configuration). It is unlikely that these steps were possible in a prebiotic environment. Thus we have to understand how fatty acids could appear in the prebiotic era. This hypothesis about the origin of fatty acids is based on the chemistry of sulfonium ylides and sulfonium salts. The most well-known among these molecules are S-melthyl-methionine and S-adenosyl methionine. The simplest sulfonium cation is the trimethylsulfonium cation. Chemists have evidence that these products can produce olefin when they are heated or flashed with UV light in some conditions. I suggest that these volatile products can allow the formation of fatty acids chains in atmospheric phase with UV and temperature using methanol as starting material. Different synthetic pathways will be

  3. Role of bioactive fatty acids in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD. PMID:27485440

  4. Activation of PPARd and RXRa stimulates fatty acid oxidatin and insulin secretion inpancreatic beta-cells

    DEFF Research Database (Denmark)

    Børgesen, Michael; Ravnskjær, Kim; Frigerio, Francesca;

    ACTIVATION OF PPARd AND RXRa STIMULATES FATTY ACID OXIDATION AND INSULIN SECRETION IN PANCREATIC b-CELLS Michael Boergesen1, Kim Ravnskjaer2, Francesca Frigerio3, Allan E. Karlsen4, Pierre Maechler3 and Susanne Mandrup1 1 Department of Biochemistry and Molecular Biology, University of Southern...... oxidation and dissipation of lipids particularly in skeletal muscle. Here we show that PPARd at the RNA as well as protein level is the most abundant PPAR subtype in the rat pancreatic ß-cell line INS-1E and in isolated rat pancreatic islets. In keeping with that, a large number of PPAR target genes...... involved in fatty acid uptake and oxidation. This correlates with a 5-fold induction of 14C-Oleate ß-oxidation when INS-1E cells are exposed to PPARd and RXR agonists. Notably, culture of INS-1E cells with oleate and other unsaturated fatty acids in the presence of an RXR agonist induces the same subset...

  5. Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women's Health Initiative Memory Study.

    Directory of Open Access Journals (Sweden)

    William S Harris

    Full Text Available The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio have been reported, as have adverse relations with saturated fatty acids and D6D ratio.To determine the associations between red blood cell (RBC fatty acid distributions and incident type 2 diabetes.Prospective observational cohort study nested in the Women's Health Initiative Memory Study.General population.Postmenopausal women.Self-reported incident type 2 diabetes.There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR 0.88, 95% confidence interval (CI 0.81-0.95 per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04-1.25; and HR 1.24, 95% CI 1.14-1.35, respectively. None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids.Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.

  6. Inhibition of fatty acid desaturation in sycamore cells deprived of iron.

    Science.gov (United States)

    Pascal, N; Dorne, A J

    1994-10-10

    The growth of isolated sycamore cells in a medium devoid of iron induced a marked reduction of the unsaturation level of fatty acids: the proportion of linolenic acid (C18:3) in polar lipids (phospholipids and galactolipids) decreased whereas a parallel increase in the proportions of oleic (C18:1) and linoleic (C18:2) acid was observed. In our experimental conditions, no direct effect of iron deprivation on fatty acid and glycerolipid biosynthesis could be observed. When sycamore cells were incubated in the presence of [14C]acetate, the level of unsaturation in fatty acids was very strongly reduced: no polyunsaturated fatty acids were synthesized in iron-deprived cells: only [14C]palmitic and [14C]oleic acids accumulated in glycerolipids. In contrast, sycamore cells grown in an iron-containing medium in the presence of [14C]acetate were able to synthesize glycerolipids containing 14C-labelled C18:2 and C18:3. We concluded that, in sycamore cells, iron is essential for C18:1-->C18:2-->C18:3 desaturations. In contrast, C18:0-->C18:1 desaturation is much less sensitive to iron deprivation under our experimental conditions.

  7. Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells.

    Science.gov (United States)

    da Silva, E P; Nachbar, R T; Levada-Pires, A C; Hirabara, S M; Lambertucci, R H

    2016-01-01

    During physical activity, increased reactive oxygen species production occurs, which can lead to cell damage and in a decline of individual's performance and health. The use of omega-3 polyunsaturated fatty acids as a supplement to protect the immune system has been increasing; however, their possible benefit to the anti-oxidant system is not well described. Thus, the aim of this study was to evaluate whether the omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) can be beneficial to the anti-oxidant system in cultured skeletal muscle cells. C2C12 myocytes were differentiated and treated with either eicosapentaenoic acid or docosahexaenoic acid for 24 h. Superoxide content was quantified using the dihydroethidine oxidation method and superoxide dismutase, catalase, and glutathione peroxidase activity, and expression was quantified. We observed that the docosahexaenoic fatty acids caused an increase in superoxide production. Eicosapentaenoic acid induced catalase activity, while docosahexaenoic acid suppressed superoxide dismutase activity. In addition, we found an increased protein expression of the total manganese superoxide dismutase and catalase enzymes when cells were treated with eicosapentaenoic acid. Taken together, these data indicate that the use of eicosapentaenoic acid may present both acute and chronic benefits; however, the treatment with DHA may not be beneficial to muscle cells. PMID:26386577

  8. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  9. Involvement of triacylglycerol in the metabolism of fatty acids by cultured neuroblastoma and glioma cells

    International Nuclear Information System (INIS)

    The metabolism (chain elongation, desaturation, and incorporation into complex lipids) of thirteen different radiolabeled fatty acids and acetate was examined in N1E-115 neuroblastoma and C-6 glioma cell lines in culture. During 6-hr incubations, all fatty acids were extensively (14-80%) esterified to complex lipids, mainly choline phosphoglycerides and triacylglycerol. With trienoic and tetraenoic substrates, inositol and ethanolamine phosphoglycerides also contained up to 30% of the labeled fatty acids; plasmalogen contained up to half of the label in the ethanolamine phosphoglyceride fraction of neuroblastoma cells. Chain elongation and delta 9, delta 6, and delta 5 desaturation occurred in both cell lines; delta 4 desaturation was not observed. Seemingly anomalous utilization of arachidic acid and some selectivity based on the geometric configuration of double bonds was observed. These studies indicate that these cell lines are capable of modulating cellular membrane composition by a combination of selective exclusion and removal of inappropriate acyl chains and of modification of other acyl chains by desaturation and chain elongation. The time courses and patterns of modification and incorporation of exogenous substrates into phospholipids and triacylglycerol suggest that exogenous unsaturated fatty acid may be incorporated into triacylglycerol and later released for further metabolism and incorporation into phospholipids. This supports a role for triacylglycerol in the synthesis of membrane complex lipids in cell lines derived from neural tissue

  10. Regulation of immune cell function by short-chain fatty acids

    OpenAIRE

    Corrêa-Oliveira, Renan; Fachi, José Luís; Vieira, Aline; Sato, Fabio Takeo; Vinolo, Marco Aurélio R

    2016-01-01

    Short-chain fatty acids (SCFAs) are bacterial fermentation products, which are chemically composed by a carboxylic acid moiety and a small hydrocarbon chain. Among them, acetic, propionic and butyric acids are the most studied, presenting, respectively, two, three and four carbons in their chemical structure. These metabolites are found in high concentrations in the intestinal tract, from where they are uptaken by intestinal epithelial cells (IECs). The SCFAs are partially used as a source of...

  11. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories.

    Science.gov (United States)

    Zhou, Yongjin J; Buijs, Nicolaas A; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l(-1) of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l(-1)) and fatty alcohols (1.5 g l(-1)), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value. PMID:27222209

  12. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories.

    Science.gov (United States)

    Zhou, Yongjin J; Buijs, Nicolaas A; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l(-1) of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l(-1)) and fatty alcohols (1.5 g l(-1)), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value.

  13. Polyunsaturated fatty acid-derived lipid mediators and T cell function

    Directory of Open Access Journals (Sweden)

    Anna eNicolaou

    2014-02-01

    Full Text Available Fatty acids are involved in T cell biology both as nutrients important for energy production as well as signalling molecules. In particular, polyunsaturated fatty acids are known to exhibit a range of immunomodulatory properties that progress through T cell mediated events, although the molecular mechanisms of these actions have not yet been fully elucidated. Some of these immune activities are linked to polyunsaturated fatty acid-induced alteration of the composition of cellular membranes and the consequent changes in signalling pathways linked to membrane raft associated proteins. However, significant aspects of the polyunsaturated fatty acid bioactivities are mediated through their transformation to specific lipid mediators, products of cyclooxygenase, lipoxygenase or cytochrome P450 enzymatic reactions. Resulting bioactive metabolites including prostaglandins, leukotrienes and endocannabinoids are produced by and/or act upon T leukocytes through cell surface receptors and have been shown to alter T cell activation and differentiation, proliferation, cytokine production, motility and homing events. Detailed appreciation of the mode of action of these lipids presents opportunities for the design and development of therapeutic strategies aimed at regulating T cell function.

  14. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

    Science.gov (United States)

    Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

  15. Effects of bleomycin and antioxidants on the fatty acid profile of testicular cancer cell membranes.

    Science.gov (United States)

    Cort, A; Ozben, T; Melchiorre, M; Chatgilialoglu, C; Ferreri, C; Sansone, A

    2016-02-01

    Bleomycin is used in chemotherapy regimens for the treatment of patients having testicular germ-cell tumor (TGCT). There is no study in the literature investigating the effects of bleomycin on membrane lipid profile in testicular cancer cells. We investigated membrane fatty acid (FA) profiles isolated, derivatized and analyzed by gas chromatography of NTera-2 testicular cancer cells incubated with bleomycin (Bleo) for 24 h in the absence and presence of N-Acetyl-L-Cysteine (NAC) and curcumin (Cur) as commonly used antioxidant adjuvants. At the same time the MAPK pathway and EGFR levels were followed up. Bleomycin treatment increased significantly saturated fatty acids (SFA) of phospholipids at the expense of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Bleomycin also led to a significant increase in the trans lipid isomers of oleic and arachidonic acids due to its free radical producing effect. Incubation with bleomycin increased the p38 MAPK and JNK levels and downregulated EGFR pathway. Coincubation of bleomycin with NAC reversed effects caused by bleomycin. Our results highlight the important role of membrane fatty acid remodeling occurring during the use of bleomycin and its concurrent use with antioxidants which can adjuvate the cytotoxic effects of the chemotherapeutic agents. PMID:26656160

  16. Whole cell fatty acid analysis as a tool for classification of phytopathogenic pseudomonas bacteria.

    NARCIS (Netherlands)

    Janse, J.D.

    1992-01-01

    In this thesis some members of the plant pathogenic bacterial genus Pseudomonas have been studied. Conventional morphological, biochemical, physiological and pathogenitcity tests as well as a 'finger-print' technique, viz. automated whole cell fatty acid analysis, were used. The taxonomy of the plan

  17. Hepatic fat is not associated with beta-cell function or postprandial free fatty acid response

    NARCIS (Netherlands)

    Rijkelijkhuizen, J.M.; Doesburg, T.; Girman, C.J.; Mari, A.; Rhodes, T.; Gastaldelli, A.; Nijpels, M.G.A.A.M.; Dekker, J.M.

    2009-01-01

    We evaluated the association of hepatic fat with beta-cell function estimated from the oral glucose tolerance test. In addition, we tested the hypothesis that postprandial free fatty acid (FFA) suppression after a meal tolerance test (MTT) is linked to hepatic fat. Individuals with normal glucose me

  18. Omega-3 Fatty Acids

    Science.gov (United States)

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

  19. Immune cell membrane fatty acids and inflammatory marker, C-reactive protein, in patients with multiple sclerosis

    OpenAIRE

    Smuts, Cornelius; Hon, G; Hassan, M; van Rensburg, SJ; Abel, S; Marais de, W; Van Jaarsveld, P; Erasmus, R; Matsha, T.

    2009-01-01

    Measurement of fatty acids in biological fluids and cell membranes including leucocytes from multiple sclerosis patients is inconsistent. The objective of the present study was to investigate the fatty acid composition within the different membrane phospholipid fractions in peripheral blood mononuclear cells in multiple sclerosis patients, and correlate with severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale and Functional System Scores. The fatty aci...

  20. The fatty acid profile of rainbow trout liver cells modulates their tolerance to methylmercury and cadmium.

    Science.gov (United States)

    Ferain, Aline; Bonnineau, Chloé; Neefs, Ineke; Rees, Jean François; Larondelle, Yvan; Schamphelaere, Karel A C De; Debier, Cathy

    2016-08-01

    The polyunsaturated fatty acid (PUFA) composition of fish tissues, which generally reflects that of the diet, affects various cellular properties such as membrane structure and fluidity, energy metabolism and susceptibility to oxidative stress. Since these cellular parameters can play an important role in the cellular response to organic and inorganic pollutants, a variation of the PUFA supply might modify the toxicity induced by such xenobiotics. In this work, we investigated whether the cellular fatty acid profile has an impact on the in vitro cell sensitivity to two environmental pollutants: methylmercury and cadmium. Firstly, the fatty acid composition of the rainbow trout liver cell line RTL-W1 was modified by enriching the growth medium with either alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), linoleic acid (LA, 18:2n-6), arachidonic acid (AA, 20:4n-6) or docosapentaenoic acid (DPA, 22:5n-6). These modified cells and their control (no PUFA enrichment) were then challenged for 24h with increasing concentrations of methylmercury or cadmium. We observed that (i) the phospholipid composition of the RTL-W1 cells was profoundly modulated by changing the PUFA content of the growth medium: major modifications were a high incorporation of the supplemented PUFA in the cellular phospholipids, the appearance of direct elongation and desaturation metabolites in the cellular phospholipids as well as a change in the gross phospholipid composition (PUFA and monounsaturated fatty acid (MUFA) levels and n-3/n-6 ratio); (ii) ALA, EPA and DPA enrichment significantly protected the RTL-W1 cells against both methylmercury and cadmium; (iv) DHA enrichment significantly protected the cells against cadmium but not methylmercury; (v) AA and LA enrichment had no impact on the cell tolerance to both methylmercury and cadmium; (vi) the abundance of 20:3n-6, a metabolite of the n-6 biotransformation pathway, in

  1. Conjugated linoleic acids influence fatty acid metabolism in ovine ruminal epithelial cells.

    Science.gov (United States)

    Masur, F; Benesch, F; Pfannkuche, H; Fuhrmann, H; Gäbel, G

    2016-04-01

    Conjugated linoleic acids (CLA), particularly cis-9,trans-11 (c9t11) and trans-10,cis-12 (t10c12), are used as feed additives to adapt to constantly increasing demands on the performance of lactating cows. Under these feeding conditions, the rumen wall, and the rumen epithelial cells (REC) in particular, are directly exposed to high amounts of CLA. This study determined the effect of CLA on the fatty acid (FA) metabolism of REC and expression of genes known to be modulated by FA. Cultured REC were incubated with c9t11, t10c12, and the structurally similar FA linoleic acid (LA), oleic acid (OA), and trans-vaccenic acid (TVA) for 48 h at a concentration of 100µM. Cellular FA levels were determined by gas chromatography. Messenger RNA expression levels of stearoyl-CoA desaturase (SCD) and monocarboxylate transporter (MCT) 1 and 4 were quantified by reverse transcription-quantitative PCR. Fatty acid evaluation revealed significant effects of CLA, LA, OA, and TVA on the amount of FA metabolites of β-oxidation and elongation and of metabolites related to desaturation by SCD. The observed changes in FA content point (among others) to the ability of REC to synthesize c9t11 from TVA endogenously. The mRNA expression levels of SCD identified a decrease after CLA, LA, OA, or TVA treatment. In line with the changes in mRNA expression, we found reduced amounts of C16:1n-7 cis-9 and C18:1n-9 cis-9, the main products of SCD. The expression of MCT1 mRNA increased after c9t11 and t10c12 treatment, and CLA c9t11 induced an upregulation of MCT4. Application of peroxisome proliferator-activated receptor (PPAR) α antagonist suggested that activation of PPARα is involved in the changes of MCT1, MCT4, and SCD mRNA expression induced by c9t11. Participation of PPARγ in the changes of MCT1 and SCD mRNA expression was shown by the application of the respective antagonist. The study demonstrates that exposure to CLA affects both FA metabolism and regulatory pathways within REC. PMID

  2. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

    International Nuclear Information System (INIS)

    Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of 125I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid

  3. Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Sarah A. Brigandi

    2015-05-01

    Full Text Available Omega-6 (n-6 and omega-3 (n-3 polyunsaturated fatty acids (PUFA are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA and n-3 docosahexaenoic acid (DHA were particularly decreased (p < 0.001. In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2 were higher in a subset of the autistic participants (n = 20 compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism.

  4. Polyunsaturated fatty acids in the modulation of T-cell signalling.

    Science.gov (United States)

    Akhtar Khan, Naim

    2010-01-01

    n-3 polyunsaturated fatty acids (PUFA) have been shown to modulate immune responses. These agents, being considered as adjuvant immunosuppressants, have been used in the treatment of various inflammatory and autoimmune diseases. However, the molecular mechanisms of action of n-3 PUFA-induced immunosuppressive effects are not well-understood. Since exogenous n-3 PUFA, under in vitro and in vivo conditions, are efficiently incorporated into T-cell plasma membranes, a number of recent studies have demonstrated that these agents may modulate T-cell signalling. In this review, the interactions of n-3 PUFA with the second messenger cascade initiated during early and late events of T-cell activation are discussed. We particularly focus on how these fatty acids can modulate the production of diacylglycerol and the activation of protein kinase C, mitogen activated protein kinase, calcium signalling and translocation of transcriptional factors, implicated in the regulation of gene transcription in T-cells.

  5. Omega-3 fatty acid supplementation in cancer therapy. Does eicosapentanoic acid influence the radiosensitivity of tumor cells?

    Energy Technology Data Exchange (ETDEWEB)

    Manda, Katrin; Kriesen, Stephan; Hildebrandt, Guido [Rostock Univ. (Germany). Dept. of Radiotherapy; Fietkau, Rainer; Klautke, Gunther [Univ. Hospital Erlangen, Erlangen (Germany). Dept. of Radiation Oncology

    2011-02-15

    Purpose: The aim of this study was to evaluate whether the omega-3 polyunsaturated fatty acid cis-5,8,11,14,17-eicosapentanoic acid (EPA) can enhance the radiosensitivity of different human tumor cell lines. Materials and Methods: Colon adenocarcinoma cells HT-29, and two glioblastoma multiforme tumor cells T98G and U251 were cultured under standard conditions. Cell growth was observed during administration with different concentrations of EPA, using it as the free fatty acid dissolved in ethanol or bound to bovine serum albumin. To investigate the influence of EPA (free and bound) on radiosensitivity, tumor cells were pretreated 30 minutes or 24 hours prior to irradiation with the fatty acid. Cell survival was measured by colony-forming assays. Results: When combined with irradiation, incubation with EPA was found to result in enhanced radiosensitivity with substantial variation: while there was strong radiosensitization for HT-29 and U251 cells, almost no effect for T98G cells was observed. A marked radiosensitization was clearly dependent on the treatment schedule. Conclusion: The observations suggest that EPA is not only a nutritional adjuvant but also may be a potential candidate to enhance the efficacy of irradiation on human cancer cells. (orig.)

  6. Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells

    Science.gov (United States)

    Astakhova, Lidiia; Ngara, Mtakai; Babich, Olga; Prosekov, Aleksandr; Asyakina, Lyudmila; Dyshlyuk, Lyubov; Midtvedt, Tore; Zhou, Xiaoying; Ernberg, Ingemar; Matskova, Liudmila

    2016-01-01

    The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype. PMID:27441625

  7. Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells.

    Science.gov (United States)

    Astakhova, Lidiia; Ngara, Mtakai; Babich, Olga; Prosekov, Aleksandr; Asyakina, Lyudmila; Dyshlyuk, Lyubov; Midtvedt, Tore; Zhou, Xiaoying; Ernberg, Ingemar; Matskova, Liudmila

    2016-01-01

    The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype. PMID:27441625

  8. Fatty acid esters of phloridzin induce apoptosis of human liver cancer cells through altered gene expression.

    Directory of Open Access Journals (Sweden)

    Sandhya V G Nair

    Full Text Available Phloridzin (phlorizin or phloretin 2'-O-glucoside is known for blocking intestinal glucose absorption. We have investigated the anticarcinogenic effect of phloridzin and its novel derivatives using human cancer cell lines. We have synthesised novel acylated derivatives of phloridzin with six different long chain fatty acids by regioselective enzymatic acylation using Candida Antarctica lipase B. The antiproliferative effects of the new compounds were investigated in comparison with the parent compounds, phloridzin, aglycone phloretin, the six free fatty acids and chemotherapeutic drugs (sorafenib, doxorubicin and daunorubicin using human hepatocellular carcinoma HepG2 cells, human breast adenocarcinoma MDA-MB-231 cells and acute monocytic leukemia THP-1 cells along with normal human and rat hepatocytes. The fatty acid esters of phloridzin inhibited significantly the growth of the two carcinoma and leukemia cells while similar treatment doses were not toxic to normal human or rat hepatocytes. The antiproliferative potency of fatty esters of phloridzin was comparable to the potency of the chemotherapeutic drugs. The fatty acid esters of phloridzin inhibited DNA topoisomerases IIα activity that might induce G0/G1 phase arrest, induced apoptosis via activation of caspase-3, and decreased ATP level and mitochondrial membrane potential in HepG2 cells. Based on the high selectivity on cancer cells, decosahexaenoic acid (DHA ester of phloridzin was selected for gene expression analysis using RT2PCR human cancer drug target array. Antiproliferative effect of DHA ester of phloridzin could be related to the down regulation of anti-apoptotic gene (BCL2, growth factor receptors (EBFR family, IGF1R/IGF2, PDGFR and its downstream signalling partners (PI3k/AKT/mTOR, Ras/Raf/MAPK, cell cycle machinery (CDKs, TERT, TOP2A, TOP2B as well as epigenetics regulators (HDACs. These results suggest that fatty esters of phloridzin have potential chemotherapeutic effects

  9. Polyunsaturated fatty acids affect the localization and signaling of PIP3/AKT in prostate cancer cells.

    Science.gov (United States)

    Gu, Zhennan; Wu, Jiansheng; Wang, Shihua; Suburu, Janel; Chen, Haiqin; Thomas, Michael J; Shi, Lihong; Edwards, Iris J; Berquin, Isabelle M; Chen, Yong Q

    2013-09-01

    AKT is a serine-threonine protein kinase that plays important roles in cell growth, proliferation and apoptosis. It is activated after binding to phosphatidylinositol phosphates (PIPs) with phosphate groups at positions 3,4 and 3,4,5 on the inositol ring. In spite of extensive research on AKT, one aspect has been largely overlooked, namely the role of the fatty acid chains on PIPs. PIPs are phospholipids composed of a glycerol backbone with fatty acids at the sn-1 and sn-2 position and inositol at the sn-3 position. Here, we show that polyunsaturated fatty acids (PUFAs) modify phospholipid content. Docosahexaenoic acid (DHA), an ω3 PUFA, can replace the fatty acid at the sn-2 position of the glycerol backbone, thereby changing the species of phospholipids. DHA also inhibits AKT(T308) but not AKT(S473) phosphorylation, alters PI(3,4,5)P3 (PIP3) and phospho-AKT(S473) protein localization, decreases pPDPK1(S241)-AKT and AKT-BAD interaction and suppresses prostate tumor growth. Our study highlights a potential novel mechanism of cancer inhibition by ω3 PUFA through alteration of PIP3 and AKT localization and affecting the AKT signaling pathway.

  10. Halogenated fatty acids

    DEFF Research Database (Denmark)

    Mu, Huiling; Wesén, Clas; Sundin, Peter

    1997-01-01

    , chlorinated lipids have been found in meat exposed to hypochlorite disinfected water, and in chlorine-treated flour and in products made from such flour. Following exposure to chlorine bleached pulp mill effluents, aquatic organisms may have elevated concentrations of chlorinated fatty acids in their lipids......Chlorinated fatty acids have been found to be major contributors to organohalogen compounds in fish, bivalves, jellyfish, and lobster, and they have been indicated to contribute considerably to organohalogens in marine mammals. Brominated fatty acids have been found in marine sponges. Also...

  11. Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells

    OpenAIRE

    Li, Junqin; Dong, Lihua; Wei, Dapeng; Wang, Xiaodong; Zhang, Shuo; Li, Hua

    2014-01-01

    This study aimed to investigate the role of fatty acid synthase (FASN) in the epithelial-mesenchymal transition (EMT) of breast cancer cells. MCF-7 cells and MCF-7 cells overexpressing mitogen-activated protein kinase 5 (MCF-7-MEK5) were used in this study. MCF-7-MEK5 cells showed stable EMT characterized by increased vimentin and decreased E-cadherin expression. An In vivo animal model was established using the orthotopic injection of MCF-7 or MCF-7-MEK5 cells. Real-time quantitative PCR and...

  12. Childrens' learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels.

    Science.gov (United States)

    Kirby, A; Woodward, A; Jackson, S; Wang, Y; Crawford, M A

    2010-01-01

    Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs), particularly omega-3, in their red blood cells and plasma, and that supplementation with omega-3 fatty acids may alleviate behavioural symptoms in this population. However, in order to compare levels it seems appropriate to establish fatty acid levels in a mainstream school aged population and if levels relate to learning and behaviour. To date no study has established this. For this study, cheek cell samples from 411 typically developing school children were collected and analysed for PUFA content, in order to establish the range in this population. In addition, measures of general classroom attention and behaviour were assessed in these children by teachers and parents. Cognitive performance tests were also administered in order to explore whether an association between behaviour and/or cognitive performance and PUFA levels exists. Relationships between PUFA levels and socio-economic status were also explored. Measures of reading, spelling and intelligence did not show any association with PUFA levels, but some associations were noted with the level of omega-3 fatty acids and teacher and parental reports of behaviour, with some evidence that higher omega-3 levels were associated with decreased levels of inattention, hyperactivity, emotional and conduct difficulties and increased levels of prosocial behaviour. These findings are discussed in relation to previous findings from omega-3 supplementation studies with children. PMID:20172688

  13. Development of an in vitro model of essential fatty acid deficiency in fish cells.

    Science.gov (United States)

    Tocher, D R; Dick, J R; Sargent, J R

    1995-11-01

    Levels of eicosapentaenoic acid (EPA; 20:5, n-3) greatly exceed those of arachidonic acid (AA; 20:4, n-6) in the tissue phospholipids of most fish species. Despite this, it is 20:4, n-6-derived eicosanoids that are produced predominantly in fish cells. The development of an essential fatty acid (EFA)-deficient fish cell line would greatly assist the study of this selectivity and so several fish cell lines were cultured in EFA-deficient (EFAD) media. All n-3 and n-6 polyunsaturated fatty acids (PUFA) and total PUFA were considerably reduced in all lines, except turbot fin (TF) in which total n-9 PUFA doubled from 13.8% to 27.5% of total fatty acids. In the topminnow hepatocarcinoma cell line (PLHC-1), there was almost complete depletion of both n-3 and n-6 PUFA and in TF cells, no n-3 PUFA were detected. In the carp epithelial papilloma cell line (EPC), both n-6 and n-3 PUFA were reduced by approximately 70%. The reduced PUFA in cells cultured in EFAD media was compensated to a large extent in most cell lines by significantly increased percentages of monounsaturated fatty acids, particularly 18:1, n-9. Total n-9 PUFA were significantly increased in all cell lines by culture in EFAD media, with 20:2, n-9 significantly increased in all cell lines. There were relatively small increases, but often significant, in 20:3, n-9 in all cell lines. Of the cell lines investigated, only EPC and PLHC-1 showed proliferation after four passages in EFAD medium, although the growth rates were reduced in comparison with media supplemented with serum, but EPC was the only cell line able to survive and proliferate in long-term culture on EFAD medium. The EFAD-EPC line is a potentially useful model system for the study of the effects of EFA deficiency on cell structure and function and eicosanoid metabolism in fish. PMID:8596777

  14. Omega-6 Fatty Acids

    Science.gov (United States)

    ... are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of ... in black currant seed, borage seed, and evening primrose oils. Omega-6 fatty acids are used for ...

  15. PPARd IS A LIPID SENSOR AND A REGULATOR OF FATTY ACID OXIDATION IN PANCREATIC β-CELLS

    DEFF Research Database (Denmark)

    Ravnskjær, Kim; Nielsen, Tina; Børgesen, Michael;

    islets and in the insulinoma cell line INS-1E. This is reflected at the functional level in activity assays using a PPRE-driven luciferase reporter construct. The fatty acids oleic, arachidonic and linolenic acid are able to acivate this construct synergistically with the synthetic RXR agonist LG100268....... Selective activation of PPARd in INS-1E cells with the PPARd agonist L165041 in the presence or absence of the RXRa agonist LG100268 induces luciferase activity 3- and 7-fold respectively and mimics the effect of the fatty acids. The same subset genes involved in fatty acid uptake and oxidation...

  16. Beef conjugated linoleic acid isomers reduce human cancer cell growth even when associated with other beef fatty acids

    OpenAIRE

    De La Torre, Anne; Debiton, Eric; Juaneda, Pierre; Durand, Denis; Chardigny, Jean-Michel; Barthomeuf, Chantal; Bauchart, Dominique; Gruffat, Dominique

    2006-01-01

    Although many data are available concerning anticarcinogenic effects of industrial conjugated linoleic acid (CLA), few studies have reported the antitumour properties of CLA mixtures originating from ruminant products. The aim of the present study was to investigate the in vitro antiproliferative effects of beef CLA mixtures on breast, lung, colon, melanoma and ovarian human cancer cell lines. For this purpose, four fatty acid (FA) extracts prepared from beef lipid and varying in their CLA co...

  17. Fatty Acid Biosynthesis IX

    DEFF Research Database (Denmark)

    Carey, E. M.; Hansen, Heinz Johs. Max; Dils, R.

    1972-01-01

    # 1. I. [I-14C]Acetate was covalently bound to rabbit mammary gland fatty acid synthetase by enzymic transacylation from [I-14C]acetyl-CoA. Per mole of enzyme 2 moles of acetate were bound to thiol groups and up to I mole of acetate was bound to non-thiol groups. # 2. 2. The acetyl-fatty acid...... synthetase complex was isolated free from acetyl-CoA. It was rapidly hydrolysed at 30°C, but hydrolysis was greatly diminished at o°C and triacetic lactone synthesis occurred. In the presence of malonyl-CoA and NADPH, all the acetate bound to fatty acid synthetase was incorporated into long-chain fatty acids....... Hydrolysis of bound acetate and incorporation of bound acetate into fatty acids were inhibited to the same extent by guanidine hydrochloride. # 3. 3. Acetate was also covalently bound to fatty acid synthetase by chemical acetylation with [I-14C]acetic anhydride in the absence of CoASH. A total of 60 moles...

  18. Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE-19 Cells.

    Science.gov (United States)

    Koskela, Ali; Reinisalo, Mika; Petrovski, Goran; Sinha, Debasish; Olmiere, Céline; Karjalainen, Reijo; Kaarniranta, Kai

    2016-05-11

    Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62) and LC3 (microtubule-associated protein 1A/1B-light chain 3) were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage.

  19. Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE-19 Cells

    Directory of Open Access Journals (Sweden)

    Ali Koskela

    2016-05-01

    Full Text Available Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE cells and age-related macular degeneration (AMD. Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62 and LC3 (microtubule-associated protein 1A/1B-light chain 3 were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage.

  20. Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE-19 Cells.

    Science.gov (United States)

    Koskela, Ali; Reinisalo, Mika; Petrovski, Goran; Sinha, Debasish; Olmiere, Céline; Karjalainen, Reijo; Kaarniranta, Kai

    2016-01-01

    Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62) and LC3 (microtubule-associated protein 1A/1B-light chain 3) were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage. PMID:27187449

  1. Proteomics-Based Metabolic Modeling Reveals That Fatty Acid Oxidation (FAO) Controls Endothelial Cell (EC) Permeability*

    Science.gov (United States)

    Patella, Francesca; Schug, Zachary T.; Persi, Erez; Neilson, Lisa J.; Erami, Zahra; Avanzato, Daniele; Maione, Federica; Hernandez-Fernaud, Juan R.; Mackay, Gillian; Zheng, Liang; Reid, Steven; Frezza, Christian; Giraudo, Enrico; Fiorio Pla, Alessandra; Anderson, Kurt; Ruppin, Eytan; Gottlieb, Eyal; Zanivan, Sara

    2015-01-01

    Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability. PMID:25573745

  2. Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Shen Junhui

    2012-07-01

    Full Text Available Abstract Background Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3 and eicosapentaenoic acid (EPA, 20:5 ω-3. The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood. Methods RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF secretion were evaluated. Results Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA and α-linolenic acid (ALA, while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed

  3. Compartmentation of hepatic fatty-acid-binding protein in liver cells and its effect on microsomal phosphatidic acid biosynthesis.

    Science.gov (United States)

    Bordewick, U; Heese, M; Börchers, T; Robenek, H; Spener, F

    1989-03-01

    Fatty-acid-binding proteins are known to occur in the cytosol of mammalian cells and to bind fatty acids and their CoA-esters. Application of the postembedding protein A-gold labeling method with antibody against the hepatic type fatty-acid-binding protein (hFABP) to cross-sections of liver cells and a newly developed gel-chromatographic immunofluorescence assay established qualitatively (1) that hFABP in mitochondria was confined to outer mitochondrial membranes, (2) the presence of this protein in microsomes and (3) that nuclei were also filled with hFABP. Quantitative data elaborated with a non-competitive ELISA confirmed these results. A significant difference to the distribution of cardiac FABP in heart muscle cells, where this type of protein was found in cytosol, matrix and nuclei, was observed (Börchers et al. (1989) Biochim. Biophys. Acta, in the press). hFABP-containing rat liver microsomes were incubated with long-chain acyl-CoAs in the presence of hFABP (isolated from rat liver cytosol) in a study on the acylation of sn-glycerol-3-phosphate and lysophosphatidic acid. Both acyltransferases were stimulated by addition of hFABP to the incubation medium. The morphological, immunochemical as well as kinetic data infer a direct interaction of hFABP with microsomal membranes in liver cells.

  4. Receptors for short-chain fatty acids in brush cells at the gastric groove

    Directory of Open Access Journals (Sweden)

    Julia Anna-Maria Eberle

    2014-04-01

    Full Text Available In the stomach of rodents clusters of brush cells are arranged at the gastric groove, immediately at the transition zone from the non-glandular reservoir compartment to the glandular digestive compartment. Based on their taste cell-like molecular phenotype it has been speculated that the cells may be capable to sense constituents of the ingested food, however, searches for nutrient receptors have not been successful. In this study, it was hypothesized that the cells may express receptors for short-chain fatty acids, metabolites generated by microorganisms during the storage of ingested food in the murine forestomach, which lacks the acidic milieu of more posterior regions of the stomach and is colonized with numerous microbiota. Experimental approaches, including RT-PCR analysis and immunohistochemical studies, revealed that the majority of these brush cells express the G-protein coupled receptor types GPR41 (FFAR3 and GPR43 (FFAR2, which are activated by short-chain fatty acids. Both, the GPR41 receptor proteins as well as an appropriate G-protein, α-gustducin, were found to be segregated at the apical brush border of the cells, indicating a direct contact with the luminal content of this gastric region. The exposure of microvillar processes with appropriate receptors and signaling elements to the gastric lumen suggests that the brush cells may in fact be capable to sense the short-chain fatty acids which originate from fermentation processes during the retention of ingested food in the anterior part of the stomach.

  5. Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells

    OpenAIRE

    Zhao, Mei; Ralat, Maria A.; Da Silva, Vanessa; Garrett, Timothy J; Melnyk, Stephan; James, S. Jill; Gregory, Jesse F.

    2012-01-01

    Vitamin B-6 deficiency has been reported to alter n-6 and n-3 fatty acid profiles in plasma and tissue lipids; however, the mechanisms underlying such metabolic changes remain unclear. The objective of this study was to determine the effects of vitamin B-6 restriction on fatty acid profiles and fatty acid synthesis in HepG2 cells. Cells were cultured for 6 wk in media with four different vitamin B-6 concentrations (10, 20, 50, and 2,000 nM added pyridoxal, representing deficient, marginal, ad...

  6. Effect of free fatty acids and lysolipids on cellular uptake of doxorubicin in human breast cancer cell lines

    DEFF Research Database (Denmark)

    Rasmussen, Nicolaj; Andersen, Jonas; Jespersen, Henrik;

    2010-01-01

    and lysolipids. Dox uptake was quantified by flow cytometry and fluorescence microscopy. We observed no increased Dox uptake in any of the breast cancer cell lines, suggesting that growth inhibitory effects observed earlier subsequent to the addition of free fatty acids to cancer cells are not caused......, the liposome could deliver membrane permeability enhancers in addition to the drug to increase the targeted anticancer effect. In this study, we examined the effect on Dox uptake in the breast cancer cell lines MDA-MB-231, MCF7, and MCF7-MDR when incubated with a large panel of different free fatty acids......Several fatty acids and lysolipids have been shown earlier to increase the permeability of membranes of artificial liposomes, thereby increasing the release of drugs such as doxorubicin (Dox) contained within them. Free fatty acids can also inhibit cancer cell growth in vitro, and it has been...

  7. Effects of elaidic acid, a predominant industrial trans fatty acid, on bacterial growth and cell surface hydrophobicity of lactobacilli.

    Science.gov (United States)

    Wu, Qinglong; Shah, Nagendra P

    2014-12-01

    The consumption of trans fatty acids (TFAs) increases the risk of cardiovascular diseases and coronary heart disease in human, and there are no effective ways to remove TFAs after consumption. The aim of this study was to investigate the effects of elaidic acid on bacterial growth, cell surface hydrophobicity of lactobacilli, and metabolism of elaidic acid by lactobacilli. Lactobacilli were inoculated in MRS broth containing 0, 100, 200, and 500 mg/L of elaidic acid. Viable cell counts of lactobacilli were enumerated, concentrations of elaidic acid were determined, and cell surface hydrophobicity of lactobacilli was measured. The results showed that the growth of lactobacilli was significantly inhibited by 500 mg/L of elaidic acid, however, a cell count of 8.50 log10 CFU/mL was still reached for tested lactobacilli after 24-h incubation. In particular, a reduction of elaidic acid was found for tested lactobacilli after 24-h incubation as compared to its initial concentration of 200 mg/L. However, cell surface hydrophobicity showed no correlations with the metabolism of elaidic acid by lactobacilli. Moreover, elaidic acid was able to influence cell surface hydrophobicity, and the decrease in hydrophobicity was more obvious in Lactobacillus paracasei and Lactobacillus casei compared with that in other tested lactobacilli. This study suggests that elaidic acid could change physiochemical surface properties of lactobacilli and the lactobacilli have the potential to reduce TFAs.

  8. Regulatory Activity of Polyunsaturated Fatty Acids in T-Cell Signaling

    Science.gov (United States)

    Kim, Wooki; Khan, Naim A.; McMurray, David N.; Prior, Ian A.; Wang, Naisyin; Chapkin, Robert S.

    2010-01-01

    n-3 polyunsaturated fatty acids (PUFA) are considered to be authentic immunosuppressors and appear to exert beneficial effects with respect to certain immune-mediated diseases. In addition to promoting T-helper 1 (Th1) cell to T-helper 2 (Th2) cell effector T-cell differentiation, n-3 PUFA may also exert anti-inflammatory actions by inducing apoptosis in Th1 cells. With respect to mechanisms of action, effects range from the modulation of membrane receptors to gene transcription via perturbation of a number of second messenger cascades. In this review, the putative targets of anti-inflammatory n-3 PUFA, activated during early and late events of T-cell activation will be discussed. Studies have demonstrated that these fatty acids alter plasma membrane micro-organization (lipid rafts) at the immunological synapse, the site where T-cells and antigen presenting cells (APC) form a physical contact for antigen initiated T-cell signaling. In addition, the production of diacylglycerol and the activation of different isoforms of protein kinase C (PKC), mitogen activated protein kinase (MAPK), calcium signaling, and nuclear translocation/activation of transcriptional factors, can be modulated by n-3 PUFA. Advantages and limitations of diverse methodologies to study the membrane lipid raft hypothesis, as well as apparent contradictions regarding the effect of n-3 PUFA on lipid rafts will be critically presented. PMID:20176053

  9. Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport.

    OpenAIRE

    Ibrahimi, A.; Sfeir, Z; Magharaie, H; Amri, E Z; Grimaldi, P.; Abumrad, N A

    1996-01-01

    An adipocyte membrane glycoprotein, (FAT), homologous to human CD36, has been previously implicated in the binding/transport of long-chain fatty acids. It bound reactive derivatives of long-chain fatty acids and binding was specific and associated with significant inhibition of fatty acid uptake. Tissue distribution of the protein and regulation of its expression were also consistent with its postulated role. In this report, we have examined the effects of FAT expression on rates and properti...

  10. Phase angle correlates with n-3 fatty acids and cholesterol in red cells of Nigerian children with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Huang Yung-Sheng

    2003-05-01

    Full Text Available Abstract Objective To determine the cholesterol content and fatty acid composition of red cell membrane phospholipids (PL of children with sickle cell disease (SCD and to correlate these levels with whole body phase angle that is related to the integrity and function of cell membranes. Study design Blood samples were obtained from 69 children with SCD and 72 healthy age- and gender-matched controls in Nigeria for the determination of the cholesterol content and proportions of fatty acids in red cell PL. Bioelectrical impedance analysis was used to obtain resistance (R and reactance (Xc from which phase angle was calculated as arctan Xc/R. Cholesterol (normalized to lipid phosphorus and the proportions of individual fatty acids were correlated with phase angle. Results The proportions of palmitic (p Conclusions The fatty acid composition and cholesterol content of tissue membranes in SCD correlate with the phase shift measured by bioelectrical impedance analysis. Phase angle measurements may provide a non-invasive method for monitoring interventions aimed at altering the lipid composition of membranes.

  11. Electrogenicity of hepatocellular fatty acid uptake.

    Science.gov (United States)

    Elsing, C; Kassner, A; Gajdzik, L; Graf, J; Stremmel, W

    1998-08-18

    Sensitivity of cellular fatty acids uptake to the membrane potential difference is still a matter of controversy. For direct evaluation of potential sensitivity the effect of changing membrane potential on uptake of a fluorescent long chain fatty acid derivative, 12-NBD-stearate, in isolated rat hepatocytes, was examined. Changes in membrane potential were achieved by patch clamp procedures. Fatty acid influx was simultaneously determined by recording of cell fluorescence. Hyperpolarization from -30 to -70 mV accelerated fatty acid influx whereas depolarization to +50 mV reduced uptake. After obtaining equilibrium hyperpolarization increased cell fluorescence, whereas depolarization pushed NBD-stearate out of cells. Potential sensitivity of uptake was dependent on the fatty acid concentrations in the medium with most prominent effects at low unbound concentrations. These data show that, at low fatty acid concentrations, uptake is, in part, driven by an intracellular negative electric membrane potential.

  12. Halogenated fatty acids

    DEFF Research Database (Denmark)

    Mu, Huiling; Sundin, Peter; Wesén, Clas

    1997-01-01

    Halogenated fatty acids are the major contributors to organohalogen compounds in lipids of marine mammals, fish, and bivalves. For the initial characterization of these recently noticed compounds, a determination of the halogen concentration has usually been combined with some lipid isolation...... and separation method. This review covers separation by solid phase chromatography, gel permeation chromatography, and liquid-liquid extraction, followed by halogen determination. All studies performed according to this outline have indicated that the major organohalogen compounds are chlorinated fatty acids...... bound in different lipids. For the detection and identification of individual, halogenated fatty acid methyl esters (FAMEs) liberated from the lipids, gas chromatography (GC) has been employed together with detection methods such as electron capture detection, electrolytic conductivity detection (ELCD...

  13. Mechanism of cAMP-induced H+ -efflux of Dictyostelium cells: a role for fatty acids

    Indian Academy of Sciences (India)

    H Flaadt; R Schaloske; D Malchow

    2000-09-01

    Aggregating Dictyostelium cells release protons when stimulated with cAMP. To find out whether the protons are generated by acidic vesicles or in the cytosol, we permeabilized the cells and found that this did not alter the cAMP-response. Proton efflux in intact cells was inhibited by preincubation with the V-type H+ ATPase inhibitor concanamycin A and with the plasma membrane H+ ATPase blocker miconazole. Surprisingly, miconazole also inhibited efflux in permeabilized cells, indicating that this type of H+ ATPase is present on intracellular vesicles as well. Vesicular acidification was inhibited by miconazole and by concanamycin A, suggesting that the acidic vesicles contain both V-type and P-type H+ ATPases. Moreover, concanamycin A and miconazole acted in concert, both in intact cells and in vesicles. The mechanism of cAMP-induced Ca2+-fluxes involves phospholipase A2 activity. Fatty acids circumvent the plasma membrane and stimulate vesicular Ca2+-efflux. Here we show that arachidonic acid elicited H+-efflux not only from intact cells but also from acidic vesicles. The target of regulation by arachidonic acid seemed to be the vesicular Ca2+-relase channel.

  14. Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

    Science.gov (United States)

    Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

    2003-01-01

    Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery. Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells. To assess the role of calcium in the DHA-induced acidification, we conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+) buffer. We observed that there was no difference in the degree of DHA-induced transient acidification in both the experimental conditions, though pHi recovery was faster in 0% Ca2+ medium than that in 100% Ca2+ medium. In the presence of BAPTA, a calcium chelator, a rapid recovery of DHA-induced acidosis was observed. Furthermore, addition of CaCl2 into 0% Ca2+ medium curtailed DHA-evoked rapid pHi recovery. In 0% Ca2+ medium, containing BAPTA, DHA did not evoke increases in [Ca2+]i, though this fatty acid still induced a rapid acidification in these cells. These observations suggest that calcium is implicated in the long-lasting DHA-induced acidosis. DHA-induced rapid acidification may be due to its deprotonation in the plasma membrane (flip-flop model), as suggested by the following observations: (1) DHA with a –COOH group induced intracellular acidification, but this fatty acid with a –COOCH3 group failed to do so, and (2) DHA, but not propionic acid, -induced acidification was completely reversed by addition of fatty acid-free bovine serum albumin in these cells. These results suggest that DHA induces acidosis via deprotonation and Ca2+ mobilization in human T-cells. PMID:14645139

  15. Determination of tolerable fatty acids and cholera toxin concentrations using human intestinal epithelial cells and BALB/c mouse macrophages.

    Science.gov (United States)

    Tamari, Farshad; Tychowski, Joanna; Lorentzen, Laura

    2013-01-01

    The positive role of fatty acids in the prevention and alleviation of non-human and human diseases have been and continue to be extensively documented. These roles include influences on infectious and non-infectious diseases including prevention of inflammation as well as mucosal immunity to infectious diseases. Cholera is an acute intestinal illness caused by the bacterium Vibrio cholerae. It occurs in developing nations and if left untreated, can result in death. While vaccines for cholera exist, they are not always effective and other preventative methods are needed. We set out to determine tolerable concentrations of three fatty acids (oleic, linoleic and linolenic acids) and cholera toxin using mouse BALB/C macrophages and human intestinal epithelial cells, respectively. We solubilized the above fatty acids and used cell proliferation assays to determine the concentration ranges and specific concentrations of the fatty acids that are not detrimental to human intestinal epithelial cell viability. We solubilized cholera toxin and used it in an assay to determine the concentration ranges and specific concentrations of cholera toxin that do not statistically decrease cell viability in BALB/C macrophages. We found the optimum fatty acid concentrations to be between 1-5 ng/μl, and that for cholera toxin to be < 30 ng per treatment. This data may aid future studies that aim to find a protective mucosal role for fatty acids in prevention or alleviation of cholera infections. PMID:23748896

  16. Molecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation.

    Science.gov (United States)

    Blottière, Hervé M; Buecher, Bruno; Galmiche, Jean-Paul; Cherbut, Christine

    2003-02-01

    Short-chain fatty acids (SCFA), particularly butyrate, were shown to regulate cell proliferation in vitro and in vivo. Indeed, butyrate is the major fuel for colonic epithelial cells, and it can influence cell proliferation through the release of growth factors or gastrointestinal peptides such as gastrin, or through modulation of mucosal blood flow. Lastly, SCFA can act directly on genes regulating cell proliferation, and butyrate is the main SCFA to display such an effect. Butyrate inhibits histone deacetylase, which will allow histone hyperacetylation. Such hyperacetylation leads to transcription of several genes, including p21/Cip1. Moreover, it will allow cyclin D3 hyper-expression by inhibiting its degradation. The induction of the cyclin-dependent kinase inhibitory protein p21/Cip1 accounts for cell arrest in the G1 phase of the cell cycle. However, in the absence of p21 other mechanisms are initiated, leading to inhibition of cell proliferation. PMID:12740064

  17. Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation.

    Science.gov (United States)

    Kim, Chang H; Park, Jeongho; Kim, Myunghoo

    2014-12-01

    T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues for T cell differentiation. A mounting body of evidence indicates that the microbial metabolites short-chain fatty acids (SCFAs) have profound effects on T cells and directly and indirectly regulate their differentiation. We review the current status of our understanding of SCFA functions in regulation of peripheral T cell activity and discuss their impact on tissue inflammation. PMID:25550694

  18. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Directory of Open Access Journals (Sweden)

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-25

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

  20. Fatty acids of Thiobacillus thiooxidans.

    Science.gov (United States)

    Levin, R A

    1971-12-01

    Fatty acid spectra were made on Thiobacillus thiooxidans cultures both in the presence and absence of organic compounds. Small additions of glucose or acetate had no significant effect either on growth or fatty acid content. The addition of biotin had no stimulatory effect but did result in slight quantitative changes in the fatty acid spectrum. The predominant fatty acid was a C(19) cyclopropane acid.

  1. Immunomodulatory Effectiveness of Fish Oil and omega-3 Fatty Acids in Human Non-melanoma Skin Carcinoma Cells.

    Science.gov (United States)

    Rehman, Khurram; Mohd Amin, Mohd Cairul Iqbal; Yuen, Ng Pei; Zulfakar, Mohd Hanif

    2016-01-01

    Fish oil is composed of various fatty acids among which omega-3 fatty acids are considered as most beneficial. The effects of fish oil on the activity of a topical anticancer drug, imiquimod, and the immunomodulatory activity of omega-3 fatty acids was investigated in human basal and squamous cell carcinoma cell lines. Imiquimod-fish oil mixture exhibited higher carcinoma cell growth inhibition and immunomodulatory activity than imiquimod alone, especially against squamous cell carcinoma cells. Omega-3 fatty acids exhibited growth inhibition of both basal cell and squamous cell carcinoma cell lines and modulated the immune response. Omega-3 fatty acids of fish oil serve as inducers of interleukin-10, an anti-inflammatory cytokine, and as suppressors of interleukin-6 and tumor necrosis factor-alpha, which not only depress tumor growth but also adequately control the inflammatory side effects of imiquimod. Thus, imiquimod administration with fish oil could be beneficial for inhibition of non-melanoma skin carcinoma cells but further in vivo studies are needed to understand their role in skin cancer.

  2. CPT1α over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

    International Nuclear Information System (INIS)

    To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1α (CPT1α). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1α transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1α over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1α over-expressing cells in a concentration-dependent manner. Both, PA and CPT1α over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1α, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo

  3. Omega-3 Polyunsaturated Fatty Acids Enhance Neuronal Differentiation in Cultured Rat Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Masanori Katakura

    2013-01-01

    Full Text Available Polyunsaturated fatty acids (PUFAs can induce neurogenesis and recovery from brain diseases. However, the exact mechanisms of the beneficial effects of PUFAs have not been conclusively described. We recently reported that docosahexaenoic acid (DHA induced neuronal differentiation by decreasing Hes1 expression and increasing p27kip1 expression, which causes cell cycle arrest in neural stem cells (NSCs. In the present study, we examined the effect of eicosapentaenoic acid (EPA and arachidonic acid (AA on differentiation, expression of basic helix-loop-helix transcription factors (Hes1, Hes6, and NeuroD, and the cell cycle of cultured NSCs. EPA also increased mRNA levels of Hes1, an inhibitor of neuronal differentiation, Hes6, an inhibitor of Hes1, NeuroD, and Map2 mRNA and Tuj-1-positive cells (a neuronal marker, indicating that EPA induced neuronal differentiation. EPA increased the mRNA levels of p21cip1 and p27kip1, a cyclin-dependent kinase inhibitor, which indicated that EPA induced cell cycle arrest. Treatment with AA decreased Hes1 mRNA but did not affect NeuroD and Map2 mRNA levels. Furthermore, AA did not affect the number of Tuj-1-positive cells or cell cycle progression. These results indicated that EPA could be involved in neuronal differentiation by mechanisms alternative to those of DHA, whereas AA did not affect neuronal differentiation in NSCs.

  4. Liver Fatty Acid Binding Protein and Obesity

    OpenAIRE

    Atshaves, B.P.; Martin, G G; Hostetler, H.A.; McIntosh, A.L.; Kier, A B; Schroeder, F.

    2010-01-01

    While low levels of unesterified long chain fatty acids (LCFAs) are normal metabolic intermediates of dietary and endogenous fat, LCFAs are also potent regulators of key receptors/enzymes, and at high levels become toxic detergents within the cell. Elevated levels of LCFAs are associated with diabetes, obesity, and metabolic syndrome. Consequently, mammals evolved fatty acid binding proteins (FABPs) that bind/sequester these potentially toxic free fatty acids in the cytosol and present them f...

  5. Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells

    Directory of Open Access Journals (Sweden)

    Wai Wing So

    2015-08-01

    Full Text Available Omega-3 (n-3 fatty acids are dietary long-chain fatty acids with an array of health benefits. Previous research has demonstrated the growth-inhibitory effect of n-3 fatty acids on different cancer cell lines in vitro, yet their anti-tumor effects and underlying action mechanisms on human neuroblastoma LA-N-1 cells have not yet been reported. In this study, we showed that docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA exhibited time- and concentration-dependent anti-proliferative effect on the human neuroblastoma LA-N-1 cells, but had minimal cytotoxicity on the normal or non-tumorigenic cells, as measured by MTT reduction assay. Mechanistic studies indicated that DHA and EPA triggered G0/G1 cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Moreover, DHA and EPA could also induce apoptosis in LA-N-1 cells as revealed by an increase in DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization. Up-regulation of Bax, activated caspase-3 and caspase-9 proteins, and down-regulation of Bcl-XL protein, might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of DHA and EPA on LA-N-1 cells might be mediated, at least in part, via triggering of cell cycle arrest and apoptosis. Therefore, DHA and EPA are potential anti-cancer agents which might be used for the adjuvant therapy or combination therapy with the conventional anti-cancer drugs for the treatment of some forms of human neuroblastoma with minimal toxicity.

  6. TRP channels, omega-3 fatty acids, and oxidative stress in neurodegeneration: from the cell membrane to intracellular cross-links

    Directory of Open Access Journals (Sweden)

    M. Leonelli

    2011-11-01

    Full Text Available The transient receptor potential channels family (TRP channels is a relatively new group of cation channels that modulate a large range of physiological mechanisms. In the nervous system, the functions of TRP channels have been associated with thermosensation, pain transduction, neurotransmitter release, and redox signaling, among others. However, they have also been extensively correlated with the pathogenesis of several innate and acquired diseases. On the other hand, the omega-3 polyunsaturated fatty acids (n-3 fatty acids have also been associated with several processes that seem to counterbalance or to contribute to the function of several TRPs. In this short review, we discuss some of the remarkable new findings in this field. We also review the possible roles played by n-3 fatty acids in cell signaling that can both control or be controlled by TRP channels in neurodegenerative processes, as well as both the direct and indirect actions of n-3 fatty acids on TRP channels.

  7. Differential modulation of enterocyte-like Caco-2 cells after exposure to short-chain fatty acids

    NARCIS (Netherlands)

    Malago, J.J.; Koninkx, J.F.J.G.; Douma, P.M.; Dirkzwager, A.; Veldman, K.T.; Hendriks, H.G.C.J.M.; Dijk, van J.E.

    2003-01-01

    The response of intestinal epithelial cells to short-chain fatty acids, which are increasingly used as food additives, was investigated. Human small intestinal epithelial cell model Caco-2 cells were exposed to formate, propionate and butyrate to assess their effect on cellular growth, metabolism, d

  8. Muscle cells challenged with saturated fatty acids mount an autonomous inflammatory response that activates macrophages

    Directory of Open Access Journals (Sweden)

    Pillon Nicolas J

    2012-10-01

    Full Text Available Abstract Obesity is associated with chronic low-grade inflammation. Within adipose tissue of mice fed a high fat diet, resident and infiltrating macrophages assume a pro-inflammatory phenotype characterized by the production of cytokines which in turn impact on the surrounding tissue. However, inflammation is not restricted to adipose tissue and high fat-feeding is responsible for a significant increase in pro-inflammatory cytokine expression in muscle. Although skeletal muscle is the major disposer of dietary glucose and a major determinant of glycemia, the origin and consequence of muscle inflammation in the development of insulin resistance are poorly understood. We used a cell culture approach to investigate the vectorial crosstalk between muscle cells and macrophages upon exposure to physiological, low levels of saturated and unsaturated fatty acids. Inflammatory pathway activation and cytokine expression were analyzed in L6 muscle cells expressing myc-tagged GLUT4 (L6GLUT4myc exposed to 0.2 mM palmitate or palmitoleate. Conditioned media thereof, free of fatty acids, were then tested for their ability to activate RAW264.7 macrophages. Palmitate -but not palmitoleate- induced IL-6, TNFα and CCL2 expression in muscle cells, through activation of the NF-κB pathway. Palmitate (0.2 mM alone did not induce insulin resistance in muscle cells, yet conditioned media from palmitate-challenged muscle cells selectively activated macrophages towards a pro-inflammatory phenotype. These results demonstrate that low concentrations of palmitate activate autonomous inflammation in muscle cells to release factors that turn macrophages pro-inflammatory. We hypothesize that saturated fat-induced, low-grade muscle cell inflammation may trigger resident skeletal muscle macrophage polarization, possibly contributing to insulin resistance in vivo.

  9. Lipotoxic effect of p21 on free fatty acid-induced steatosis in L02 cells.

    Directory of Open Access Journals (Sweden)

    Jie-wei Wang

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasingly regarded as a hepatic manifestation of metabolic syndrome. Though with high prevalence, the mechanism is poorly understood. This study aimed to investigate the effects of p21 on free fatty acid (FFA-induced steatosis in L02 cells. We therefore analyzed the L02 cells with MG132 and siRNA treatment for different expression of p21 related to lipid accumulation and lipotoxicity. Cellular total lipid was stained by Oil Red O, while triglyceride content, cytotoxicity assays, lipid peroxidation markers and anti-oxidation levels were measured by enzymatic kits. Treatment with 1 mM FFA for 48 hr induced magnificent intracellular lipid accumulation and increased oxidative stress in p21 overload L02 cells compared to that in p21 knockdown L02 cells. By increasing oxidative stress and peroxidation, p21 accelerates FFA-induced lipotoxic effect in L02 cells and might provide information about potentially new targets for drug development and treatments of NAFLD.

  10. The Effects of Omega-3 Fatty Acids on Matrix Metalloproteinase-9 Production and Cell Migration in Human Immune Cells: Implications for Multiple Sclerosis

    OpenAIRE

    Lynne Shinto; Gail Marracci; Lauren Bumgarner; Vijayshree Yadav

    2011-01-01

    In multiple sclerosis (MS), compromised blood-brain barrier (BBB) integrity contributes to inflammatory T cell migration into the central nervous system. Matrix metalloproteinase-9 (MMP-9) is associated with BBB disruption and subsequent T cell migration into the CNS. The aim of this paper was to evaluate the effects of omega-3 fatty acids on MMP-9 levels and T cell migration. Peripheral blood mononuclear cells (PBMC) from healthy controls were pretreated with two types of omega-3 fatty acids...

  11. Trans fatty acids induce vascular inflammation and reduce vascular nitric oxide production in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Naomi G Iwata

    Full Text Available Intake of trans fatty acids (TFA, which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived-dairy products and meat on endothelial NF-κB activation and nitric oxide (NO production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans, Linoelaidic (trans-C18:2 (9 trans, 12 trans, and Transvaccenic (trans-C18:1 (11 trans for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation.

  12. Fishy business: effect of omega-3 fatty acids on zinc transporters and free zinc availability in human neuronal cells.

    Science.gov (United States)

    De Mel, Damitha; Suphioglu, Cenk

    2014-08-15

    Omega-3 (ω-3) fatty acids are one of the two main families of long chain polyunsaturated fatty acids (PUFA). The main omega-3 fatty acids in the mammalian body are α-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Central nervous tissues of vertebrates are characterized by a high concentration of omega-3 fatty acids. Moreover, in the human brain, DHA is considered as the main structural omega-3 fatty acid, which comprises about 40% of the PUFAs in total. DHA deficiency may be the cause of many disorders such as depression, inability to concentrate, excessive mood swings, anxiety, cardiovascular disease, type 2 diabetes, dry skin and so on. On the other hand, zinc is the most abundant trace metal in the human brain. There are many scientific studies linking zinc, especially excess amounts of free zinc, to cellular death. Neurodegenerative diseases, such as Alzheimer's disease, are characterized by altered zinc metabolism. Both animal model studies and human cell culture studies have shown a possible link between omega-3 fatty acids, zinc transporter levels and free zinc availability at cellular levels. Many other studies have also suggested a possible omega-3 and zinc effect on neurodegeneration and cellular death. Therefore, in this review, we will examine the effect of omega-3 fatty acids on zinc transporters and the importance of free zinc for human neuronal cells. Moreover, we will evaluate the collective understanding of mechanism(s) for the interaction of these elements in neuronal research and their significance for the diagnosis and treatment of neurodegeneration.

  13. Fishy Business: Effect of Omega-3 Fatty Acids on Zinc Transporters and Free Zinc Availability in Human Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Damitha De Mel

    2014-08-01

    Full Text Available Omega-3 (ω-3 fatty acids are one of the two main families of long chain polyunsaturated fatty acids (PUFA. The main omega-3 fatty acids in the mammalian body are α-linolenic acid (ALA, docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA. Central nervous tissues of vertebrates are characterized by a high concentration of omega-3 fatty acids. Moreover, in the human brain, DHA is considered as the main structural omega-3 fatty acid, which comprises about 40% of the PUFAs in total. DHA deficiency may be the cause of many disorders such as depression, inability to concentrate, excessive mood swings, anxiety, cardiovascular disease, type 2 diabetes, dry skin and so on. On the other hand, zinc is the most abundant trace metal in the human brain. There are many scientific studies linking zinc, especially excess amounts of free zinc, to cellular death. Neurodegenerative diseases, such as Alzheimer’s disease, are characterized by altered zinc metabolism. Both animal model studies and human cell culture studies have shown a possible link between omega-3 fatty acids, zinc transporter levels and free zinc availability at cellular levels. Many other studies have also suggested a possible omega-3 and zinc effect on neurodegeneration and cellular death. Therefore, in this review, we will examine the effect of omega-3 fatty acids on zinc transporters and the importance of free zinc for human neuronal cells. Moreover, we will evaluate the collective understanding of mechanism(s for the interaction of these elements in neuronal research and their significance for the diagnosis and treatment of neurodegeneration.

  14. Serum fatty acids and risk of advanced β cell autoimmunity: a nested case-control study among children with HLA-conferred susceptibility to type 1 diabetes

    OpenAIRE

    Virtanen, SM; Niinistö, Sari; Nevalainen, Jaakko; Salminen, Irma; Takkinen, Hanna-Mari; Kääriä, Suvi; Uusitalo, Liisa; Alfthan, Georg; Kenward, Mike; Veijola, Riitta; Simell, O.; Ilonen, Jorma; Knip, Mikael

    2010-01-01

    Abstract Background/ Objectives: N-3 (omega-3) fatty acids have been reported to decrease the risk for development of ? cell autoimmunity and clinical type 1 diabetes. We set out to examine whether different serum fatty acids are associated with the development of advanced ? cell autoimmunity in children carrying HLA-DQB1-conferred susceptibility to type 1 diabetes. Subjects/Methods: Within a cohort, serum total fatty acid composition of 108 children with advanced ? cell autoimm...

  15. Effect of fatty acids on leukocyte function

    Directory of Open Access Journals (Sweden)

    Pompéia C.

    2000-01-01

    Full Text Available Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization.

  16. The Effect of Saturated Fatty Acids on Methanogenesis and Cell Viability of Methanobrevibacter ruminantium

    Directory of Open Access Journals (Sweden)

    Xuan Zhou

    2013-01-01

    Full Text Available Saturated fatty acids (SFAs are known to suppress ruminal methanogenesis, but the underlying mechanisms are not well known. In the present study, inhibition of methane formation, cell membrane permeability (potassium efflux, and survival rate (LIVE/DEAD staining of pure ruminal Methanobrevibacter ruminantium (DSM 1093 cell suspensions were tested for a number of SFAs. Methane production rate was not influenced by low concentrations of lauric (C12; 1 μg/mL, myristic (C14; 1 and 5 μg/mL, or palmitic (C16; 3 and 5 μg/mL acids, while higher concentrations were inhibitory. C12 and C14 were most inhibitory. Stearic acid (C18, tested at 10–80 μg/mL and ineffective at 37°C, decreased methane production rate by half or more at 50°C and ≥50 μg/mL. Potassium efflux was triggered by SFAs (C12 = C14 > C16 > C18 = control, corroborating data on methane inhibition. Moreover, the exposure to C12 and C14 decreased cell viability to close to zero, while 40% of control cells remained alive after 24 h. Generally, tested SFAs inhibited methanogenesis, increased cell membrane permeability, and decreased survival of M. ruminantium in a dose- and time-dependent way. These results give new insights into how the methane suppressing effect of SFAs could be mediated in methanogens.

  17. A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells.

    Science.gov (United States)

    Mondal, Arijit; Guria, Tanmoy; Maity, Tapan Kumar; Bishayee, Anupam

    2016-09-22

    Amaranthus spinosus Linn. (Family: Amaranthaceae) has been shown to be useful in preventing and mitigating adverse pathophysiological conditions and complex diseases. However, only limited information is available on the anticancer potential of this plant. In this study, we examined the antiproliferative and pro-apoptotic effects of a novel fatty acid isolated from A. spinosus-(14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate-against HepG2 human liver cancer cells. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine cell viability, flow cytometry assay for cell cycle analysis, and Western blot analysis to measure protein expression of Cdc2), cyclin B1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2). The MTT assay showed that the fatty acid markedly inhibited the proliferation of HepG2 cells in a dosage-dependent fashion, with a half maximal inhibitory concentration (IC50) value of 25.52 µmol/L. This antiproliferative result was superior to that of another known fatty acid, linoleic acid (IC50 38.65 µmol/L), but comparable to that of standard anticancer drug doxorubicin (IC50 24.68 µmol/L). The novel fatty acid also induced apoptosis mediated by downregulation of cyclin B1, upregulation of Bax, and downregulation of Bcl-2, resulting in the G₂/M transition arrest. Our results provide the first experimental evidence that a novel fatty acid isolated from A. spinosus exhibits significant antiproliferative activity mediated through the induction of apoptosis in HepG2 cells. These encouraging results may facilitate the development of A. spinosus fatty acid for the prevention and intervention of hepatocellular carcinoma.

  18. A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells.

    Science.gov (United States)

    Mondal, Arijit; Guria, Tanmoy; Maity, Tapan Kumar; Bishayee, Anupam

    2016-01-01

    Amaranthus spinosus Linn. (Family: Amaranthaceae) has been shown to be useful in preventing and mitigating adverse pathophysiological conditions and complex diseases. However, only limited information is available on the anticancer potential of this plant. In this study, we examined the antiproliferative and pro-apoptotic effects of a novel fatty acid isolated from A. spinosus-(14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate-against HepG2 human liver cancer cells. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine cell viability, flow cytometry assay for cell cycle analysis, and Western blot analysis to measure protein expression of Cdc2), cyclin B1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2). The MTT assay showed that the fatty acid markedly inhibited the proliferation of HepG2 cells in a dosage-dependent fashion, with a half maximal inhibitory concentration (IC50) value of 25.52 µmol/L. This antiproliferative result was superior to that of another known fatty acid, linoleic acid (IC50 38.65 µmol/L), but comparable to that of standard anticancer drug doxorubicin (IC50 24.68 µmol/L). The novel fatty acid also induced apoptosis mediated by downregulation of cyclin B1, upregulation of Bax, and downregulation of Bcl-2, resulting in the G₂/M transition arrest. Our results provide the first experimental evidence that a novel fatty acid isolated from A. spinosus exhibits significant antiproliferative activity mediated through the induction of apoptosis in HepG2 cells. These encouraging results may facilitate the development of A. spinosus fatty acid for the prevention and intervention of hepatocellular carcinoma. PMID:27669220

  19. Free fatty acid palmitate impairs the vitality and function of cultured human bladder smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Andreas Oberbach

    Full Text Available BACKGROUND: Incidence of urinary tract infections is elevated in patients with diabetes mellitus. Those patients show increased levels of the saturated free fatty acid palmitate. As recently shown metabolic alterations induced by palmitate include production and secretion of the pro-inflammatory cytokine interleukine-6 (IL-6 in cultured human bladder smooth muscle cells (hBSMC. Here we studied the influence of palmitate on vital cell properties, for example, regulation of cell proliferation, mitochondrial enzyme activity and antioxidant capacity in hBSMC, and analyzed the involvement of major cytokine signaling pathways. METHODOLOGY/PRINCIPAL FINDINGS: HBSMC cultures were set up from bladder tissue of patients undergoing cystectomy and stimulated with palmitate. We analyzed cell proliferation, mitochondrial enzyme activity, and antioxidant capacity by ELISA and confocal immunofluorescence. In signal transduction inhibition experiments we evaluated the involvement of NF-κB, JAK/STAT, MEK1, PI3K, and JNK in major cytokine signaling pathway regulation. We found: (i palmitate decreased cell proliferation, increased mitochondrial enzyme activity and antioxidant capacity; (ii direct inhibition of cytokine receptor by AG490 even more strongly suppressed cell proliferation in palmitate-stimulated cells, while counteracting palmitate-induced increase of antioxidant capacity; (iii in contrast knockdown of the STAT3 inhibitor SOCS3 increased cell proliferation and antioxidant capacity; (iv further downstream JAK/STAT3 signaling cascade the inhibition of PI3K or JNK enhanced palmitate induced suppression of cell proliferation; (v increase of mitochondrial enzyme activity by palmitate was enhanced by inhibition of PI3K but counteracted by inhibition of MEK1. CONCLUSIONS/SIGNIFICANCE: Saturated free fatty acids (e.g., palmitate cause massive alterations in vital cell functions of cultured hBSMC involving distinct major cytokine signaling pathways. Thereby

  20. Growth inhibitory effect of polyunsaturated fatty acids (PUFAs on colon cancer cells via their growth inhibitory metabolites and fatty acid composition changes.

    Directory of Open Access Journals (Sweden)

    Chengcheng Zhang

    Full Text Available Colorectal cancer is common. Polyunsaturated fatty acids (PUFAs exert growth-inhibitory and pro-apoptotic effects on colon cancer cells. Metabolites of PUFAs such as prostaglandins (PGs, leukotrienes (LTs and lipoxins (LXs play a significant role in colon cancer.Human colon cancer LoVo and RKO cells were cultured with different concentration of PUFAs and 5-fluorouracil (5-FU in vitro. Cell morphological changes, fatty acid composition, formation of PGE2, LTB4 and LXA4 and expression of COX-2, ALOX5, PGD synthase (PGDS, microsomal prostaglandin E synthase (mPGES were assessed in LoVo and RKO cells when supplemented with PUFAs and 5-FU.PUFAs and 5-FU inhibited growth of LoVo and RKO cells to the same extent at the doses used and produced significant alterations in their shape. As expected, higher concentrations of supplemented PUFAs were noted in the cells compared to control. LA, GLA, AA, ALA and EPA supplementation to LoVo cells suppressed production of PGE2, LTB4,and ALOX5, mPGES expression, but enhanced that of LXA4; whereas DHA enhanced PGE2 and LXA4 synthesis but decreased LTB4 formation and COX-2, ALOX5, mPGES expression. In contrast, 5-FU enhanced formation of PGE2, LTB4 and mPGES expression, but suppressed LXA4 synthesis and COX-2 expression. PGE2, LTB4 synthesis and ALOX5 expression was suppressed by LA, GLA, ALA and DHA; whereas AA, EPA and 5-FU enhanced PGE2 but paradoxically AA decreased and EPA and 5-FU enhanced LTB4 synthesis in RKO cells. All the PUFAs tested enhanced, while 5-FU decreased LXA4 formation in RKO cells; whereas GLA, AA, and 5-FU augmented while LA, ALA, EPA and DHA enhanced COX-2 expression in RKO cells.Tumoricidal action of PUFAs on colorectal LoVo and RKO cancer cells in vitro was associated with increased formation of LXA4, decreased synthesis of PGE2 and LTB4 and suppressed expression of COX-2, ALOX5, mPGES, whereas 5-FU produced contrasting actions on these indices.

  1. Unsaturated fatty acids and phytosterols regulate cholesterol transporter genes in Caco-2 and HepG2 cell lines.

    Science.gov (United States)

    Park, Youngki; Carr, Timothy P

    2013-02-01

    Dietary consumption of phytosterols and certain fatty acids has been shown to reduce cholesterol absorption and plasma cholesterol concentrations. However, it has not been fully elucidated whether phytosterols or fatty acids can alter the expression of cholesterol transporters by functioning as signaling molecules. This study tested the hypothesis that various fatty acids and phytosterols commonly found in the food supply can modulate the expression of transporters including Niemann-Pick C1-like 1, low-density lipoprotein receptor, and scavenger receptor class B type I and 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the intestine and liver. Caco-2 cells were used as models of enterocytes, and HepG2 cells were used as a model of hepatocytes. The cells were treated for 18 hours with 100 μmol/L of a fatty acid, or for 24 hours with 10 μmol/L of 25α-hydroxycholesterol, or 100 μmol/L of cholesterol, sitosterol, and stigmasterol to measure expression of genes involved in cholesterol transport using quantitative real-time polymerase chain reaction. Polyunsaturated fatty acids in Caco-2 cells and sterols in HepG2 cells significantly reduced the messenger RNA expression levels of Niemann-Pick C1-like 1, scavenger receptor class B type I, low-density lipoprotein receptor, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Importantly, sitosterol and stigmasterol reduced the messenger RNA levels of genes to a similar extent as cholesterol. The data support the hypothesis that unsaturated fatty acid and phytosterols can act as signaling molecules and alter the expression of genes involved in cholesterol transport and metabolism.

  2. Role of Changes in Cell Fatty Acids Composition in the Increasing of Frost Resistance of Winter Wheat Suspension Culture

    Directory of Open Access Journals (Sweden)

    I.V. Lyubushkina

    2013-11-01

    Full Text Available Influences of low temperatures (4 and 8 ° С on the frost tolerance and fatty acid compositions of cells in a winter wheat suspension culture have been studied. It has been found that treatment of the culture with 4 °C (7 days did not protect cells from subsequent freezing temperature action (-8 °С, 6 h and was not accompanied significant changes in the fatty acid composition. On the contrary, the treatment of the culture with the temperature 8 °C (7 days prevented the death caused by freezing temperature and the content of saturated fatty acids decreased: pentadecanoic acid (by 35,0%, palmitic acid (by 19,9% and stearic acid (by 65,4%, and the content of α-linolenic acid increased by 94%. That was the cause of the double bond index (DBI increase by 16%. The role of fatty acids composition changes in the process of increasing frost tolerance in plants are discussed.

  3. Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

    Science.gov (United States)

    Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

    2016-07-01

    Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system.

  4. Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans ☆

    OpenAIRE

    Vauzour, D.; Pascual-Teresa, Sonia de; Minihane, Anne-Marie

    2015-01-01

    © 2015 The Authors. Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we ...

  5. Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation

    Science.gov (United States)

    Li, Yanli; Tang, Yuan; Wang, Shoujie; Zhou, Jing; Zhou, Jia; Lu, Xiao; Bai, Xiaochun; Wang, Xiang-Yang; Chen, Zhengliang; Zuo, Daming

    2016-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A, and IFN-γ). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis. PMID:27679638

  6. Pilot study of omega-3 fatty acid supplements in sickle cell disease.

    Science.gov (United States)

    Okpala, Iheanyi; Ibegbulam, Obike; Duru, Augustine; Ocheni, Sunday; Emodi, Ifeoma; Ikefuna, Anthony; Umar, Garba; Asinobi, Isaac; Madu, Anazoeze; Okoye, Augustine; Nwagha, Tessy; Oguonu, Uche; Uamai, Ify; Agwu, Obineche; Nonyelu, Charles; Anike, Uche; Agu, Kingsley; Anigbo, Chukwudi; Chukwura, Awele; Ugwu, Ogechukwu; Herrada, Sagrario

    2011-07-01

    In a previous retrospective study, it was observed that the greater the amounts of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the blood, the lesser the number of complications of sickle cell disease (SCD) and the higher the steady state haemoglobin level. SCD causes ischaemia-reperfusion injury and inflammation; which can be ameliorated by a metabolite of DHA that down-regulates expression of pro-inflammatory genes. The objectives of this prospective pilot study were to evaluate the effects of DHA and EPA supplements in SCD, and test the hypothesis that these effects are mediated partly by reducing inflammation. Oral DHA and EPA supplements were given to 16 SCD patients for 6 months. We then compared pre- and post-supplementation values of number of crisis, steady state Hb, plasma unconjugated bilirubin and three indices of inflammation: plasma interleukin-6, blood neutrophil and platelet counts. There was a significant reduction in the plasma level of unconjugated bilirubin, and the number of sickle cell crisis; but not in the markers of inflammation. The pilot data suggest that DHA and EPA supplements reduce the number of crisis and steady state haemolysis in SCD; but provide no evidence that these effects are mediated by reducing inflammation.

  7. Regulation of immune cell function by short-chain fatty acids.

    Science.gov (United States)

    Corrêa-Oliveira, Renan; Fachi, José Luís; Vieira, Aline; Sato, Fabio Takeo; Vinolo, Marco Aurélio R

    2016-04-01

    Short-chain fatty acids (SCFAs) are bacterial fermentation products, which are chemically composed by a carboxylic acid moiety and a small hydrocarbon chain. Among them, acetic, propionic and butyric acids are the most studied, presenting, respectively, two, three and four carbons in their chemical structure. These metabolites are found in high concentrations in the intestinal tract, from where they are uptaken by intestinal epithelial cells (IECs). The SCFAs are partially used as a source of ATP by these cells. In addition, these molecules act as a link between the microbiota and the immune system by modulating different aspects of IECs and leukocytes development, survival and function through activation of G protein coupled receptors (FFAR2, FFAR3, GPR109a and Olfr78) and by modulation of the activity of enzymes and transcription factors including the histone acetyltransferase and deacetylase and the hypoxia-inducible factor. Considering that, it is not a surprise, the fact that these molecules and/or their targets are suggested to have an important role in the maintenance of intestinal homeostasis and that changes in components of this system are associated with pathological conditions including inflammatory bowel disease, obesity and others. The aim of this review is to present a clear and updated description of the effects of the SCFAs derived from bacteria on host immune system, as well as the molecular mechanisms involved on them. PMID:27195116

  8. Polyunsaturated Fatty Acids in Children

    OpenAIRE

    Lee, Ji-Hyuk

    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-im...

  9. Fatty acid biosynthesis in actinomycetes

    OpenAIRE

    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 fo...

  10. [Oxygen and temperature effects on the fatty acid composition in sycamore cells (Acer pseudoplatanus L.) (author's transl)].

    Science.gov (United States)

    Rebeille, F; Bligny, R; Douce, R

    1980-10-01

    Temperature and oxygen effects on the degree of unsaturation of membrane fatty acids have been investigated with sycamore cells in suspension culture. Sycamore cells were incubated with [14C]acetate at temperature varying from 15 to 25 degrees C and at O2 concentration from 12.5 to 305 muM. It was found that: (i) no significant difference was observed in the distribution of radioactivity between oleate and linoleate with different temperatures; (ii) in marked contrast, the aeration conditions during growth of plant cell cultures affected the fatty acid pattern of the total lipids: by maintaining the oxygen concentration below 60 muM, the molar proportion of oleate increased dramatically whereas that of the linoleate decreased. Under these conditions, the aeration of the culture medium (250 muM) induced a rapid transformation of oleate to linoleate. These results cast further doubt on the importance of the temperature on the degree of unsaturation of the fatty acids in sycamore cells, but confirmed evidence that the formation of unsurated fatty acids by plant cells was indeed controlled by the oxygen concentration in solution.

  11. Fatty acid oxidation in skeletal and cardiac muscle

    International Nuclear Information System (INIS)

    The biochemical investigations described in this thesis deal with two aspects of fatty acid oxidation in muscle: a comparison of the use of cell-free and cellular systems for oxidation measurements, and studies on the assay and the role of the fatty acid binding protein in fatty acid metabolism. The fatty acid oxidation rates are determined radiochemically by the sum of 14CO2 and 14C-labeled acid-soluble products formed during oxidation of [14C]-fatty acids. A radiochemical procedure for the assay of fatty acid binding by proteins is described. (Auth.)

  12. Curcuminoids and ω-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon γ production

    Directory of Open Access Journals (Sweden)

    Milan eFiala

    2015-05-01

    Full Text Available Pancreatic cancer has a poor prognosis attributed in part to immune suppression and deactivation of natural killer (NK cells. Curcuminoids have a potential for improving the therapy of pancreatic cancer given promising results in cancer models and a clinical trial, but their oral absorption is limited. Our objective in this study is to show curcuminoid anti-oncogenic effects alone and together with human NK cells. We tested curcuminoids in an emulsion of ω-3 fatty acids and anti-oxidants (Smartfish regarding their direct cytocidal effect and enhancement of the cytocidal activity of NK cells in pancreatic ductal adenocarcinoma (PDAC cells (Mia Paca 2 and L3.6. Curcuminoids (at > 10 microM with ω-3 fatty acids and anti-oxidants or with the lipidic mediator resolvin D1 (RvD1 (26 nM induced high caspase-3 activity in PDAC cells. Importantly, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 significantly potentiated NK cell cytocidal function and protected them against degradation. In a co-culture of cancer cells with NK cells, interferon-γ ( IFN-γ production by NK cells was not altered by ω-3 fatty acids with anti-oxidants or by RvD1 but was inhibited by curcuminoids. The inhibition was not eliminated by ω-3 fatty acids or RvD1 but was relieved by removing curcuminoids after adding NK cells. In conclusion, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 have increased cytotoxic activity on PDAC cells alone and with NK cells. The effects of curcuminoids with ω-3 fatty acids and anti-oxidants on pancreatic cancer will be investigated in a mouse model with humanized immune system.

  13. Involvement of Fatty Acid Binding Protein 5 and PPARβ/δ in Prostate Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Elwin Morgan

    2010-01-01

    Full Text Available Fatty acid binding protein 5 (FABP5 delivers ligands from the cytosol directly to the nuclear receptor PPARβ/δ and thus facilitates the ligation and enhances the transcriptional activity of the receptor. We show here that expression levels of both FABP5 and PPARβ/δ are correlated with the tumorigenic potential of prostate cancer cell lines. We show further that FABP5 comprises a direct target gene for PPARβ/δ and thus the binding protein and its cognate receptor are engaged in a positive feedback loop. The observations demonstrate that, similarly to effects observed in mammary carcinomas, activation of the FABP5/PPARβ/δ pathway induces PPARβ/δ target genes involved in cell survival and growth and enhances cell proliferation and anchorage-independent growth in prostate cancer cells. Furthermore, the data show that downregulation of either FABP5 or PPARβ/δ inhibits the growth of the highly malignant prostate cancer PC3M cells. These studies suggest that the FABP5/PPARβ/δ pathway may play a general role in facilitating tumor progression and that inhibition of the pathway may comprise a novel strategy in treatment of cancer.

  14. Orthogonal Fatty Acid Biosynthetic Pathway Improves Fatty Acid Ethyl Ester Production in Saccharomyces cerevisiae.

    Science.gov (United States)

    Eriksen, Dawn T; HamediRad, Mohammad; Yuan, Yongbo; Zhao, Huimin

    2015-07-17

    Fatty acid ethyl esters (FAEEs) are a form of biodiesel that can be microbially produced via a transesterification reaction of fatty acids with ethanol. The titer of microbially produced FAEEs can be greatly reduced by unbalanced metabolism and an insufficient supply of fatty acids, resulting in a commercially inviable process. Here, we report on a pathway engineering strategy in Saccharomyces cerevisiae for enhancing the titer of microbially produced FAEEs by providing the cells with an orthogonal route for fatty acid synthesis. The fatty acids generated from this heterologous pathway would supply the FAEE production, safeguarding endogenous fatty acids for cellular metabolism and growth. We investigated the heterologous expression of a Type-I fatty acid synthase (FAS) from Brevibacterium ammoniagenes coupled with WS/DGAT, the wax ester synthase/acyl-coenzyme that catalyzes the transesterification reaction with ethanol. Strains harboring the orthologous fatty acid synthesis yielded a 6.3-fold increase in FAEE titer compared to strains without the heterologous FAS. Variations in fatty acid chain length and degree of saturation can affect the quality of the biodiesel; therefore, we also investigated the diversity of the fatty acid production profile of FAS enzymes from other Actinomyces organisms. PMID:25594225

  15. Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans.

    Science.gov (United States)

    Vauzour, David; Tejera, Noemi; O'Neill, Colette; Booz, Valeria; Jude, Baptiste; Wolf, Insa M A; Rigby, Neil; Silvan, Jose Manuel; Curtis, Peter J; Cassidy, Aedin; de Pascual-Teresa, Sonia; Rimbach, Gerald; Minihane, Anne Marie

    2015-03-01

    Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status. PMID:25573539

  16. Albumin-bound fatty acids induce mitochondrial oxidant stress and impair antioxidant responses in proximal tubular cells

    NARCIS (Netherlands)

    Ishola, D. A.; Post, J. A.; van Timmeren, M. M.; Bakker, S. J. L.; Goldschmeding, R.; Koomans, H. A.; Braam, B.; Joles, J. A.

    2006-01-01

    Albumin induces oxidative stress and cytokine production in proximal tubular cells (PTECs). Albumin-bound fatty acids (FAs) enhance tubulopathic effects of albumin in vivo. We proposed that FA aggravation of albumin-induced oxidative stress in PTECs might be involved. We hypothesized that mitochondr

  17. Metabolism of red-cell lipids I. Incorporation in vitro of fatty acids into phospholipids from mature erythrocytes

    NARCIS (Netherlands)

    Mulder, E.; Deenen, L.L.M. van

    1965-01-01

    Erythrocytes freed from leucocytes and reticulocytes were demonstrated to incorporate fatty acids into their phosphoglycerides. This ability was decreased in the order rat, rabbit, man, ox and sheep. Lysis of the cells caused an increase of the rate of incorporation thereby abolishing the difference

  18. Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines

    OpenAIRE

    Sugiyama Takayuki; Teratani Takumi; Takayama Tatsuya; Takaoka Naohisa; Mugiya Soichi; Ozono Seiichiro

    2011-01-01

    Abstract Background Improving the treatment of renal cell carcinoma (RCC) will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7), also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC,...

  19. Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells

    OpenAIRE

    Elmasri, Harun; Karaaslan, Cagatay; Teper, Yaroslav; Ghelfi, Elisa; Weng, Meiqian; Ince, Tan A.; Kozakewich, Harry; Bischoff, Joyce; Cataltepe, Sule

    2009-01-01

    Fatty acid binding protein 4 (FABP4) plays an important role in maintaining glucose and lipid homeostasis. FABP4 has been primarily regarded as an adipocyte- and macrophage-specific protein, but recent studies suggest that it may be more widely expressed. We found strong FABP4 expression in the endothelial cells (ECs) of capillaries and small veins in several mouse and human tissues, including the heart and kidney. FABP4 was also detected in the ECs of mature human placental vessels and infan...

  20. Efficient production of omega-3 fatty acid desaturase (sFat-1)-transgenic pigs by somatic cell nuclear transfer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Omega-3(ω-3) fatty acid desaturase transgenic pigs may improve carcass fatty acid composition. The use of transgenic pigs is also an excellent large animal model for studying the role of ω-3 fatty acids in the prevention and treatment of coronary heart disease and cancer. Transgenic pigs carrying synthesized fatty acid desaturase-1 gene (sFat-1) from Caenorhabditis briggsae by somatic cell nuclear transfer (SCNT) were produced for the first time in China. Porcine fetal fibroblast cells were transfected with a sFat-1 expression cassette by the liposome-mediated method. Transgenic embryos were reconstructed by nuclear transfer of positive cells into enucleated in vitro matured oocytes. A total of 1889 reconstructed embryos were transferred into 10 naturally cycling gilts. Nine early pregnancies were established, 7 of which went to term. Twenty-one piglets were born. The cloning efficiency was 1.1% (born piglets/transferred embryos). The integration of the sFat-1 gene was confirmed in 15 live cloned piglets by PCR and Southern blot except for 2 piglets. Expression of the sFat-1 gene in 12 of 13 piglets was detected with RT-PCR. The data demonstrates that an efficient system for sFat-1 transgenic cloned pigs was developed, which led to the successful production of piglets expressing the sFat-1 gene.

  1. Omega-3 fatty acids (image)

    Science.gov (United States)

    Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega- ... fish including tuna, salmon, and mackerel. Other important omega 3 fatty acids are found in dark green leafy vegetables, flaxseed ...

  2. Inhibitory effect of schisandrin B on free fatty acid-induced steatosis in L-02 cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Hong Chu; Hui Wang; Yan Ye; Ping-Kei Chan; Si-Yuan Pan; Wang-Fun Fong; Zhi-Ling Yu

    2011-01-01

    AIM: To investigate the effects of schisandrin B (Sch B) on free fatty acid (FFA)-induced steatosis in L-02 cells. METHODS: Cellular steatosis was induced by incubating L-02 cells with a FFA mixture (oleate and palmitate at the ratio of 2:1) for 24 h. Cytotoxicity and apoptosis were evaluated by 3-(4, 5-dmethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay and Annexin V/propidium iodide staining, respectively. Cellular total lipid was determined using a photocolorimetric method after Nile red staining, and triglyceride content was measured using an enzymatic kit. To study the effects of Sch B on steatosis, L-02 cells were treated with Sch B (1-100 μmol/L) in the absence or presence of 1 mmol/L FFA for 24 h, and cellular total lipid and triglyceride levels were measured. To explore the mechanisms of action of Sch B in the steatotic L-02 cells, mRNA levels of several regulators of hepatic lipid metabolism including adipose differentiation related protein (ADRP), sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ were measured by quantitative real-time polymerase chain reaction (PCR), and protein levels of ADRP and SREBP-1 were measured by immunoblotting. RESULTS: Treatment with 1 mmol/L FFA for 24 h induced intracellular lipid accumulation in L-02 cells comparable to that in human steatotic livers without causing apparent apoptosis and cytotoxicity. Sch B mitigated cellular total lipid and triglyceride accumulations in the steatotic L-02 cells in a dose-dependent manner. Quantitative real-time PCR and Western blot analyses revealed that treatment of L-02 cells with 100 μmol/L Sch B reverted the FFA-stimulated up-regulation of ADRP and SREBP-1.

  3. Histone deacetylase inhibitor upregulates peroxisomal fatty acid oxidation and inhibits apoptotic cell death in abcd1-deficient glial cells.

    Directory of Open Access Journals (Sweden)

    Jaspreet Singh

    Full Text Available In X-ALD, mutation/deletion of ALD gene (ABCD1 and the resultant very long chain fatty acid (VLCFA derangement has dramatically opposing effects in astrocytes and oligodendrocytes. While loss of Abcd1 in astrocytes produces a robust inflammatory response, the oligodendrocytes undergo cell death leading to demyelination in X-linked adrenoleukodystrophy (X-ALD. The mechanisms of these distinct pathways in the two cell types are not well understood. Here, we investigated the effects of Abcd1-knockdown and the subsequent alteration in VLCFA metabolism in human U87 astrocytes and rat B12 oligodendrocytes. Loss of Abcd1 inhibited peroxisomal β-oxidation activity and increased expression of VLCFA synthesizing enzymes, elongase of very long chain fatty acids (ELOVLs (1 and 3 in both cell types. However, higher induction of ELOVL's in Abcd1-deficient B12 oligodendrocytes than astrocytes suggests that ELOVL pathway may play a prominent role in oligodendrocytes in X-ALD. While astrocytes are able to maintain the cellular homeostasis of anti-apoptotic proteins, Abcd1-deletion in B12 oligodendrocytes downregulated the anti-apototic (Bcl-2 and Bcl-xL and cell survival (phospho-Erk1/2 proteins, and upregulated the pro-apoptotic proteins (Bad, Bim, Bax and Bid leading to cell loss. These observations provide insights into different cellular signaling mechanisms in response to Abcd1-deletion in two different cell types of CNS. The apoptotic responses were accompanied by activation of caspase-3 and caspase-9 suggesting the involvement of mitochondrial-caspase-9-dependent mechanism in Abcd1-deficient oligodendrocytes. Treatment with histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA corrected the VLCFA derangement both in vitro and in vivo, and inhibited the oligodendrocytes loss. These observations provide a proof-of principle that HDAC inhibitor SAHA may have a therapeutic potential for X-ALD.

  4. Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro

    Institute of Scientific and Technical Information of China (English)

    SU Jie-ying; LI Hong-liang; YANG Wen-ying; XIAO Jian-zhong; DU Rui-qin; SHEN Xiao-xia; CAI Zhe; ZHANG Lan; SHU Jun

    2010-01-01

    Background Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However,whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.Methods The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.Results Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.Conclusion UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.

  5. 21 CFR 172.860 - Fatty acids.

    Science.gov (United States)

    2010-04-01

    ... acid, caprylic acid, lauric acid, myristic acid, oleic acid, palmitic acid, and stearic acid. (b) The... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Fatty acids. 172.860 Section 172.860 Food and Drugs... Multipurpose Additives § 172.860 Fatty acids. The food additive fatty acids may be safely used in food and...

  6. Cell survival during complete nutrient deprivation depends on lipid droplet-fueled β-oxidation of fatty acids.

    Science.gov (United States)

    Cabodevilla, Ainara G; Sánchez-Caballero, Laura; Nintou, Eleni; Boiadjieva, Violeta G; Picatoste, Fernando; Gubern, Albert; Claro, Enrique

    2013-09-27

    Cells exposed to stress of different origins synthesize triacylglycerols and generate lipid droplets (LD), but the physiological relevance of this response is uncertain. Using complete nutrient deprivation of cells in culture as a simple model of stress, we have addressed whether LD biogenesis has a protective role in cells committed to die. Complete nutrient deprivation induced the biogenesis of LD in human LN18 glioblastoma and HeLa cells and also in CHO and rat primary astrocytes. In all cell types, death was associated with LD depletion and was accelerated by blocking LD biogenesis after pharmacological inhibition of Group IVA phospholipase A2 (cPLA2α) or down-regulation of ceramide kinase. Nutrient deprivation also induced β-oxidation of fatty acids that was sensitive to cPLA2α inhibition, and cell survival in these conditions became strictly dependent on fatty acid catabolism. These results show that, during nutrient deprivation, cell viability is sustained by β-oxidation of fatty acids that requires biogenesis and mobilization of LD.

  7. Robotic milking and milk quality: effects on bacterial counts, somatic cell counts, freezing point and free fatty acids

    Directory of Open Access Journals (Sweden)

    Yvonne van der Vorst

    2010-01-01

    Full Text Available Changes in milk quality after the introduction of automatic milking systems (AM-systems on dairy farms in TheNetherlands, Germany and Denmark were examined and the data were compared with milk quality results of farms withconventional milking technology. After introduction, a small, but significant increase in total bacterial count, somatic cellcount, freezing point and free fatty acids was observed. The highest levels for total plate count and cell count are foundin the first six months after introduction. After this period the milk quality slightly improves to a more stable level.Risk factors related with milk quality concern general farm characteristics, animal health, AM-system, cleaning and cooling,housing, management skills of the farmer and the hygiene on the farm. Total plate count was significantly relatedto milk yield of the herd, cleaning of the area around the AM-system and the overall hygiene on the farm. Bulk milksomatic cell count appeared to be significantly related to milk yield of the herd and the number of milkings before replacementof the liners. An increased milking frequency is not the only explanation of increased free fatty acid levels. Technicalfactors related to free fatty acids mainly concerned the air inlet in the teat cups, bubbling (excessive air inlet and a toolong post run time of the milk pump. However, several questions regarding the causes of increased free fatty acid levelsremained unclear.

  8. Differential effect of maternal diet supplementation with α-Linolenic adcid or n-3 long-chain polyunsaturated fatty acids on glial cell phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat brains

    Directory of Open Access Journals (Sweden)

    Cruz-Hernandez Cristina

    2010-01-01

    Full Text Available Abstract Background Dietary long-chain polyunsaturated fatty acids (LC-PUFA are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE and phosphatidylserine (PS in the neonates. Methods Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55% and eicosapentaenoic acid (EPA, 0.75% of total fatty acids or α-linolenic acid (ALA, 2.90%. At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA profile. Data were analyzed by bivariate and multivariate statistics. Results In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P Conclusion The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.

  9. Effect of ω-3 polyunsaturated fatty acids on the growth of IEC-6 cells injured by heavy metals

    OpenAIRE

    Zhang, Feng; Yu, Haining; Ni, Xiaofeng; ZHU, Jing; Wang, Shanshan; Shen, Shengrong

    2016-01-01

    Environmental pollution is a current area of focus worldwide, particularly heavy metal pollution. Feasible prevention or therapeutic strategies are required. Exploration of the correlation between ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and intestinal epithelial cells injured by heavy metals may be of significance for intestinal health. In the present study, the effects of ω-3 PUFAs on the rat intestinal crypt cell line (IEC-6) injured by heavy metals and its mechanisms were determined ac...

  10. Effect of polyunsaturated fatty acids and phospholipids on [3H]-vitamin E incorporation into pulmonary artery endothelial cell membranes

    International Nuclear Information System (INIS)

    Vitamin E, a dietary antioxidant, is presumed to be incorporated into the lipid bilayer of biological membranes to an extent proportional to the amount of polyunsaturated fatty acids or phospholipids in the membrane. In the present study we evaluated the distribution of incorporated polyunsaturated fatty acids (PUFA) and phosphatidylethanolamine (PE) in various membranes of pulmonary artery endothelial cells. We also studied whether incorporation of PUFA or PE is responsible for increased incorporation of [3H]-vitamin E into the membranes of these cells. Following a 24-hr incubation with linoleic acid (18:2), 18:2 was increased by 6.9-, 9.2-, and 13.2-fold in plasma, mitochondrial, and microsomal membranes, respectively. Incorporation of 18:2 caused significant increases in the unsaturation indexes of mitochondrial and microsomal polyunsaturated fatty acyl chains (P less than .01 versus control in both membranes). Incubation with arachidonic acid (20:4) for 24 hr resulted in 1.5-, 2.3-, and 2.4-fold increases in 20:4 in plasma, mitochondrial, and microsomal membranes, respectively. The unsaturation indexes of polyunsaturated fatty acyl chains of mitochondrial and microsomal membranes also increased (P less than .01 versus control in both membranes). Although incubations with 18:2 or 20:4 resulted in several-fold increases in membrane 18:2 or 20:4 fatty acids, incorporation of [3H]-vitamin E into these membranes was similar to that in controls. Following a 24-hr incubation with PE, membrane PE content was significantly increased, and [3H]-vitamin E incorporation was also increased to a comparable degree, i.e., plasma membrane greater than mitochondria greater than microsomes. Endogenous vitamin E content of the cells was not altered because of increased incorporation of PE and [3H]-vitamin E

  11. Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.

    Directory of Open Access Journals (Sweden)

    Jung-Ha Park

    Full Text Available The life span of intestinal epithelial cells (IECs is short (3-5 days, and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen-free (SPF mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs.

  12. Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.

    Science.gov (United States)

    Park, Jung-Ha; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Kitamura, Yasuaki; Imada, Shinya; Usui, Yutaro; Hatano, Naoya; Shinohara, Masakazu; Saito, Yasuyuki; Murata, Yoji; Matozaki, Takashi

    2016-01-01

    The life span of intestinal epithelial cells (IECs) is short (3-5 days), and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen-free (SPF) mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs) as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs. PMID:27232601

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

    Directory of Open Access Journals (Sweden)

    Je Min Lee

    2016-01-01

    Full Text Available 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.

  14. Activation of PPARα by Fatty Acid Accumulation Enhances Fatty Acid Degradation and Sulfatide Synthesis.

    Science.gov (United States)

    Yang, Yang; Feng, Yuyao; Zhang, Xiaowei; Nakajima, Takero; Tanaka, Naoki; Sugiyama, Eiko; Kamijo, Yuji; Aoyama, Toshifumi

    2016-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first reaction in the mitochondrial fatty acid β-oxidation pathway. VLCAD deficiency is associated with the accumulation of fat in multiple organs and tissues, which results in specific clinical features including cardiomyopathy, cardiomegaly, muscle weakness, and hepatic dysfunction in infants. We speculated that the abnormal fatty acid metabolism in VLCAD-deficient individuals might cause cell necrosis by fatty acid toxicity. The accumulation of fatty acids may activate peroxisome proliferator-activated receptor (PPAR), a master regulator of fatty acid metabolism and a potent nuclear receptor for free fatty acids. We examined six skin fibroblast lines, derived from VLCAD-deficient patients and identified fatty acid accumulation and PPARα activation in these cell lines. We then found that the expression levels of three enzymes involved in fatty acid degradation, including long-chain acyl-CoA synthetase (LACS), were increased in a PPARα-dependent manner. This increased expression of LACS might enhance the fatty acyl-CoA supply to fatty acid degradation and sulfatide synthesis pathways. In fact, the first and last reactions in the sulfatide synthesis pathway are regulated by PPARα. Therefore, we also measured the expression levels of enzymes involved in sulfatide metabolism and the regulation of cellular sulfatide content. The levels of these enzymes and cellular sulfatide content both increased in a PPARα-dependent manner. These results indicate that PPARα activation plays defensive and compensative roles by reducing cellular toxicity associated with fatty acids and sulfuric acid. PMID:27644403

  15. Conjugated Linoleic Acid (CLA) inhibits expression of the Spot 14 (THRSP) and fatty acid synthase genes and impairs the growth of human breast cancer and liposarcoma cells

    OpenAIRE

    Donnelly, Christina; Olsen, Arne M.; Lewis, Lionel D; Eisenberg, Burton L.; Eastman, Alan; Kinlaw, William B

    2009-01-01

    Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes required for fatty acid synthesis in normal and malignant mammary epithelial and adipose cells. Havartine and Bauman reported that conjugated linoleic acid (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues, and reduces milk fat production in cows. We hypothesized that CLA inhibits S14 gene expression in human breast cancer and liposarcoma cells, and that this will retard their growth. Ex...

  16. Fatty acid control of growth of human cervical and endometrial cancer cells.

    OpenAIRE

    Gleeson, R P; Ayub, M.; Wright, J T; Wood, C B; Habib, N.A.; Soutter, W P; Sullivan, M. H.; White, J. O.

    1990-01-01

    Stearic acid and iodo-stearic and inhibited cell growth in a cervical cancer cell line (HOG-1) in a dose-related manner, with a half maximal effect at 50 microM stearic acid. Addition of oleic acid abrogated the effect of stearic acid. EGF-stimulated DNA synthesis and growth of HOG-1 cells was inhibited in the presence of stearic acid without any apparent effect on EGF receptor number or affinity.

  17. Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated Synthesis of Monounsaturated Fatty Acids.

    Science.gov (United States)

    Southam, Andrew D; Khanim, Farhat L; Hayden, Rachel E; Constantinou, Julia K; Koczula, Katarzyna M; Michell, Robert H; Viant, Mark R; Drayson, Mark T; Bunce, Chris M

    2015-06-15

    The redeployed drug combination of bezafibrate and medroxyprogesterone acetate (designated BaP) has potent in vivo anticancer activity in acute myelogenous leukemia (AML) and endemic Burkitt lymphoma (eBL) patients; however, its mechanism-of-action is unclear. Given that elevated fatty acid biosynthesis is a hallmark of many cancers and that these drugs can affect lipid metabolism, we hypothesized that BaP exerts anticancer effects by disrupting lipogenesis. We applied mass spectrometry-based lipidomics and gene and protein expression measurements of key lipogenic enzymes [acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and stearoyl CoA desaturase 1 (SCD1)] to AML and eBL cell lines treated with BaP. BaP treatment decreased fatty acid and phospholipid biosynthesis from (13)C D-glucose. The proportion of phospholipid species with saturated and monounsaturated acyl chains was also decreased after treatment, whereas those with polyunsaturated chains increased. BaP decreased SCD1 protein levels in each cell line (0.46- to 0.62-fold; P < 0.023) and decreased FASN protein levels across all cell lines (0.87-fold decrease; P = 1.7 × 10(-4)). Changes to ACC1 protein levels were mostly insignificant. Supplementation with the SCD1 enzymatic product, oleate, rescued AML and e-BL cells from BaP cell killing and decreased levels of BaP-induced reactive oxygen species, whereas supplementation with the SCD1 substrate (and FASN product), palmitate, did not rescue cells. In conclusion, these data suggest that the critical anticancer actions of BaP are decreases in SCD1 levels and monounsaturated fatty acid synthesis. To our knowledge, this is the first time that clinically available antileukemic and antilymphoma drugs targeting SCD1 have been reported. PMID:25943877

  18. Inhibitory effect of schisandrin B on free fatty acid-induced steatosis in L-02 cells

    Science.gov (United States)

    Chu, Jian-Hong; Wang, Hui; Ye, Yan; Chan, Ping-Kei; Pan, Si-Yuan; Fong, Wang-Fun; Yu, Zhi-Ling

    2011-01-01

    AIM: To investigate the effects of schisandrin B (Sch B) on free fatty acid (FFA)-induced steatosis in L-02 cells. METHODS: Cellular steatosis was induced by incubating L-02 cells with a FFA mixture (oleate and palmitate at the ratio of 2:1) for 24 h. Cytotoxicity and apoptosis were evaluated by 3-(4, 5-dmethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay and Annexin V/propidium iodide staining, respectively. Cellular total lipid was determined using a photocolorimetric method after Nile red staining, and triglyceride content was measured using an enzymatic kit. To study the effects of Sch B on steatosis, L-02 cells were treated with Sch B (1-100 μmol/L) in the absence or presence of 1 mmol/L FFA for 24 h, and cellular total lipid and triglyceride levels were measured. To explore the mechanisms of action of Sch B in the steatotic L-02 cells, mRNA levels of several regulators of hepatic lipid metabolism including adipose differentiation related protein (ADRP), sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ were measured by quantitative real-time polymerase chain reaction (PCR), and protein levels of ADRP and SREBP-1 were measured by immunoblotting. RESULTS: Treatment with 1 mmol/L FFA for 24 h induced intracellular lipid accumulation in L-02 cells comparable to that in human steatotic livers without causing apparent apoptosis and cytotoxicity. Sch B mitigated cellular total lipid and triglyceride accumulations in the steatotic L-02 cells in a dose-dependent manner. Quantitative real-time PCR and Western blot analyses revealed that treatment of L-02 cells with 100 μmol/L Sch B reverted the FFA-stimulated up-regulation of ADRP and SREBP-1. CONCLUSION: Sch B inhibits FFA-induced steatosis in L-02 cells by, at least in part, reversing the up-regulation of ADRP and SREBP-1. PMID:21633637

  19. The effect of short-chain fatty acids on human monocyte-derived dendritic cells

    DEFF Research Database (Denmark)

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné;

    2015-01-01

    The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood...... illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions....

  20. Adipose Tissue Fatty Acid Storage Factors: Effects of Depot, Sex and Fat Cell Size

    OpenAIRE

    Hames, Kazanna C.; Koutsari, Christina; Santosa, Sylvia; Bush, Nikki C.; Jensen, Michael D.

    2015-01-01

    Background/Objectives Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetases (ACS; the first step in fat metabolism), and diacylglycerol acetyl-transferase (DGAT; the final step of triglyceride synthesis). Our goal was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots, and adipocyte size. Subje...

  1. Electron spin resonance studies on intact cells and isolated lipid droplets from fatty acid-modified L1210 murine leukemia.

    Science.gov (United States)

    Simon, I; Burns, C P; Spector, A A

    1982-07-01

    It has been suggested that the formation of cytoplasmic lipid droplets may produce an artifact and be responsible for the differences in membrane physical properties detected in lipid-modified cells using fluorescence polarization or spin label probes. To investigate this, the electron spin resonance spectra of lipid droplets isolated from the cytoplasm of L1210 leukemia cells were compared with spectra obtained from the intact cell. Mice bearing the L1210 leukemia were fed diets containing either 16% sunflower oil or 16% coconut oil in order to modify the fatty acid composition of the tumor. A microsome-rich fraction prepared from L1210 cells grown in animals fed the sunflower oil-rich diet contained more polyenoic fatty acids (52 versus 29%), while microsomes from L1210 cells grown in animals fed the coconut oil-rich diets contained more monoenoic fatty acids (37 versus 12%). The order parameter calculated for lipid droplets labeled with the 5-nitroxystearic acid spin probe was only about one-half that of intact cells, whereas it was similar to that obtained for pure triolein droplets suspended in buffer. Order parameters of the inner hyperfine splittings calculated from the spectra of cells grown in the sunflower oil-fed animals [0.543 +/- 0.001 (S.E.)] were lower than those from the cells grown in animals fed the coconut oil diets (0.555 +/- 0.002) (p less than 0.005). In contrast, the order parameters of the lipid droplets isolated from the cells grown in animals fed sunflower oil (0.303 +/- 0.029) or coconut oil (0.295 +/- 0.021) were not significantly different, indicating that motion of a spin label probe in the highly fluid cytoplasmic lipid droplets is not affected by these types of modifications in cellular fatty acid composition. Therefore, the electron spin resonance changes that are observed in the intact cells cannot be due to localization of the probe in cytoplasmic lipid droplets. These results support the conclusion that the electron spin

  2. Veal fatty acid composition of different breeds

    OpenAIRE

    Ivica Kos; Jelena Ramljak; Ante Ivanković; Miljenko Konjačić; Nikolina Kelava

    2010-01-01

    Veal fatty acid composition in M. Longissimus thoracis was investigated in different calf breeds (Simmental, Holstein, Simmental x Holstein). Calves were reared on the same farm under identical feeding and handling conditions. Simmental calves had higher polyunsaturated fatty acid (PUFA) but lower saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) values than Holstein and crossbreed calves (P

  3. Understanding the effects of mature adipocytes and endothelial cells on fatty acid metabolism and vascular tone in physiological fatty tissue for vascularized adipose tissue engineering.

    Science.gov (United States)

    Huber, Birgit; Volz, Ann-Cathrin; Kluger, Petra J

    2015-11-01

    Engineering of large vascularized adipose tissue constructs is still a challenge for the treatment of extensive high-graded burns or the replacement of tissue after tumor removal. Communication between mature adipocytes and endothelial cells is important for homeostasis and the maintenance of adipose tissue mass but, to date, is mainly neglected in tissue engineering strategies. Thus, new co-culture strategies are needed to integrate adipocytes and endothelial cells successfully into a functional construct. This review focuses on the cross-talk of mature adipocytes and endothelial cells and considers their influence on fatty acid metabolism and vascular tone. In addition, the properties and challenges with regard to these two cell types for vascularized tissue engineering are highlighted.

  4. Susceptibility of pancreatic beta cells to fatty acids is regulated by LXR/PPARalpha-dependent stearoyl-coenzyme A desaturase.

    Directory of Open Access Journals (Sweden)

    Karine H Hellemans

    Full Text Available Chronically elevated levels of fatty acids-FA can cause beta cell death in vitro. Beta cells vary in their individual susceptibility to FA-toxicity. Rat beta cells were previously shown to better resist FA-toxicity in conditions that increased triglyceride formation or mitochondrial and peroxisomal FA-oxidation, possibly reducing cytoplasmic levels of toxic FA-moieties. We now show that stearoyl-CoA desaturase-SCD is involved in this cytoprotective mechanism through its ability to transfer saturated FA into monounsaturated FA that are incorporated in lipids. In purified beta cells, SCD expression was induced by LXR- and PPARalpha-agonists, which were found to protect rat, mouse and human beta cells against palmitate toxicity. When their SCD was inhibited or silenced, the agonist-induced protection was also suppressed. A correlation between beta cell-SCD expression and susceptibility to palmitate was also found in beta cell preparations isolated from different rodent models. In mice with LXR-deletion (LXRbeta(-/- and LXRalphabeta(-/-, beta cells presented a reduced SCD-expression as well as an increased susceptibility to palmitate-toxicity, which could not be counteracted by LXR or PPARalpha agonists. In Zucker fatty rats and in rats treated with the LXR-agonist TO1317, beta cells show an increased SCD-expression and lower palmitate-toxicity. In the normal rat beta cell population, the subpopulation with lower metabolic responsiveness to glucose exhibits a lower SCD1 expression and a higher susceptibility to palmitate toxicity. These data demonstrate that the beta cell susceptibility to saturated fatty acids can be reduced by stearoyl-coA desaturase, which upon stimulation by LXR and PPARalpha agonists favors their desaturation and subsequent incorporation in neutral lipids.

  5. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation

    Science.gov (United States)

    Patsoukis, Nikolaos; Bardhan, Kankana; Chatterjee, Pranam; Sari, Duygu; Liu, Bianling; Bell, Lauren N.; Karoly, Edward D.; Freeman, Gordon J.; Petkova, Victoria; Seth, Pankaj; Li, Lequn; Boussiotis, Vassiliki A.

    2015-01-01

    During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid β-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade. PMID:25809635

  6. The Effects of Omega-3 Fatty Acids on Matrix Metalloproteinase-9 Production and Cell Migration in Human Immune Cells: Implications for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lynne Shinto

    2011-01-01

    Full Text Available In multiple sclerosis (MS, compromised blood-brain barrier (BBB integrity contributes to inflammatory T cell migration into the central nervous system. Matrix metalloproteinase-9 (MMP-9 is associated with BBB disruption and subsequent T cell migration into the CNS. The aim of this paper was to evaluate the effects of omega-3 fatty acids on MMP-9 levels and T cell migration. Peripheral blood mononuclear cells (PBMC from healthy controls were pretreated with two types of omega-3 fatty acids, eicosapentaenoic acid (EPA, and docosahexaenoic acid (DHA. Cell supernatants were used to determine MMP-9 protein and activity levels. Jurkat cells were pretreated with EPA and DHA and were added to fibronectin-coated transwells to measure T cell migration. EPA and DHA significantly decreased MMP-9 protein levels, MMP-9 activity, and significantly inhibited human T cell migration. The data suggest that omega-3 fatty acids may benefit patients with multiple sclerosis by modulating immune cell production of MMP-9.

  7. The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice

    Directory of Open Access Journals (Sweden)

    Kopecky Jan

    2011-08-01

    Full Text Available Abstract Background Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA of marine origin exert multiple beneficial effects on health. Our previous study in mice showed that reduction of adiposity by LC n-3 PUFA was associated with both, a shift in adipose tissue metabolism and a decrease in tissue cellularity. The aim of this study was to further characterize the effects of LC n-3 PUFA on fat cell proliferation and differentiation in obese mice. Methods A model of inducible and reversible lipoatrophy (aP2-Cre-ERT2 PPARγL2/L2 mice was used, in which the death of mature adipocytes could be achieved by a selective ablation of peroxisome proliferator-activated receptor γ in response to i.p. injection of tamoxifen. Before the injection, obesity was induced in male mice by 8-week-feeding a corn oil-based high-fat diet (cHF and, subsequently, mice were randomly assigned (day 0 to one of the following groups: (i mice injected by corn-oil-vehicle only, i.e."control" mice, and fed cHF; (ii mice injected by tamoxifen in corn oil, i.e. "mutant" mice, fed cHF; (iii control mice fed cHF diet with15% of dietary lipids replaced by LC n-3 PUFA concentrate (cHF+F; and (iv mutant mice fed cHF+F. Blood and tissue samples were collected at days 14 and 42. Results Mutant mice achieved a maximum weight loss within 10 days post-injection, followed by a compensatory body weight gain, which was significantly faster in the cHF as compared with the cHF+F mutant mice. Also in control mice, body weight gain was depressed in response to dietary LC n-3 PUFA. At day 42, body weights in all groups stabilized, with no significant differences in adipocyte size between the groups, although body weight and adiposity was lower in the cHF+F as compared with the cHF mice, with a stronger effect in the mutant than in control mice. Gene expression analysis documented depression of adipocyte maturation during the reconstitution of adipose tissue in the cHF+F mutant mice. Conclusion

  8. Jasmonic Acid Effect on the Fatty Acid and Terpenoid Indole Alkaloid Accumulation in Cell Suspension Cultures of Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Guitele Dalia Goldhaber-Pasillas

    2014-07-01

    Full Text Available The stress response after jasmonic acid (JA treatment was studied in cell suspension cultures of Catharanthus roseus. The effect of JA on the primary and secondary metabolism was based on changes in profiles of fatty acids (FA and terpenoid indole alkaloids (TIA. According to multivariate data analyses (MVDA, three major time events were observed and characterized according to the variations of specific FA and TIA: after 0–30 min of induction FA such as C18:1, C20:0, C22:0 and C24:0 were highly induced by JA; 90–360 min after treatment was characterized by variations of C14:0 and C15:0; and 1440 min after induction JA had the largest effect on both group of metabolites were C18:1, C18:2, C18:3, C16:0, C20:0, C22:0, C24:0, catharanthine, tabersonine-like 1, serpentine, tabersonine and ajmalicine-like had the most significant variations. These results unambiguously demonstrate the profound effect of JA particularly on the accumulation of its own precursor, C18:3 and the accumulation of TIA, which can be considered as late stress response events to JA since they occurred only after 1440 min. These observations show that the early events in the JA response do not involve the de novo biosynthesis of neither its own precursor nor TIA, but is due to an already present biochemical system.

  9. Jasmonic acid effect on the fatty acid and terpenoid indole alkaloid accumulation in cell suspension cultures of Catharanthus roseus.

    Science.gov (United States)

    Goldhaber-Pasillas, Guitele Dalia; Mustafa, Natali Rianika; Verpoorte, Robert

    2014-01-01

    The stress response after jasmonic acid (JA) treatment was studied in cell suspension cultures of Catharanthus roseus. The effect of JA on the primary and secondary metabolism was based on changes in profiles of fatty acids (FA) and terpenoid indole alkaloids (TIA). According to multivariate data analyses (MVDA), three major time events were observed and characterized according to the variations of specific FA and TIA: after 0-30 min of induction FA such as C18:1, C20:0, C22:0 and C24:0 were highly induced by JA; 90-360 min after treatment was characterized by variations of C14:0 and C15:0; and 1440 min after induction JA had the largest effect on both group of metabolites were C18:1, C18:2, C18:3, C16:0, C20:0, C22:0, C24:0, catharanthine, tabersonine-like 1, serpentine, tabersonine and ajmalicine-like had the most significant variations. These results unambiguously demonstrate the profound effect of JA particularly on the accumulation of its own precursor, C18:3 and the accumulation of TIA, which can be considered as late stress response events to JA since they occurred only after 1440 min. These observations show that the early events in the JA response do not involve the de novo biosynthesis of neither its own precursor nor TIA, but is due to an already present biochemical system. PMID:25029072

  10. Effect of Marine Omega 3 Fatty Acids on Methylmercury-Induced Toxicity in Fish and Mammalian Cells In Vitro

    Directory of Open Access Journals (Sweden)

    O. J. Nøstbakken

    2012-01-01

    Full Text Available Methylmercury (MeHg is a ubiquitous environmental contaminant which bioaccumulates in marine biota. Fish constitute an important part of a balanced human diet contributing with health beneficial nutrients but may also contain contaminants such as MeHg. Interactions between the marine n-3 fatty acids eicosapentaenoic acid (20:5n-3, EPA and docosahexaenoic acid (22:6n-3, DHA with MeHg-induced toxicity were investigated. Different toxic and metabolic responses were studied in Atlantic salmon kidney (ASK cell line and the mammalian kidney-derived HEK293 cell line. Both cell lines were preincubated with DHA or EPA prior to MeHg-exposure, and cell toxicity was assessed differently in the cell lines by MeHg-uptake in cells (ASK and HEK293, proliferation (HEK293 and ASK, apoptosis (ASK, oxidation of the red-ox probe roGFP (HEK293, and regulation of selected toxicological and metabolic transcriptional markers (ASK. DHA was observed to decrease the uptake of MeHg in HEK293, but not in ASK cells. DHA also increased, while EPA decreased, MeHg-induced apoptosis in ASK. MeHg exposure induced changes in selected metabolic and known MeHg biomarkers in ASK cells. Both DHA and MeHg, but not EPA, oxidized roGFP in HEK293 cells. In conclusion, marine n-3 fatty acids may ameliorate MeHg toxicity, either by decreasing apoptosis (EPA or by reducing MeHg uptake (DHA. However, DHA can also augment MeHg toxicity by increasing oxidative stress and apoptosis when combined with MeHg.

  11. From microbe to man: the role of microbial short chain fatty acid metabolites in host cell biology.

    Science.gov (United States)

    Natarajan, Niranjana; Pluznick, Jennifer L

    2014-12-01

    Recent studies have highlighted a myriad of ways in which the activity and composition of the gut microbiota can affect the host organism. A primary way in which the gut microbiota affect host physiology is by the production of metabolites, such as short-chain fatty acids (SCFAs), which are subsequently absorbed into the bloodstream of the host. Although recent studies have begun to unravel the ways in which gut microbial SCFAs affect host physiology, less is understood regarding the underlying cell biological mechanisms. In this review, we will outline the known receptors and transporters for SCFAs, and review what is known about the cell biological effects of microbial SCFAs. PMID:25273884

  12. Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells

    OpenAIRE

    Aragonès Gemma; Saavedra Paula; Heras Mercedes; Cabré Anna; Girona Josefa; Masana Lluís

    2012-01-01

    Abstract Background Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro. Methods In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation a...

  13. Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

    Science.gov (United States)

    Vancura, Patrick; Wolloscheck, Tanja; Baba, Kenkichi; Tosini, Gianluca; Iuvone, P. Michael; Spessert, Rainer

    2016-01-01

    The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy—one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i.e. carnitine palmitoyltransferase-1α (Cpt-1α) and medium chain acyl-CoA dehydrogenase (Acadm) to display daily rhythms with peak values during daytime in preparations of the whole retina and microdissected photoreceptors. The cycling of both enzymes persisted in constant darkness, was dampened in mice deficient for dopamine D4 (D4) receptors and was altered in db/db mice—a model of diabetic retinopathy. The data of the present study are consistent with circadian clock-dependent and dopaminergic regulation of fatty acid oxidation in retina and its putative disturbance in diabetic retina. PMID:27727308

  14. Caveolar fatty acids and acylation of caveolin-1.

    Directory of Open Access Journals (Sweden)

    Qian Cai

    Full Text Available PURPOSE: Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane. Caveolae contain a variety of signaling proteins which provide platforms for signaling transduction. In addition to enriched with cholesterol and sphingolipids, caveolae also contain a variety of fatty acids. It has been well-established that acylation of protein plays a pivotal role in subcellular location including targeting to caveolae. However, the fatty acid compositions of caveolae and the type of acylation of caveolar proteins remain largely unknown. In this study, we investigated the fatty acids in caveolae and caveolin-1 bound fatty acids. METHODS: Caveolae were isolated from Chinese hamster ovary (CHO cells. The caveolar fatty acids were extracted with Folch reagent, methyl esterificated with BF3, and analyzed by gas chromatograph-mass spectrometer (GC/MS. The caveolin-1 bound fatty acids were immunoprecipitated by anti-caveolin-1 IgG and analyzed with GC/MS. RESULTS: In contrast to the whole CHO cell lysate which contained a variety of fatty acids, caveolae mainly contained three types of fatty acids, 0.48 µg palmitic acid, 0.61 µg stearic acid and 0.83 µg oleic acid/caveolae preparation/5 × 10(7 cells. Unexpectedly, GC/MS analysis indicated that caveolin-1 was not acylated by myristic acid; instead, it was acylated by palmitic acid and stearic acid. CONCLUSION: Caveolae contained a special set of fatty acids, highly enriched with saturated fatty acids, and caveolin-1 was acylated by palmitic acid and stearic acid. The unique fatty acid compositions of caveolae and acylation of caveolin-1 may be important for caveolae formation and for maintaining the function of caveolae.

  15. Effect of Growth factors, estradiol 17-ß, and short chain fatty acids on the intestinal HT29-MTX cells

    DEFF Research Database (Denmark)

    Giromini, Carlotta; Baldi, Antonella; Fusi, Eleonora;

    2015-01-01

    Peptides growth factors, hormones, and short chain fatty acids (SCFAs) are constantly in contact with the human bowel when secreted by gland or ingested by food, as milk and colostrum, or, as in the case of SCFAs, produced by fermentation processes. This study considers the effect of growth factors......, estradiol 17-β, and SCFAs on the metabolic activity and proliferation of undifferentiated HT29-MTX-E12 (E12) cells. In particular, the aim of the present study was the characterization of the human intestinal cell line E12 for its suitability as an in vitro intestinal model for cell-nutrient interaction...... state, showed to be a suitable in vitro model for cell-nutrient interaction studies, providing an opportunity to examine the potential role of growth factors, hormones and SCFAs in the regulation of the intestinal cell viability....

  16. Yarrowia lipolytica as an oleaginous cell factory platform for the production of fatty acid-based biofuel and bioproducts

    Directory of Open Access Journals (Sweden)

    Ali eAbghari

    2014-06-01

    Full Text Available Today’s biotechnologists seek new biocatalysts to meet the growing demand for the bioproducts. This review critically evaluates the potential use of Y. lipolytica as an oleaginous cell factory platform. This yeast has undergone extensive modifications for converting a wide range of hydrophobic and hydrophilic biomass, including alkane, oil, glycerol and sugars to fatty acid-based products. This article highlights challenges in the development of this platform and provides an overview of strategies to enhance its potential in the sustainable production of biodiesel, functional dietary lipid compounds and other value-added oleochemical compounds. Future applications of the recombinant Y. lipolytica platform are also discussed.

  17. Potential Production of Polyunsaturated Fatty Acids from Microalgae

    OpenAIRE

    Noer Abyor Handayani; Dessy Ariyanti; Hady Hadiyanto

    2011-01-01

    Currently, public awareness of healthcare importance increase. Polyunsaturated fatty acid is an essential nutrition for us, such arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid. The need of Polyunsaturated fatty acid generally derived from fish oil, but fish oil has a high risk chemical contamination. Microalgae are single cell microorganism, one of Phaeodactylum tricornutum which have relatively high content of eicosapentaenoic acid (29,8%). Biotechnology market of Polyunsat...

  18. The clinical significance of fatty acid binding proteins

    OpenAIRE

    Barbara Choromańska; Piotr Myśliwiec; Jacek Dadan; Hady Razak Hady; Adrian Chabowski

    2011-01-01

    Excessive levels of free fatty acids are toxic to cells. The human body has evolved a defense mechanism in the form of small cytoplasmic proteins called fatty acid binding proteins (FABPs) that bind long-chain fatty acids (LCFA), and then refer them to appropriate intracellular disposal sites (oxidation in mitochondria and peroxisomes or storage in the endoplasmic reticulum). So far, nine types of these proteins have been described, and their name refers to the place in which they were first ...

  19. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells.

    Science.gov (United States)

    Reigstad, Christopher S; Salmonson, Charles E; Rainey, John F; Szurszewski, Joseph H; Linden, David R; Sonnenburg, Justin L; Farrugia, Gianrico; Kashyap, Purna C

    2015-04-01

    Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To determine the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gut microbiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P cell numbers (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT production and homeostasis. PMID:25550456

  20. Influence of in vitro supplementation with lipids from conventional and Alpine milk on fatty acid distribution and cell growth of HT-29 cells

    Directory of Open Access Journals (Sweden)

    Dänicke Sven

    2011-08-01

    Full Text Available Abstract Background To date, the influence of milk and dairy products on carcinogenesis remains controversial. However, lipids of ruminant origin such as conjugated linoleic acids (CLA are known to exhibit beneficial effects in vitro and in vivo. The aim of the present study was to determine the influence of milk lipids of different origin and varying quality presenting as free fatty acid (FFA solutions on cellular fatty acid distribution, cellular viability, and growth of human colon adenocarcinoma cells (HT-29. Methods FAME of conventional and Alpine milk lipids (MLcon, MLalp and cells treated with FFA derivatives of milk lipids were analyzed by means of GC-FID and Ag+-HPLC. Cellular viability and growth of the cells were determined by means of CellTiter-Blue®-assay and DAPI-assay (4',6-diamidino-2-phenylindole dihydrochloride, respectively. Results Supplementation with milk lipids significantly decreased viability and growth of HT-29 cells in a dose- and time-dependent manner. MLalp showed a lower SFA/MUFA ratio, a 8 fold increased CLA content, and different CLA profile compared to MLcon but did not demonstrate additional growth-inhibitory effects. In addition, total concentration and fatty acid distribution of cellular lipids were altered. In particular, treatment of the cells yielded highest amounts of two types of milk specific major fatty acids (μg FA/mg cellular protein after 8 h of incubation compared to 24 h; 200 μM of MLcon (C16:0, 206 ± 43, 200 μM of MLalp (C18:1 c9, (223 ± 19. Vaccenic acid (C18:1 t11 contained in milk lipids was converted to c9,t11-CLA in HT-29 cells. Notably, the ratio of t11,c13-CLA/t7,c9-CLA, a criterion for pasture feeding of the cows, was significantly changed after incubation for 8 h with lipids from MLalp (3.6 - 4.8, compared to lipids from MLcon (0.3 - 0.6. Conclusions Natural lipids from conventional and Alpine milk showed similar growth inhibitory effects. However, different changes in cellular

  1. Curcuminoids and ω-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon γ production

    OpenAIRE

    Milan eFiala; Ramesh eHalder; Anasheh eAlmasi; Bien eSagong; Jessica eLeung; Anahid eJewett

    2015-01-01

    Pancreatic cancer has a poor prognosis attributed in part to immune suppression and deactivation of natural killer (NK) cells. Curcuminoids have a potential for improving the therapy of pancreatic cancer given promising results in cancer models and a clinical trial, but their oral absorption is limited. Our objective in this study is to show curcuminoid anti-oncogenic effects alone and together with human NK cells. We tested curcuminoids in an emulsion of ω-3 fatty acids and anti-oxidants (S...

  2. Residual Host Cell Protein Promotes Polysorbate 20 Degradation in a Sulfatase Drug Product Leading to Free Fatty Acid Particles.

    Science.gov (United States)

    Dixit, Nitin; Salamat-Miller, Nazila; Salinas, Paul A; Taylor, Katherine D; Basu, Sujit K

    2016-05-01

    This study investigated the root cause behind an observed free fatty acid particle formation and resulting Polysorbate 20 (PS20) loss for a sulfatase drug product upon long-term storage at 5 ± 3°C. Reversed- phase chromatography with mass spectrometric analysis as well as charged aerosol detection was used to characterize the peaks associated with the intact and degraded PS20. Additionally, a proteomics study was undertaken to identify the residual host cell proteins in the sulfatase drug substance. PS20 stability studies were conducted in the presence of sulfatase, a sulfatase inhibitor, putative phospholipase B-like 2, and mock drug substance produced using a null cell line vector under experimental conditions optimized for PS20 degradation. This study provides the first published evidence where the residual host cell protein present in the drug substance was identified and experimentally shown to catalyze the breakdown of PS20 in a protein formulation over time, resulting in free fatty acid particles and PS20 loss. This study demonstrates the importance of early detection of potential impurities in the protein drug substance that may contribute to polysorbate degradation to make a judicious selection of the surfactant and its optimized concentration for the final drug product. PMID:27032893

  3. FATTY ACIDS PROFILE IN A HIGH CELL DENSITY CULTURE OF ARACHIDONIC ACID-RICH PARIETOCHLORIS INCISA (TREBOUXIOPHYCEAE,CHLOROPHYTA) EXPOSED TO HIGH PFD

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The changes in arachidonic acid (AA) and fatty acids profiles along the growth curve of Parietochloris incisa, a coccoid snow green alga, were studied in a 2.8 cm light-path flat photobioreactor, exposed to strong photon flux density [PFD, 2400 μEmol/(m2*s)]. Sixteen fatty acids were identified by gas chromatography showing that AA was the dominant fatty acid (33%-41%) followedby linoleic acid (17%-21%). AA content was closely investigated with respect tototal fatty acids (TFA), ash free dry weight (AFDW) of cell mass as well as total culture content. These parameters were influenced significantly in a similar manner by culture growth phase, i.e., slightly decreasing in the lag period, gradually increasing in the logarithmic phase, becoming maximal at the early stationary phase, starting to decrease at the late stationary phase, sharply dropping at the decline phase. The increase in AA per culture volume during the logarithmic phase was not only associated with the increase in AFDW but also connected with a corresponding increase in AA/TFA, TFA/AFDW as well as AA/AFDW. The sharp decrease in AA content of the culture during the decline phase was mainly due to the decrease in AA/TFA, TFA/AFDW and AA/AFDW, although AFDW declined only a smallextent. Maximal AA concentration, obtained at the early stationary phase, was 900 mg/L culture volume, and the average daily net increase of AA during 9 days logarithmic growth was 1.7 g/(m2*day). Therefore, harvesting prior to the declinephase in a batch culture, or at steady state in continuous culture mode seems best for high AA production. The latter possibility was also further confirmed bycontinuous culture with 5 gradients of harvesting rate. ``

  4. The fatty acid beta-oxidation pathway is important for decidualization of endometrial stromal cells in both humans and mice.

    Science.gov (United States)

    Tsai, Jui-He; Chi, Maggie M-Y; Schulte, Maureen B; Moley, Kelle H

    2014-02-01

    Embryo implantation and development requires the endometrial stromal cells (ESCs) to undergo decidualization. This differentiation process requires glucose utilization, and blockade of the pentose phosphate pathway inhibits decidualization of ESCs both in vitro and in vivo. Glucose and fatty acids are energy substrates for many cell types, and fatty acid beta-oxidation is critical for embryo implantation. Here, we investigated whether beta-oxidation is required for decidualization of ESCs. As assessed by marker gene expression, decidualization of human primary ESCs was blocked by reducing activity of carnitine calmitoyltransferase I, the rate-limiting enzyme in beta-oxidation, either by short hairpin RNA-mediated silencing or by treatment with the inhibitor etomoxir. Ranolazine (RAN), a partial beta-oxidation inhibitor, blocked early decidualization of a human ESC line. However, decidualization resumed after several days, most likely due to a compensatory up-regulation of GLUT1 expression and an increase in glucose metabolism. Simultaneous inhibition of the beta-oxidation pathway with RAN and the pentose phosphate pathway with glucosamine (GlcN) impaired in vitro decidualization of human ESCs more strongly than inhibition of either pathway alone. These findings were confirmed in murine ESCs in vitro, and exposure to RAN plus GlcN inhibited decidualization in vivo in a deciduoma model. Finally, intrauterine implantation of time-release RAN and GlcN pellets reduced pup number. Importantly, pup number returned to normal after the end of the pellet-active period. This work indicates that both fatty acids and glucose metabolism pathways are important for ESC decidualization, and suggests novel pathways to target for the design of future nonhormonal contraceptives.

  5. N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Wenqing Cao

    Full Text Available Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6, eicosapentaenoic acid (EPA, C20:5 shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa MCF-7 and T47D cells. 17 β-estradiol (E2 enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2. E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0 as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ERα agonist failed to elicit, and ERα knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1 may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.

  6. Potential Production of Polyunsaturated Fatty Acids from Microalgae

    Directory of Open Access Journals (Sweden)

    Noer Abyor Handayani

    2011-07-01

    Full Text Available Currently, public awareness of healthcare importance increase. Polyunsaturated fatty acid is an essential nutrition for us, such arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid. The need of Polyunsaturated fatty acid generally derived from fish oil, but fish oil has a high risk chemical contamination. Microalgae are single cell microorganism, one of Phaeodactylum tricornutum which have relatively high content of eicosapentaenoic acid (29,8%. Biotechnology market of Polyunsaturated fatty acid is very promising for both foods and feeds, because the availability of abundant raw materials and suitable to develop in the tropics. This literature review discusses about the content of Polyunsaturated fatty acid in microalgae, omega-3, omega-6, Polyunsaturated fatty acid production processes, and applications in public health

  7. Maastricht essential fatty acid birth cohort

    NARCIS (Netherlands)

    Van der Wurff, Inge; De Groot, Renate; Stratakis, Nikos; Gielen, Marij; Hornstra, Gerard; Zeegers, Maurice

    2016-01-01

    The Maastricht Essential Fatty Acid Birth cohort (MEFAB) was established in 1989 to study the changes in fatty acid concentration during pregnancy and how this related to the fatty acid concentrations of the neonate. The original sample contains data of 1203 subjects. Some participants whom particip

  8. The science of fatty acids and inflammation.

    Science.gov (United States)

    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

  9. Fatty acid effects on fibroblast cholesterol synthesis

    International Nuclear Information System (INIS)

    Two cell lines of normal (CRL 1475, GM5565) and of familial hypercholesterolemia (FH) (CM 486,488) fibroblasts were preincubated with medium containing the growth factor ITS, 2.5 mg/ml fatty acid-free BSA, or 35.2 μmol/ml of these fatty acids complexed with 2.5 mg BSA/ml: stearic (18:0), caprylic (8:0), oleic (18:1;9), linoleic (18:2;9,12), linolenic (18:3;9,12,15), docosahexaenoic (22:6;4,7,10,13,16,19)(DHA) or eicosapentaenoic (20:5;5,8,11,14,17)(EPA). After 20 h, cells were incubated for 2 h with 0.2 μCi [14C]acetate/ml. Cells were hydrolyzed; an aliquot was quantitated for radioactivity and protein. After saponification and extraction with hexane, radioactivity in the aqueous and organic phases was determined. The FH cells always incorporated 30-90% more acetate/mg protein than normal cells but the pattern of the fatty acid effects was similar in both types. When the values were normalized to 1 for the BSA-only group, cells with ITS had the greatest [14C]acetate incorporation (1.45) followed by the caprylic group (1.14). Cells incubated with 18:3, 20:6 or 22:6 incorporated about the same amount as BSA-only. Those preincubated with 18:2, 18:1, 18:0 showed the least acetate incorporation (0.87, 0.59 and 0.52, respectively). The percentage of total 14C counts which extracted into hexane was much greater in FH cells; however, these values varied with the fatty acid, e.g., 1.31(18:0) and 0.84(8:0) relative to 1

  10. Thyroid hormone responsive (THRSP) promotes the synthesis of medium-chain fatty acids in goat mammary epithelial cells.

    Science.gov (United States)

    Yao, D W; Luo, J; He, Q Y; Wu, M; Shi, H B; Wang, H; Wang, M; Xu, H F; Loor, J J

    2016-04-01

    In nonruminants, thyroid hormone responsive (THRSP) is a crucial protein for cellular de novo lipogenesis. However, the role of THRSP in regulating the synthesis of milk fatty acid composition in goat mammary gland remains unknown. In the present study, we compared gene expression of THRSP among different goat tissues. Results revealed that THRSP had the highest expression in subcutaneous fat, and expression was higher during lactation compared with the dry period. Overexpression of THRSP upregulated the expression of fatty acid synthase (FASN), stearoyl-coenzyme A desaturase 1 (SCD1), diacylglycerol acyltransferase 2 (DGAT2), and glycerol-3-phosphate acyltransferase (GPAM) in goat mammary epithelial cells. In contrast, overexpression of THRSP led to downregulation of thrombospondin receptor (CD36) and had no effect on the expression of acetyl-coenzyme A carboxylase α (ACACA) and sterol regulatory element binding transcription factor1 (SREBF1). In addition, overexpressing THRSP in vitro resulted in a significant increase in triacylglycerol (TAG) concentration and the concentrations of C12:0 and C14:0. Taken together, these results highlight an important role of THRSP in regulating lipogenesis in goat mammary epithelial cells. PMID:26851858

  11. Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

    OpenAIRE

    Yao, Qinghua; Fu, Ting; Wang, Lu; LAI, YUEBIAO; Wang, Yuqi; Xu, Chao; Huang, Lulu; Guo, Yong

    2015-01-01

    The present study identified that ω-3 long chain polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that ω-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and...

  12. The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions

    OpenAIRE

    Walker, Celia G.; West, Annette L.; Browning, Lucy M; Jackie Madden; Gambell, Joanna M; Jebb, Susan A.; Calder, Philip C.

    2015-01-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify...

  13. Effect of fatty acids on energy coupling processes in mitochondria.

    Science.gov (United States)

    Wojtczak, L; Schönfeld, P

    1993-11-01

    Long-chain fatty acids are natural uncouplers of oxidative phosphorylation in mitochondria. The protonophoric mechanism of this action is due to transbilayer movement of undissociated fatty acid in one direction and the passage of its anion in the opposite direction. The transfer of the dissociated form of fatty acid can be, at least in some kinds of mitochondrion, facilitated by adenine nucleotide translocase. Apart from dissipating the electrochemical proton gradient, long-chain fatty acids decrease the activity of the respiratory chain by mechanism(s) not fully understood. In intact cells and tissues fatty acids operate mostly as excellent respiratory substrates, providing electrons to the respiratory chain. This function masks their potential uncoupling effect which becomes apparent only under special physiological or pathological conditions characterized by unusual fatty acid accumulation. Short- and medium-chain fatty acids do not have protonophoric properties. Nevertheless, they contribute to energy dissipation because of slow intramitochondrial hydrolysis of their activation products, acyl-AMP and acyl-CoA. Long-chain fatty acids increase permeability of mitochondrial membranes to alkali metal cations. This is due to their ionophoric mechanism of action. Regulatory function of fatty acids with respect to specific cation channels has been postulated for the plasma membrane of muscle cells, but not demonstrated in mitochondria. Under cold stress, cold acclimation and arousal from hibernation the uncoupling effect of fatty acids may contribute to increased thermogenesis, especially in the muscle tissue. In brown adipose tissue, the special thermogenic organ of mammals, long-chain fatty acids promote operation of the unique natural uncoupling protein, thermogenin. As anionic amphiphiles, long-chain fatty acids increase the negative surface charge of biomembranes, thus interfering in their enzymic and transporting functions. PMID:8399375

  14. Docosahexaenoic acid (DHA, an essential fatty acid for the proper functioning of neuronal cells: their role in mood disorders

    Directory of Open Access Journals (Sweden)

    2009-06-01

    Full Text Available The brain and the nervous system are tissues with high contents of two polyunsaturated fatty acids: arachidonic acid (20:4, omega-6, AA and docosahexaenoic acid (22:6, omega-3, DHA. Despite their abundance in these tissues, AA and DHA cannot be re-synthesized in mammals. However, the concentration of these fatty acids can be modulated by dietary intake. AA and DHA must be provided by the diet as such (preformed or through the respective omega-6 and omega-3 precursors from vegetable origin. Linoleic acid, the precursor of AA is very abundant in the western diet and therefore the formation of AA from linoleic acid is not restrictive. On the other hand, alpha linolenic acid, the precursor of DHA is less available in our diet and preformed DHA is highly restrictive in some populations. During the last period of gestation and during the early post natal period, neurodevelopment occurs exceptionally quickly, and significant amounts of omega-6 and omega-3 polyunsaturated fatty acids, especially DHA, are critical to allow neurite outgrowth and the proper brain and retina development and function. In this review various functions of DHA in the nervous system, its metabolism into phospholipids, and its involvement in different neurological and mood disorders, such as Alzheimer’s disease, depression, and others are revised.

    El cerebro y el sistema nervioso son tejidos con un alto contenido de dos ácidos grasos poliinsaturados: el ácido araquidónico (20:4, omega-6, AA y el ácido docosahexaenoico (22:6, omega-3, DHA. A pesar de la abundancia de estos ácidos grasos en dichos tejidos los mamíferos no los pueden sintetizar de novo. Sin embargo, la concentración de estos ácidos grasos puede ser modificada por la dieta. El AA y el DHA pueden ser aportados por la dieta como tales (preformados o a partir de los respectivos precursores de origen vegetal. El ácido linoleico, precursor del AA es muy abundante en la dieta occidental, por lo cual la

  15. L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP.

    Science.gov (United States)

    Gao, Na; Qu, Xia; Yan, Jin; Huang, Qi; Yuan, Hao-Yong; Ouyang, Dong-Sheng

    2010-12-01

    Liver fatty acid-binding protein (L-FABP, FABP1) is a highly conserved key factor in lipid metabolism. This study was undertaken to verify whether the T94A mutation in the L-FABP gene affects fatty acid uptake and intracellular esterification into specific lipid pools. Candidate SNPs were recreated using site-directed mutagenesis and tested for physical function in stably transfected Chang liver cell lines. We found that the T94A mutant of L-FABP lowered FFA uptake but had no effect on FFA efflux. L-FABP T94A-expressing cells showed decreased triglyceride content and increased cholesterol accumulation compared to the wild-type control for cells incubated with an FFA mixture (oleate: palmitate, 2:1 ratio). In conclusion, our study provided additional indications of the functional relevance of the L-FABP T94A SNP in hepatic fatty acid and lipid metabolism in humans.

  16. The Refsum disease marker phytanic acid, a branched chain fatty acid, affects Ca2+ homeostasis and mitochondria, and reduces cell viability in rat hippocampal astrocytes.

    Science.gov (United States)

    Kahlert, Stefan; Schönfeld, Peter; Reiser, Georg

    2005-02-01

    The saturated branched chain fatty acid, phytanic acid, a degradation product of chlorophyll, accumulates in Refsum disease, an inherited peroxisomal disorder with neurological clinical features. To elucidate the pathogenic mechanism, we investigated the influence of phytanic acid on cellular physiology of rat hippocampal astrocytes. Phytanic acid (100 microM) induced an immediate transient increase in cytosolic Ca2+ concentration, followed by a plateau. The peak of this biphasic Ca2+ response was largely independent of extracellular Ca2+, indicating activation of cellular Ca2+ stores by phytanic acid. Phytanic acid depolarized mitochondria without causing in situ swelling of mitochondria. The slow decrease of mitochondrial potential is not consistent with fast and simultaneous opening of the mitochondrial permeability transition pore. However, phytanic acid induced substantial generation of reactive oxygen species. Phytanic acid caused astroglia cell death after a few hours of exposure. We suggest that the cytotoxic effect of phytanic acid seems to be due to a combined action on Ca2+ regulation, mitochondrial depolarization, and increased ROS generation in brain cells.

  17. Omega-3 fatty acid supplementation in horses

    Directory of Open Access Journals (Sweden)

    Tanja Hess

    2014-12-01

    Full Text Available Polyunsaturated omega-3 fatty acids (n-3 PUFA are a family of essential fatty acids with many biological activities. These fatty acids are incorporated into cell membranes, changing their structural and functional characteristics. N-3 PUFA can act by modulating inflammatory responses at different levels. Omega-3 PUFA can be converted in the body to longer-chain n-3 PUFA at a limited rate and are differently converted in body systems. It appears that when specific longer-chain n-3 PUFA are desired these need to be supplemented directly in the diet. In different species some evidence indicates a potential effect on improving insulin sensitivity. Recently, a novel class of n-3 PUFA-derived anti-inflammatory mediators have been recognized, termed E-series and D-series resolvins, formed from EPA and DHA, respectively. N-3 PUFA derived resolvins and protectins are heavily involved in the resolution of inflammation. Supplementation with n-3 fatty acids in horses may help manage chronic inflammatory conditions such as osteoarthritis, equine metabolic syndrome, laminitis, and thereby help to improve longevity of sport horse.

  18. Overproduction of fatty acids in engineered Saccharomyces cerevisiae.

    Science.gov (United States)

    Li, Xiaowei; Guo, Daoyi; Cheng, Yongbo; Zhu, Fayin; Deng, Zixin; Liu, Tiangang

    2014-09-01

    The long hydrocarbon fatty acyl chain is energy rich, making it an ideal precursor for liquid transportation fuels and high-value oleo chemicals. As Saccharomyces cerevisiae has many advantages for industrial production compared to Escherichia coli. Here, we attempted to engineer Saccharomyces cerevisiae for overproduction of fatty acids. First, disruption of the beta-oxidation pathway, elimination of the acyl-CoA synthetases, overexpression of different thioesterases and acetyl-CoA carboxylase ACC1, and engineering the supply of precursor acetyl-CoA. The engineered strain XL122 produced more than 120 mg/L of fatty acids. In parallel, we inactivated ADH1, the dominant gene for ethanol production, to redirect the metabolic flux to fatty acids synthesis. The engineered strain DG005 produced about 140 mg/L fatty acids. Additionally, Acetyl-CoA carboxylase was identified as a critical bottleneck of fatty acids synthesis in S. cerevisiae with a cell-free system. However, overexpression of ACC1 has little effect on fatty acids biosynthesis. As it has been reported that phosphorylation of ACC1 may influent its activity, so phosphorylation sites of ACC1 were further identified. Although the regulatory mechanisms remain unclear, our results provide rationale for future studies to target this critical step. All these efforts, particularly the discovery of the limiting step are critical for developing a "cell factory" for the overproduction of fatty acids by using type I fatty acids synthase in yeast or other fungi. PMID:24752690

  19. The effect of short-chain fatty acids on human monocyte-derived dendritic cells.

    Science.gov (United States)

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné; Geisler, Carsten; Hansen, Morten; Krejsgaard, Thorbjørn; Biagi, Elena; Andersen, Mads Hald; Brigidi, Patrizia; Ødum, Niels; Litman, Thomas; Woetmann, Anders

    2015-01-01

    The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions. PMID:26541096

  20. Molten fatty acid based microemulsions.

    Science.gov (United States)

    Noirjean, Cecile; Testard, Fabienne; Dejugnat, Christophe; Jestin, Jacques; Carriere, David

    2016-06-21

    We show that ternary mixtures of water (polar phase), myristic acid (MA, apolar phase) and cetyltrimethylammonium bromide (CTAB, cationic surfactant) studied above the melting point of myristic acid allow the preparation of microemulsions without adding a salt or a co-surfactant. The combination of SANS, SAXS/WAXS, DSC, and phase diagram determination allows a complete characterization of the structures and interactions between components in the molten fatty acid based microemulsions. For the different structures characterized (microemulsion, lamellar or hexagonal phases), a similar thermal behaviour is observed for all ternary MA/CTAB/water monophasic samples and for binary MA/CTAB mixtures without water: crystalline myristic acid melts at 52 °C, and a thermal transition at 70 °C is assigned to the breaking of hydrogen bounds inside the mixed myristic acid/CTAB complex (being the surfactant film in the ternary system). Water determines the film curvature, hence the structures observed at high temperature, but does not influence the thermal behaviour of the ternary system. Myristic acid is partitioned in two "species" that behave independently: pure myristic acid and myristic acid associated with CTAB to form an equimolar complex that plays the role of the surfactant film. We therefore show that myristic acid plays the role of a solvent (oil) and a co-surfactant allowing the fine tuning of the structure of oil and water mixtures. This solvosurfactant behaviour of long chain fatty acid opens the way for new formulations with a complex structure without the addition of any extra compound. PMID:27241163

  1. Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sailaja Polavarapu

    Full Text Available In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs tested on human neuroblastoma IMR-32 (0.5 × 10(4 cells/100 µl of IMR cells (EPA > DHA > ALA = GLA = AA > DGLA = LA: ∼ 60, 40, 30, 10-20% respectively at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2 and leukotrienes (LTD4 and LTE4 tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4, 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA and 10(S,17(S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S,17(SDiHDoHE, metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.

  2. Kupffer cells modulate hepatic fatty acid oxidation during infection with PR8 influenza.

    Science.gov (United States)

    Tarasenko, Tatyana N; Singh, Larry N; Chatterji-Len, Milani; Zerfas, Patricia M; Cusmano-Ozog, Kristina; McGuire, Peter J

    2015-11-01

    In response to infection, patients with inborn errors of metabolism may develop a functional deterioration termed metabolic decompensation. The biochemical hallmarks of this disruption of metabolic homeostasis are disease specific and may include acidosis, hyperammonemia or hypoglycemia. In a model system previously published by our group, we noted that during influenza infection, mice displayed a depression in hepatic mitochondrial enzymes involved in nitrogen metabolism. Based on these findings, we hypothesized that this normal adaptation may extend to other metabolic pathways, and as such, may impact various inborn errors of metabolism. Since the liver is a critical organ in inborn errors of metabolism, we carried out untargeted metabolomic profiling of livers using mass spectrometry in C57Bl/6 mice infected with influenza to characterize metabolic adaptation. Pathway analysis of metabolomic data revealed reductions in CoA synthesis, and long chain fatty acyl CoA and carnitine species. These metabolic adaptations coincided with a depression in hepatic long chain β-oxidation mRNA and protein. To our surprise, the metabolic changes observed occurred in conjunction with a hepatic innate immune response, as demonstrated by transcriptional profiling and flow cytometry. By employing an immunomodulation strategy to deplete Kupffer cells, we were able to improve the expression of multiple genes involved in β-oxidation. Based on these findings, we are the first to suggest that the role of the liver as an immunologic organ is central in the pathophysiology of hepatic metabolic decompensation in inborn errors of metabolism due to respiratory viral infection.

  3. Inhibition of de novo Palmitate Synthesis by Fatty Acid Synthase Induces Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling Pathways, and Reprogramming Gene Expression

    Directory of Open Access Journals (Sweden)

    Richard Ventura

    2015-08-01

    Research in context: Fatty acid synthase (FASN is a vital enzyme in tumor cell biology; the over-expression of FASN is associated with diminished patient prognosis and resistance to many cancer therapies. Our data demonstrate that selective and potent FASN inhibition with TVB-3166 leads to selective death of tumor cells, without significant effect on normal cells, and inhibits in vivo xenograft tumor growth at well-tolerated doses. Candidate biomarkers for selecting tumors highly sensitive to FASN inhibition are identified. These preclinical data provide mechanistic and pharmacologic evidence that FASN inhibition presents a promising therapeutic strategy for treating a variety of cancers.

  4. Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells.

    Science.gov (United States)

    Rebollo, Alba; Roglans, Núria; Baena, Miguel; Sánchez, Rosa M; Merlos, Manel; Alegret, Marta; Laguna, Juan C

    2014-04-01

    Fructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous induction of fatty acid synthesis and inhibition of fatty acid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fatty acid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25mM for 24h. The expression and activity of the enzymes and transcription factors relating to fatty acid β-oxidation were evaluated. Fructose inhibited the activity of fatty acid β-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor α (PPARα). Similar results were observed in FaO and HepG2 cells and human hepatocytes. PPARα downregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive and acetylated peroxisome proliferator activated receptor gamma coactivator 1α, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing PPARα expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation.

  5. Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells.

    Science.gov (United States)

    Rebollo, Alba; Roglans, Núria; Baena, Miguel; Sánchez, Rosa M; Merlos, Manel; Alegret, Marta; Laguna, Juan C

    2014-04-01

    Fructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous induction of fatty acid synthesis and inhibition of fatty acid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fatty acid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25mM for 24h. The expression and activity of the enzymes and transcription factors relating to fatty acid β-oxidation were evaluated. Fructose inhibited the activity of fatty acid β-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor α (PPARα). Similar results were observed in FaO and HepG2 cells and human hepatocytes. PPARα downregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive and acetylated peroxisome proliferator activated receptor gamma coactivator 1α, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing PPARα expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation. PMID:24434080

  6. Cell type-specific modulation of lipid mediator's formation in murine adipose tissue by omega-3 fatty acids.

    Science.gov (United States)

    Kuda, Ondrej; Rombaldova, Martina; Janovska, Petra; Flachs, Pavel; Kopecky, Jan

    2016-01-15

    Mutual interactions between adipocytes and immune cells in white adipose tissue (WAT) are involved in modulation of lipid metabolism in the tissue and also in response to omega-3 polyunsaturated fatty acids (PUFA), which counteract adverse effects of obesity. This complex interplay depends in part on in situ formed anti- as well as pro-inflammatory lipid mediators, but cell types engaged in the synthesis of the specific mediators need to be better characterized. We used tissue fractionation and metabolipidomic analysis to identify cells producing lipid mediators in epididymal WAT of mice fed for 5 weeks obesogenic high-fat diet (lipid content 35% wt/wt), which was supplemented or not by omega-3 PUFA (4.3 mg eicosapentaenoic acid and 14.7 mg docosahexaenoic acid per g of diet). Our results demonstrate selective increase in levels of anti-inflammatory lipid mediators in WAT in response to omega-3, reflecting either their association with adipocytes (endocannabinoid-related N-docosahexaenoylethanolamine) or with stromal vascular cells (pro-resolving lipid mediator protectin D1). In parallel, tissue levels of obesity-associated pro-inflammatory endocannabinoids were suppressed. Moreover, we show that adipose tissue macrophages (ATMs), which could be isolated using magnetic force from the stromal vascular fraction, are not the major producers of protectin D1 and that omega-3 PUFA lowered lipid load in ATMs while promoting their less-inflammatory phenotype. Taken together, these results further document specific roles of various cell types in WAT in control of WAT inflammation and metabolism and they suggest that also other cells but ATMs are engaged in production of pro-resolving lipid mediators in response to omega-3 PUFA.

  7. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture.

    Directory of Open Access Journals (Sweden)

    Ramazan Kurt

    Full Text Available Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α-based combination therapy in chronic hepatitis C virus (HCV infection. Previously, we reported that free fatty acid (FFA-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1, which is why the antiviral activity of IFN-α against HCV is impaired.To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment.HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α and Type III IFN (IFN-λ was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA in the FFA-treated HCV cell culture model was investigated.FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ, which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated cell culture

  8. Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal Epithelial Cell Lines in vitro.

    Science.gov (United States)

    Asarat, M; Vasiljevic, T; Apostolopoulos, V; Donkor, O

    2015-01-01

    Short-chain fatty acids (SCFAs) including acetate, propionate and butyrate play an important role in the physiological functions of epithelial cells and colonocytes, such as immune response regulation. Human intestinal epithelial cells (IECs) contribute in intestinal immune response via different ways, such as production of different immune factors including Interleukin (IL) IL-8, which act as chemoattractant for neutrophils, and subsequently enhance inflammation. Therefore, we aimed to evaluate the effects of SCFAs on IECs viability and production of IL-8 in vitro. SCFAs were co-cultured with either normal intestinal epithelial (T4056) or adenocarcinoma derived (HT-29) cell lines for 24-96 h in the presence of E.coli lipopolysaccharides (LPS). Cell viability, proliferation, production of IL-8 and expression of IL-8 mRNA were determined in the cell cultures. The result showed that 20 mM of SCFAs was non-cytotoxic to T4056 and enhanced their growth, whereas the growth of HT-29 was inhibited. The SCFAs down regulated LPS-stimulated IL-8 secretion with different response patterns, but no obvious effects on the release of IL-8 from non LPS- stimulated cells. In conclusion, SCFAs showed regulatory effect on release of LPS-stimulated IL-8 as well as the expression of mRNA of IL-8; these might explain the anti-inflammatory and anti-carcinogenic mechanism of SCFAs. PMID:26436853

  9. Opposite Regulation of CD36 Ubiquitination by Fatty Acids and Insulin: EFFECTS ON FATTY ACID UPTAKE*

    OpenAIRE

    Smith, Jill; Su, Xiong; El-Maghrabi, Raafat; Stahl, Philip D.; Abumrad, Nada A.

    2008-01-01

    FAT/CD36 is a membrane scavenger receptor that facilitates long chain fatty acid uptake by muscle. Acute increases in membrane CD36 and fatty acid uptake have been reported in response to insulin and contraction. In this study we have explored protein ubiquitination as one potential mechanism for the regulation of CD36 level. CD36 expressed in Chinese hamster ovary (CHO) or HEK 293 cells was found to be polyubiquitinated via a process involving both lysines 48 and 63 of ubiquitin. Using CHO c...

  10. Production of extracellular fatty acid using engineered Escherichia coli

    Directory of Open Access Journals (Sweden)

    Liu Hui

    2012-04-01

    Full Text Available Abstract Background As an alternative for economic biodiesel production, the microbial production of extracellular fatty acid from renewable resources is receiving more concerns recently, since the separation of fatty acid from microorganism cells is normally involved in a series of energy-intensive steps. Many attempts have been made to construct fatty acid producing strains by targeting genes in the fatty acid biosynthetic pathway, while few studies focused on the cultivation process and the mass transfer kinetics. Results In this study, both strain improvements and cultivation process strategies were applied to increase extracellular fatty acid production by engineered Escherichia coli. Our results showed overexpressing ‘TesA and the deletion of fadL in E. coli BL21 (DE3 improved extracellular fatty acid production, while deletion of fadD didn’t strengthen the extracellular fatty acid production for an undetermined mechanism. Moreover, the cultivation process controls contributed greatly to extracellular fatty acid production with respect to titer, cell growth and productivity by adjusting the temperature, adding ampicillin and employing on-line extraction. Under optimal conditions, the E. coli strain (pACY-‘tesA-ΔfadL produced 4.8 g L−1 extracellular fatty acid, with the specific productivity of 0.02 g h−1 g−1dry cell mass, and the yield of 4.4% on glucose, while the ratios of cell-associated fatty acid versus extracellular fatty acid were kept below 0.5 after 15 h of cultivation. The fatty acids included C12:1, C12:0, C14:1, C14:0, C16:1, C16:0, C18:1, C18:0. The composition was dominated by C14 and C16 saturated and unsaturated fatty acids. Using the strain pACY-‘tesA, similar results appeared under the same culture conditions and the titer was also much higher than that ever reported previously, which suggested that the supposedly superior strain did not necessarily perform best for the efficient production of desired

  11. Epidermal Fatty Acid Binding Protein (E-FABP) Is Not Required for the Generation or Maintenance of Effector and Memory T Cells following Infection with Listeria monocytogenes.

    Science.gov (United States)

    Li, Bing; Schmidt, Nathan W

    2016-01-01

    Following activation of naïve T cells there are dynamic changes in the metabolic pathways used by T cells to support both the energetic needs of the cell and the macromolecules required for growth and proliferation. Among other changes, lipid metabolism undergoes dynamic transitions between fatty acid oxidation and fatty acid synthesis as cells progress from naïve to effector and effector to memory T cells. The hydrophobic nature of lipids requires that they be bound to protein chaperones within a cell. Fatty acid binding proteins (FABPs) represent a large class of lipid chaperones, with epidermal FABP (E-FABP) expressed in T cells. The objective of this study was to determine the contribution of E-FABP in antigen-specific T cell responses. Following infection with Listeria monocytogenes, we observed similar clonal expansion, contraction and formation of memory CD8 T cells in WT and E-FABP-/- mice, which also exhibited similar phenotypic and functional characteristics. Analysis of Listeria-specific CD4 T cells also revealed no defect in the expansion, contraction, and formation of memory CD4 T cells in E-FABP-/- mice. These data demonstrate that E-FABP is dispensable for antigen-specific T cell responses following a bacterial infection. PMID:27588422

  12. Kupffer cells modulate hepatic fatty acid oxidation during infection with PR8 influenza.

    Science.gov (United States)

    Tarasenko, Tatyana N; Singh, Larry N; Chatterji-Len, Milani; Zerfas, Patricia M; Cusmano-Ozog, Kristina; McGuire, Peter J

    2015-11-01

    In response to infection, patients with inborn errors of metabolism may develop a functional deterioration termed metabolic decompensation. The biochemical hallmarks of this disruption of metabolic homeostasis are disease specific and may include acidosis, hyperammonemia or hypoglycemia. In a model system previously published by our group, we noted that during influenza infection, mice displayed a depression in hepatic mitochondrial enzymes involved in nitrogen metabolism. Based on these findings, we hypothesized that this normal adaptation may extend to other metabolic pathways, and as such, may impact various inborn errors of metabolism. Since the liver is a critical organ in inborn errors of metabolism, we carried out untargeted metabolomic profiling of livers using mass spectrometry in C57Bl/6 mice infected with influenza to characterize metabolic adaptation. Pathway analysis of metabolomic data revealed reductions in CoA synthesis, and long chain fatty acyl CoA and carnitine species. These metabolic adaptations coincided with a depression in hepatic long chain β-oxidation mRNA and protein. To our surprise, the metabolic changes observed occurred in conjunction with a hepatic innate immune response, as demonstrated by transcriptional profiling and flow cytometry. By employing an immunomodulation strategy to deplete Kupffer cells, we were able to improve the expression of multiple genes involved in β-oxidation. Based on these findings, we are the first to suggest that the role of the liver as an immunologic organ is central in the pathophysiology of hepatic metabolic decompensation in inborn errors of metabolism due to respiratory viral infection. PMID:26319418

  13. High content of long-chain n-3 polyunsaturated fatty acids in red blood cells of Kenyan Maasai despite low dietary intake

    Directory of Open Access Journals (Sweden)

    Kiage-Mokua Beatrice N

    2011-08-01

    Full Text Available Abstract Background Increasing land restrictions and a reduced livestock-to-human ratio during the 20th century led the Maasai to lead a more sedentary, market-orientated lifestyle. Although plant-derived food nowadays contributes substantially to their diet, dairy products being high in saturated fatty acids (SFA and low in polyunsaturated fatty acids (PUFA still are an important energy source. Since reliable data regarding the Maasai diet date back to the 1980s, the study objective was to document current diet practices in a Kenyan Maasai community and to investigate the fatty acid distribution in diet and red blood cells. Methods A cross-sectional study was conducted among 26 Maasai (20 women, 6 men from Loodokilani, Kajiado District, Kenya. Food intake was described by the subjects via 24-h recall, and both food and blood samples were analysed. Results Two main foods - milk and ugali - constituted the Maasai diet in this region. A total of 0.9 L of milk and 0.6 kg of ugali were consumed per person and day to yield an energy intake of 7.6 MJ/d per person. A major proportion of ingested food contributing 58.3% to the total dietary energy (en% was plant-derived, followed by dairy products representing 41.1 en%. Fat consumed (30.5 en% was high in SFA (63.8% and low in PUFA (9.2%. Long-chain n-3 PUFA (EPA, DPA and DHA made up only 0.15% of the ingested fatty acids, but 5.9% of red blood cell fatty acids. Conclusion The study indicates the Maasai diet is rich in SFA and low in PUFA. Nevertheless, red blood cells are composed of comparable proportions of long-chain n-3 PUFA to populations consuming higher amounts of this fatty acid group.

  14. The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation.

    Science.gov (United States)

    Hinnebusch, Brian F; Meng, Shufen; Wu, James T; Archer, Sonia Y; Hodin, Richard A

    2002-05-01

    The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial fermentation within the colon and is thought to be protective in regard to colon carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA, a variety of other SCFA also exist in the colonic lumen. Butyrate is thought to exert its cellular effects through the induction of histone hyperacetylation. We sought to determine the effects of a variety of the SCFA on colon carcinoma cell growth, differentiation and apoptosis. HT-29 or HCT-116 (wild-type and p21-deleted) cells were treated with physiologically relevant concentrations of various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel electrophoresis and immunoblotting. Growth and apoptotic effects were studied by flow cytometry, and differentiation effects were assessed using transient transfections and Northern blotting. Propionate (C3) and valerate (C5) caused growth arrest and differentiation in human colon carcinoma cells. The magnitude of their effects was associated with a lesser degree of histone hyperacetylation compared with butyrate. Acetate (C2) and caproate (C6), in contrast, did not cause histone hyperacetylation and also had no appreciable effects on cell growth or differentiation. SCFA-induced transactivation of the differentiation marker gene, intestinal alkaline phosphatase (IAP), was blocked by histone deacetylase (HDAC), further supporting the critical link between SCFA and histones. Butyrate also significantly increased apoptosis, whereas the other SCFA studied did not. The growth arrest induced by the SCFA was characterized by an increase in the expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1 (CB1). In p21-deleted HCT-116 colon cancer cells, the SCFA did not alter the rate of proliferation. These data suggest that the antiproliferative, apoptotic and differentiating properties of the various SCFA are linked to the degree of induced histone

  15. Upregulation of peroxisome proliferator-activated receptors and liver fatty acid binding protein in hepatic cells of broiler chicken supplemented with conjugated linoleic acids

    OpenAIRE

    Suriya Kumari Ramiah; Goh Y. Meng; Mahdi Ebrahimi

    2015-01-01

    Since conjugated linoleic acid (CLA) has structural and physiological characteristics similar to peroxisome proliferators, it is hypothesized that CLA would upregulate peroxisome proliferator-activated receptor (PPAR) and liver fatty acid binding protein (LFABP) in the liver of broiler chicken. The aim of the present study was to determine fatty acid composition of liver in CLA-fed broiler chickens and the genes associated with hepatic lipid metabolism. A total of 180-day-old broiler chicks w...

  16. Curcumin inhibits intracellular fatty acid synthase and induces apoptosis in human breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Fan, Huijin; Liang, Yan; Jiang, Bing; Li, Xiabing; Xun, Hang; Sun, Jia; He, Wei; Lau, Hay Tong; Ma, Xiaofeng

    2016-05-01

    High levels of fatty acid synthase (FAS) expression have been found in many tumors, including prostate, breast, and ovarian cancers, and inhibition of FAS has been reported to obstruct tumor growth in vitro and in vivo. Curcumin is one of the major active ingredients of Curcuma longa, which has been proven to inhibit the growth of cancer cells. In the present study, we investigated the potential activity of curcumin as a FAS inhibitor for chemoprevention of breast cancer. As a result, curcumin induced human breast cancer MDA-MB-231 cell apoptosis with the half-inhibitory concentration value of 3.63 ± 0.26 µg/ml, and blocked FAS activity, expression and mRNA level in a dose-dependent manner. Curcumin also regulated B-cell lymphoma 2 (Bcl-2), Bax and p-Akt protein expression in MDA-MB-231 cells. Moreover, FAS knockdown showed similar effect as curcumin. All these results suggested that curcumin may induce cell apoptosis via inhibiting FAS. PMID:26985864

  17. Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Sugiyama Takayuki

    2011-07-01

    Full Text Available Abstract Background Improving the treatment of renal cell carcinoma (RCC will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7, also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC, overexpress FABP7. The abundant expression of FABP7 in primary RCCs compared to certain RCC-derived cell lines may allow the definition of the molecular components of FABP7's regulatory system. Results We determined FABP7 mRNA levels in six RCC cell lines. Two were highly expressed, whereas the other and the embryonic kidney cell line (HEK293 were weakly expressed FABP7 transcripts. Western blot analysis of the cell lines detected strong FABP7 expression only in one RCC cell line. Promoter activity in the RCC cell lines was 3- to 21-fold higher than that of HEK293. Deletion analysis demonstrated that three FABP7 promoter regions contributed to upregulated expression in RCC cell lines, but not in the HEK293 cell. Competition analysis of gel shifts indicated that OCT1, OCT6, and nuclear factor I (NFI bound to the FABP7 promoter region. Supershift experiments indicated that BRN2 (POU3F2 and NFI bound to the FABP7 promoter region as well. There was an inverse correlation between FABP7 promoter activity and BRN2 mRNA expression. The FABP7-positive cell line's NFI-DNA complex migrated faster than in other cell lines. Levels of NFIA mRNA were higher in the HEK293 cell line than in any of the six RCC cell lines. In contrast, NFIC mRNA expression was lower in the HEK293 cell line than in the six RCC cell lines. Conclusions Three putative FABP7 promoter regions drive reporter gene expression in RCC cell lines, but not in the HEK293 cell line. BRN2 and NFI may be key

  18. Gastric or rectal instillation of short-chain fatty acids stimulates epithelial cell proliferation of small and large intestine in rats.

    Science.gov (United States)

    Ichikawa, Hirofumi; Shineha, Ryuzaburo; Satomi, Susumu; Sakata, Takashi

    2002-05-01

    Short-chain fatty acids stimulate gut epithelial cell proliferation in vivo, although the difference between oral and rectal routes is unknown. Accordingly, we examined the effect of oral or rectal administration of these acids. We instilled a mixture of acetic acid, propionic acid, and n-butyric acid (150, 60, and 60 mmol/liter, respectively; pH 6.5) or saline (270 mM, pH 6.5) into the stomach (2 ml) or rectum (1 ml) three times daily for five days in rats fed an elemental diet. We measured crypt cell production rate of the jejunum, ileum, and distal colon of these rats. The crypt cell production rate of these segments was higher in rats with gastric or rectal instillation of short-chain fatty acids than in saline controls. The rectal route was slightly more effective than the gastric route. The above results indicated that the instillation of short-chain fatty acids orally or rectally stimulated gut epithelial cell proliferation. PMID:12018914

  19. Inhibitory effect of polyunsaturated fatty acids on apoptosis induced by etoposide, okadaic acid and AraC in Neuro2a cells

    Directory of Open Access Journals (Sweden)

    Tomizawa,Kazuhito

    2007-06-01

    Full Text Available Neuronal apoptosis is involved in neurodegenerative diseases such as Alzheimer's disease and Parkinson.s disease. An efficient means of preventing it remains to be found. Some n-3 polyunsaturated fatty acids (PUFAs such as docosahexaenoic acid (DHA, 22 : 6n-3 and eicosapentaenoic acid (EPA, 20 : 5n-3 have been reported to be protective against the neuronal apoptosis and neuronal degeneration seen after spinal cord injury (SCI [1]. However, it is unclear which kinds of PUFAs have the most potent ability to inhibit neuronal apoptosis and whether the simultaneous treatment of PUFAs inhibits the apoptosis. In the present study, we compared the abilities of various n-3- and n-6- PUFAs to inhibit the apoptosis induced after the administration of different apoptotic inducers, etoposide, okadaic acid, and AraC, in mouse neuroblastoma cells (Neuro2a. Preincubation with DHA (22 : 6n-3, eicosapentaenoic acid (EPA, 20 : 5n-3, alpha-linolenic acid (alpha-LNA, 18 : 3n-3, linoleic acid (LA, 18 : 2n-6, arachidonic acid (AA, 20 : 4n-3, and gamma-linolenic acid (gamma-LNA, 18 : 3n-6 significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells. There were no significant differences of the anti-apoptotic eff ect among the PUFAs. These results suggest that PUFAs may not be effective for inhibiting neuronal cell death after acute and chronic neurodegenerative disorders. However, dietary supplementation with PUFAs may be beneficial as a potential means to delay the onset of the diseases and/or their rate of progression.

  20. Fatty acids, eicosanoids and PPAR gamma.

    Science.gov (United States)

    Marion-Letellier, Rachel; Savoye, Guillaume; Ghosh, Subrata

    2016-08-15

    Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the family of nuclear nuclear receptors and is mainly expressed in adipose tissue, hematopoietic cells and the large intestine. Contrary to other nuclear receptors that mainly bind a single specific ligand, there are numerous natural PPARγ ligands, in particular fatty acids or their derivatives called eicosanoids. PPARγ have pleiotropic functions: (i) glucose and lipid metabolism regulation, (ii) anti-inflammatory properties, (iii) oxidative stress inhibition, (iv) improvement of endothelial function. Its role has been mainly studied by the use synthetic agonists. In this review, we will focus on the effects of PPARγ mediated through fatty acids and how these have beneficial health properties. PMID:26632493

  1. Induction of Gnrh mRNA expression by the ω-3 polyunsaturated fatty acid docosahexaenoic acid and the saturated fatty acid palmitate in a GnRH-synthesizing neuronal cell model, mHypoA-GnRH/GFP.

    Science.gov (United States)

    Tran, Dean Q; Ramos, Ernesto H; Belsham, Denise D

    2016-05-01

    Gonadotropin-releasing hormone (GnRH) neurons coordinate reproduction. However, whether GnRH neurons directly sense free fatty acids (FFAs) is unknown. We investigated the individual effects of the FFAs docosahexaenoic acid (DHA), palmitate, palmitoleate, and oleate (100 μM each) on Gnrh mRNA expression in the mHypoA-GnRH/GFP neuronal cell model. We report that 2 h exposure to palmitate or DHA increases Gnrh transcription. Using the inhibitors AH7614, K252c, U0126, wortmannin, and LY294002, we demonstrate that the effect of DHA is mediated through GPR120 to downstream PKC/MAPK and PI3K signaling. Our results indicate that the effect of palmitate may depend on palmitoyl-coA synthesis and PI3K signaling. Finally, we demonstrate that both DHA and palmitate increase Gnrh enhancer-derived RNA levels. Overall, these studies provide evidence that GnRH neurons directly sense FFAs. This will advance our understanding of the mechanisms underlying FFA sensing in the brain and provides insight into the links between nutrition and reproductive function. PMID:26923440

  2. Curcuminoids and ω-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon γ production

    OpenAIRE

    Halder, Ramesh C.; Almasi, Anasheh; Sagong, Bien; Leung, Jessica; Jewett, Anahid; Fiala, Milan

    2015-01-01

    Pancreatic cancer has a poor prognosis attributed in part to immune suppression and deactivation of natural killer (NK) cells. Curcuminoids have a potential for improving the therapy of pancreatic cancer given promising results in cancer models and a clinical trial, but their oral absorption is limited. Our objective in this study is to show curcuminoid anti-oncogenic effects alone and together with human NK cells. We tested curcuminoids in an emulsion of ω-3 fatty acids and anti-oxidants (“S...

  3. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis. PMID:26968402

  4. Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study

    OpenAIRE

    Johns, I.; Goff, L; Bluck, L. J.; Griffin, B. A.; Jebb, S. A.; Lovegrove, J. A. (Julie A.); Sanders, T A B; G. Frost; Dornhorst, A.

    2014-01-01

    Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. ...

  5. Heart-type fatty-acid-binding protein (FABP3 is a lysophosphatidic acid-binding protein in human coronary artery endothelial cells

    Directory of Open Access Journals (Sweden)

    Ryoko Tsukahara

    2014-01-01

    Full Text Available Fatty-acid-binding protein 3, muscle and heart (FABP3, also known as heart-type FABP, is a member of the family of intracellular lipid-binding proteins. It is a small cytoplasmic protein with a molecular mass of about 15 kDa. FABPs are known to be carrier proteins for transporting fatty acids and other lipophilic substances from the cytoplasm to the nucleus, where these lipids are released to a group of nuclear receptors such as peroxisome proliferator-activated receptors (PPARs. In this study, using lysophosphatidic acid (LPA-coated agarose beads, we have identified FABP3 as an LPA carrier protein in human coronary artery endothelial cells (HCAECs. Administration of LPA to HCAECs resulted in a dose-dependent increase in PPARγ activation. Furthermore, the LPA-induced PPARγ activation was abolished when the FABP3 expression was reduced using small interfering RNA (siRNA. We further show that the nuclear fraction of control HCAECs contained a significant amount of exogenously added LPA, whereas FABP3 siRNA-transfected HCAECs had a decreased level of LPA in the nucleus. Taken together, these results suggest that FABP3 governs the transcriptional activities of LPA by targeting them to cognate PPARγ in the nucleus.

  6. Fatty acid content of selected seed oils.

    Science.gov (United States)

    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.

  7. Antibacterial Targets in Fatty Acid Biosynthesis

    OpenAIRE

    Wright, H. Tonie; Reynolds, Kevin A.

    2007-01-01

    The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for development of new anti-bacterial agents. The extended use of the anti-tuberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for anti-bacterial development. Differences in subcellular organization of the bacterial and eukaryotic multi-enzyme fatty acid synthase systems offer the prospect of inhibitors with host vs...

  8. CD4+ T-cell activation is differentially modulated by bacteria-primed dendritic cells, but is generally down-regulated by n-3 polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Lund, Pia; Kjær, Tanja;

    2010-01-01

    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...... 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......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...

  9. CD4+ T‐cell activation is differentially modulated by bacteria‐primed dendritic cells, but is generally down‐regulated by n‐3 polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Lund, Pia; Kjær, Tanja;

    2010-01-01

    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...... 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......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...

  10. Veal fatty acid composition of different breeds

    Directory of Open Access Journals (Sweden)

    Ivica Kos

    2010-01-01

    Full Text Available Veal fatty acid composition in M. Longissimus thoracis was investigated in different calf breeds (Simmental, Holstein, Simmental x Holstein. Calves were reared on the same farm under identical feeding and handling conditions. Simmental calves had higher polyunsaturated fatty acid (PUFA but lower saturated fatty acid (SFA and monounsaturated fatty acid (MUFA values than Holstein and crossbreed calves (P<0,05. The PUFA/SFA ratio was the highest in Simmental calves and the lowest in Holstein calves. Simmental calves also had the highest n-6/n-3 ratio while the crossbreed calves had the lowest n-6/n-3 ratio.

  11. Medium-chain fatty acid reduces lipid accumulation by regulating expression of lipid-sensing genes in human liver cells with steatosis.

    Science.gov (United States)

    Wang, Baogui; Fu, Jing; Li, Lumin; Gong, Deming; Wen, Xuefang; Yu, Ping; Zeng, Zheling

    2016-01-01

    Accumulation of lipids in the liver can lead to cell dysfunction and steatosis, an important factor in pathogenesis causing non-alcoholic fatty liver disease. The mechanisms related to lipid deposition in the liver, however, remain poorly understood. This study was aimed to investigate the effects of medium-chain fatty acid (MCFA) on the lipolysis and expression of lipid-sensing genes in human liver cells with steatosis. A cellular steatosis model, which is suitable to experimentally investigate the impact of fat accumulation in the liver, was established in human normal liver cells (LO2 cells) with a mixture of free fatty acids (oleate/palmitate, 2:1) at 200 μm for 24 h incubation. MCFA was found to down-regulate expression of liver X receptor-α, sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase, CD 36 and lipoprotein lipase in this cellular model, and have positive effects on adipose triglyceride lipase and hormone-sensitive lipase. These results suggest that MCFA may reduce lipid accumulation by regulating key lipid-sensing genes in human liver cells with steatosis. PMID:26932533

  12. Bioconversion of α-linolenic acid into n-3 long-chain polyunsaturated fatty acid in hepatocytes and ad hoc cell culture optimisation.

    Directory of Open Access Journals (Sweden)

    Ramez Alhazzaa

    Full Text Available This study aimed to establish optimal conditions for a cell culture system that would allow the measurement of 18:3n-3 (ALA bioconversion into n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA, and to determine the overall pathway kinetics. Using rat hepatocytes (FaO as model cells, it was established that a maximum 20:5n-3 (EPA production from 50 µM ALA initial concentration was achieved after 3 days of incubation. Next, it was established that a gradual increase in the ALA concentration from 0 up to 125 µM lead to a proportional increase in EPA, without concomitant increase in further elongated or desaturated products, such as 22:5n-3 (DPA and 22:6n-3 (DHA in 3 day incubations. Of interest, ALA bioconversion products were observed in the culture medium. Therefore, in vitro experiments disregarding the medium fatty acid content are underestimating the metabolism efficiency. The novel application of the fatty acid mass balance (FAMB method on cell culture system (cells with medium enabled quantifying the apparent enzymatic activities for the biosynthesis of n-3 LC-PUFA. The activity of the key enzymes was estimated and showed that, under these conditions, 50% (Km of the theoretical maximal (V max = 3654 µmol.g(-1 of cell protein.hour(-1 Fads2 activity on ALA can be achieved with 81 µM initial ALA. Interestingly, the apparent activity of Elovl2 (20:5n-3 elongation was the slowest amongst other biosynthesis steps. Therefore, the possible improvement of Elovl2 activity is suggested toward a more efficient DHA production from ALA. The present study proposed and described an ad hoc optimised cell culture conditions and methodology towards achieving a reliable experimental platform, using FAMB, to assist in studying the efficiency of ALA bioconversion into n-3 LC-PUFA in vitro. The FAMB proved to be a powerful and inexpensive method to generate a detailed description of the kinetics of n-3 LC-PUFA biosynthesis enzymes activities in vitro.

  13. Effects of medium-chain fatty acids on the structure and immune response of IPEC-J2 cells.

    Science.gov (United States)

    Martínez-Vallespín, B; Vahjen, W; Zentek, J

    2016-10-01

    Medium-chain fatty acids (MCFAs) have been suggested as an alternative to the use of antibiotics in animal nutrition with promising results. First, we studied the sensitivity of Salmonella Enteritidis and an enteropathogenic Escherichia coli strain against caprylic (C8), capric (C10) and lauric (C12) acids. A porcine in vitro model using the porcine cell line IPEC-J2 was used to test the effects of MCFAs on structural and immunological traits without and with a concomitant challenge with E. coli or S. Enteritidis. The three MCFAs exerted an inhibitory effect on bacterial growth, stronger for C12 than C8 or C10, S. Enteritidis being more sensitive than the E. coli strain. Flow cytometry showed a numeric concentration dependent increase in the adhesion of E. coli or S. Enteritidis to IPEC-J2 cells. Measurement of transepithelial electrical resistance after bacterial challenge showed negative effects of all MCFAs on IPEC-J2 cells at the highest concentrations. Immune parameters were affected by C8, since a concentration dependent effect starting at 5 mM was observed for mRNA expression of IL-6 and TLR-4 (up-regulated) and IL-8 (down-regulated). TLR-4 was up-regulated with C10 at 2 and 5 mM. The three MCFAs affected also the epithelial morphology through down-regulation of Occludin and up-regulation of Claudin-4 expression. In conclusion, the three MCFAs under study influenced bacterial growth rates and modified the gene expression to a different degree in the cell line IPEC-J2 but the effect on the morphological structure and response of the cells after bacterial challenge could not be assessed. Although these tests show a prior estimation of MCFAs effects in intestinal epithelium, in vivo confirmation is still needed. PMID:27553650

  14. Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell-Mediated Ureteritis and Hydronephrosis.

    Science.gov (United States)

    Park, Jeongho; Goergen, Craig J; HogenEsch, Harm; Kim, Chang H

    2016-03-01

    Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10(+) regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell-mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell-derived inflammatory cytokines such as IFN-γ and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs. PMID:26819206

  15. Study of Thiosemicarbazone Derivative of Essential Fatty Acid

    OpenAIRE

    Borhade, Shobha

    2014-01-01

    Essential fatty acids results in numerous health benefits. Only two fatty acids are known to be essential for human alpha-linolenic acid (an omega-3 fatty acid) and linoleic acid (an omega-6 fatty acid).The importance of omega-3 fatty acids for physical well-being has been recognised for several decades . Omega-3 fatty acids have anti-inflammatory, antithrombotic, antiarrhythmic and hypolipidaemic effects. Cannabis sativa (Hemp) is an angiosperm belonging to the cannabaceae family and cannabi...

  16. Intake of fatty acids in Western Europe with emphasis on trans fatty acids: The TRANSFAIR study

    NARCIS (Netherlands)

    Hulshof, K.F.A.M; Erp van - Baart, M.A.; Anttolainen, M.; Becker, W.; Church, S.M.; Couet, C.; Hermann-Kunz, E.; Kesteloot, H.; Leth, T.; Martins, I.; Moreiras, O.; Moschandreas, J.; Pizzoferrato, L.; Rimestad, A.H.; Thorgeirsdottir, H.; Amelsvoort, J.M.M. van; Aro, A.; Kafatos, A.G.; Lanzmann-Petithory, D.; Poppel, G. van

    1999-01-01

    Objective: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. Design and subjects: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fa

  17. 21 CFR 172.859 - Sucrose fatty acid esters.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sucrose fatty acid esters. 172.859 Section 172.859... CONSUMPTION Multipurpose Additives § 172.859 Sucrose fatty acid esters. Sucrose fatty acid esters identified...) Sucrose fatty acid esters are the mono-, di-, and tri-esters of sucrose with fatty acids and are...

  18. Preventive effects of omega-3 and omega-6 Fatty acids on peroxide mediated oxidative stress responses in primary human trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Theofilos Tourtas

    Full Text Available Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H₂O₂, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H₂O₂ further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H₂O₂ stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H₂O₂ mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H₂O₂ induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side

  19. Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus.

    Science.gov (United States)

    Douglas, Donna N; Pu, Christopher Hao; Lewis, Jamie T; Bhat, Rakesh; Anwar-Mohamed, Anwar; Logan, Michael; Lund, Garry; Addison, William R; Lehner, Richard; Kneteman, Norman M

    2016-01-22

    Cytopathic effects are currently believed to contribute to hepatitis C virus (HCV)-induced liver injury and are readily observed in Huh7.5 cells infected with the JFH-1 HCV strain, manifesting as apoptosis highly correlated with growth arrest. Reactive oxygen species, which are induced by HCV infection, have recently emerged as activators of AMP-activated protein kinase. The net effect is ATP conservation via on/off switching of metabolic pathways that produce/consume ATP. Depending on the scenario, this can have either pro-survival or pro-apoptotic effects. We demonstrate reactive oxygen species-mediated activation of AMP-activated kinase in Huh7.5 cells during HCV (JFH-1)-induced growth arrest. Metabolic labeling experiments provided direct evidence that lipid synthesis is attenuated, and β-oxidation is enhanced in these cells. A striking increase in nuclear peroxisome proliferator-activated receptor α, which plays a dominant role in the expression of β-oxidation genes after ligand-induced activation, was also observed, and we provide evidence that peroxisome proliferator-activated receptor α is constitutively activated in these cells. The combination of attenuated lipid synthesis and enhanced β-oxidation is not conducive to lipid accumulation, yet cellular lipids still accumulated during this stage of infection. Notably, the serum in the culture media was the only available source for polyunsaturated fatty acids, which were elevated (2-fold) in the infected cells, implicating altered lipid import/export pathways in these cells. This study also provided the first in vivo evidence for enhanced β-oxidation during HCV infection because HCV-infected SCID/Alb-uPA mice accumulated higher plasma ketones while fasting than did control mice. Overall, this study highlights the reprogramming of hepatocellular lipid metabolism and bioenergetics during HCV infection, which are predicted to impact both the HCV life cycle and pathogenesis. PMID:26627833

  20. Nonesterified Fatty Acid-Induced Endoplasmic Reticulum Stress in Cattle Cumulus Oocyte Complexes Alters Cell Metabolism and Developmental Competence.

    Science.gov (United States)

    Sutton-McDowall, Melanie L; Wu, Linda L Y; Purdey, Malcolm; Abell, Andrew D; Goldys, Ewa M; MacMillan, Keith L; Thompson, Jeremy G; Robker, Rebecca L

    2016-01-01

    Reduced oocyte quality has been associated with poor fertility of high-performance dairy cows during peak lactation, due to negative energy balance. We examined the role of nonesterified fatty acids (NEFAs), known to accumulate within follicular fluid during under- and overnutrition scenarios, in causing endoplasmic reticulum (ER) stress of in vitro maturated cattle cumulus-oocyte complexes (COCs). NEFA concentrations were: palmitic acid (150 μM), oleic acid (200 μM), and steric acid (75 μM). Abattoir-derived COCs were randomly matured for 24 h in the presence of NEFAs and/or an ER stress inhibitor, salubrinal. Total and hatched blastocyst yields were negatively impacted by NEFA treatment compared with controls, but this was reversed by salubrinal. ER stress markers, activating transcription factor 4 (Atf4) and heat shock protein 5 (Hspa5), but not Atf6, were significantly up-regulated by NEFA treatment within whole COCs but reversed by coincubation with salubrinal. Likewise, glucose uptake and lactate production, measured in spent medium samples, showed a similar pattern, suggesting that cumulus cell metabolism is sensitive to NEFAs via an ER stress-mediated process. In contrast, while mitochondrial DNA copy number was recovered in NEFA-treated oocytes, oocyte autofluorescence of the respiratory chain cofactor, FAD, was lower following NEFA treatment of COCs, and this was not reversed by salubrinal, suggesting the negative impact was via reduced mitochondrial function. These results reveal the significance of NEFA-induced ER stress on bovine COC developmental competence, revealing a potential therapeutic target for improving oocyte quality during peak lactation. PMID:26658709

  1. Essential fatty acids and lipid mediators. Endocannabinoids

    Directory of Open Access Journals (Sweden)

    G. Caramia

    2012-03-01

    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.

  2. Fatty Acid Composition of Agaricus bisporus (Lange) Sing.

    OpenAIRE

    Aktümsek, Abdurrahman; ÖZTÜRK, Celâleddin; KAŞIK, Giyasettin

    1998-01-01

    Fatty acid compositions of fruit body, stem, lamellae and total of Agaricus bisporus were seperately analysed by GLC. In the all fatty acid compositions of A. bisporus, linoleic acid were predominant. Percentages of linoleic acid were varied between 53.45 - 68.78%. It was showed that the other major fatty acids were palmitic, oleic and stearic acid in the fatty acid compositions.

  3. Polyunsaturated fatty acids for multiple sclerosis treatment

    Directory of Open Access Journals (Sweden)

    Monserrat Kong-González

    2015-01-01

    Full Text Available INTRODUCTION Fatty acids have an important role in structure and function of the nervous system. Recently, epidemiologic studies on neurodegenerative disorders have evaluated the usefulness of polyunsaturated fatty acids on multiple sclerosis. OBJECTIVE To examine recent studies, clinical trials, and reviews on the therapeutic effect of polyunsaturated fatty acids in multiple sclerosis. METHODS We conducted a search in MEDLINE/PubMed and Cochrane Library with the terms "fatty acids", "omega-3" and "omega-6" in combination with "multiple sclerosis". Articles were selected according to their relevance on the topic. RESULTS Epidemiologic studies have shown benefits of dietary supplementation with polyunsaturated fatty acids -especially omega-3- in relation to inflammatory, autoimmune and neurodegenerative disorders. In contrast, the studies do not show a beneficial effect of polyunsaturated fatty acids in multiple sclerosis. However, there are limitations related to design and sample issues in these studies CONCLUSIONS There is some evidence of a protective effect of polyunsaturated fatty acids on the risk of multiple sclerosis. Despite this, to date controlled trials have not produced definite results on the benefits of supplementation with polyunsaturated fatty acids in patients with multiple sclerosis. Any potential benefit will have to be confirmed in the long term.

  4. Historical perspectives on fatty acid chemistry

    Science.gov (United States)

    Fatty acids are basic renewable chemical building blocks that can be used as intermediates for a multitude of products. Today the global value of fatty acids exceeds 18 billion dollars and is expected to increase to nearly 26 billion over the period from 2014-2019. From it auspicious beginnings, the...

  5. High ω3-polyunsaturated fatty acids in fat-1 mice prevent streptozotocin-induced Purkinje cell degeneration through BDNF-mediated autophagy

    OpenAIRE

    Dong Ho Bak; Enji Zhang; Min-Hee Yi; Do-Kyung Kim; Kyu Lim; Jwa-Jin Kim; Dong Woon Kim

    2015-01-01

    Loss of Purkinje cells has been implicated in the development of diabetic neuropathy, and this degeneration is characterized by impairment of autophagic processes. We evaluated whether fat-1 transgenic mice, a well-established animal model that endogenously synthesizes ω3 polyunsaturated fatty acids (ω3-PUFA), are protected from Purkinje cell degeneration in streptozotocin (STZ)-treated model with fat-1 mice. STZ-treated fat-1 mice did not develop hyperglycemia, motor deficits, or Purkinje ce...

  6. Solution Structure and Backbone Dynamics of Human Liver Fatty Acid Binding Protein: Fatty Acid Binding Revisited

    OpenAIRE

    Cai, Jun; Lücke, Christian; Chen, Zhongjing; Qiao, Ye; Klimtchuk, Elena; Hamilton, James A.

    2012-01-01

    Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the p...

  7. FATTY ACID COMPOSITION OF Capsicum GENUS PEPPERS

    Directory of Open Access Journals (Sweden)

    Gisele Teixeira de Souza Sora

    2015-08-01

    Full Text Available Fatty acids have a great metabolic and structural importance. Evaluation of fatty acid composition of peppers is still incomplete. Pulps and seeds from six varieties of the genus Capsicum were evaluated in this work with respect to their contents in fatty acids. A total of 25 different fatty acids, including some with odd number of carbons were identified in the samples. The most abundant fatty acids were palmitic (16:0, oleic (18:1n-9 and linoleic (18:2n-6 acids. The polyunsaturated:saturated fatty acid (PUFA/SFA ratios for all peppers were high due to the elevated amounts of polyunsaturated acids, particularly linoleic acid. In the pulps, the omega-6/omega-3 ratios ranging from 1.28 to 4.33, were relatively adequate if one considers that ratios between 0.25 and 1.0 in the human diet are regarded as highly appropriate. In the seeds, the levels of omega-3 were very low whereas the levels of omega-6 were high, leading to very inadequate omega-6/omega-3 ratios ranging from 74.2 to 279.6. Principal component analysis (PCA explained 93.49% of the total variance of the data. Considering the PUFA/SFA ratio and omega-6/omega-3 ratio, our data suggest that, among the peppers of the genus Capsicum evaluated in this work, the bell pepper and orange habanero pepper present the best nutritional characteristics concerning fatty acid composition.

  8. The selective target of capsaicin on FASN expression and de novo fatty acid synthesis mediated through ROS generation triggers apoptosis in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Hathaichanok Impheng

    Full Text Available The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs by blocking the fatty acid synthase (FASN enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm. Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting

  9. M-CSF from Cancer Cells Induces Fatty Acid Synthase and PPARβ/δ Activation in Tumor Myeloid Cells, Leading to Tumor Progression

    Directory of Open Access Journals (Sweden)

    Jonghanne Park

    2015-03-01

    Full Text Available We investigate crosstalk between cancer cells and stromal myeloid cells. We find that Lewis lung carcinoma cells significantly induce PPARβ/δ activity in myeloid cells in vitro and in vivo. Myeloid cell-specific knockout of PPARβ/δ results in impaired growth of implanted tumors, and this is restored by adoptive transfer of wild-type myeloid cells. We find that IL-10 is a downstream effector of PPARβ/δ and facilitates tumor cell invasion and angiogenesis. This observation is supported by the finding that the CD11blowIL-10+ pro-tumoral myeloid cell is scarcely detected in tumors from myeloid-cell-specific PPARβ/δ knockout mice, where vessel densities are also decreased. Fatty acid synthase (FASN is shown to be an upstream regulator of PPARβ/δ in myeloid cells and is induced by M-CSF secreted from tumor cells. Our study gives insight into how cancer cells influence myeloid stromal cells to get a pro-tumoral phenotype.

  10. Intake of fatty acids in Western Europe with emphasis on trans fatty acids: The TRANSFAIR study

    DEFF Research Database (Denmark)

    Hulshof, K. F. A. M.; Erp-Baart, M. A. van; Anttolainen, M.;

    1999-01-01

    Objective: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. Design and subjects: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters...... of fatty acids and total fat in adults and/or the total population using the best available national food consumption data set. Results: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat...... and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries...

  11. CFTR depletion results in changes in fatty acid composition and promotes lipogenesis in intestinal Caco 2/15 cells.

    Directory of Open Access Journals (Sweden)

    Geneviève Mailhot

    Full Text Available BACKGROUND: Abnormal fatty acid composition (FA in plasma and tissue lipids frequently occurs in homozygous and even in heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR mutations. The mechanism(s underlying these abnormalities remained, however, poorly understood despite the potentially CFTR contributing role. METHODOLOGY/PRINCIPAL FINDINGS: The aim of the present study was to investigate the impact of CFTR depletion on FA uptake, composition and metabolism using the intestinal Caco-2/15 cell line. shRNA-mediated cftr gene silencing induced qualitative and quantitative modifications in FA composition in differentiated enterocytes as determined by gas-liquid chromatography. With the cftr gene disruption, there was a 1,5 fold increase in the total FA amount, largely attributable to monounsaturated and saturated FA compared to controls. The activity of delta-7 desaturase, estimated by the 16:1(n-7/16:0, was significantly higher in knockdown cells and consistent with the striking elevation of the n-7 FA family. When incubated with [14C]-oleic acid, CFTR-depleted cells were capable of quick incorporation and export to the medium concomitantly with the high protein expression of L-FABP known to promote intracellular FA trafficking. Accordingly, lipoprotein vehicles (CM, VLDL, LDL and HDL, isolated from CFTR knockdown cells, exhibited higher levels of radiolabeled FA. Moreover, in the presence of [14C]-acetate, knockdown cells exhibited enhanced secretion of newly synthesized phospholipids, triglycerides, cholesteryl esters and free FA, thereby suggesting a stimulation of the lipogenic pathway. Conformably, gene expression of SREBP-1c, a key lipogenic transcription factor, was increased while protein expression of the phosphorylated and inactive form of acetylCoA carboxylase was reduced, confirming lipogenesis induction. Finally, CFTR-depleted cells exhibited lower gene expression of transcription factors (PPARalpha

  12. Short chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway

    OpenAIRE

    Park, Jeongho; Kim, Myunghoo; Kang, Seung G; Jannasch, Amber Hopf; Cooper, Bruce; Patterson, John; Chang H Kim

    2014-01-01

    Microbial metabolites such as short chain fatty acids (SCFAs) are highly produced in the intestine and potentially regulate the immune system. We studied the function of SCFAs in regulation of T cell differentiation into effector and regulatory T cells. We report that SCFAs can directly promote T cell differentiation into T cells producing IL-17, IFN-γ, and/or IL-10 depending on cytokine milieu. This effect of SCFAs on T cells is independent of GPR41- or GPR43 but dependent on direct histone ...

  13. Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides

    OpenAIRE

    Joshua A. Jackman; Bo Kyeong Yoon; Danlin Li; Nam-Joon Cho

    2016-01-01

    Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a br...

  14. Oxidized Fatty Acids as Inter-Kingdom Signaling Molecules

    OpenAIRE

    Pohl, Carolina H.; Johan L. F. Kock

    2014-01-01

    Oxylipins or oxidized fatty acids are a group of molecules found to play a role in signaling in many different cell types. These fatty acid derivatives have ancient evolutionary origins as signaling molecules and are ideal candidates for inter-kingdom communication. This review discusses examples of the ability of organisms from different kingdoms to “listen” and respond to oxylipin signals during interactions. The interactions that will be looked at are signaling between animals and plants; ...

  15. Fatty acid content, health and risk indices, physicochemical composition, and somatic cell counts of milk from organic and conventional farming systems in tropical south-eastern Mexico.

    Science.gov (United States)

    Delgadillo-Puga, Claudia; Sánchez-Muñoz, Bernardo; Nahed-Toral, José; Cuchillo-Hilario, Mario; Díaz-Martínez, Margarita; Solis-Zabaleta, Roman; Reyes-Hernández, Aurora; Castillo-Domíguez, Rosa Maria

    2014-06-01

    Organic agriculture and livestock farming is claimed to promote animal welfare and can offer animal products with better hygienic-sanitary quality, based on principles of health, ecology, fairness, and care. However, no clear advantages of organic milk (OM) versus conventional milk (CM) from tropical conditions are available. The aims of the study were to determine fatty acid profile, health-promoting (HPI) and thrombogenic (TI) indices, physicochemical composition, and somatic cell counts (SCC) of OM and CM in tropical south-eastern Mexico. Female cross-breed cows (400-600 kg) were employed. CM had larger values of saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) (63.6 %; 4.57 %) than OM (61.48 %; 4.22 %), while OM resulted in a larger value of monounsaturated fatty acid (MUFA) (34.3 %) than CM (31.7 %). HPI and TI showed that OM was more favorable than CM. Milk production and physicochemical composition (PC) as well as density had no significant difference, while SCC was significantly lower in OM than in CM on a monthly basis. These results showed that OM promotes a healthful and balanced diet, and is already produced by sustainable ecologic technologies employing traditional agrosilvopastoral management, which is more environmentally friendly and promotes ecological resilience. PMID:24715204

  16. Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development.

    Science.gov (United States)

    Wong, Bernice H; Chan, Jia Pei; Cazenave-Gassiot, Amaury; Poh, Rebecca W; Foo, Juat Chin; Galam, Dwight L A; Ghosh, Sujoy; Nguyen, Long N; Barathi, Veluchamy A; Yeo, Sia W; Luu, Chi D; Wenk, Markus R; Silver, David L

    2016-05-13

    Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs. PMID:27008858

  17. Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E2 signaling in fat stromal cells

    Directory of Open Access Journals (Sweden)

    Ruan Diana

    2012-08-01

    Full Text Available Abstract Background The molecular mechanisms of dietary oils (such as fish oil and unsaturated fatty acids, which are widely used by the public for anti-inflammation and vascular protection, have not been settled yet. In this study, prostaglandin E2 (PGE2-mediated calcium signaling was used to screen dietary oils and eight unsaturated fatty acids for identification of their anti-inflammatory mechanisms. Isolated fat/stromal cells expressing endogenous PGE2 receptors and an HEK293 cell line specifically expressing the recombinant human PGE2 receptor subtype-1 (EP1 were cultured and used in live cell calcium signaling assays. The different dietary oils and unsaturated fatty acids were used to affect cell signaling under the specific stimulation of a pathological amount of inflammatory PGE2. Results It was identified that fish oil best inhibited the PGE2 signaling in the primary cultured stromal cells. Second, docosahexaenoic acid (DHA, found in abundance in fish oil, was identified as a key factor of inhibition of PGE2 signaling. Eicosapentaenoic acid (EPA, another major fatty acid found in fish oil and tested in this study was found to have small effect on EP1 signaling. The study suggested one of the four PGE2 subtype receptors, EP1 as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP1 expressed in HEK293 cells as a target. Conclusion This study demonstrated the new mechanism behind the positive effects of dietary fish oils in inhibiting inflammation originates from the rich concentration of DHA, which can directly inhibit the inflammatory EP1-mediated PGE2 receptor signaling, and that the inflammatory response stimulated by PGE2 in the fat stromal cells, which directly related to metabolic diseases, could be down regulated by fish oil and DHA. These findings also provided direct evidence to support the use of dietary oils and unsaturated fatty acids for protection against heart

  18. Fatty-acid metabolism is involved in stress-resistance mechanisms of Caenorhabditis elegans

    OpenAIRE

    Horikawa, Makoto; Sakamoto, Kazuichi

    2009-01-01

    Fatty acids are the major components of the phospholipid bilayer and are involved in several functions of cell membrane. We previously reported that fatty-acid metabolism is involved in the regulation of DAF-2/insulin signal in Caenorhabditis elegans. In this study, we investigate the role of fatty-acid metabolism in stress resistance with respect to daf-16 in nematode. We found that fatty-acid metabolism regulates heat, osmotic, and oxidative-stress resistance in C. elegans. RNA interference...

  19. Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, and Inflammation

    OpenAIRE

    Kim, Chang; Park, Jeongho; Kim, Myunghoo

    2014-01-01

    T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues ...

  20. Antineoplastic unsaturated fatty acids from Fijian macroalgae.

    Science.gov (United States)

    Jiang, Ren-Wang; Hay, Mark E; Fairchild, Craig R; Prudhomme, Jacques; Roch, Karine Le; Aalbersberg, William; Kubanek, Julia

    2008-10-01

    Phytochemical analysis of Fijian populations of the green alga Tydemania expeditionis led to the isolation of two unsaturated fatty acids, 3(zeta)-hydroxy-octadeca-4(E),6(Z),15(Z)-trienoic acid (1) and 3(zeta)-hydroxy-hexadeca-4(E),6(Z)-dienoic acid (2), along with the known 3(zeta)-hydroxy-octadeca-4(E),6(Z)-dienoic acid (4). Investigations of the red alga Hydrolithon reinboldii led to identification of a glycolipid, lithonoside (3), and five known compounds, 15-tricosenoic acid, hexacosa-5,9-dienoic methyl ester, beta-sitosterol, 10(S)-hydroxypheophytin A, and 10(R)-hydroxypheophytin A. The structures of 1-3 were elucidated by spectroscopic methods (1D and 2D NMR spectroscopy and ESI-MS). Compounds 1, 2, and 4, containing conjugated double bonds, demonstrated moderate inhibitory activity against a panel of tumor cell lines (including breast, colon, lung, prostate and ovarian cells) with IC(50) values ranging from 1.3 to 14.4 microM. The similar cell selectivity patterns of these three compounds suggest that they might act by a common, but unknown, mechanism of action.

  1. Fatty Acid Composition of Meat from Ruminants, with Special Emphasis on trans Fatty Acids

    DEFF Research Database (Denmark)

    Leth, Torben; Ovesen, L.; Hansen, K.

    1998-01-01

    The fatty acid composition was determined in 39 samples of beef, 20 samples of veal, and 34 samples of lamb, representative of the supply of ruminant meat in Denmark. Five cuts of beef and veal and three cuts of lamb with increasing fat content were selected, and analysis of the fatty acid methyl......, respectively). Cis monounsaturated fatty acids were 49.2 +/- 3.1, 44.9 +/- 1.8, and 37.7 +/- 1.7, and polyunsaturated fatty acids were 3.3 +/- 0.7, 5.8 +/- 2.0, and 5.0 +/- 0.1 g/100 g fatty acids in beef, veal, and lamb, respectively. Beef contained 2.1 +/- 0.8 g trans C-18:1 per 100 g fatty acids, about half...... that found in veal (4.0 +/- 1.2 g/100 g fatty acids) and lamb (4.5 +/- 0.6 g/100 g fatty acids). Trans C-16:1 was 0.24 +/- 0.01, 0.14 +/- 0.02, and 0.79 +/- 0.02 g/100 g fatty acids in beef, veal, and lamb, respectively. Only small variations in trans and other fatty acids could be demonstrated between cuts...

  2. Omega-3 fatty acids and cardiovascular disease.

    Science.gov (United States)

    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.

  3. The evolution of lipids part 2. Which was comfortable isoprenoid alcohol or fatty acid as the membrane lipids of the common ancestral cell?

    Science.gov (United States)

    Itoh, Y.; Itoh, T.

    A cell is the most fundamental and essential structural unit of all living organisms on the Earth. Even though we will disclose many genomic DNA sequences, the structures and functions of their products, and interactions of them, it isn't possible to create an organism in vitro without cell membrane or barriers with which separate an inner water part from the outer environments. What kinds of molecule were concentrated in the prebiotic soup to be the cradle of genetic materials? Which was comfortable isoprenoid alcohol or fatty acid as the membrane lipids of the common ancestral cell? The struct u ral units of DNA, RNA, and proteins are simple, well organized and common in all the living organisms on the Earth. On the other hand, a great number of molecular species of the membrane lipids are present and each of them is specific for the individual species. Major lipids of all living organisms are derived from a variety of glycerophospholipids, s ulfolipids , glycolipid, phosphosulfoglycolipids, or triterpen family. Where do these molecules distribute in a phylogenetic tree? Among procaryotes, bacterial membrane glycerolipids basically consist of fatty acids as hydrocarbon chains, however, archaeal that do isoprenoid alcohol chains. How did the number of carbon in a fatty acid chain or an isoprenoid chain select ? Which might have an advantage for an easy way to obtain enough length of the membrane lipids, fatty acid or isoprenoid, in the prebiotic soup ? Precursor of an isoprenoid , a mevalonic acid, that is easily soluble in water and also soluble in polar organic solvent. The characteristics of the molecules should be suitable for their functions. In this presentation, based on the comparison of the molecular species of lipids in widespread living organisms including Archaea, Bacteria, and Eucarya, the evolutional position of each molecule will be discussed.

  4. Molar extinction coefficients of some fatty acids

    DEFF Research Database (Denmark)

    Sandhu, G.K.; Singh, K.; Lark, B.S.;

    2002-01-01

    The attenuation of gamma rays in some fatty acids, viz. formic acid (CH2O2), acetic acid (C2H4O2), propionic acid (C3H6O2), butyric acid (C4H8O2), n-hexanoic acid (C6H12O2), n-caprylic acid (C8H16O2), lauric acid (C12H24O2), myristic acid (C14H28O2), palmitic acid (C16H32O2), oleic acid (C18H34O2...

  5. The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE2 synthesis and cytotoxicity in human colorectal carcinoma cell lines

    NARCIS (Netherlands)

    Dommels, Y.E.M.; Haring, M.M.G.; Keestra, N.G.M.; Alink, G.M.; Bladeren, P.J. van; Ommen, B. van

    2003-01-01

    This study was conducted to investigate the role of the enzyme cyclooxygenase (COX) and its prostaglandin product PGE2 in n-6 and n-3 polyunsaturated fatty acid (PUFA)-mediated effects on cellular proliferation of two human colorectal carcinoma cell lines. The long chain PUFAs eicosapentaenoic acid

  6. Inhibition of fatty acid synthesis in rat hepatocytes by exogenous polyunsaturated fatty acids is caused by lipid peroxidation

    DEFF Research Database (Denmark)

    Mikkelsen, L.; Hansen, Harald S.; Grunnet, N.;

    1993-01-01

    by the peroxidized PUFA. Arachidonic acid and eicosapentaenoic acid showed a dose- and time-dependent cytotoxicity. Two other antioxidants: 50 µM a-tocopherol acid succinate and 1 µM N,N'-diphenyl-1,4-phenylenediamine, both proved more efficient than a-tocopherol phosphate. There was a significant correlation......Rat hepatocyte long-term cultures were utilized to investigate the impact of different polyunsaturated fatty acids (PUFA) on the insulin-induced de novo fatty acid synthesis in vitro. The addition of 0.5 mM albumin-complexed oleic, linoleic, columbinic, arachidonic, eicosapentaenoic...... or docosahexaenoic acid resulted in a marked suppression of fatty acid synthesis. By evaluation of cell viability (determined as the leakage of lactate dehydrogenase (LDH)) it turned our, that the antioxidant used (50 µM a-tocopherol phosphate) had a low antioxidant activity, resulting in cytotoxic effects...

  7. Ghrelin reduces hepatic mitochondrial fatty acid beta oxidation.

    Science.gov (United States)

    Rigault, C; Le Borgne, F; Georges, B; Demarquoy, J

    2007-04-01

    Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiologically induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver. Liver has a key position in lipid metabolism as it allows the metabolic orientation of fatty acids between oxidation and esterification. We investigated the effects of peripheral ghrelin administration on 2 crucial parameters of fatty acid oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either given to rats prior to the hepatocyte preparation and culture or used to treat hepatocytes prepared from control animals. Direct incubation of ghrelin to raw hepatocytes did not induce any change in the studied parameters. In hepatocytes prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial fatty acid oxidation while no alteration of the L-carnitine-related parameters were observed. These results suggested (a) that ghrelin has no direct effect on liver, and (b) that when administrated to a whole organism, ghrelin may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation. PMID:17556859

  8. Evaluation of fatty acid content of some Iranian fast foods with emphasis on trans fatty acids.

    Science.gov (United States)

    Asgary, Seddigheh; Nazari, Bahar; Sarrafzadegan, Nizal; Parkhideh, Sahar; Saberi, Salbali; Esmaillzadeh, Ahmad; Azadbakht, Leila

    2009-01-01

    Although the disadvantages of trans fatty acids (TFAs) are widely mentioned, limited data are available on the TFAs contents of Iranian foods, including fast foods. The aim of this study was to quantify the amounts of common fatty acids in several fast foods in Iran, with specific focus on TFAs. The most commonly consumed fast foods in Iran: sausage, calbas, hamburgers and pizzas, were randomly selected seven times from products available in supermarkets and restaurants. Each time a 10 g sample was drawn and prepared for fatty acid analysis. Total and individual fatty acids were quantified according to standard methods by gas chromatography with 60 meter capillary column and flame ionization detector. The most common saturated fatty acids in Iranian fast foods is stearic acid (C18:0) which ranged from 14.0% to 20.9%. Saturated fatty acid content in calbas was significantly higher than that found in other groups. Trans fatty acids constitute almost 23.6% to 30.6% of total fatty acids of these products. The most common TFA in these fast foods was elaidic acid (C18:1 9t). Total cis unsaturated fatty acid content of tested fast foods varied from 25.3%(in sausage) to 46.8(in calbas) with oleic acid (C18:1 9c) followed by linoleic acid (C18:2) being the most common fatty acids in these products. This study showed higher TFAs contents in commercially available fast foods compared to the amounts recommended by dietary guidelines in Iran. Further studies must assess the effects of these fatty acids on human health. PMID:19713177

  9. Transgenesis of humanized fat1 promotes n-3 polyunsaturated fatty acid synthesis and expression of genes involved in lipid metabolism in goat cells.

    Science.gov (United States)

    Fan, Yixuan; Ren, Caifang; Wang, Zhibo; Jia, Ruoxin; Wang, Dan; Zhang, Yanli; Zhang, Guomin; Wan, Yongjie; Huang, Mingrui; Wang, Feng

    2016-01-15

    The n-3 fatty acid desaturase gene fat1 codes for the n-3 desaturase enzyme, which can convert n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. The n-3 PUFAs are essential components required for normal cellular function and have preventive and therapeutic effects on many diseases. Goat is an important domestic animal for human consumption of meat and milk. To elevate the concentrations of n-3 PUFAs and examine the regulatory mechanism of fat1 in PUFA metabolism in goat cells, we successfully constructed a humanized fat1 expression vector and confirmed the efficient expression of fat1 in goat ear skin-derived fibroblast cells (GEFCs) by qRT-PCR and Western blot analysis. Fatty acid analysis showed that fat1 overexpression significantly increased the levels of total n-3 PUFAs and decreased the levels of total n-6 PUFAs in GEFCs. In addition, qRT-PCR results indicate that the FADS1 and FADS2 desaturase genes, ELOV2 and ELOV5 elongase genes, ACO and CPT1 oxidation genes, and PPARa and PPARγ transcription factors are up-regulated, and transcription factors of SREBP-1c gene are down-regulated in the fat1 transgenic goat cells. Overall, fat1-overexpression resulted in an increase in the n-3 fatty acids and altered expression of PUFA synthesis related genes in GEFCs. This work lays a foundation for both the production of fat1 transgenic goats and further study of the mechanism of fat1 function in the PUFAs metabolism.

  10. Transgenesis of humanized fat1 promotes n-3 polyunsaturated fatty acid synthesis and expression of genes involved in lipid metabolism in goat cells.

    Science.gov (United States)

    Fan, Yixuan; Ren, Caifang; Wang, Zhibo; Jia, Ruoxin; Wang, Dan; Zhang, Yanli; Zhang, Guomin; Wan, Yongjie; Huang, Mingrui; Wang, Feng

    2016-01-15

    The n-3 fatty acid desaturase gene fat1 codes for the n-3 desaturase enzyme, which can convert n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. The n-3 PUFAs are essential components required for normal cellular function and have preventive and therapeutic effects on many diseases. Goat is an important domestic animal for human consumption of meat and milk. To elevate the concentrations of n-3 PUFAs and examine the regulatory mechanism of fat1 in PUFA metabolism in goat cells, we successfully constructed a humanized fat1 expression vector and confirmed the efficient expression of fat1 in goat ear skin-derived fibroblast cells (GEFCs) by qRT-PCR and Western blot analysis. Fatty acid analysis showed that fat1 overexpression significantly increased the levels of total n-3 PUFAs and decreased the levels of total n-6 PUFAs in GEFCs. In addition, qRT-PCR results indicate that the FADS1 and FADS2 desaturase genes, ELOV2 and ELOV5 elongase genes, ACO and CPT1 oxidation genes, and PPARa and PPARγ transcription factors are up-regulated, and transcription factors of SREBP-1c gene are down-regulated in the fat1 transgenic goat cells. Overall, fat1-overexpression resulted in an increase in the n-3 fatty acids and altered expression of PUFA synthesis related genes in GEFCs. This work lays a foundation for both the production of fat1 transgenic goats and further study of the mechanism of fat1 function in the PUFAs metabolism. PMID:26474750

  11. Single-cell analysis of insulin-regulated fatty acid uptake in adipocytes

    OpenAIRE

    Varlamov, Oleg; Somwar, Romel; Cornea, Anda; Kievit, Paul; Grove, Kevin L.; Roberts, Charles T.

    2010-01-01

    Increased body fat correlates with the enlargement of average fat cell size and reduced adipose tissue insulin sensitivity. It is currently unclear whether adipocytes, as they accumulate more triglycerides and grow in size, gradually become less insulin sensitive or whether obesity-related factors independently cause both the enlargement of adipocyte size and reduced adipose tissue insulin sensitivity. In the first instance, large and small adipocytes in the same tissue would exhibit differen...

  12. Arylacetamide deacetylase attenuates fatty-acid-induced triacylglycerol accumulation in rat hepatoma cells

    OpenAIRE

    Lo, Vivien; Erickson, Bruce; Thomason-Hughes, Michaela; Ko, Kerry W.S.; Dolinsky, Vernon W.; Nelson, Randy; Lehner, Richard

    2010-01-01

    Mobilization of hepatic triacylglycerol stores provides substrates for mitochondrial β-oxidation and assembly of VLDLs; however, the identity of lipolytic enzymes involved in the regulation of this process remains largely unknown. Arylacetamide deacetylase (AADA) shares homology with hormone-sensitive lipase and therefore could potentially participate in hepatic lipid metabolism, including the regulation of hepatic triacylglycerol levels. We have established McArdle-RH7777 (rat hepatoma) cell...

  13. The microbial metabolites, short chain fatty acids, regulate colonic Treg cell homeostasis

    OpenAIRE

    Smith, Patrick M.; Howitt, Michael R.; Panikov, Nicolai; Michaud, Monia; Gallini, Carey Ann; Bohlooly-Y, Mohammad; Glickman, Jonathan N.; Wendy S. Garrett

    2013-01-01

    Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined t...

  14. Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A.

    Directory of Open Access Journals (Sweden)

    Francesca Nardi

    Full Text Available AIMS/HYPOTHESIS: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA, whereas mono and polyunsaturated fatty acids (MUFA and PUFA not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A. This study investigated the effects of oleic acid (OA; a MUFA, linoleic acid (LOA; a PUFA and palmitate (PA; a SFA in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. PRINCIPAL FINDINGS: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt- and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine307phosphorylation - events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A. CONCLUSIONS/INTERPRETATION: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A.

  15. Essential fatty acids as transdermal penetration enhancers

    OpenAIRE

    Van Zyl, Lindi; du Preez, Jan; Gerber, Minja; Du Plessis, Jeanetta; Viljoen, Joe

    2015-01-01

    The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F and Pheroid™ technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid™ delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release ...

  16. Synthesis of new fatty acids amides from aminolysis of fatty acid methyl esters (FAMEs)

    International Nuclear Information System (INIS)

    Recent biochemical and pharmacological studies have led to the characterization of different fatty acid amides as a new family of biologically active lipids. Here, we describe the synthesis of new amides from C16:0, 18:0, 18:1 and 18:1, OH fatty acids (FFA) families with cyclic and acyclic amines and demonstrate for the first time that these compounds produce cytotoxic effects. Application of this method to the synthesis of fatty acid amides was performed using the esters aminolysis as a key step and various carboxylic amides were prepared in good yield from fatty acid methyl esters (FAMEs). (author)

  17. Fatty acid oxidation and ketogenesis in astrocytes

    International Nuclear Information System (INIS)

    Astrocytes were derived from cortex of two-day-old rat brain and grown in primary culture to confluence. The metabolism of the fatty acids, octanoate and palmitate, to CO2 in oxidative respiration and to the formation of ketone bodies was examined by radiolabeled tracer methodology. The net production of acetoacetate was also determined by measurement of its mass. The enzymes in the ketogenic pathway were examined by measuring enzymic activity and/or by immunoblot analyses. Labeled CO2 and labeled ketone bodies were produced from the oxidation of fatty acids labeled at carboxy- and ω-terminal carbons, indicating that fatty acids were oxidized by β-oxidation. The results from the radiolabeled tracer studies also indicated that a substantial proportion of the ω-terminal 4-carbon unit of the fatty acids bypassed the β-ketothiolase step of the β-oxidation pathway. The [14C]acetoacetate formed from the [1-14C]labeled fatty acids, obligated to pass through the acetyl-CoA pool, contained 50% of the label at carbon 3 and 50% at carbon 1. In contrast, the [14C]acetoacetate formed from the (ω-1)labeled fatty acids contained 90% of the label at carbon 3 and 10% at carbon 1

  18. FATTY ACID COMPOSITION OF SOME LEAFY VEGETABLES OF BANGLADESH

    Directory of Open Access Journals (Sweden)

    Kamal Karmakar, Tanvir Muslim* and Md. Azizur Rahman

    2013-02-01

    Full Text Available Fatty acid composition of six different leafy vegetables of Bangladesh was investigated. The amount of bound fatty acids was found to be higher than the free fatty acids in all the leafy vegetables. Different fatty acids were identified and their relative proportions were determined by GLC from the leafy vegetables.

  19. Expression of fatty acid synthase in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Dorn, Christoph; Riener, Marc-Oliver; Kirovski, Georgi; Saugspier, Michael; Steib, Kathrin; Weiss, Thomas S; Gäbele, Erwin; Kristiansen, Glen; Hartmann, Arndt; Hellerbrand, Claus

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fatty acid synthase (FASN) catalyzes the last step in fatty acid biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fatty acids by de novo lipogenesis. The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of primary human hepatocytes with fatty acids dose-dependently induced cellular lipid-accumulation and FASN expression, while stimulation with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore, FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for the progression of NAFLD. PMID:20606731

  20. Fatty acid transfer between multilamellar liposomes and fatty acid-binding proteins.

    Science.gov (United States)

    Brecher, P; Saouaf, R; Sugarman, J M; Eisenberg, D; LaRosa, K

    1984-11-10

    A simple experimental system was developed for studying the movement of long-chain fatty acids between multilamellar liposomes and soluble proteins capable of binding fatty acids. Oleic acid was incorporated into multilamellar liposomes containing cholesterol and egg yolk lecithin and incubated with albumin or hepatic fatty acid-binding protein. It was found that the fatty acid transferred from the liposomes to either protein rapidly and selectively under conditions where phospholipid and cholesterol transfer did not occur. More than 50% of the fatty acid contained within liposomes could become protein bound, suggesting that the fatty acid moved readily between and across phospholipid bilayers. Transfer was reduced at low pH, and this reduction appeared to result from decreased dissociation of the protonated fatty acid from the bilayer. Liposomes made with dimyristoyl or dipalmitoyl lecithin and containing 1 mol per cent palmitic acid were used to show the effect of temperature on fatty acid transfer. Transfer to either protein did not occur at temperatures where the liposomes were in a gel state but occurred rapidly at temperatures at or above the transition temperatures of the phospholipid used. PMID:6490659

  1. Changes in plasma and erythrocyte omega-6 and omega-3 fatty acids in response to intravenous supply of omega-3 fatty acids in patients with hepatic colorectal metastases

    OpenAIRE

    Al-Taan, Omer; Stephenson, James A; Spencer, Laura; Pollard, Cristina; West, Annette L.; Calder, Philip C.; Metcalfe, Matthew; Dennison, Ashley R

    2013-01-01

    Background Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are functionally the most important omega-3 polyunsaturated fatty acids (PUFAs). Oral supply of these fatty acids increases their levels in plasma and cell membranes, often at the expense of the omega-6 PUFAs arachidonic acid (ARA) and linoleic acid. This results in an altered pattern of lipid mediator production to one which is less pro-inflammatory. We investigated whether short term intravenous supply of omega-3 PUFAs co...

  2. Production of unusual fatty acids in rapeseed

    Directory of Open Access Journals (Sweden)

    Roscoe Thomas

    2002-01-01

    Full Text Available Vegetable-derived oils are of interest for industrial applications partly because of the chemical similarity of plant oils to mineral oils but also because of the economic need to reduce overproduction of seed oils for nutritional use. Complex oils can be produced in seeds as a low cost agricultural product based on renewable solar energy that requires less refining and is biodegradable and thus produces less adverse effects on the environment. In addition, biotechnologies have accelerated selection programmes and increased the genetic diversity available for the development of new varieties of oilseeds with specific fatty acid compositions. In the developing oilseed, energy and carbon are stored as lipid under the form of triacylglycerol, that is, a glycerol molecule to which three fatty acids are esterified. Fatty acids comprise a linear chain of carbon atoms, the first of which carries an organic acid group. The chain length and the presence of double bonds determine the properties of the fatty acid which in turn determine the physical and chemical properties of the oil of storage lipids and hence their economic value. In addition to the common C16- and C18-saturated and unsaturated fatty acids of membrane lipids, the seed storage lipids of many plant species contain unusual fatty acids (UFAs which can vary in chain length, in the degree of unsaturation, possess double bonds in unusual positions, or can contain additional functional groups such as hydroxy, epoxy, cyclic and acetylenic groups [1]. These unusual fatty acids are of value as industrial feedstocks and their uses include the production of fuels and lubricants, soap and detergents, paints and varnishes, adhesives and plastics (Figure 1.

  3. HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia.

    Science.gov (United States)

    Su, Jingjing; Zhou, Houguang; Tao, Yinghong; Guo, Zhuangli; Zhang, Shuo; Zhang, Yu; Huang, Yanyan; Tang, Yuping; Hu, Renming; Dong, Qiang

    2015-01-01

    Cell cycle processes play a vital role in vascular endothelial proliferation and dysfunction. Cell division cycle protein 14 (Cdc14) is an important cell cycle regulatory phosphatase. Previous studies in budding yeast demonstrated that Cdc14 could trigger the inactivation of mitotic cyclin-dependent kinases (Cdks), which are required for mitotic exit and cytokinesis. However, the exact function of human Cdc14 (hCdc14) in cell cycle regulation during vascular diseases is yet to be elucidated. There are two HCdc14 homologs: hCdc14A and hCdc14B. In the current study, we investigated the potential role of hCdc14A in high glucose-, free fatty acids (FFAs)-, and hypoxia-induced injury in cultured human brain vascular endothelial cells (HBVECs). Data revealed that high glucose, FFA, and hypoxia down-regulated hCdc14A expression remarkably, and also affected the expression of other cell cycle-related proteins such as cyclin B, cyclin D, cyclin E, and p53. Furthermore, the combined addition of the three stimuli largely blocked cell cycle progression, decreased cell proliferation, and increased apoptosis. We also determined that hCdc14A was localized mainly to centrosomes during interphase and spindles during mitosis using confocal microscopy, and that it could affect the expression of other cycle-related proteins. More importantly, the overexpression of hCdc14A accelerated cell cycle progression, enhanced cell proliferation, and promoted neoplastic transformation, whereas the knockdown of hCdc14A using small interfering RNA produced the opposite effects. Therefore, these findings provide novel evidence that hCdc14A might be involved in cell cycle regulation in cultured HBVECs during high glucose-, FFA-, and hypoxia-induced injury.

  4. Digestion and absorption of fatty acids in the ruminant

    OpenAIRE

    Cuvelier, Christine; Cabaraux, Jean-François; Dufrasne, Isabelle; Istasse, Louis; Hornick, Jean-Luc

    2005-01-01

    From a biochemical point of view, in ruminants, there are two major groups of fatty acids. They are firstly the volatile fatty acids from the rumen metabolism of dietary carbohydrates, and secondly the fatty acids from the rumen metabolism of lipids. This second group is made of the fatty acids synthesized by the microorganisms of the rumen and the fatty acids originating from the hydrolysis of dietary triacylglycerols, which are mostly hydrogenated by microorganisms in the rumen before intes...

  5. Trivalent chromium alleviates oleic acid induced steatosis in SMMC-7721 cells by decreasing fatty acid uptake and triglyceride synthesis.

    Science.gov (United States)

    Wang, Song; Wang, Jian; Zhang, Xiaonan; Hu, Linlin; Fang, Zhijia; Huang, Zhiwei; Shi, Ping

    2016-10-01

    Trivalent chromium [Cr(III)] has been shown as an essential trace element for human health. Previous studies depict that Cr(III) plays important roles in maintaining normal glucose and lipid metabolism, whereas its effect on the hepatic lipid metabolism is still unknown. In the present study, we investigated the effects and underlying mechanisms of Cr on hepatic steatosis induced by oleic acid (OA) in human hepatoma SMMC-7721 cells. Hepatic steatosis model was co-administered with Cr. Indexes of lipid accumulation were determined and associated genes expression were analyzed. The data showed that OA could induce lipid accumulation and triglyceride (TG) content in SMMC-7721 cells, and significantly increase the expression of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2). This steatosis effect of OA was ameliorated by Cr. The TG accumulation and up-regulation of CD36 and DGAT2 genes followed steatosis induction were inhibited by Cr. After the treatment of Cr, excessive intracellular OA content was also attenuated. Furthermore, Cr still performed inhibitory effect of DGAT2 expression at the presence of DGAT2 agonist or inhibitor, which indicated that the inhibitory effect of Cr on lipogenesis is associated with the downregulation of DGAT2 expression. These findings demonstrate that Cr alleviates hepatic steatosis via suppressing CD36 expression to prevent fatty acid uptake, as well as suppressing DGAT2 expression to inhibit TG synthesis. It suggests that CD36 and DGAT2 might become the novel drug targets for their properties in hepatic steatosis. Most importantly, Cr may be a potential anti-steatosis candidate to offer protective effects against liver damage. PMID:27497686

  6. β-Hydroxybutyrate Facilitates Fatty Acids Synthesis Mediated by Sterol Regulatory Element-Binding Protein1 in Bovine Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Min Zhang

    2015-11-01

    Full Text Available Background/Aims: In dairy cows, β-hydroxybutyrate (BHBA is utilized as precursors of de novo synthesized fatty acids in mammary gland. Ketotic cows are characterized by excessive negative energy balance (NEB, which can further increase the blood BHBA concentration. Sterol regulatory element-binding protein1 (SREBP1 and cell death-inducing DNA fragmentation factor-alpha-like effector α (Cidea play crucial roles in lipid synthesis. Therefore, we hypothesized that BHBA could stimulate SREBP1/Cidea pathway to increase milk fat synthesis in bovine mammary epithelial cells. Methods: Bovine mammary epithelial cells were treated with different concentrations of BHBA and transfected with adenovirus to silence SREBP1 expression. The effects of BHBA on the lipid synthesis in bovine mammary epithelial cells were investigated. Results: The results showed that BHBA could significantly increase the expression of SREBP1, fatty acid synthase (FAS, acetyl-CoA carboxylase α (ACC-α, Cidea and diacylglycerol transferase-1 (DGAT-1, as well as the triglycerides (TG content in bovine mammary epithelial cells. BHBA treatment also increased the transfer of mature SREBP1 to nucleus compared with control group. However, SREBP1 silencing could significantly down-regulate the overexpression of FAS, ACC-α, Cidea and DGAT-1, as well as TG content induced by BHBA. Conclusion: The present data indicate that BHBA can significantly increase TG secretion mediated by SREBP1 in bovine mammary epithelial cells.

  7. Study of fatty acid-bacteria interactions

    International Nuclear Information System (INIS)

    Complete text of publication follows. During our work we investigated fatty acid-bacteria interactions. The antibacterial property of fatty acids was reported by several authors. Despite of them there is not reassuring explanation about the mechanism of the antibacterial activity of these compounds. An effect can considerably change in case of different structured fatty acids. Our earlier studies conduct that small changes in the structures can modify changes in their behavior towards bacteria. The stearic acid does not cause any antibacterial effects during the first few hours of the investigation, may even help the bacterial growth. However, linolic acid (C18:2) shows a strong antibacterial effect during the first hours. After 24 hours this effect wears out and the bacteria have adapted to the stress. We studied the antibacterial activity using direct bioautography. This method has the advantage to allow examining lipophilic compounds. The linoleic acid decomposes in time under different physiological conditions creating numerous oxidized molecules. This may be the reason of its antimicrobial effect. For studying this phenomenon we used infrared and mass spectroscopic methods. We applied infrared spectroscopy for indicating any changes in the spectra of the fatty acids after the interaction of fatty acids with bacteria. So we are able to deduct on what could happen during these process. We paid great attention towards the changes of double bonds, on methylation and demethylation processes. Using mass spectroscopy we searched for oxidized products that may play important role in this process. These studies are only part of our more widespreading investigations, dealing with the antimicrobial properties of fatty acids.

  8. Proportions of rumen volatile fatty acids in relation to milk fatty acid profiles

    NARCIS (Netherlands)

    Vlaeminck, B.; Fievez, V.; Dhanoa, M.S.; Vuuren, van A.M.; Dewhurst, R.J.

    2003-01-01

    Three experiments were conducted in order to develop and validate principal component (PC) regressions for predicting rumen volatile fatty acid (VFA) proportions, based on a combination of milk odd and branched chain fatty acids (MOBCFA). Grass- or legume silage and concentrate-based diets were fed

  9. PPAR{delta} is a fatty acid sensor, which enhances mitochondrial oxidation in insulin

    DEFF Research Database (Denmark)

    Ravnskjaer, Kim; Frigerio, Francesca; Boergesen, Michael;

    2010-01-01

    RNA-mediated knockdown we demonstrate that the ability of unsaturated fatty acids to stimulate fatty acid metabolism is dependent on PPARdelta. Activation of PPARdelta increases the fatty acid oxidation potential in INS-1E beta-cells, enhances glucose-stimulated insulin secretion (GSIS) from islets, and protects GSIS...... against adverse effects on GSIS associated with prolonged fatty acid exposure. The presented results indicate that the nuclear receptor PPARdelta is a fatty acid sensor that adapts beta-cell mitochondrial function to long-term changes in unsaturated fatty acid levels. As maintenance of mitochondrial...... metabolism is essential to preserve beta-cell function, these data indicate that dietary or pharmacological activation of PPARdelta and RXR may be beneficial in the prevention of beta-cell dysfunction....

  10. Effect of the ratios of unsaturated fatty acids on the expressions of genes related to fat and protein in the bovine mammary epithelial cells.

    Science.gov (United States)

    Sheng, R; Yan, S M; Qi, L Z; Zhao, Y L

    2015-04-01

    The objective of this study was to evaluate the effects of the different ratios of unsaturated fatty acids (UFAs) (oleic acid, linoleic acid, and linolenic acid) on the cell viability and triacylglycerol (TAG) content, as well as the mRNA expression of the genes related to lipid and protein synthesis in bovine mammary epithelial cells (BMECs). Primary cells were isolated from the mammary glands of Holstein dairy cows and were passaged twice. Afterward, the cells were randomly allocated to six treatments, five UFA-treated groups, and one control group. For all of the treatments, the the fetal bovine serum in the culture solution was replaced with fatty acid-free BSA (1 g/L), and the cells were treated with different ratios of oleic, linoleic, and linolenic acids (0.75:4:1, 1.5:10:1, 2:13.3:1, 3:20:1, and 4:26.7:1) for 48 h, which were group 1 to group 5. The control culture solution contained only fatty acid-free BSA without UFAs (0 μM). The results indicated that the cell viability was not affected by adding different ratios of UFAs, but the accumulation of TAG was significantly influenced by supplementing with different ratios of UFAs. Adding different ratios of UFAs suppressed the expression of ACACA and FASN but had the opposite effect on the abundances of FABP3 and CD36 mRNA. The expression levels of PPARG, SPEBF1, CSN1S1, and CSN3 mRNA in the BMECs were affected significantly after adding different ratios of UFAs. Our results suggested that groups 1, 2, and 3 (0.75:4:1, 1.5:10:1, and 2:13.3:1) had stronger auxo-action on fat synthesis in the BMECs, where group 3 (2:13.3:1) was the best, followed by group 4 (3:20:1). However, group 5 (4:26.7:1) was the worst. Genes related to protein synthesis in the BMECs were better promoted in groups 2 and 3, and group 3 had the strongest auxo-action, whereas the present study only partly examined the regulation of protein synthesis at the transcriptional level; more studies on translation level are needed in the future

  11. Upregulation of peroxisome proliferator-activated receptors and liver fatty acid binding protein in hepatic cells of broiler chicken supplemented with conjugated linoleic acids

    Directory of Open Access Journals (Sweden)

    Suriya Kumari Ramiah

    2015-09-01

    Full Text Available Since conjugated linoleic acid (CLA has structural and physiological characteristics similar to peroxisome proliferators, it is hypothesized that CLA would upregulate peroxisome proliferator-activated receptor (PPAR and liver fatty acid binding protein (LFABP in the liver of broiler chicken. The aim of the present study was to determine fatty acid composition of liver in CLA-fed broiler chickens and the genes associated with hepatic lipid metabolism. A total of 180-day-old broiler chicks were randomly assigned to two diets containing 0 and 2.5% CLA and fed for 6 weeks. Fatty acid (FA composition of liver and PPAR α and γ and L-FABP were analyzed. It has been demonstrated that CLA was found in the liver of CLA-feed chicken compared to control group. Hepatic PPAR α and γ mRNA levels were upregulated 1.2 and 3-fold in CLA-fed chickens compared to chickens fed diet without CLA respectively. A similar response of upregulation was observed for L-FABP mRNA expression. Our data highlights the role of PPARs as a core regulator in the regulation of lipid metabolism in chicken liver.

  12. Rapid lipid enrichment in omega3 fatty acids: plasma data.

    Science.gov (United States)

    Carpentier, Yvon A; Peltier, Sebastien; Portois, Laurence; Sener, Abdullah; Malaisse, Willy J

    2008-03-01

    The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion to normal subjects was recently reported to enrich within 60 min the phospholipid content of leucocytes and platelets in long-chain polyunsaturated omega3 fatty acids. The present study, conducted in second generation omega3-depleted rats, aimed at investigating whether such a procedure may also increase within 60 min the phospholipid content of omega3 fatty acids in cells located outwards the bloodstream, in this case liver cells, and whether this coincides with correction of the perturbation in the liver triglyceride fatty acid content and profile otherwise prevailing in these rats. This first report deals mainly with the fatty acid pattern of plasma lipids in male omega3-depleted rats that were non-injected or injected with either the omega3-rich emulsion or a control medium-chain triglyceride:olive oil emulsion. The results provide information on the fate of the exogenous lipids present in the lipid emulsions and injected intravenously 60 min before sacrifice. Moreover, in the uninjected omega3-depleted rats the comparison between individual plasma and liver measurements indicated positive correlations in the fatty acid profile of phospholipids and triglycerides. PMID:18288383

  13. Association of n3 and n6 polyunsaturated fatty acids in red blood cell membrane and plasma with severity of normal tension glaucoma

    Institute of Scientific and Technical Information of China (English)

    Man; Yu; Bo; Chen; Bo; Gong; Ping; Shuai; Zheng-Zheng; Wu; Wei; Lin

    2015-01-01

    AIM: To determine whether red blood cell(RBC)membrane and plasma lipids, particularly long-chain polyunsaturated fatty acids such as eicosapentaenoic acid(EPA), docosahexaenoic acid(DHA), arachidonic acid(AA) are significantly correlated with severity of normal tension glaucoma(NTG).METHODS: This study included 35 patients with NTG and 12 healthy normal control subjects, matched for age and sex with the study group. The stage of glaucoma was determined according to the Hodapp-Parrish-Anderson classification. Lipids were extracted from RBC membranes and plasma, and fatty acid methyl esters prepared and analyzed by gas chromatography-mass spectrometry(GC-MS).RESULTS: When RBC lipids were analyzed, the levels of EPA, the levels of DHA and the ratio of n3 to n6 were positively associated with the Humphrey Perimetry mean Deviation(MD) score(r =0.617, P <0.001; r =0.727, P <0.001 and r =0.720, P <0.001, respectively), while the level of AA was negatively associated with the MD score(r =-0.427, P =0.001). When plasma lipids were analyzed,there was a significant positive relationship between the levels of EPA and the MD score(r =0.648, P <0.001), and the levels of AA were inversely correlated with the MD score(r =-0.638, P <0.001). CONCLUSION: The levels of n3 and n6 polyunsaturated fatty acids in RBC membrane and plasma lipids were associated with severity of NTG.

  14. Effect of three fatty acids from the leaf extract of Tiliacora triandra on P-glycoprotein function in multidrug-resistant A549RT-eto cell line

    Directory of Open Access Journals (Sweden)

    Chutima Kaewpiboon

    2014-01-01

    Full Text Available Background: Cancer cells have the ability to develop resistance to chemotherapy drugs, which then leads to a reduced effectiveness and success of the treatment. Multidrug resistance (MDR involves the resistance in the same cell/tissue to a diverse range of drugs of different structures. One of the characteristics of MDR is an overexpression of P-glycoprotein (P-gp, which causes the efflux of the accumulated drug out of the cell. The MDR human non-small cell lung carcinoma cell line with a high P-gp expression level (A549RT-eto was used to investigate the bioactive compounds capable of reversing the etoposide resistance in this cell line. Materials and Methods: The leaves of Tiliacora triandra were sequentially extracted with hexane, dichloromethane, methanol and water. Only the hexane extract reduced the etoposide resistance of the A549RT-eto cell line, and was further fractionated by column chromatography using the TLC-pattern and the restoration of etoposide sensitivity as the selection criteria. Results: The obtained active fraction (F22 was found by nuclear magnetic resonance and gas chromatography-mass spectroscopy analyses to be comprised of a 49.5:19.6:30.9 (w/w/w mixture of hexadecanoic: octadecanoic acid: (Z-6-octadecenoic acids. This stoichiometric mixture was recreated using pure fatty acids (MSFA and gave a similar sensitization to etoposide and enhanced the relative rate of rhodamine-123 accumulation to a similar extent as F22, supporting the action via reducing P-gp activity. In contrast, the fatty acids alone did not show this effect. Conclusion: This is the first report of the biological activity from the leaves of T. triandra as a potential source of a novel chemosensitizer.

  15. Small changes in environmental parameters lead to alterations in antibiotic resistance, cell morphology and membrane fatty acid composition in Staphylococcus lugdunensis.

    Directory of Open Access Journals (Sweden)

    Marcus J Crompton

    Full Text Available Staphylococcus lugdunensis has emerged as a major cause of community-acquired and nosocomial infections. This bacterium can rapidly adapt to changing environmental conditions to survive and capitalize on opportunities to colonize and infect through wound surfaces. It was proposed that S. lugdunensis would have underlying alterations in metabolic homeostasis to provide the necessary levels of adaptive protection. The aims of this project were to examine the impacts of subtle variations in environmental conditions on growth characteristics, cell size and membrane fatty acid composition in S. lugdunensis. Liquid broth cultures of S. lugdunensis were grown under varying combinations of pH (6-8, temperature (35-39°C and osmotic pressure (0-5% sodium chloride w/w to reflect potential ranges of conditions encountered during transition from skin surfaces to invasion of wound sites. The cells were harvested at the mid-exponential phase of growth and assessed for antibiotic minimal inhibitory concentration (MIC, generation time, formation of small colony variants, cell size (by scanning electron microscopy and membrane fatty acid composition. Stress regimes with elevated NaCl concentrations resulted in significantly higher antibiotic resistance (MIC and three of the combinations with 5% NaCl had increased generation times (P<0.05. It was found that all ten experimental growth regimes, including the control and centroid cultures, yielded significantly different profiles of plasma membrane fatty acid composition (P<0.0001. Alterations in cell size (P<0.01 were also observed under the range of conditions with the most substantial reduction occurring when cells were grown at 39°C, pH 8 (514±52 nm, mean ± Standard Deviation compared with cells grown under control conditions at 37°C with pH 7 (702±76 nm, P<0.01. It was concluded that S. lugdunensis responded to slight changes in environmental conditions by altering plasma membrane fatty acid composition

  16. Omega-3 fatty acids and cognitive function in women

    OpenAIRE

    Robinson, Jennifer G.; Ijioma, Nkechinyere; Harris, William

    2010-01-01

    Omega-3 fatty acids (FAs) could play an important role in maintaining cognitive function in aging individuals. The omega-3 FA docosahexaenoic acid is a major constituent of neuronal membranes and, along with the other long-chain omega-3 FAs from fish such as eicosapentaentoic acid, has been shown to have a wide variety of beneficial effects on neuronal functioning, inflammation, oxidation and cell death, as well as on the development of the characteristic pathology of Alzheimer’s disease. Ome...

  17. Production of hydroxylated fatty acids in genetically modified plants

    Energy Technology Data Exchange (ETDEWEB)

    Somerville, Chris (Portola Valley, CA); Broun, Pierre (Burlingame, CA); van de Loo, Frank (Weston, AU); Boddupalli, Sekhar S. (Manchester, MI)

    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.

  18. Molar extinction coefficients of some fatty acids

    Science.gov (United States)

    Sandhu, G. K.; Singh, Kulwant; Lark, B. S.; Gerward, L.

    2002-10-01

    The attenuation of gamma rays in some fatty acids, viz. formic acid (CH 2O 2), acetic acid (C 2H 4O 2), propionic acid (C 3H 6O 2), butyric acid (C 4H 8O 2), n-hexanoic acid (C 6H 12O 2), n-caprylic acid (C 8H 16O 2), lauric acid (C 12H 24O 2), myristic acid (C 14H 28O 2), palmitic acid (C 16H 32O 2), oleic acid (C 18H 34O 2) and stearic acid (C 18H 36O 2), has been measured at the photon energies 81, 356, 511, 662, 1173 and 1332 keV. Experimental values for the molar extinction coefficient, the effective atomic number and the electron density have been derived and compared with theoretical calculations. There is good agreement between experiment and theory.

  19. Fatty acids in recent sediments in the St. Lawrence estuary

    Science.gov (United States)

    Rodier, L.; Khalil, M. F.

    1982-11-01

    Surface sediments along the Rimouski section in the St. Lawrence estuary were sampled at the surface and at 10 cm depth. Fatty acids were extracted and analysed. Saturated and unsaturated fatty acid contents at the two depths vary with the nature of the sediments. The clay sediments rich in organic matter contain more fatty acids than the corresponding sand or gravel. Unsaturated fatty acids were more abundant in the surface sediments. Some iso- and anteiso-odd carbon fatty acids were detected in the sediments; these acids could indicate a microbial activity. Correlation is made with the fatty acid contents of the water column together with the surface microlayer of the estuarine water.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hopperton, Kathryn E., E-mail: kathryn.hopperton@mail.utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Duncan, Robin E., E-mail: robin.duncan@uwaterloo.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Bazinet, Richard P., E-mail: richard.bazinet@utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Archer, Michael C., E-mail: m.archer@utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada)

    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

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

    Science.gov (United States)

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

    2016-04-01

    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

  2. Fatty Acid Compositions of Six Wild Edible Mushroom Species

    Directory of Open Access Journals (Sweden)

    Pelin Günç Ergönül

    2013-01-01

    Full Text Available 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.

  3. NMR-based metabolomics reveals that conjugated double bond content and lipid storage efficiency in HepG2 cells are affected by fatty acid cis/trans configuration and chain length

    DEFF Research Database (Denmark)

    Najbjerg, Heidi; Young, Jette F; Bertram, Hanne Christine S.

    2011-01-01

    from conjugated double bonds (5.65, 5.94, and 6.28 ppm) in cells exposed to vaccenic acid, revealing that vaccenic acid upon uptake by the HepG2 cells is converted into a conjugated fatty acid. Upon exposure of the HepG2 cells to either butyric acid (C4:0), caproic acid (C6:0), lauric acid (C12......In the present study the metabolic response to various fatty acids was investigated in HepG2 cells by using a 1HNMRbased approach. To elucidate the effect of cis/trans configuration, the cells were exposed to either oleic acid (C18:1 cis-9), elaidic acid (C18:1 trans-9), vaccenic acid (C18:1 trans......-11), linoleic acid (C18:2), or palmitic acid (C16:0), and multivariate data analysis revealed a strong effect of fatty acid on the lipophilic metabolite fraction. Inspection of the spectra revealed that the difference between the observed responses could be ascribed to the appearance of resonances...

  4. O2-triggered changes of membrane fatty acid composition have no effect on Arrhenius discontinuities of respiration in sycamore (Acer pseudoplatanus L.) cells.

    Science.gov (United States)

    Bligny, R; Rebeillé, F; Douce, R

    1985-08-01

    Sycamore cells (Acer pseudoplatanus L.) in suspension culture were grown at 25 degrees C in culture medium containing two oxygen concentrations: 250 microM O2 (standard conditions) and 10 microM O2 (O2-limiting conditions). The decrease of O2 concentration in the culture medium did not modify significantly the relative proportion of each phospholipid. In contrast, the molar proportion of fatty acids was dramatically changed in all lipid classes of the cell membranes; the average percentage of oleate increased from 3 to 45% whereas that of linoleate decreased from 49 to 22%. When normal culture conditions were restored (250 microM O2), oleate underwent a rapid desaturation process; the loss of oleic acid was associated with a stoichiometric appearance of linoleic acid at a rate of about 4 nmol of oleate desaturated/h/10(6) cells. Under these conditions, no change in the Arrhenius-type plots of the rate of sycamore cell respiration was observed; the values of the transition temperature and of the Arrhenius activation energy (Ea) associated with the cell respiration as well as with the respiration-associated enzymes remained unchanged. Thus it was concluded that the fact that a strong decrease in the fraction of unsaturated fatty acid residues present in the mitochondria had no effect on electron transport rates and Arrhenius plot discontinuities casts doubt on the significance of such changes in terms of chilling injury. Finally it is suggested that some of the Arrhenius discontinuities observed at the level of membrane enzyme could be the consequence of intrinsic thermotropic changes in protein arrangement independent of lipid fluidity.

  5. Omega-3 Fatty Acids and Skeletal Muscle Health.

    Science.gov (United States)

    Jeromson, Stewart; Gallagher, Iain J; Galloway, Stuart D R; Hamilton, D Lee

    2015-11-19

    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.

  6. [Supplementation with omega fatty acids in various diseases].

    Science.gov (United States)

    Sicińska, Paulina; Pytel, Edyta; Kurowska, Joanna; Koter-Michalak, Maria

    2015-07-24

    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.

  7. Omega-3 Fatty Acids and Skeletal Muscle Health

    Directory of Open Access Journals (Sweden)

    Stewart Jeromson

    2015-11-01

    Full Text Available 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.

  8. Fatty acid induced remodeling within the human liver fatty acid-binding protein.

    Science.gov (United States)

    Sharma, Ashwani; Sharma, Amit

    2011-09-01

    We crystallized human liver fatty acid-binding protein (LFABP) in apo, holo, and intermediate states of palmitic acid engagement. Structural snapshots of fatty acid recognition, entry, and docking within LFABP support a heads-in mechanism for ligand entry. Apo-LFABP undergoes structural remodeling, where the first palmitate ingress creates the atomic environment for placement of the second palmitate. These new mechanistic insights will facilitate development of pharmacological agents against LFABP. PMID:21757748

  9. Fatty Acid Induced Remodeling within the Human Liver Fatty Acid-binding Protein*

    OpenAIRE

    Sharma, Ashwani; Sharma, Amit

    2011-01-01

    We crystallized human liver fatty acid-binding protein (LFABP) in apo, holo, and intermediate states of palmitic acid engagement. Structural snapshots of fatty acid recognition, entry, and docking within LFABP support a heads-in mechanism for ligand entry. Apo-LFABP undergoes structural remodeling, where the first palmitate ingress creates the atomic environment for placement of the second palmitate. These new mechanistic insights will facilitate development of pharmacological agents against ...

  10. Regulation of Inflammation by Short Chain Fatty Acids

    Directory of Open Access Journals (Sweden)

    Renato T. Nachbar

    2011-10-01

    Full Text Available 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.

  11. Microbial electrochemical monitoring of volatile fatty acids during anaerobic digestion

    DEFF Research Database (Denmark)

    Jin, Xiangdan; Angelidaki, Irini; Zhang, Yifeng

    2016-01-01

    Volatile fatty acid (VFA) concentration is known as an important indicator to control and optimize anaerobic digestion (AD) process. In this study, an innovative VFA biosensor was developed based on the principle of a microbial desalination cell. The correlation between current densities and VFA...

  12. Establishing a relationship between prolactin and altered fatty acid β-Oxidation via carnitine palmitoyl transferase 1 in breast cancer cells

    International Nuclear Information System (INIS)

    Mammary carcinomas have been associated with a high-fat diet, and the rate of breast cancer in overweight post-menopausal women is up to 50% higher than in their normal-weight counterparts. Epidemiological studies suggest that prolactin (PRL) plays a role in the progression of breast cancer. The current study examined breast cancer as a metabolic disease in the context of altered fatty acid catabolism by examining the effect of PRL on carnitine palmitoyl transferase 1 (CPT1), an enzyme that shuttles long-chain fatty acids into the mitochondrial matrix for β-oxidation. The effect of PRL on the adenosine 5'-monophosphate-activated protein kinase (AMPK) energy sensing pathway was also investigated. MCF-7 and MDA-MB-231 breast cancer cells and 184B5 normal breast epithelial cells treated with 100 ng/ml of PRL for 24 hr were used as in vitro models. Real-time PCR was employed to quantify changes in mRNA levels and Western blotting was carried out to evaluate changes at the protein level. A non-radioactive CPT1 enzyme activity assay was established and siRNA transfections were performed to transiently knock down specific targets in the AMPK pathway. PRL stimulation increased the expression of CPT1A (liver isoform) at the mRNA and protein levels in both breast cancer cell lines, but not in 184B5 cells. In response to PRL, a 20% increase in CPT1 enzyme activity was observed in MDA-MB-231 cells. PRL treatment resulted in increased phosphorylation of the α catalytic subunit of AMPK at Thr172, as well as phosphorylation of acetyl-CoA carboxylase (ACC) at Ser79. A siRNA against liver kinase B1 (LKB1) reversed these effects in breast cancer cells. PRL partially restored CPT1 activity in breast cancer cells in which CPT1A, LKB1, or AMPKα-1 were knocked down. PRL enhances fatty acid β-oxidation by stimulating CPT1 expression and/or activity in MCF-7 and MDA-MB-231 breast cancer cells. These PRL-mediated effects are partially dependent on the LKB1-AMPK pathway, although

  13. Conjugated linoleic acid isomers and their precursor fatty acids regulate peroxisome proliferator-activated receptor subtypes and major peroxisome proliferator responsive element-bearing target genes in HepG2 cell model*

    OpenAIRE

    Benjamin, Sailas; Flotho, Silke; Börchers, Torsten; Spener, Friedrich

    2013-01-01

    The purpose of this study was to examine the induction profiles (as judged by quantitative reverse transcription polymerase chain reaction (qRT-PCR)) of peroxisome proliferator-activated receptor (PPAR) α, β, γ subtypes and major PPAR-target genes bearing a functional peroxisome proliferator responsive element (PPRE) in HepG2 cell model upon feeding with cis-9,trans-11-octadecadienoic acid (9-CLA) or trans-10,cis-12-octadecadienoic acid (10-CLA) or their precursor fatty acids (FAs). HepG2 cel...

  14. Baker's Yeast Deficient in Storage Lipid Synthesis Uses cis-Vaccenic Acid to Reduce Unsaturated Fatty Acid Toxicity.

    Science.gov (United States)

    Sec, Peter; Garaiova, Martina; Gajdos, Peter; Certik, Milan; Griac, Peter; Hapala, Ivan; Holic, Roman

    2015-07-01

    The role of cis-vaccenic acid (18:1n-7) in the reduction of unsaturated fatty acids toxicity was investigated in baker's yeast Saccharomyces cerevisiae. The quadruple mutant (QM, dga1Δ lro1Δ are1Δ are2Δ) deficient in enzymes responsible for triacylglycerol and steryl ester synthesis has been previously shown to be highly sensitive to exogenous unsaturated fatty acids. We have found that cis-vaccenic acid accumulated during cultivation in the QM cells but not in the corresponding wild type strain. This accumulation was accompanied by a reduction in palmitoleic acid (16:1n-7) content in the QM cells that is consistent with the proposed formation of cis-vaccenic acid by elongation of palmitoleic acid. Fatty acid analysis of individual lipid classes from the QM strain revealed that cis-vaccenic acid was highly enriched in the free fatty acid pool. Furthermore, production of cis-vaccenic acid was arrested if the mechanism of fatty acids release to the medium was activated. We also showed that exogenous cis-vaccenic acid did not affect viability of the QM strain at concentrations toxic for palmitoleic or oleic acids. Moreover, addition of cis-vaccenic acid to the growth medium provided partial protection against the lipotoxic effects of exogenous oleic acid. Transformation of palmitoleic acid to cis-vaccenic acid is thus a rescue mechanism enabling S. cerevisiae cells to survive in the absence of triacylglycerol synthesis as the major mechanism for unsaturated fatty acid detoxification.

  15. Omega-3 Fatty Acids Modulate Weibel-Palade Body Degranulation and Actin Cytoskeleton Rearrangement in PMA-Stimulated Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Corinna S. Bürgin-Maunder

    2013-11-01

    Full Text Available Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF in cytoplasmic Weibel-Palade bodies (WPBs. We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical vein endothelial cells (HUVECs. HUVECs were incubated with or without 75 or 120 µM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37 °C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA, and this was assessed by immunocytochemical staining for vWF. Actin reorganization was determined using phalloidin-TRITC staining. We found that PMA stimulated WPB degranulation, and that this was significantly reduced by prior incubation of cells with LC n-3 PUFAs. In these cells, WPBs had rounded rather than rod-shaped morphology and localized to the perinuclear region, suggesting interference with cytoskeletal remodeling that is necessary for complete WPB degranulation. In line with this, actin rearrangement was altered in cells containing perinuclear WPBs, where cells exhibited a thickened actin rim in the absence of prominent cytoplasmic stress fibers. These findings indicate that LC n-3 PUFAs provide some protection against WBP degranulation, and may contribute to an improved understanding of the anti-thrombotic effects previously attributed to LC n-3 PUFAs.

  16. Essential fatty acids and human brain.

    Science.gov (United States)

    Chang, Chia-Yu; Ke, Der-Shin; Chen, Jen-Yin

    2009-12-01

    The human brain is nearly 60 percent fat. We've learned in recent years that fatty acids are among the most crucial molecules that determine your brain's integrity and ability to perform. Essential fatty acids (EFAs) are required for maintenance of optimal health but they can not synthesized by the body and must be obtained from dietary sources. Clinical observation studies has related imbalance dietary intake of fatty acids to impaired brain performance and diseases. Most of the brain growth is completed by 5-6 years of age. The EFAs, particularly the omega-3 fatty acids, are important for brain development during both the fetal and postnatal period. Dietary decosahexaenoic acid (DHA) is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Beyond their important role in building the brain structure, EFAs, as messengers, are involved in the synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. The goal of this review is to give a new understanding of how EFAs determine our brain's integrity and performance, and to recall the neuropsychiatric disorders that may be influenced by them. As we further unlock the mystery of how fatty acids affect the brain and better understand the brain's critical dependence on specific EFAs, correct intake of the appropriate diet or supplements becomes one of the tasks we undertake in pursuit of optimal wellness.

  17. Copper toxicity towards Saccharomyces cerevisiae: dependence on plasma membrane fatty acid composition.

    Science.gov (United States)

    Avery, S V; Howlett, N G; Radice, S

    1996-01-01

    One major mechanism of copper toxicity towards microorganisms is disruption of plasma membrane integrity. In this study, the influence of plasma membrane fatty acid composition on the susceptibility of Saccharomyces cerevisiae to Cu2+ toxicity was investigated. Microbial fatty acid composition is highly variable, depending on both intrinsic and environmental factors. Manipulation was achieved in this study by growth in fatty acid-supplemented medium. Whereas cells grown under standard conditions contained only saturated and monounsaturated fatty acids, considerable incorporation of the diunsaturated fatty acid linoleate (18:2) (to more than 65% of the total fatty acids) was observed in both whole-cell homogenates and plasma membrane-enriched fractions from cells grown in linoleate-supplemented medium. Linoleate enrichment had no discernible effect on the growth of S. cerevisiae. However, linoleate-enriched cells were markedly more susceptible to copper-induced plasma membrane permeabilization. Thus, after addition of Cu(NO3)2, rates of cellular K+ release (loss of membrane integrity) were at least twofold higher from linoleate-supplemented cells than from unsupplemented cells; this difference increased with reductions in the Cu2+ concentration supplied. Levels of cellular Cu accumulation were also higher in linoleate-supplemented cells. These results were correlated with a very marked dependence of whole-cell Cu2+ toxicity on cellular fatty acid unsaturation. For example, within 10 min of exposure to 5 microM Cu2+, only 3% of linoleate-enriched cells remained viable (capable of colony formation). In contrast, 100% viability was maintained in cells previously grown in the absence of a fatty acid supplement. Cells displaying intermediate levels of linoleate incorporation showed intermediate Cu2+ sensitivity, while cells enriched with the triunsaturated fatty acid linolenate (18:3) were most sensitive to Cu2+. These results demonstrate for the first time that changes

  18. Changes of phosphatidylcholine and fatty acids in germ cells during testicular maturation in three developmental male morphotypes of Macrobrachium rosenbergii revealed by imaging mass spectrometry.

    Science.gov (United States)

    Siangcham, Tanapan; Chansela, Piyachat; Hayasaka, Takahiro; Masaki, Noritaka; Sroyraya, Morakot; Poljaroen, Jaruwan; Suwansa-ard, Saowaros; Engsusophon, Attakorn; Hanna, Peter J; Sobhon, Prasert; Setou, Mitsutoshi

    2015-01-01

    Testis maturation, germ cell development and function of sperm, are related to lipid composition. Phosphatidylcholines (PCs) play a key role in the structure and function of testes. As well, increases of polyunsaturated fatty acids (PUFA) and highly unsaturated fatty acids (HUFA), especially arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are essential for male fertility. This study is the first report to show the composition and distribution of PCs and total fatty acids (FAs) in three groups of seminiferous tubules (STs) classified by cellular associations [i.e., A (STs with mostly early germ cells), B (STs with mostly spermatids), and C (STs with spermatozoa)], in three morphotypes of Macrobrachium rosenbergii, [i.e., small male (SM), orange claw male (OC), and blue claw male (BC)]. Thin layer chromatography exhibited levels of PCs reaching maxima in STs of group B. Imaging mass spectrometry showed remarkably high signals corresponding to PC (16:0/18:1), PC (18:0/18:2), PC (18:2/20:5), and PC (16:0/22:6) in STs of groups A and B. Moreover, most signals were detected in the early developing cells and the intertubular area, but not at the area containing spermatozoa. Finally, gas chromatography-mass spectrometry indicated that the major FAs present in the testes were composed of 14:0, 16:0, 17:0, 18:0, 16:1, 18:1, 18:2, 20:1, 20:2, 20:4, 20:5, and 22:6. The testes of OC contained the greatest amounts of these FAs while the testes of BC contained the least amounts of these FAs, and there was more EPA (20:5) in the testes of SM and OC than those in the BC. The increasing amounts of FAs in the SM and OC indicate that they are important for spermatogenesis and spermiogenesis. This knowledge will be useful in formulating diets containing PUFA and HUFA for prawn broodstocks in order to improve testis development, and lead to increased male fecundity.

  19. Changes of phosphatidylcholine and fatty acids in germ cells during testicular maturation in three developmental male morphotypes of Macrobrachium rosenbergii revealed by imaging mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Tanapan Siangcham

    Full Text Available Testis maturation, germ cell development and function of sperm, are related to lipid composition. Phosphatidylcholines (PCs play a key role in the structure and function of testes. As well, increases of polyunsaturated fatty acids (PUFA and highly unsaturated fatty acids (HUFA, especially arachidonic acid (ARA, eicosapentaenoic acid (EPA, and docosahexaenoic acid (DHA are essential for male fertility. This study is the first report to show the composition and distribution of PCs and total fatty acids (FAs in three groups of seminiferous tubules (STs classified by cellular associations [i.e., A (STs with mostly early germ cells, B (STs with mostly spermatids, and C (STs with spermatozoa], in three morphotypes of Macrobrachium rosenbergii, [i.e., small male (SM, orange claw male (OC, and blue claw male (BC]. Thin layer chromatography exhibited levels of PCs reaching maxima in STs of group B. Imaging mass spectrometry showed remarkably high signals corresponding to PC (16:0/18:1, PC (18:0/18:2, PC (18:2/20:5, and PC (16:0/22:6 in STs of groups A and B. Moreover, most signals were detected in the early developing cells and the intertubular area, but not at the area containing spermatozoa. Finally, gas chromatography-mass spectrometry indicated that the major FAs present in the testes were composed of 14:0, 16:0, 17:0, 18:0, 16:1, 18:1, 18:2, 20:1, 20:2, 20:4, 20:5, and 22:6. The testes of OC contained the greatest amounts of these FAs while the testes of BC contained the least amounts of these FAs, and there was more EPA (20:5 in the testes of SM and OC than those in the BC. The increasing amounts of FAs in the SM and OC indicate that they are important for spermatogenesis and spermiogenesis. This knowledge will be useful in formulating diets containing PUFA and HUFA for prawn broodstocks in order to improve testis development, and lead to increased male fecundity.

  20. Fatty Acid Content of Indonesian Aquatic Microalgae

    Directory of Open Access Journals (Sweden)

    TRI PRARTONO

    2010-12-01

    Full Text Available High utilization of fossil fuel increases the level of carbon dioxide in the atmosphere and results in global warming phenomenon. These things establish the world’s thought to look for the other alternative energy that can reduce the use of fossil fuel even to be replaced by the substitute. Recently, Indonesia has been doing the research of microalgae as a feedstock of an alternative biofuel. Fatty acid content that microalgae have is also high to produce biofuel. The steps used in this research is a 7 days cultivation, harvesting, extraction using hexane, and fatty acid identification using Gas Chromatography of microalgae species. Fatty acid component in some species such as Chlorella sp., Scenedesmus sp., Nannochloropsis sp., and Isochrysis sp. is between 0.21-29.5%; 0.11-25.16%; 0.30-42.32%; 2.06-37.63%, respectively, based on dry weight calculation. The high content of fatty acid in some species of microalgae showed the potential to be the feedstock of producing biofuel in overcoming the limited utilization from petroleum (fossil fuel presently.

  1. Trans Fatty Acids and Cardiovascular Disease

    NARCIS (Netherlands)

    Mozaffarian, D.; Katan, M.B.; Ascherio, A.; Stampfer, M.J.; Willett, W.C.

    2006-01-01

    Trans fats, unsaturated fatty acids with at least one double bond in the trans configuration (Figure 1), are formed during the partial hydrogenation of vegetable oils, a process that converts vegetable oils into semisolid fats for use in margarines, commercial cooking, and manufacturing processes. F

  2. Fatty acid composition of forage herb species

    DEFF Research Database (Denmark)

    Warner, D.; Jensen, Søren Krogh; Cone, J.W.;

    2010-01-01

    The use of alternative forage species in grasslands for intensive livestock production is receiving renewed attention. Data on fatty acid composition of herbs are scarce, so four herbs (Plantago lanceolata, Achillea millefolium, Cichorium intybus, Pastinaca sativa) and one grass species (timothy...

  3. Polyunsaturated fatty acids in emerging psychosis.

    Science.gov (United States)

    Mossaheb, Nilufar; Schloegelhofer, Monika; Schaefer, Miriam R; Fusar-Poli, Paolo; Smesny, Stefan; McGorry, Pat; Berger, Gregor; Amminger, G Paul

    2012-01-01

    The role of polyunsaturated fatty acids and their metabolites for the cause and treatment of psychotic disorders are widely discussed. The efficacy as an augmenting agent in chronic schizophrenia seems to be small or not present, however epidemiological data, as well as some recent controlled studies in emerging psychosis point towards possible preventive effects of long-chain polyunsaturated fatty acids in early and very early stages of psychotic disorders and some potential secondary or tertiary beneficial long-term effects in later, more chronic stages, in particular for metabolic or extra-pyramidal side effects. In this comprehensive review, we describe the physiology and metabolism of polyunsaturated fatty acids, phospholipases, epidemiological evidence and the effect of these fatty acids on the brain and neurodevelopment. Furthermore, we examine the available evidence in indicated prevention in emerging psychosis, monotherapy, add-on therapy and tolerability. The neuroprotective potential of n-3 LC-PUFAs for indicated prevention, i.e. delaying transition to psychosis in high-risk populations needs to be further explored.

  4. Dietary Fatty Acids and Predementia Syndromes

    Directory of Open Access Journals (Sweden)

    Vincenzo Solfrizzi

    2009-01-01

    Full Text Available An increasing body of epidemiological evidence suggests that elevated saturated fatty acids (SFA could have negative effects on age-related cognitive decline (ARCD. Furthermore, a reduction of risk for cognitive decline and mild cognitive impairment (MCI has been found in population samples with elevated fish consumption, and high intake of monounsaturated fatty acids (MUFA and polyunsaturated fatty acids (PUFA, particularly n-3 PUFA. However, recent findings from clinical trials with n-3 PUFA supplementation showed efficacy on depressive symptoms in non–Vapolipoprotein E (APOE ε4 carriers, and on cognitive symptoms only in very mild Alzheimer's disease (AD subgroups, MCI patients, and cognitively unimpaired non-APOE ε4 carriers. These data, together with epidemiological evidence, support the idea that n-3 PUFA may play a role in maintaining adequate cognitive functioning in predementia syndromes, but not when the AD process has already taken over. Therefore, at present, no definitive dietary recommendations on fish and unsaturated fatty acids consumption, or lower intake of saturated fat, in relation to the risk for dementia and cognitive decline are possible.

  5. Fatty acids composition of 10 microalgal species

    OpenAIRE

    Thidarat Noiraksar; Piyawan Srivilas; Jarunan Pratoomyot

    2005-01-01

    Fatty acids composition of 10 species of microalgae was determined at the exponential phase and the stationary phase. The microalgae consist of two species of diatoms, Bacillariophyceae, (Nitzschia cf. ovalis, Thalassiosira sp.) five species of green microalgae, Prasinophyceae (Tetraselmis sp.) and Chlorophyceae, (Dictyosphaerium pulchellum, Stichococcus sp., Chlorella sp., Scenedesmus falcatus) and three species of blue green microalgae, Cyanophyceae (Anacystis sp., Synechococcus sp., Synech...

  6. Alterations in sheep peripheral blood mononuclear cell proliferation and cytokine release by polyunsaturated fatty acid supplementation in the diet under high ambient temperature.

    Science.gov (United States)

    Ciliberti, Maria Giovanna; Albenzio, Marzia; Annicchiarico, Giovanni; Sevi, Agostino; Muscio, Antonio; Caroprese, Mariangela

    2015-02-01

    The aim of this study was to investigate the effects of polyunsaturated fatty acid (PUFA) supplementation from different sources in the diet of dairy sheep under high ambient temperatures on ex vivo lymphocyte proliferation and inflammatory responses. The experiment was carried out during summer: 32 Comisana ewes were divided into 4 groups of 8. The FS group was supplemented with whole flaxseed, the AG group was supplemented with Ascophyllum nodosum, the FS+AG group was supplemented with a combination of flaxseed and A. nodosum. The fourth group (CON group) was a control and received a diet containing no supplement. The average maximum temperature was around 33°C during wk 2 and 3, whereas the mean temperature never decreased below 26°C. Following 15 d of treatment with respective diets, peripheral blood mononuclear cells (PBMC) from sheep who received a diet supplemented with A. nodosum had impaired cell proliferation responses and IL-6 production after mitogen stimulation compared with PBMC from FS+AG sheep. In addition, PBMC from AG sheep displayed impaired cell proliferation compared with cells from the CON group. The FS+AG cells produced lower levels of IL-10 than CON cells, and higher IL-6 than AG and CON cells. Results demonstrated that the supplementation with PUFA from different sources in a sheep's diet can influence their immunological responses under high ambient temperatures depending on the composition of fatty acid supplementation. In particular, synergistic effects of different PUFA from flaxseed and A. nodosum, simultaneously administrated in the sheep diet, were observed on activation of inflammation response. PMID:25497814

  7. Fatty acid content of honeycombs depending on the level of technogenic loading on the environment

    Directory of Open Access Journals (Sweden)

    V. Y. Vishchur

    2016-02-01

    Full Text Available The content of heavy metals, non-etherified and anionic forms of fatty acids, and also fatty acids of common lipids in honeycomb cells, obtained from hives placed in areas with high, medium and low levels of technogenic loading is investigated. The hives were located at the educational apiary of Lviv National University of Veterinary Medicine and Biotechnologies named after S.Z. Gzhytskyj (area with very heavy traffic and industrial activity and in private beekeeping farms in the town Vynnyky and the village Chyzhyky, Pustomyty district, Lviv region (areas with lower intensity of traffic and industrial activity. Our research has shown that the newly-built honeycomb cells obtained from hives placed in the territory with medium and low levels of technogenic loading contain a lower quantity of such heavy metals as iron, zinc, cuprum, chromium, nickel, lead and cadmium. The total amount of non-etherified fatty acids with even and odd number of carbon atoms in the chain, monounsaturated fatty acids of n-7 and n-9 families and polyunsaturated fatty acids of n-3 and n-6 families was higher in these honeycombs. However, the total concentration of anionic forms of fatty acids with even and odd number of carbon atoms in the chain, monounsaturated fatty acids of n-7 and n-9 families and polyunsaturated fatty acids of n-3 and n-6 families was lower in these honeycombs. Due to the above-mentioned monounsaturated and polyunsaturated fatty acids the amount of fatty acids of common lipids rises. It leads to increase in the antibacterial and antifungal properties of honeycomb cells and reduction of fragility of their walls. The greatest changes in concentration of heavy metals, non-etherified and anionic form of fatty acids, and also fatty acids of common lipids occur in the newly built honeycomb cells in the territory with low technogenic loading on the environment.

  8. Methods of refining and producing isomerized fatty acid esters and fatty acids from natural oil feedstocks

    Science.gov (United States)

    Snead, Thomas E.; Cohen, Steven A.; Gildon, Demond L.; Beltran, Leslie V.; Kunz, Linda A.; Pals, Tessa M.; Quinn, Jordan R; Behrends, Jr., Raymond T.; Bernhardt, Randal J.

    2016-07-05

    Methods are provided for refining natural oil feedstocks and producing isomerized esters and acids. The methods comprise providing a C4-C18 unsaturated fatty ester or acid, and isomerizing the fatty acid ester or acid in the presence of heat or an isomerization catalyst to form an isomerized fatty ester or acid. In some embodiments, the methods comprise forming a dibasic ester or dibasic acid prior to the isomerizing step. In certain embodiments, the methods further comprise hydrolyzing the dibasic ester to form a dibasic acid. In certain embodiments, the olefin is formed by reacting the feedstock in the presence of a metathesis catalyst under conditions sufficient to form a metathesized product comprising olefins and esters, separating the olefins from the esters in the metathesized product, and transesterifying the esters in the presence of an alcohol to form a transesterified product having unsaturated esters.

  9. Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    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

  10. N-3 polyunsaturated fatty acids modulate B cell activity in pre-clinical models: Implications for the immune response to infections.

    Science.gov (United States)

    Whelan, Jarrett; Gowdy, Kymberly M; Shaikh, Saame Raza

    2016-08-15

    B cell antigen presentation, cytokine production, and antibody production are targets of pharmacological intervention in inflammatory and infectious diseases. Here we review recent pre-clinical evidence demonstrating that pharmacologically relevant levels of n-3 polyunsaturated fatty acids (PUFA) derived from marine fish oils influence key aspects of B cell function through multiple mechanisms. N-3 PUFAs modestly diminish B cell mediated stimulation of classically defined naïve CD4(+) Th1 cells through the major histocompatibility complex (MHC) class II pathway. This is consistent with existing data showing that n-3 PUFAs suppress the activation of Th1/Th17 cells through direct effects on helper T cells and indirect effects on antigen presenting cells. Mechanistically, n-3 PUFAs lower antigen presentation and T cell signaling by disrupting the formation of lipid microdomains within the immunological synapse. We then review data to show that n-3 PUFAs boost B cell activation and antibody production in the absence and presence of antigen stimulation. This has potential benefits for several clinical populations such as the aged and obese that have poor humoral immunity. The mode of action by which n-3 PUFA boost B cell activation and antibody production remains unclear, but may involve Th2 cytokines, enhanced production of specialized proresolving lipid mediators, and targeting of protein lateral organization in lipid microdomains. Finally, we highlight evidence to show that different n-3 PUFAs are not biologically equivalent, which has implications for the development of future interventions to target B cell activity.

  11. Role of T-Cell Polarization and Inflammation and Their Modulation by n-3 Fatty Acids in Gestational Diabetes and Macrosomia

    Directory of Open Access Journals (Sweden)

    A. Hichami

    2016-01-01

    Full Text Available Th (T helper cells are differentiated into either Th1 or Th2 phenotype. It is generally considered that Th1 phenotype is proinflammatory, whereas Th2 phenotype exerts anti-inflammatory or protective effects. Gestational diabetes mellitus (GDM has been associated with a decreased Th1 phenotype, whereas macrosomia is marked with high expression of Th1 cytokines. Besides, these two pathological situations are marked with high concentrations of inflammatory mediators like tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6, known to play a pivotal role in insulin resistance. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs may exert a beneficial effect by shifting Th1/Th2 balance to a Th2 phenotype and increasing insulin sensitivity. In this paper, we shed light on the role of T-cell malfunction that leads to an inflammatory and pathophysiological state, related to insulin resistance in GDM and macrosomia. We will also discuss the nutritional management of these pathologies by dietary n-3 polyunsaturated fatty acids (PUFAs.

  12. Role of T-Cell Polarization and Inflammation and Their Modulation by n-3 Fatty Acids in Gestational Diabetes and Macrosomia.

    Science.gov (United States)

    Hichami, A; Grissa, O; Mrizak, I; Benammar, C; Khan, N A

    2016-01-01

    Th (T helper) cells are differentiated into either Th1 or Th2 phenotype. It is generally considered that Th1 phenotype is proinflammatory, whereas Th2 phenotype exerts anti-inflammatory or protective effects. Gestational diabetes mellitus (GDM) has been associated with a decreased Th1 phenotype, whereas macrosomia is marked with high expression of Th1 cytokines. Besides, these two pathological situations are marked with high concentrations of inflammatory mediators like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), known to play a pivotal role in insulin resistance. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) may exert a beneficial effect by shifting Th1/Th2 balance to a Th2 phenotype and increasing insulin sensitivity. In this paper, we shed light on the role of T-cell malfunction that leads to an inflammatory and pathophysiological state, related to insulin resistance in GDM and macrosomia. We will also discuss the nutritional management of these pathologies by dietary n-3 polyunsaturated fatty acids (PUFAs). PMID:27313878

  13. Determination of Fatty Acid in Asparagus by Gas Chromatography

    Directory of Open Access Journals (Sweden)

    Zehra HAJRULAI-MUSLIU

    2016-05-01

    Full Text Available Asparagus contain a lot of macronutrients and micronutrients including folate, dietary fibre (soluble and insoluble and phenolic compounds. Also asparagus is a good source of unsaturated linoleic and linolenic fatty acids which are precursors for Eicosapentanoic acid (EPA and Docosahexanoic acid (DHA. Unsaturated fatty acids have important biological effects and they have important role in human health. The objective of this study was to analyze fatty acid composition of asparagus as a potential source of linoleic and linolenic acid - a precursor for EPA and DHA. For this reason we analyzed fifty seven samples of asparagus collected from the local market. We used AOAC 996.06 method and analyses were performed with gas chromatograph with flame-ionization detector (GC-FID. The highest concentration of fatty acid in the asparagus was linoleic acid (C18:2n6 which content in asparagus is 25.620±1.0%. Also, asparagus is good source of -linolenic fatty acid (C18:3n3 and content of this fatty acid in asparagus is 8.840±0.3%. The omega-6 to omega-3 (n6/n3 ratio in asparagus was 3.19. Polyunsaturated fatty acids (PUFAs were higher than monounsaturated fatty acids (MUFAs, and from saturated fatty acids, palmitic acid was most frequent with 24.324±1.0%. From our study we can conclude that asparagus is very good source of unsaturated fatty acids, especially linoleic and linolenic fatty acids.

  14. Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

    DEFF Research Database (Denmark)

    Wensaas, Andreas J; Rustan, Arild C; Just, Marlene;

    2008-01-01

    Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence...... these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA....... EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased...

  15. Supercritical CO₂ extraction of oil, fatty acids and flavonolignans from milk thistle seeds: Evaluation of their antioxidant and cytotoxic activities in Caco-2 cells.

    Science.gov (United States)

    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

  16. Fatty acid composition of human milk and infant formulas

    Directory of Open Access Journals (Sweden)

    Ivančica Delaš

    2005-04-01

    Full Text Available The appropriate fatty acid composition of membrane lipids is necessary for structure and function of the developing nervous system. Rapid synthesis of brain tissue occurs during the last trimester of pregnancy and the early postnatal weeks. This synthesis of brain structure involves the formation of complex lipids, many of which contain significant quantities of essential fatty acids and their higher homologs. This study was undertaken to elucidate how fatty acid compositions of available diets for infants meet the requirements for essential fatty acids. Samples of infant formulas, present on the market, as well as milk samples obtained from breast feeding mothers, were extracted by chloroform : methanol mixtures in order to obtain total lipids. Fatty acid methyl esters were prepared and fatty acid composition was revealed by gas chromatography. Special interest was directed to the content of long chain polyunsaturated fatty acids. The results have shown that infant formulas, designed to substitute mothers’ breast milk, contain medium chain fatty acids (C 10:0, C 12:0, along with the other saturated fatty acids, in the amounts acceptable for infants’ energy consumption. Although linoleic acid (C18:2, n-6 was present at the level expected to cover needs for essential fatty acids, most of the tested products did not contain sufficient amounts of long chain polyunsaturated fatty acids, despite the fact that these fatty acids are necessary for undisturbed brain development, ignoring the strong recommendations that they should be used as a supplement in infants’ food.

  17. Tailored fatty acid synthesis via dynamic control of fatty acid elongation

    OpenAIRE

    Torella, Joseph P.; Ford, Tyler J.; Kim, Scott N.; Chen, Amanda M.; Way, Jeffrey C; Silver, Pamela A

    2013-01-01

    Medium-chain fatty acids (MCFAs, 4–12 carbons) are valuable as precursors to industrial chemicals and biofuels, but are not canonical products of microbial fatty acid synthesis. We engineered microbial production of the full range of even- and odd-chain–length MCFAs and found that MCFA production is limited by rapid, irreversible elongation of their acyl-ACP precursors. To address this limitation, we programmed an essential ketoacyl synthase to degrade in response to a chemical inducer, there...

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

    OpenAIRE

    Beld, Joris; Lee, D. John; Burkart, Michael D.

    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. ...

  19. Glucose supplementation-induced changes in the Auxenochlorella protothecoides fatty acid composition suitable for biodiesel production.

    Science.gov (United States)

    Krzemińska, Izabela; Oleszek, Marta

    2016-10-01

    This study evaluates the effect of different concentrations of glucose supplementation on growth, lipid accumulation, and the fatty acid profile in the Auxenochlorella protothecoides. Addition of glucose promoted the growth rate and decreased the chlorophyll content. Compared with photoautotrophic cells, an increase in the lipid content was observed in mixotrophic cells. The glucose addition induced changes in the fatty acid profile. Higher content of saturated fatty acids was found in the case of cells growing in the glucose-free medium. Oleic acid was the predominant component in mixotrophic cells supplemented with 5gL(-1) glucose, while linoleic acids dominated in cultures supplemented with both 1 and 3gL(-1) glucose. The use of glucose was associated with decreased levels of linolenic acid and PUFA. The changes in the fatty acid profile in mixotrophic cells are favourable for biodiesel production. PMID:27485282

  20. Naturally occurring fatty acids: source, chemistry and uses

    Science.gov (United States)

    Natural occurring fatty acids are a large and complex class of compounds found in plants and animals. Fatty acids are abundant and of interest because of their renewability, biodegradability, biocompatibility, low cost, and fascinating chemistry. Of the many fatty acids, only 20-25 of them are widel...

  1. Adipose tissue fatty acid patterns and changes in anthropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre;

    2011-01-01

    Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns in adipose tissue...

  2. A Review of the Metabolic Origins of Milk Fatty Acids

    Directory of Open Access Journals (Sweden)

    Anamaria COZMA

    2013-08-01

    Full Text Available Milk fat and its fatty acid profile are important determinants of the technological, sensorial, and nutritional properties of milk and dairy products. The two major processes contributing to the presence of fatty acids in ruminant milk are the mammary lipogenesis and the lipid metabolism in the rumen. Among fatty acids, 4:0 to 12:0, almost all 14:0 and about a half of 16:0 in milk fat derive from de novo synthesis within the mammary gland. De novo synthesis utilizes as precursors acetate and butyrate produced through carbohydrates ruminal fermentation and involves acetyl-CoA carboxylase and fatty acid synthetase as key enzymes. The rest of 16:0 and all of the long-chain fatty acids derive from mammary uptake of circulating lipoproteins and nonesterified fatty acids that originate from digestive absorption of lipids and body fat mobilization. Further, long-chain fatty acids as well as medium-chain fatty acids entering the mammary gland can be desaturated via Δ-9 desaturase, an enzyme that acts by adding a cis-9-double bond on the fatty acid chain. Moreover, ruminal biohydrogenation of dietary unsaturated fatty acids results in the formation of numerous fatty acids available for incorporation into milk fat. Ruminal biohydrogenation is performed by rumen microbial population as a means of protection against the toxic effects of polyunsaturated fatty acids. Within the rumen microorganisms, bacteria are principally responsible for ruminal biohydrogenation when compared to protozoa and anaerobic fungi.

  3. G-protein-coupled receptors for free fatty acids

    DEFF Research Database (Denmark)

    Milligan, Graeme; Ulven, Trond; Murdoch, Hannah;

    2014-01-01

    of these receptors. However, ongoing clinical trials of agonists of free fatty acid receptor 1 suggest that this receptor and other receptors for free fatty acids may provide a successful strategy for controlling hyperglycaemia and providing novel approaches to treat diabetes. Receptors responsive to free fatty acid...

  4. Interactions between zinc, essential fatty acids and prostaglandins: relevance to acrodermatitis enteropathica, total parenteral nutrition, the glucagonoma syndrome, diabetes, anorexia nervosa and sickle cell anaemia.

    Science.gov (United States)

    Horrobin, D F; Cunnane, S C

    1980-03-01

    Many of the features of zinc deficiency and of essential fatty acid (EFA) deficiency are similar in both animals and humans. The two agents interact in various ways. EFAs are important in zinc absorption, probably after conversion to prostaglandins (PGs). Zinc seems necessary for at least two stages in EFA metabolism, the conversion of linoleic acid to gamma-linolenic acid, and the mobilisation of dihomogammalinolenic acid (DGLA) for the synthesis of 1 series PGs. Zinc may also be important in the conversion of DGLA to arachidonic acid and in arachidonic acid mobilisation for 2 series PG formation. These interactions shed considerable light on a number of clinical syndromes, including acrodermatitis enteropathica, total parenteral nutrition, diabetes mellitus, the glucagonoma syndrome and sickle cell anaemia. There is substantial evidence to suggest that anorexia nervosa is due to a combined deficiency of zinc and EFAs. Understanding of the roles of zinc and EFAs in these various clinical situations is likely to lead to improved therapy. PMID:6253772

  5. Marine lipids and the bioavailability of omega-3 fatty acids

    DEFF Research Database (Denmark)

    Mu, Huiling; Müllertz, Anette

    2015-01-01

    Marine lipids are enriched with omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids are important membrane lipids and have many recognized health benefits, the bioavailability of these fatty acids can therefore be important for achieving...... of omega-3 fatty acids has been reported to be affected by several factors; among the important factors were the digestion and absorption processes of omega-3 containing lipids in the gastrointestinal tract. Both lipid structures and food structures can affect the bioavailability of omega-3 fatty acids....... Human studies have shown that the relative bioavailability of omega-3 fatty acids from fish oil (triglyceride formulation) was similar to that from fish, whereas lower relative bioavailability was observed from fatty acid ethyl ester (FAEE) formulation in comparison with other lipid formulations...

  6. Prevention of Sports Injuries by Marine Omega-3 Fatty Acids.

    Science.gov (United States)

    Bryhn, Morten

    2015-01-01

    Sport injuries are common and costly for the professional athlete, the "weekend warrior," and the community. Acute injuries are treated according to current guidelines with the aim of bringing the athlete back into the arena. These guidelines have not taken into account new scientific results of the inflammatory process following a trauma. The 4 hallmarks of inflammation, namely, pain, swelling, redness, and heat, are results of an adequate inflammatory response with the aim of bringing the affected tissue back to restitution (Latin: restitutio ad integrum). Cooling of the affected limb and anti-inflammatory drugs are widely used but may deter healing. The healing process is governed by fatty acids of the omega-3 and omega-6 series. In order to facilitate healing, these fatty acids have to be present in significant amounts in the affected tissues before the trauma occurs. This is particularly relevant for marine omega-3 fatty acids, which are often running low due to insignificant intake of seafood, common in individuals practicing sports. High-energy sports often lead to head and brain trauma. Continuous head traumata may even result in later mental defects. Saturation of brain cells with omega-3 fatty acids, in particular docosahexaenoic acid (DHA), may facilitate healing after brain trauma, thereby counteracting negative long-term results. The present understanding of a normal inflammatory process leading to restitution will be discussed along with data from recent scientific trials.

  7. The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T

    International Nuclear Information System (INIS)

    The short fatty acid, butyrate, which is produced by intestinal anaerobic bacteria in the colon, has inhibitory activity on histone deacetylases (HDACs). Treatment of the human colon cancer cell line, LS174T, with 1-2 mM sodium butyrate stimulated MUC2 mucin production, as determined by histological PAS staining of carbohydrate chains of mucin, and confirmed at the protein and mRNA levels by immunoblotting with anti-MUC2 antibody and real-time RT-PCR, respectively. Increases in acetylated histone H3 in the LS174T cells treated with butyrate suggest inhibition of HDACs in these cells. Butyrate-stimulated MUC2 production in the LS174T cells was inhibited by the MEK inhibitor, U0126, implicating the involvement of extracellular signal-regulated kinase (ERK) cascades in this process. Proliferation of the LS174T cells was inhibited by butyrate treatment. Although apoptotic nuclear DNA fragmentation could not be detected, cell-cycle arrest at the G0/G1 phase in the butyrate-treated cells was demonstrated by flow cytometry. Thus butyrate, an HDAC inhibitor, inhibits proliferation of LS174T cells but stimulates MUC2 production in individual cells

  8. Fatty acid solubilizer from the oral disk of the blowfly.

    Directory of Open Access Journals (Sweden)

    Yuko Ishida

    Full Text Available BACKGROUND: Blowflies are economic pests of the wool industry and potential vectors for epidemics. The establishment of a pesticide-free, environmentally friendly blowfly control strategy is necessary. Blowflies must feed on meat in order to initiate the cascade of events that are involved in reproduction including juvenile hormone synthesis, vitellogenesis, and mating. During feeding blowflies regurgitate salivary lipase, which may play a role in releasing fatty acids from triglycerides that are found in food. However, long-chain fatty acids show low solubility in aqueous solutions. In order to solubilize and ingest the released hydrophobic fatty acids, the blowflies must use a solubilizer. METHODOLOGY: We applied native PAGE, Edman degradation, cDNA cloning, and RT-PCR to characterize a protein that accumulated in the oral disk of the black blowfly, Phormia regina. In situ hybridization was carried out to localize the expression at the cellular level. A fluorescence competitive binding assay was used to identify potential ligands of this protein. CONCLUSION: A protein newly identified from P. regina (PregOBP56a belonged to the classic odorant-binding protein (OBP family. This gene was expressed in a cluster of cells that was localized between pseudotracheae on the oral disk, which are not accessory cells of the taste peg chemosensory sensilla that normally synthesize OBPs. At pH 7 and pH 6, PregOBP56a bound palmitic, stearic, oleic, and linoleic acids, that are mainly found in chicken meat. The binding affinity of PregOBP56a decreased at pH 5. We propose that PregOBP56a is a protein that solubilizes fatty acids during feeding and subsequently helps to deliver the fatty acids to the midgut where it may help in the process of reproduction. As such, PregOBP56a is a potential molecular target for controlling the blowfly.

  9. Glucose amplifies fatty acid-induced endoplasmic reticulum stress in pancreatic beta-cells via activation of mTORC1.

    Directory of Open Access Journals (Sweden)

    Etti Bachar

    Full Text Available BACKGROUND: Palmitate is a potent inducer of endoplasmic reticulum (ER stress in beta-cells. In type 2 diabetes, glucose amplifies fatty-acid toxicity for pancreatic beta-cells, leading to beta-cell dysfunction and death. Why glucose exacerbates beta-cell lipotoxicity is largely unknown. Glucose stimulates mTORC1, an important nutrient sensor involved in the regulation of cellular stress. Our study tested the hypothesis that glucose augments lipotoxicity by stimulating mTORC1 leading to increased beta-cell ER stress. PRINCIPAL FINDINGS: We found that glucose amplifies palmitate-induced ER stress by increasing IRE1alpha protein levels and activating the JNK pathway, leading to increased beta-cell apoptosis. Moreover, glucose increased mTORC1 activity and its inhibition by rapamycin decreased beta-cell apoptosis under conditions of glucolipotoxicity. Inhibition of mTORC1 by rapamycin did not affect proinsulin and total protein synthesis in beta-cells incubated at high glucose with palmitate. However, it decreased IRE1alpha expression and signaling and inhibited JNK pathway activation. In TSC2-deficient mouse embryonic fibroblasts, in which mTORC1 is constitutively active, mTORC1 regulated the stimulation of JNK by ER stressors, but not in response to anisomycin, which activates JNK independent of ER stress. Finally, we found that JNK inhibition decreased beta-cell apoptosis under conditions of glucolipotoxicity. CONCLUSIONS/SIGNIFICANCE: Collectively, our findings suggest that mTORC1 mediates glucose amplification of lipotoxicity, acting through activation of ER stress and JNK. Thus, mTORC1 is an important transducer of ER stress in beta-cell glucolipotoxicity. Moreover, in stressed beta-cells mTORC1 inhibition decreases IRE1alpha protein expression and JNK activity without affecting ER protein load, suggesting that mTORC1 regulates the beta-cell stress response to glucose and fatty acids by modulating the synthesis and activity of specific

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

    Directory of Open Access Journals (Sweden)

    Megan M. Robblee

    2016-03-01

    Full Text Available 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.

  11. Epoxidation of Palm Kernel Oil Fatty Acids

    OpenAIRE

    Michelle Ni Fong Fong; Jumat Salimon

    2013-01-01

    Epoxidation of palm kernel oil fatty acids using formic acid and hydrogen peroxide was carried out effectively using a homogeneous reaction. It was found that epoxidation reaction occurred optimally at a temperature of 40oC and reaction time of 120 minits. The oxirane conversion was the highest at 1.46mol and 0.85mol of hydrogen peroxide and formic acid respectively. It was found that a maximum of 99% relative conversion of ethylenic oxirane was obtained, similar to the conversion of iodine v...

  12. Modulation of human erythrocyte shape and fatty acids by diet.

    Science.gov (United States)

    Parsons, H G; Hill, R; Pencharz, P; Kuksis, A

    1986-08-21

    A semi-synthetic diet (Vivonex) was administered via nasogastric tube to three cystic fibrosis patients with pancreatic exocrine deficiency for 14 days to gain weight. Dietary essential fatty acids were provided as safflower oil, which constituted 1.3% of total calories. Plasma and red blood cells were analyzed for the content and composition of lipids at the start of the diet and at days 7 and 14 of the dietary period, and the results were correlated with the morphology of the cells. Feeding Vivonex to the patients led to an essential fatty acid deficiency, which was manifested in a 50% decrease in the linoleic acid content of the phosphatidylcholine of plasma and red blood cells at days 7 and 14 and in a 20% decrease in the linoleic acid content of red cell phosphatidylethanolamine at day 14. There was no significant alteration in the levels or composition of the other phospholipid classes and in the free cholesterol/phospholipid ratio. The decrease in the linoleic acid content of the erythrocytes was accompanied by a dramatic increase in the proportion of cells as echinocytes. We conclude that restricted linoleic acid availability in cystic fibrosis patients causes a change in red blood cell shape either directly by decreasing the linoleoylphosphatidylcholine content of the membrane or indirectly by affecting enzyme activity. PMID:3741859

  13. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    Science.gov (United States)

    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 %.

  14. Chemical composition and fatty acid contents in farmed freshwater prawns

    Directory of Open Access Journals (Sweden)

    Carolina de Gasperi Portella

    2013-08-01

    Full Text Available The objective of this work was to evaluate the chemical composition and fatty acid contents of Amazonian and giant river prawns. After four-month farming, with the same diet for both species, palmitic and stearic acids were the main saturated fatty acids. Oleic acid was the main monounsatured fatty acid, and the eicosapentaenoic and docosahexaenoic acids were the most abundant polyunsaturated acids. Amazonian prawn has higher levels of protein and polyunsaturated fatty acids than those of the giant river prawn, which shows its potential for aquaculture.

  15. Saturated free fatty acids and apoptosis in microvascular mesangial cells: palmitate activates pro-apoptotic signaling involving caspase 9 and mitochondrial release of endonuclease G

    Directory of Open Access Journals (Sweden)

    Simonson Michael S

    2005-01-01

    Full Text Available Abstract Background In type 2 diabetes, free fatty acids (FFA accumulate in microvascular cells, but the phenotypic consequences of FFA accumulation in the microvasculature are incompletely understood. Here we investigated whether saturated FFA induce apoptosis in human microvascular mesangial cells and analyzed the signaling pathways involved. Methods Saturated and unsaturated FFA-albumin complexes were added to cultured human mesangial cells, after which the number of apoptotic cells were quantified and the signal transduction pathways involved were delineated. Results The saturated FFA palmitate and stearate were apoptotic unlike equivalent concentrations of the unsaturated FFA oleate and linoleate. Palmitate-induced apoptosis was potentiated by etomoxir, an inhibitor of mitochondrial β-oxidation, but was prevented by an activator of AMP-kinase, which increases fatty acid β-oxidation. Palmitate stimulated an intrinsic pathway of pro-apoptotic signaling as evidenced by increased mitochondrial release of cytochrome-c and activation of caspase 9. A caspase 9-selective inhibitor blocked caspase 3 activation but incompletely blocked apoptosis in response to palmitate, suggesting an additional caspase 9-independent pathway. Palmitate stimulated mitochondrial release of endonuclease G by a caspase 9-independent mechanism, thereby implicating endonuclease G in caspase 9-indpendent regulation of apoptosis by saturated FFA. We also observed that the unsaturated FFA oleate and linoleate prevented palmitate-induced mitochondrial release of both cytochrome-c and endonuclease G, which resulted in complete protection from palmitate-induced apoptosis. Conclusions Taken together, these results demonstrate that palmitate stimulates apoptosis by evoking an intrinsic pathway of proapoptotic signaling and identify mitochondrial release of endonuclease G as a key step in proapoptotic signaling by saturated FFA and in the anti-apoptotic actions of unsaturated FFA.

  16. Regulation of Insulin Secretion and Expression of SUR1 Gene by Chronic Exposure to Free Fatty Acids in Rat Pancreatic β Cells

    Institute of Scientific and Technical Information of China (English)

    袁莉; 邓秀玲; 陈璐璐; 周愍

    2004-01-01

    To study the effects of free fatty acids on insulin secretion and expression of SUR1 gene in rat pancreatic B cells in vitro, and to explore the molecular mechanisms in lipotoxicity inducing insulin secretion dysfunction, pancreatic islet cells were isolated and digested from male SD rats.Purified islets were incubated with either 0.25 mmol/L palmitate or 0. 125 mmol/L oleate for 48 h in vitro. Then islets were stimulated with either 5.6 mmol/L or 16.7 mmol/L glucose for 1 h. Insulin release was measured by using radioimmunoassay, and the expression of SUR1 gene mRNA was quantified by reserve transcription-polymerase chain reaction (RT-PCR). The islets exposed to both palmitate and oleate for 48 h showed an increased basal and a decreased glucose-indused insulin release as compared with control islets. Palmitate increased basal insulin secretion by 110 % (P<0.01), decreased glucose stimulated insulin secretion by 43 % (P<0.01) ; while oleate increased basal insulin secretion by 80 % (P<0.01) and decreased glucose stimulated insulin secretion by 32 % (P<0.05). RT-PCR showed that oleate significantly suppressed SUR1 gene expression by 64 % (P<0.01)as compared with the control group, while palmitate group manifested a light decrease of 15 % (P >0.05) of SUR1 gene expression. Our results suggested that chronic exposure to free fatty acids of pancreatic β cells inhibited glucose stimulated insulin secretion. Regulation of SUR1 gene expression may be involved in such effects, which may also be one of the molecular mechanisms in lipotoxocity inducing β cells secretion dysfunction.

  17. Potential probiotic lactic acid bacteria of human origin induce antiproliferation of colon cancer cells via synergic actions in adhesion to cancer cells and short-chain fatty acid bioproduction.

    Science.gov (United States)

    Thirabunyanon, Mongkol; Hongwittayakorn, Penrat

    2013-01-01

    The activities and modes of probiotic action of lactic acid bacteria isolated from infant feces were investigated for alternative application in the prevention and biotherapy of colon cancer. From a total of 81 isolates of Gram-positive rod and cocci bacteria obtained from healthy infants, only 15 isolates had the probiotic criteria which included growth inhibition against eight food-borne pathogens, no blood hemolysis, and tolerance to gastrointestinal tract properties such as pH 2.5 and 0.3 % bile salt. Four probiotic bacteria showed antiproliferation of colon cancer cells with the use of MTT and Trypan blue exclusion assay at the rates of 17-35 %. Through comparison of probiotic 16S rRNA sequences, they were identified as Pediococcus pentosaceus FP3, Lactobacillus salivarius FP25, L. salivarius FP35, and Enterococcus faecium FP51. Finding the mechanism of proliferative inhibition of colon cancer cells in this study indicated synergic induction by probiotic bacteria directly adhered to these cancer cells and triggered the bioproduction of short-chain fatty acids, mainly butyric and propionic acids. This study suggested that the use of these probiotics may be suitable as an alternative bioprophylactic and biotherapeutic strategy for colon cancer. PMID:23239414

  18. [THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    Science.gov (United States)

    Titov, V N; Malyshev, P P; Amelyushkina, V A; Aripovsky, A V; Smirnov, G P; Polevaya, T Yu; Kabo, S I; Kukhartchuk, V V

    2015-10-01

    The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100-endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of ω-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and

  19. Randomized Controlled Trial Examining the Effects of Fish Oil and Multivitamin Supplementation on the Incorporation of n-3 and n-6 Fatty Acids into Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Andrew Pipingas

    2014-05-01

    Full Text Available The present randomized, placebo-controlled, double-blind, parallel-groups clinical trial examined the effects of fish oil and multivitamin supplementation on the incorporation of n-3 and n-6 fatty acids into red blood cells. Healthy adult humans (n = 160 were randomized to receive 6 g of fish oil, 6 g of fish oil plus a multivitamin, 3 g of fish oil plus a multivitamin or a placebo daily for 16 weeks. Treatment with 6 g of fish oil, with or without a daily multivitamin, led to higher eicosapentaenoic acid (EPA composition at endpoint. Docosahexaenoic acid (DHA composition was unchanged following treatment. The long chain LC n-3 PUFA index was only higher, compared to placebo, in the group receiving the combination of 6 g of fish oil and the multivitamin. Analysis by gender revealed that all treatments increased EPA incorporation in females while, in males, EPA was only significantly increased by the 6 g fish oil multivitamin combination. There was considerable individual variability in the red blood cell incorporation of EPA and DHA at endpoint. Gender contributed to a large proportion of this variability with females generally showing higher LC n-3 PUFA composition at endpoint. In conclusion, the incorporation of LC n-3 PUFA into red blood cells was influenced by dosage, the concurrent intake of vitamin/minerals and gender.

  20. Fatty acid composition of ostrich (Struthio camelus abdominal adipose tissue

    Directory of Open Access Journals (Sweden)

    Daniela Belichovska

    2015-03-01

    Full Text Available Fatty acid composition of foods has a great impact on nutrition and health. Therefore, thе determination and knowledge of the fatty acid composition of food is very important for nutrition. Due to the high nutritional characteristics of ostrich meat and its products, the research determining their quality is of topical interest. The aim of the present investigation was the determination of fatty acid composition of ostrich adipose tissue. The content of fatty acids was determined according to AOAC Official Methods of Analysis and determination was performed using a gas chromatograph with a flame-ionization detector (GC-FID. The results are expressed as a percentage of the total content of fatty acids. The method was validated and whereupon the following parameters were determined: linearity, precision, recovery, limit of detection and limit of quantification. The repeatability was within of 0.99 to 2.15%, reproducibility from 2.01 to 4.57%, while recovery ranged from 94.89 to 101.03%. According to these results, this method is accurate and precise and can be used for analysis of fatty acids in foods. It was concluded that the content of saturated fatty acids (SFA accounted 34.75%, of monounsaturated fatty acids (MUFA 38.37%, of polyunsaturated fatty acids (PUFA 26.88%, of total unsaturated fatty acids (UFA 65.25% and of desirable fatty acids (DFA (total unsaturated + stearic acid 70.37% of the analysed samples. The ratio polyunsaturated/saturated fatty acids accounted 0.77. The most present fatty acid is the oleic (C18:1n9c with 28.31%, followed by palmitic (C16:0 with 27.12% and linoleic (C18:2n6c acid with 25.08%. Other fatty acids are contained in significantly lower quantities.

  1. Essential fatty acid requirements of cats: pathology of essential fatty acid deficiency.

    Science.gov (United States)

    MacDonald, M L; Anderson, B C; Rogers, Q R; Buffington, C A; Morris, J G

    1984-07-01

    The pathologic changes of essential fatty acid (EFA) deficiency were studied in specific-pathogen-free, domestic shorthair cats which were fed purified diets for 1.5 to 2.5 years. Cats fed an EFA-deficient diet exhibited signs of deficiency: severe fatty degeneration of the liver, excessive fat in the kidneys, dystrophic mineralization of the adrenal glands, degeneration of the testes, and hyperkeratosis of the skin. Minor clinical pathologic changes were consistent with liver damage. Fatty acid analyses of plasma lipids revealed low concentrations of linoleate and other n6-fatty acids, and high concentrations of n7- and n9-fatty acids, consistent with EFA deficiency. These signs of deficiency were prevented by including safflower seed oil in the diet at a concentration to supply linoleate at 6.7% of dietary energy. Therefore, linoleate is an EFA for the cat, despite negligible conversion of linoleate to arachidonate in cat liver. However, in cats fed a diet containing linoleate, but lacking arachidonate, there was mild mineralization of the kidneys, and the neutral fat content of the liver was slightly higher than that of cats fed a diet containing arachidonate and other long-chain polyunsaturated fatty acids. Also, 2 of the 19 cats fed arachidonate-deficient diets developed unusual inflammatory skin lesions. In cats fed a diet containing hydrogenated coconut oil, safflower seed oil, and chicken fat, fatty livers developed despite the presence of high levels of linoleate. The fatty livers appeared to result from a specific deleterious effect of the medium-chain triglycerides in hydrogenated coconut oil. Most of the organ pathologic changes of EFA deficiency in the cat can be prevented by feeding dietary linoleate. Linoleate meets the EFA requirement for functions which depend on proper membrane structure: growth, lipid transport, normal skin and coat condition, and maintenance of the epidermal permeability barrier. However, dietary arachidonate is required by the

  2. Effects of different fatty acids and dietary lipids on adiponectin gene expression in 3T3-L1 cells and C57BL/6J mice adipose tissue.

    Science.gov (United States)

    Bueno, Allain Amador; Oyama, Lila Missae; de Oliveira, Cristiane; Pisani, Luciana Pelegrini; Ribeiro, Eliane Beraldi; Silveira, Vera Lucia Flor; Oller do Nascimento, Cláudia Maria

    2008-01-01

    Obesity is positively correlated to dietary lipid intake, and the type of lipid may play a causal role in the development of obesity-related pathologies. A major protein secreted by adipose tissue is adiponectin, which has antiatherogenic and antidiabetic properties. The aim of this study was to evaluate the effects of four different high-fat diets (enriched with soybean oil, fish oil, coconut oil, or lard) on adiponectin gene expression and secretion by the white adipose tissue (WAT) of mice fed on a selected diet for either 2 (acute treatment) or 60 days (chronic treatment). Additionally, 3T3-L1 adipocytes were treated for 48 h with six different fatty acids: palmitic, linoleic, eicosapentaenoic (EPA), docosahexaenoic (DHA), lauric, or oleic acid. Serum adiponectin concentration was reduced in the soybean-, coconut-, and lard-enriched diets in both groups. Adiponectin gene expression was lower in retroperitoneal WAT after acute treatment with all diets. The same reduction in levels of adiponectin gene expression was observed in epididymal adipose tissue of animals chronically fed soybean and coconut diets and in 3T3-L1 cells treated with palmitic, linoleic, EPA, and DHA acids. These results indicate that the intake of certain fatty acids may affect serum adiponectin levels in mice and adiponectin gene expression in mouse WAT and 3T3-L1 adipocytes. The effects appear to be time dependent and depot specific. It is postulated that the downregulation of adiponectin expression by dietary enrichment with soybean oil or coconut oil may contribute to the development of insulin resistance and atherosclerosis.

  3. Fatty acids composition of 10 microalgal species

    Directory of Open Access Journals (Sweden)

    Thidarat Noiraksar

    2005-11-01

    Full Text Available Fatty acids composition of 10 species of microalgae was determined at the exponential phase and the stationary phase. The microalgae consist of two species of diatoms, Bacillariophyceae, (Nitzschia cf. ovalis, Thalassiosira sp. five species of green microalgae, Prasinophyceae (Tetraselmis sp. and Chlorophyceae, (Dictyosphaerium pulchellum, Stichococcus sp., Chlorella sp., Scenedesmus falcatus and three species of blue green microalgae, Cyanophyceae (Anacystis sp., Synechococcus sp., Synechocystis sp..Medium for culture diatoms and green microalgae was F/2, and BG-11 media was used for Cyanophyceae. The microalgae were cultured beneath light intensity 143 μEm-2s-1, light: dark illustration 12:12 hrs., temperature 28ºC, and salinities 8-30 psu. The microalgae were harvested for analyzing fatty acid by centrivugal machine at 3500 rpm. for 5 min. at temperature 20ºC and stored at -80ºC prior to analysis.Fatty acids composition of microalgae differed from species to species. The majority fatty acids composition of diatoms at the exponential phase and the stationary phase were C16:1n-7 (17.12-31.47% and 28.22-42.02%, C16:0 (13.25-19.61% and 18.83-20.67%, C20:5 n-3 (16.65-26.67% and 11.32-23.68% respectively. The principle fatty acids composition of green microalgae, Prasinophyceae, Tetraselmis sp. were C18:3n-3 (16.17-16.67%, C16:0 (15.33-17.45%, C18:1n-9 (12.25-15.43%, C18:2n-6 (9.66-19.97%. The fatty acids composition of green microalgae, Chlorophyceae, were C18:3 n-3 (20.02-26.49% and 15.35- 30.63%, C16:0 (5.76-17.61% and 11.41-20.03%, C18:2n-6 (4.67-17.54% and 7.48-20.61% respectively. The major amounts of fatty acids content of blue green microalgae were C16:1n-7 (9.28-34.91% and 34.48- 35.04%, C14:0 (13.34-25.96% and 26.69-28.24%, C16:0 (5.89-29.15% and 5.70-16.81% except for Anacystis sp.which had a high amount of C18:3 n-3 (23.18-27.98% but low amount of C14:0 (3.66-4.98%.Bacillariophyceae contained the highest amount of highly unsaturated

  4. Laser signals' nonlinear change in fatty acids

    CERN Document Server

    Ghelmez-Dumitru, M; Piscureanu, M; Sterian, A

    2003-01-01

    Previous works showed that thin layers of fatty acids and fatty acid-cholesterol mixtures behaved as optical liquid crystals, even at low incident laser power. The paper presents an experimental and computer study of laser signals, emergent from such samples, in presence of fluctuations. The optical emergent laser beams' features at different incident parameters were experimentally determined for different type (c.w. and pulsed) lasers, as for example helium-neon and Nd sup 3 sup + glass lasers. The results were correlated with the amount of cholesterol in mixtures and with their response in external electric field. These measurements are in all cases affected by fluctuations. We developed some computer-based procedures, by using the TableCurve3D from Jandel Scientific software and equations Runge-Kutta in MATLAB for taking into account these fluctuations.

  5. Correlation between the different chain lengths of free fatty acid oxidation and ability of trophoblastic invasion

    Institute of Scientific and Technical Information of China (English)

    Yu Huan; Yang Zi; Ding Xiaoyan; Wang Yanling; Han Yiwei

    2014-01-01

    Background Preeclampsia (PE) is associated with abnormal fatty acid beta-oxidation (FAO),especially metabolic disorders of long-chain fatty acid oxidation.The role of FAO dysfunction in inadequate invasion is unclear.The aim of this study was to explore the influence of various lengths fatty acids oxidation on invasiveness of trophoblasts.Methods Primary human trophoblast cells and HTR8/SVneo cells were treated with fatty acids of various lengths.Morphological changes,lipid deposition and ultrastructure changes of trophoblast cells were detected.Cells invasiveness was determined by transwell insert.CPT1,CPT2 and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) protein expression were analyzed.The correlation between intracellular lipid droplets deposition and cells invasiveness was evaluated.Results Cells treated with long-chain fatty acids showed significant increased lipid droplets deposition,severe mitochondrial damage,decreased CPT2 and LCHAD protein expression (P <0.05) but no significant difference in CPT1 protein expression (P >0.05).Invasiveness of the trophoblast cells of the LC-FFA group significantly decreased (P <0.05).Intracellular lipid droplets deposition was negatively correlated with invasivenss (R=-0.745,P <0.05).Conclusion Trophoblast cells after stimulation with long chain fatty acids exist fatty acid oxidation disorders,and reduce the ability of trophoblastic invasion.

  6. Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides.

    Science.gov (United States)

    Jackman, Joshua A; Yoon, Bo Kyeong; Li, Danlin; Cho, Nam-Joon

    2016-03-03

    Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fatty acids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fatty acids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed.

  7. Evolutionary distinctiveness of fatty acid and polyketide synthesis in eukaryotes.

    Science.gov (United States)

    Kohli, Gurjeet S; John, Uwe; Van Dolah, Frances M; Murray, Shauna A

    2016-08-01

    Fatty acids, which are essential cell membrane constituents and fuel storage molecules, are thought to share a common evolutionary origin with polyketide toxins in eukaryotes. While fatty acids are primary metabolic products, polyketide toxins are secondary metabolites that are involved in ecologically relevant processes, such as chemical defence, and produce the adverse effects of harmful algal blooms. Selection pressures on such compounds may be different, resulting in differing evolutionary histories. Surprisingly, some studies of dinoflagellates have suggested that the same enzymes may catalyse these processes. Here we show the presence and evolutionary distinctiveness of genes encoding six key enzymes essential for fatty acid production in 13 eukaryotic lineages for which no previous sequence data were available (alveolates: dinoflagellates, Vitrella, Chromera; stramenopiles: bolidophytes, chrysophytes, pelagophytes, raphidophytes, dictyochophytes, pinguiophytes, xanthophytes; Rhizaria: chlorarachniophytes, haplosporida; euglenids) and 8 other lineages (apicomplexans, bacillariophytes, synurophytes, cryptophytes, haptophytes, chlorophyceans, prasinophytes, trebouxiophytes). The phylogeny of fatty acid synthase genes reflects the evolutionary history of the organism, indicating selection to maintain conserved functionality. In contrast, polyketide synthase gene families are highly expanded in dinoflagellates and haptophytes, suggesting relaxed constraints in their evolutionary history, while completely absent from some protist lineages. This demonstrates a vast potential for the production of bioactive polyketide compounds in some lineages of microbial eukaryotes, indicating that the evolution of these compounds may have played an important role in their ecological success. PMID:26784357

  8. Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides

    Directory of Open Access Journals (Sweden)

    Joshua A. Jackman

    2016-03-01

    Full Text Available Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fatty acids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fatty acids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed.

  9. Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides.

    Science.gov (United States)

    Jackman, Joshua A; Yoon, Bo Kyeong; Li, Danlin; Cho, Nam-Joon

    2016-01-01

    Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fatty acids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fatty acids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed. PMID:26950108

  10. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    Science.gov (United States)

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  11. Improved Fatty Acid Profile Soybean MON 87705

    OpenAIRE

    Directorate, Issued by Health Canada's Food

    2014-01-01

    Health Canada has notified Monsanto Canada Inc. that it has no objection to the food use of Improved Fatty Acid Profile Soybean MON 87705. The Department conducted a comprehensive assessment of this variety according to its Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based upon internationally accepted principles for establishing the safety of foods with novel traits. The following provides a summary of the notification from Monsanto Ca...

  12. Regional myocardial free fatty acid metabolism

    International Nuclear Information System (INIS)

    Experimental evidence to date has confirmed the potential value of radioactive labelled free fatty acid (FFA) and their analogs for the assessment of regional myocardial FFA metabolism despite a number of current limitations. It is emphasized that with these agents only one specific aspect of myocardial metabolism, that of FFA, can be tested and that with these compounds information on the overall metabolic state cannot always be obtained. (WU)

  13. Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion.

    Science.gov (United States)

    Iwasaki, Kanako; Harada, Norio; Sasaki, Kazuki; Yamane, Shunsuke; Iida, Keiko; Suzuki, Kazuyo; Hamasaki, Akihiro; Nasteska, Daniela; Shibue, Kimitaka; Joo, Erina; Harada, Takanari; Hashimoto, Toshihiro; Asakawa, Yoshinori; Hirasawa, Akira; Inagaki, Nobuya

    2015-03-01

    Gastric inhibitory polypeptide (GIP) is an incretin secreted from enteroendocrine K cells in response to meal ingestion. Recently free fatty acid receptor G protein-coupled receptor (GPR) 120 was identified as a lipid sensor involved in glucagon-like peptide-1 secretion. However, Gpr 120 gene expression and its role in K cells remain unclear, partly due to difficulties in separation of K cells from other intestinal epithelial cells. In this study, we purified K cells using GIP-green fluorescent protein (GFP) knock-in mice, in which K cells can be visualized by GFP fluorescence. GFP-positive cells (K cells) were observed in the small intestine but not in the stomach and colon. K cell number and GIP content in K cells were significantly higher in the upper small intestine than those in the lower small intestine. We also examined the expression levels of several free fatty acid receptors in K cells. Among free fatty acid receptors, GPR120 was highly expressed in the K cells of the upper small intestine compared with the lower small intestine. To clarify the role of GPR120 on K cells in vivo, we used GPR120-deficient mice (GPR120(-/-)). GPR120(-/-) exhibited significantly lower GIP secretion (75% reduction, P secretion. In conclusion, GPR120 is expressed abundantly in K cells of the upper small intestine and plays a critical role in lipid-induced GIP secretion.

  14. Synthesis and structural analysis of 13C-fatty acids

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The 13C-labeled fatty acids octanoic-1-13C acid and palmitic-l-13C acid were synthetically prepared from Ba 13CO3. The yield of the former was more than 90% and that of the latter was above 85%. MS, IR, 1H-NMR and 13NMR were performed to analyze the structures of the two 13C-fatty acids, compared with their unlabeled fatty acids.

  15. Effects of Light and Temperature on Fatty Acid Production in Nannochloropsis Salina

    Energy Technology Data Exchange (ETDEWEB)

    Van Wagenen, Jonathan M.; Miller, Tyler W.; Hobbs, Samuel J.; Hook, Paul W.; Crowe, Braden J.; Huesemann, Michael H.

    2012-03-12

    Accurate prediction of algal biofuel yield will require empirical determination of physiological responses to the climate, particularly light and temperature. One strain of interest, Nannochloropsis salina, was subjected to ranges of light intensity (5-850 {mu}mol m{sup -2} s{sup -1}) and temperature (13-40 C); exponential growth rate, total fatty acids (TFA) and fatty acid composition were measured. The maximum acclimated growth rate was 1.3 day{sup -1} at 23 C and 250 {mu}mol m{sup -2} s{sup -1}. Fatty acids were detected by gas chromatography with flame ionization detection (GC-FID) after transesterification to corresponding fatty acid methyl esters (FAME). A sharp increase in TFA containing elevated palmitic acid (C16:0) and palmitoleic acid (C16:1) during exponential growth at high light was observed, indicating likely triacylglycerol accumulation due to photo-oxidative stress. Lower light resulted in increases in the relative abundance of unsaturated fatty acids; in thin cultures, increases were observed in palmitoleic and eicosapentaenoeic acids (C20:5{omega}3). As cultures aged and the effective light intensity per cell converged to very low levels, fatty acid profiles became more similar and there was a notable increase of oleic acid (C18:1{omega}9). The amount of unsaturated fatty acids was inversely proportional to temperature, demonstrating physiological adaptations to increase membrane fluidity. This data will improve prediction of fatty acid characteristics and yields relevant to biofuel production.

  16. Effects of Light and Temperature on Fatty Acid Production in Nannochloropsis Salina

    Directory of Open Access Journals (Sweden)

    Braden Crowe

    2012-03-01

    Full Text Available Accurate prediction of algal biofuel yield will require empirical determination of physiological responses to the environment, particularly light and temperature. One strain of interest, Nannochloropsis salina, was subjected to ranges of light intensity (5–850 μmol m−2 s−1 and temperature (13–40 °C and its exponential growth rate, total fatty acids (TFA and fatty acid composition were measured. The maximum acclimated growth rate was 1.3 day−1 at 23 °C and 250 μmol m−2 s−1. Fatty acids were detected by gas chromatography with flame ionization detection (GC-FID after transesterification to corresponding fatty acid methyl esters (FAMEs. A sharp increase in TFA containing elevated palmitic acid (C16:0 and palmitoleic acid (C16:1 during exponential growth at high light was observed, indicating likely triacylglycerol accumulation due to photo-oxidative stress. Lower light resulted in increases in the relative abundance of unsaturated fatty acids; in thin cultures, increases were observed in palmitoleic and eicosapentaenoic acids (C20:5ω3. As cultures aged and the effective light intensity per cell converged to very low levels, fatty acid profiles became more similar and there was a notable increase of oleic acid (C18:1ω9. The amount of unsaturated fatty acids was inversely proportional to temperature, demonstrating physiological adaptations to increase membrane fluidity. These data will improve prediction of fatty acid characteristics and yields relevant to biofuel production.

  17. Efficient free fatty acid production in Escherichia coli using plant acyl-ACP thioesterases.

    Science.gov (United States)

    Zhang, Xiujun; Li, Mai; Agrawal, Arpita; San, Ka-Yiu

    2011-11-01

    Microbial biosynthesis of fatty acid-like chemicals from renewable carbon sources has attracted significant attention in recent years. Free fatty acids can be used as precursors for the production of fuels or chemicals. Free fatty acids can be produced by introducing an acyl-acyl carrier protein thioesterase gene into Escherichia coli. The presence of the acyl-ACP thioesterase will break the fatty acid elongation cycle and release free fatty acid. Depending on their sequence similarity and substrate specificity, class FatA thioesterase is active on unsaturated acyl-ACPs and class FatB prefers saturated acyl group. Different acyl-ACP thioesterases have different degrees of chain length specificity. Although some of these enzymes have been characterized from a number of sources, information on their ability to produce free fatty acid in microbial cells has not been extensively examined until recently. In this study, we examined the effect of the overexpression of acyl-ACP thioesterase genes from Diploknema butyracea, Gossypium hirsutum, Ricinus communis and Jatropha curcas on free fatty acid production. In particular, we are interested in studying the effect of different acyl-ACP thioesterase on the quantities and compositions of free fatty acid produced by an E. coli strain ML103 carrying these constructs. It is shown that the accumulation of free fatty acid depends on the acyl-ACP thioesterase used. The strain carrying the acyl-ACP thioesterase gene from D. butyracea produced approximately 0.2g/L of free fatty acid while the strains carrying the acyl-ACP thioesterase genes from R. communis and J. curcas produced the most free fatty acid at a high level of more than 2.0 g/L at 48 h. These two strains accumulated three major straight chain free fatty acids, C14, C16:1 and C16 at levels about 40%, 35% and 20%, respectively. PMID:22001432

  18. Fatty acid profiles of some Fabaceae seed oils

    Science.gov (United States)

    The fatty acid profiles of six seed oils of the Fabaceae (Leguminosae) family are reported and discussed. These are the seed oils of Centrosema pubescens, Clitoria ternatea, Crotalaria mucronata, Macroptilium lathyroides, Pachyrhizus erosus, and Senna alata. The most common fatty acid in the fatty a...

  19. Seasonal changes in oleosomic lipids and fatty acids of perennial root nodules of beach pea.

    Science.gov (United States)

    Chinnasamy, Gurusamy; Davis, Philip James; Bal, Arya Kumar

    2003-04-01

    Seasonal changes in the fatty acid composition of phospholipids (PL), monoglycerides (MG), diglycerides (DG), free fatty acids (FA) and triglycerides (TG) separated from oleosomes (lipid bodies) of perennial root nodules of beach pea (Lathyrus maritimus) were analysed. Thin layer chromatography (TLC) revealed that PL and MG are the major lipids in nodule oleosomes. The fatty acid profile and overall double bond index (DBI) varied among lipid classes depending upon the season. High DBI in PL and MG found during late winter and early spring indicated that they may play a major role in winter survival and regeneration of perennial nodules. The DBI of DG was high at the end of the fall season and the DBI of FA and TG was high in summer months. The dominant fatty acids are C16:0 followed by C18:0 and C18:1. The levels of many unsaturated fatty acids such as C18:1, C18:2 and C18:3 increased while saturated fatty acid C18:0 decreased during winter. These unsaturated fatty acids possibly play an important role in the protection of nodule cells from cold stress. Nodules seem to retain some fatty acids and selectively utilize specific fatty acids to survive the winter and regenerate in spring. PMID:12756915

  20. Protection of INS-1 Cells from Free Fatty Acid-induced Apoptosis by Inhibiting the Glycogen Synthase Kinase-3

    Institute of Scientific and Technical Information of China (English)

    WU Wei; LUO Xiaoping

    2007-01-01

    To examine the role of glycogen synthase kinase 3 (GSK-3) in the apoptosis of pancreatic β-cells to better understand the pathogenesis and to find new approach to the treatment of type 2 dia-betes, apoptosis was induced by oleic acid (OA) in INS-1 cells and the activity of GSK-3 was inhib-ited by LiCl. The PI staining and flow cytometry were employed for the evaluation of apoptosis. The phosphorylation level of GSK-3 was detected by Western blotting. The results showed that OA at 0.4 mmol/L could cause conspicuous apoptosis of INS-1 cells and the activity of GSK-3 was significantly increased. After the treatment with 24 mmol/L of LiCl, a inhibitor of GSK-3, the OA-induced apop-tosis of INS-1 cells was lessened and the phosphorylation of GSK-3 was increased remarkably. It is concluded that GSK-3 activation plays an important role in OA-induced apoptosis in pancreatic β-cells and inhibition of the GSK-3 activity can effectively protect INS-1 cells from the OA-induced apoptosis. Our study provides a new experimental basis and target for the clinical treatment of type-2 diabetes.

  1. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    Directory of Open Access Journals (Sweden)

    Voelker Hans

    2008-04-01

    Full Text Available Abstract Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT. Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12 or a standard diet (SD group; n = 12 ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume. Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT

  2. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    International Nuclear Information System (INIS)

    Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further

  3. The effects of fish oil and high or low linoleic acid intake on fatty acid composition of human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Damsgaard, C.T.; Frøkiær, Hanne; Lauritzen, L.

    2008-01-01

    -supplementation on tissue fatty acid composition. Healthy young men (it 64) were randomized to capsules with FO or olive oil (control) (4-4 (2-0-5-6) ml/d) and to either sunflower oil and margarine (S/B) or rapeseed oil and a butter spread (R/K) to provide a high or a low 18: 2n-6 intake. Diet was measured by 4-d weighed......Dietary intake of 18: 2n-6 and 18: 3n-3 may affect endogenous production and incorporation of n-3 long-chain PUFA (LCPUFA) from fish oils (170). This double-blinded controlled 2 x 2-factorial 8-week intervention investigates the effects of high and low 18: 2n-6 intake in combination with FO...

  4. The effects of fish oil and high or low linoleic acid intake on fatty acid composition of human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Frøkiær, Hanne; Lauritzen, Lotte

    2008-01-01

    -supplementation on tissue fatty acid composition. Healthy young men (n 64) were randomized to capsules with FO or olive oil (control) (44 (20-56) ml/d) and to either sunflower oil and margarine (S/B) or rapeseed oil and a butter spread (R/K) to provide a high or a low 18: 2n-6 intake. Diet was measured by 4-d weighed......Dietary intake of 18: 2n-6 and 18: 3n-3 may affect endogenous production and incorporation of n-3 long-chain PUFA (LCPUFA) from fish oils (FO). This double-blinded controlled 2 £ 2-factorial 8-week intervention investigates the effects of high and low 18: 2n-6 intake in combination with FO...

  5. Engineered Production of Short Chain Fatty Acid in Escherichia coli Using Fatty Acid Synthesis Pathway.

    Science.gov (United States)

    Jawed, Kamran; Mattam, Anu Jose; Fatma, Zia; Wajid, Saima; Abdin, Malik Z; Yazdani, Syed Shams

    2016-01-01

    Short-chain fatty acids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fatty acid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity. E. coli strain expressing tesBT gene yielded maximum butyric acid titer at 1.46 g L-1, followed by tesBF at 0.85 g L-1 and tesAT at 0.12 g L-1. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. The modulation of genetic factors that are known to influence long chain fatty acid production, such as deletion of the fadD and fadE that initiates the fatty acid degradation cycle and overexpression of fadR that is a global transcriptional activator of fatty acid biosynthesis and repressor of degradation cycle, did not improve the butyric acid titer significantly. Use of chemical inhibitor cerulenin, which restricts the fatty acid elongation cycle, increased the butyric acid titer by 1.7-fold in case of TesBF, while it had adverse impact in case of TesBT. In vitro enzyme assay indicated that cerulenin also inhibited short chain specific thioesterase, though inhibitory concentration varied according to the type of thioesterase used. Further process optimization followed by fed-batch cultivation under phosphorous limited condition led to production of 14.3 g L-1 butyric acid and 17.5 g L-1 total free fatty acid at 28% of theoretical yield. This study expands our understanding of SCFAs production in E. coli through FASII pathway and highlights role of genetic and process optimization to enhance the desired product. PMID:27466817

  6. Engineered Production of Short Chain Fatty Acid in Escherichia coli Using Fatty Acid Synthesis Pathway

    Science.gov (United States)

    Jawed, Kamran; Mattam, Anu Jose; Fatma, Zia; Wajid, Saima; Abdin, Malik Z.; Yazdani, Syed Shams

    2016-01-01

    Short-chain fatty acids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fatty acid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity. E. coli strain expressing tesBT gene yielded maximum butyric acid titer at 1.46 g L-1, followed by tesBF at 0.85 g L-1 and tesAT at 0.12 g L-1. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. The modulation of genetic factors that are known to influence long chain fatty acid production, such as deletion of the fadD and fadE that initiates the fatty acid degradation cycle and overexpression of fadR that is a global transcriptional activator of fatty acid biosynthesis and repressor of degradation cycle, did not improve the butyric acid titer significantly. Use of chemical inhibitor cerulenin, which restricts the fatty acid elongation cycle, increased the butyric acid titer by 1.7-fold in case of TesBF, while it had adverse impact in case of TesBT. In vitro enzyme assay indicated that cerulenin also inhibited short chain specific thioesterase, though inhibitory concentration varied according to the type of thioesterase used. Further process optimization followed by fed-batch cultivation under phosphorous limited condition led to production of 14.3 g L-1 butyric acid and 17.5 g L-1 total free fatty acid at 28% of theoretical yield. This study expands our understanding of SCFAs production in E. coli through FASII pathway and highlights role of genetic and process optimization to enhance the desired product. PMID:27466817

  7. Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

    Energy Technology Data Exchange (ETDEWEB)

    An, Lei, E-mail: anleim@yahoo.com.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Pang, Yun-Wei, E-mail: yunweipang@126.com [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Gao, Hong-Mei, E-mail: Gaohongmei_123@yahoo.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki-Iwama 319-0206 (Japan); Tao, Li, E-mail: Eunice8023@yahoo.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin 130118 (China); Miao, Kai, E-mail: miaokai7@163.com [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Wu, Zhong-Hong, E-mail: wuzhh@cau.edu.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); and others

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. Black-Right-Pointing-Pointer fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. Black-Right-Pointing-Pointer fat-1 reduces lipid deposition in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlled experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.

  8. ANALYSIS OF FATTY ACID CONTENT OF RAW MIANALYSIS OF FATTY ACID CONTENT OF RAW MILK

    Directory of Open Access Journals (Sweden)

    Juraj Čuboň

    2013-02-01

    Full Text Available In this work was analysedquality of raw cow’s milkof dairy cows which was fed with winter food ration of feed. Milk was observed in terms of the composition of milk fat and fatty acids during the months of August, October, December and February. The proportion of saturated fatty acids in milk fat was 63.22 % and it was found the highest proportion of palmitic acid 34.85%myristic acid accounted for 11.44 % and 10.86 % stearic acid. Linoleic acid, which is given special attention in view of the favourable effect on cholesterol, consisted of 3.48 % milk fat. The average proportion of unsaturated fatty acids in milk fat was 36.76 % of which 32.77 % were monounsaturated and polyunsaturated 4.0 %. A high proportion of milk fat formed monounsaturated oleic acid 30.92 %. The proportion of linoleic acid in milk fat was 3.48 % and 0.31 % linoleic acid.

  9. Effect of fatty acids and programming on the immune system

    OpenAIRE

    Fear, Alison Lindsay

    2010-01-01

    Research to date has suggested that fatty acids (FAs) may affect the immune system, through their (and those of their metabolites) effects on membranes, mediators, and gene expression. However, despite the research carried out, there still exist gaps of knowledge where further research is required. In addition, programming by diet in pregnancy may affect the immune system, due to stress and/or structural and functional changes to immune cells, but whether this effect is long-lasting is uncert...

  10. Trans fatty acids, insulin sensitivity and type 2 diabetes

    OpenAIRE

    Risérus, Ulf

    2006-01-01

    Trans fatty acids (TFA) could affect cell membrane functions, and may therefore influence peripheral insulin sensitivity and the risk of developing type 2 diabetes. It is important to understand whether low amounts of TFA consumed during long periods may promote insulin resistance and have clinically relevant effects on diabetes risk. Data from controlled intervention studies examining the effects of TFA on insulin sensitivity and type 2 diabetes are reviewed. The results show no consistent e...

  11. Omega-3 Fatty Acids and Skeletal Muscle Health

    OpenAIRE

    Stewart Jeromson; Gallagher, Iain J.; Stuart D. R. Galloway; D. Lee Hamilton

    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 muscl...

  12. Fe-Catalyzed Oxidative Cleavage of Unsaturated Fatty Acids

    NARCIS (Netherlands)

    Spannring, P.

    2013-01-01

    The oxidative cleavage of unsaturated fatty acids into aldehydes or carboxylic acids gives access to valuable products. The products can be used as chemical building blocks, as emulsifiers or in the paint or polymer industry. Ozonolysis is applied industrially to cleave the fatty acid oleic acid int

  13. n-3 Fatty Acids and Cardiovascular Events after Myocardial Infarction

    NARCIS (Netherlands)

    Kromhout, D.; Giltay, E.J.; Geleijnse, J.M.

    2010-01-01

    Background - Results from prospective cohort studies and randomized, controlled trials have provided evidence of a protective effect of n-3 fatty acids against cardiovascular diseases. We examined the effect of the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and

  14. RBC and WBC fatty acid composition following consumption of an omega 3 supplement: Lessons for future clinical trials

    Directory of Open Access Journals (Sweden)

    Ballester Oscar F

    2010-03-01

    Full Text Available Abstract Background Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of RBCs might accurately indicate incorporation of omega 3 fatty acids in the WBCs. In this report we determine and compare the changes in fatty acid compositions of red blood cells and white blood cells in response to consumption of three doses of an omega 3 fatty acid supplement. Results We found that the fraction of omega 3 fatty acids in both red blood cells and white blood cells increased following consumption of the supplement. There was a linear, dose responsive increase in the fraction of omega 3 fatty acids in red blood cells but the increase in omega 3 in white blood cells was not linear. The magnitude of increase in omega 3 fatty acids was different between the two cell types. Conclusions Fatty acid analysis of red blood cells is a good measure of compliance with supplement consumption. However, fatty acid analysis of white blood cells is needed to correlate changes in fatty acid composition of white blood cells with other biochemical changes in the white blood cells. Trial Registration ClinicalTrials.gov NCT00899353.

  15. Phytanic acid and pristanic acid, branched-chain fatty acids associated with Refsum disease and other inherited peroxisomal disorders, mediate intracellular Ca2+ signaling through activation of free fatty acid receptor GPR40.

    Science.gov (United States)

    Kruska, Nicol; Reiser, Georg

    2011-08-01

    The accumulation of the two branched-chain fatty acids phytanic acid and pristanic acid is known to play an important role in several diseases with peroxisomal impairment, like Refsum disease, Zellweger syndrome and α-methylacyl-CoA racemase deficiency. Recent studies elucidated that the toxic activity of phytanic acid and pristanic acid is mediated by multiple mitochondrial dysfunctions, generation of reactive oxygen species and Ca2+ deregulation via the InsP3-Ca2+ signaling pathway in glial cells. However, the exact signaling mechanism through which both fatty acids mediate toxicity is still under debate. Here, we studied the ability of phytanic acid and pristanic acid to activate the free fatty acid receptor GPR40, a G-protein-coupled receptor, which was described to be involved in the Ca2+ signaling of fatty acids. We treated HEK 293 cells expressing the GPR40 receptor with phytanic acid or pristanic acid. This resulted in a significant increase in the intracellular Ca2+ level, similar to the effect seen after treatment with the synthetic GPR40 agonist GW9508. Furthermore, we demonstrate that the GPR40 activation might be due to an interaction of the carboxylate moiety of fatty acids with the receptor. Our findings indicate that the phytanic acid- and pristanic acid-mediated Ca2+ deregulation can involve the activation of GPR40. Therefore, we suppose that activation of GPR40 might be part of the signaling cascade of the toxicity of phytanic and pristanic acids.

  16. TECHNOLOGY FOR OIL ENRICHED BY POLYUNSATURATED FATTY ACIDS

    Directory of Open Access Journals (Sweden)

    K. Leshukov

    2012-03-01

    Full Text Available The technology of butter with the "OmegaTrin" complex with the balanced content of polynonsaturated fat acids is developed. Studied the fatty acid composition of milk - raw materials, optimal amount of insertion of polyunsaturated fatty acids, organoleptic characteristics of enriched butter; studied physico-chemical properties and biological value (biological effectiveness of the final product, fatty acid composition of a new product, set the shelf life and developed an oil recipe.

  17. Alpha-2-glycoprotein 1(AZGP1 regulates biological behaviors of LoVo cells by down-regulating mTOR signaling pathway and endogenous fatty acid synthesis.

    Directory of Open Access Journals (Sweden)

    Ligong Chang

    Full Text Available AZGP1 is a multifaceted protein associated with lipid mobilization, a process that is regulated by FASN and other metabolic pathways such as mTOR signaling. The active mTOR signaling pathway has been found to be involved in a variety of tumors. However, it remains unclear whether it is involved in the regulation of AZGP1 and FASN. An AZGP1-expressing plasmid was transfected into a human colorectal cancer cell line (LoVo with a low expression of AZGP1. The expression of AZGP1, FASN, eIF4E, p-mTOR, p-S6,and S6K1 were measured by Western blot analysis, and target genes were detected by RT-PCR. Cell proliferation was studied using the MTT and colony formation assays. The analysis of apoptosis and the cell cycle phase were assessed by flow cytometry. The capacity of cell migration was investigated using the transwell migration assay. We found that the expression of AZGP1 was up-regulated while the expression of FASN, eIF4E, p-mTOR, p-S6, and S6K1 were down-regulated in LoVo cells after AZGP1 was expressed. The proliferation of malignant cells was reduced in AZGP1-overexpression cells, which is consistent with an increased in the G2-arrest and apoptosis rate. Furthermore, the migration of AZGP1-overexpression cells was decreased. The overexpression of AZGP1 suppressed the activation of the mTOR pathway and endogenous FASN-regulated fatty acid synthesis, mitigating the malignant phenotype of LoVo cells. Herein, we provide evidence that AZGP1 may constitute a novel tumor suppressor for LoVo colorectal cancer cells.

  18. Alpha-2-glycoprotein 1(AZGP1) regulates biological behaviors of LoVo cells by down-regulating mTOR signaling pathway and endogenous fatty acid synthesis.

    Science.gov (United States)

    Chang, Ligong; Tian, Xiaoqiang; Lu, Yinghui; Jia, Min; Wu, Peng; Huang, Peilin

    2014-01-01

    AZGP1 is a multifaceted protein associated with lipid mobilization, a process that is regulated by FASN and other metabolic pathways such as mTOR signaling. The active mTOR signaling pathway has been found to be involved in a variety of tumors. However, it remains unclear whether it is involved in the regulation of AZGP1 and FASN. An AZGP1-expressing plasmid was transfected into a human colorectal cancer cell line (LoVo) with a low expression of AZGP1. The expression of AZGP1, FASN, eIF4E, p-mTOR, p-S6,and S6K1 were measured by Western blot analysis, and target genes were detected by RT-PCR. Cell proliferation was studied using the MTT and colony formation assays. The analysis of apoptosis and the cell cycle phase were assessed by flow cytometry. The capacity of cell migration was investigated using the transwell migration assay. We found that the expression of AZGP1 was up-regulated while the expression of FASN, eIF4E, p-mTOR, p-S6, and S6K1 were down-regulated in LoVo cells after AZGP1 was expressed. The proliferation of malignant cells was reduced in AZGP1-overexpression cells, which is consistent with an increased in the G2-arrest and apoptosis rate. Furthermore, the migration of AZGP1-overexpression cells was decreased. The overexpression of AZGP1 suppressed the activation of the mTOR pathway and endogenous FASN-regulated fatty acid synthesis, mitigating the malignant phenotype of LoVo cells. Herein, we provide evidence that AZGP1 may constitute a novel tumor suppressor for LoVo colorectal cancer cells.

  19. Dual Fatty Acid Elongase Complex Interactions in Arabidopsis.

    Science.gov (United States)

    Morineau, Céline; Gissot, Lionel; Bellec, Yannick; Hematy, Kian; Tellier, Frédérique; Renne, Charlotte; Haslam, Richard; Beaudoin, Frédéric; Napier, Johnathan; Faure, Jean-Denis

    2016-01-01

    Very long chain fatty acids (VLCFAs) are involved in plant development and particularly in several cellular processes such as membrane trafficking, cell division and cell differentiation. However, the precise role of VLCFAs in these different cellular processes is still poorly understood in plants. In order to identify new factors associated with the biosynthesis or function of VLCFAs, a yeast multicopy suppressor screen was carried out in a yeast mutant strain defective for fatty acid elongation. Loss of function of the elongase 3 hydroxyacyl-CoA dehydratase PHS1 in yeast and PASTICCINO2 in plants prevents growth and induces cytokinesis defects. PROTEIN TYROSIN PHOSPHATASE-LIKE (PTPLA) previously characterized as an inactive dehydratase was able to restore yeast phs1 growth and VLCFAs elongation but not the plant pas2-1 defects. PTPLA interacted with elongase subunits in the Endoplasmic Reticulum (ER) and its absence induced the accumulation of 3-hydroxyacyl-CoA as expected from a dehydratase involved in fatty acid (FA) elongation. However, loss of PTPLA function increased VLCFA levels, an effect that was dependent on the presence of PAS2 indicating that PTPLA activity repressed FA elongation. The two dehydratases have specific expression profiles in the root with PAS2, mostly restricted to the endodermis, while PTPLA was confined in the vascular tissue and pericycle cells. Comparative ectopic expression of PTPLA and PAS2 in their respective domains confirmed the existence of two independent elongase complexes based on PAS2 or PTPLA dehydratase that are functionally interacting. PMID:27583779

  20. Neutrophil fatty acid composition: effect of a single session of exercise and glutamine supplementation.

    Science.gov (United States)

    Lagranha, C J; Alba-Loureiro, T C; Martins, E F; Pithon-Curi, T C; Curi, R

    2008-06-01

    The fatty acid composition of immune cells appears to contribute to variations of cell function. The independent and combined effects of a single session of exercise (SSE) and glutamine supplementation (GS) on neutrophil fatty acid composition were investigated. Compared to control (no treatment given--i.e. neither SSE or GS), single session of exercise decreased myristic, palmitic and eicosapentaenoic (EPA) acids, and increased lauric, oleic, linoleic, arachidonic (AA) and docosahexaenoic (DHA) acids whereas glutamine supplementation combined with SSE (GS+SSE) increased oleic acid. Polyunsaturated/saturated fatty acid ratio and Unsaturation index were higher in neutrophils from the SSE and GS groups as compared with control. These findings support the proposition that SSE and GS may modulate neutrophil function through alterations in fatty acid composition. PMID:17721676

  1. Fatty acid specificity of hormone-sensitive lipase. Implication in the selective hydrolysis of triacylglycerols.

    Science.gov (United States)

    Raclot, T; Holm, C; Langin, D

    2001-12-01

    The selective mobilization of fatty acids from white fat cells depends on their molecular structure, in particular the degree of unsaturation. The present study was designed to examine if the release of fatty acids by hormone-sensitive lipase (HSL) in vitro i) is influenced by the amount of unsaturation, ii) depends on the temperature, and iii) could explain the selective pattern of fatty acid mobilization and notably the preferential mobilization of certain highly unsaturated fatty acids. Recombinant rat and human HSL were incubated with a lipid emulsion. The hydrolysis of 35 individual fatty acids, ranging in chain length from 12 to 24 carbon atoms and in unsaturation from 0 to 6 double bonds was measured. Fatty acid composition of in vitro released NEFA was compared with that of fat cell triacylglycerols (TAG), the ratio % NEFA/% TAG being defined as the relative hydrolysis. The relative hydrolysis of individual fatty acids differed widely, ranging from 0.44 (24:1n-9) to 1.49 (18:1n-7) with rat HSL, and from 0.38 (24:1n-9) to 1.67 (18:1n-7) with human HSL. No major difference was observed between rat and human HSL. The relative release was dependent on the number of double bonds according to chain length. The amount of fatty acid released by recombinant rat HSL was decreased but remained robust at 4 degrees C compared with 37 degrees C, and the relative hydrolysis of some individual fatty acids was affected. The relative hydrolysis of fatty acids moderately, weakly, and highly mobilized by adipose tissue in vivo was similar and close to unity in vitro. We conclude that i) the release of fatty acids by HSL is only slightly affected by their degree of unsaturation, ii) the ability of HSL to efficiently and selectively release fatty acids at low temperature could reflect a cold adaptability for poikilotherms or hibernators when endogenous lipids are needed, and iii) the selectivity of fatty acid hydrolysis by HSL does not fully account for the selective pattern of

  2. A Mutant of Hepatitis B Virus X Protein (HBxΔ127 Promotes Cell Growth through A Positive Feedback Loop Involving 5-Lipoxygenase and Fatty Acid Synthase

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2010-02-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common malignant tumors worldwide. Hepatitis B virus X protein (HBx contributes to the development of HCC, whereas HBx with COOH-terminal deletion is a frequent event in the HCC tissues. Previously, we identified a natural mutant of HBx-truncated 27 amino acids at the COOH-terminal (termed HBxΔ127, which strongly enhanced cell growth. In the present study, we focused on investigating the mechanism. Accordingly, fatty acid synthase (FAS plays a crucial role in cancer cell survival and proliferation; thus, we examined the signaling pathways involving FAS. Our data showed that HBxΔ127 strongly increased the transcriptional activities of FAS in human hepatoma HepG2 and H7402 cells. Moreover, we found that 5-lipoxygenase (5-LOX was responsible for the up-regulation of FAS by using MK886 (an inhibitor of 5-LOX and 5-LOX small interfering RNA. We observed that HBxΔ127 could upregulate 5-LOX through phosphorylated extracellular signal-regulated protein kinases 1/2 and thus resulted in the increase of released leukotriene B4 (LTB4, a metabolite of 5-LOX by ELISA. The additional LTB4 could upregulate the expression of FAS in the cells as well. Interestingly, we found that FAS was able to upregulate the expression of 5-LOX in a feedback manner by using cerulenin (an inhibitor of FAS. Collectively, HBxΔ127 promotes cell growth through a positive feedback loop involving 5-LOX and FAS, in which released LTB4 is involved in the up-regulation of FAS. Thus, our finding provides a new insight into the mechanism involving the promotion of cell growth mediated by HBxΔ127.

  3. The omega-3 fatty acid, eicosapentaenoic acid (EPA, prevents the damaging effects of tumour necrosis factor (TNF-alpha during murine skeletal muscle cell differentiation

    Directory of Open Access Journals (Sweden)

    Pearson Stephen

    2008-07-01

    Full Text Available Abstract Background Eicosapentaenoic acid (EPA is a ώ-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p p p p p p Conclusion In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.

  4. Investigation of free fatty acid associated recombinant membrane receptor protein expression in HEK293 cells using Raman spectroscopy, calcium imaging, and atomic force microscopy.

    Science.gov (United States)

    Lin, Juqiang; Xu, Han; Wu, Yangzhe; Tang, Mingjie; McEwen, Gerald D; Liu, Pin; Hansen, Dane R; Gilbertson, Timothy A; Zhou, Anhong

    2013-02-01

    G-protein-coupled receptor 120 (GPR120) is a previously orphaned G-protein-coupled receptor that apparently functions as a sensor for dietary fat in the gustatory and digestive systems. In this study, a cDNA sequence encoding a doxycycline (Dox)-inducible mature peptide of GPR120 was inserted into an expression vector and transfected in HEK293 cells. We measured Raman spectra of single HEK293 cells as well as GPR120-expressing HEK293-GPR120 cells at a 48 h period following the additions of Dox at several concentrations. We found that the spectral intensity of HEK293-GPR120 cells is dependent upon the dose of Dox, which correlates with the accumulation of GPR120 protein in the cells. However, the amount of the fatty acid activated changes in intracellular calcium (Ca(2+)) as measured by ratiometric calcium imaging was not correlated with Dox concentration. Principal components analysis (PCA) of Raman spectra reveals that the spectra from different treatments of HEK293-GPR120 cells form distinct, completely separated clusters with the receiver operating characteristic (ROC) area of 1, while those spectra for the HEK293 cells form small overlap clusters with the ROC area of 0.836. It was also found that expression of GPR120 altered the physiochemical and biomechanical properties of the parental cell membrane surface, which was quantitated by atomic force microscopy (AFM). These findings demonstrate that the combination of Raman spectroscopy, calcium imaging, and AFM may provide new tools in noninvasive and quantitative monitoring of membrane receptor expression induced alterations in the biophysical and signaling properties of single living cells.

  5. JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells.

    Science.gov (United States)

    Gao, Xiu-Li; Lin, Hua; Zhao, Wei; Hou, Ya-Qin; Bao, Yong-Li; Song, Zhen-Bo; Sun, Lu-Guo; Tian, Shang-Yi; Liu, Biao; Li, Yu-Xin

    2016-03-01

    Juglans mandshurica Maxim (Juglandaceae) is a famous folk medicine for cancer treatment and some natural compounds isolated from it have been studied extensively. Previously we isolated a type of ω-9 polyunsaturated fatty acid (JA) from the bark of J. mandshurica, however little is known about its activity and the underlying mechanisms. In this study, we studied anti-tumor activity of JA on several human cancer cell lines. Results showed that JA is cytotoxic to HepG2, MDA-MB-231, SGC-7901, A549 and Huh7 cells at a concentration exerting minimal toxic effects on L02 cells. The selective toxicity of JA was better than other classical anti-cancer drugs. Further investigation indicated that JA could induce cell apoptosis, characterized by chromatin condensation, DNA fragmentation and activation of the apoptosis-associated proteins such as Caspase-3 and PARP-1. Moreover, we investigated the cellular apoptosis pathway involved in the apoptosis process in HepG2 cells. We found that proteins involved in mitochondrion (cleaved-Caspase-9, Apaf-1, HtrA2/Omi, Bax, and Mitochondrial Bax) and endocytoplasmic reticulum (XBP-1s, GRP78, cleaved-Caspase-7 and cleaved-Caspase-12) apoptotic pathways were up-regulated when cells were treated by JA. In addition, a morphological change in the mitochondrion was detected. Furthermore, we found that JA could inhibit DNA synthesis and induce G2/M cell cycle arrest. The expression of G2-to-M transition related proteins, such as CyclinB1 and phosphorylated-CDK1, were reduced. In contrast, the G2-to-M inhibitor p21 was increased in JA-treated cells. Overall, our results suggest that JA can induce mitochondrion- and endocytoplasmic reticulum-mediated apoptosis, and G2/M phase arrest in HepG2 cells, making it a promising therapeutic agent against hepatoma.

  6. Metabolomics of dietary fatty acid restriction in patients with phenylketonuria.

    Directory of Open Access Journals (Sweden)

    Ulrike Mütze

    Full Text Available BACKGROUND: Patients with phenylketonuria (PKU have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA. Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. METHODOLOGY/PRINCIPAL FINDINGS: 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6-C18 in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS. Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re- absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6 a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B(2 and thromboxane B(3 release did not differ from that of healthy controls. CONCLUSION/SIGNIFICANCE: Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta

  7. The natural diyne-furan fatty acid EV-086 is an inhibitor of fungal delta-9 fatty acid desaturation with efficacy in a model of skin dermatophytosis.

    Science.gov (United States)

    Knechtle, Philipp; Diefenbacher, Melanie; Greve, Katrine B V; Brianza, Federico; Folly, Christophe; Heider, Harald; Lone, Museer A; Long, Lisa; Meyer, Jean-Philippe; Roussel, Patrick; Ghannoum, Mahmoud A; Schneiter, Roger; Sorensen, Alexandra S

    2014-01-01

    Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity in vitro against Candida, Aspergillus, and Trichophyton spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of Saccharomyces cerevisiae deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in S. cerevisiae, depending on the delta-9 fatty acid desaturase OLE1. Delta-9 unsaturated fatty acids-but not saturated fatty acids-antagonized the EV-086-mediated growth inhibition, and transcription of the OLE1 gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086-phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical Trichophyton infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses.

  8. FadD is required for utilization of endogenous fatty acids released from membrane lipids.

    Science.gov (United States)

    Pech-Canul, Ángel; Nogales, Joaquina; Miranda-Molina, Alfonso; Álvarez, Laura; Geiger, Otto; Soto, María José; López-Lara, Isabel M

    2011-11-01

    FadD is an acyl coenzyme A (CoA) synthetase responsible for the activation of exogenous long-chain fatty acids (LCFA) into acyl-CoAs. Mutation of fadD in the symbiotic nitrogen-fixing bacterium Sinorhizobium meliloti promotes swarming motility and leads to defects in nodulation of alfalfa plants. In this study, we found that S. meliloti fadD mutants accumulated a mixture of free fatty acids during the stationary phase of growth. The composition of the free fatty acid pool and the results obtained after specific labeling of esterified fatty acids with a Δ5-desaturase (Δ5-Des) were in agreement with membrane phospholipids being the origin of the released fatty acids. Escherichia coli fadD mutants also accumulated free fatty acids released from membrane lipids in the stationary phase. This phenomenon did not occur in a mutant of E. coli with a deficient FadL fatty acid transporter, suggesting that the accumulation of fatty acids in fadD mutants occurs inside the cell. Our results indicate that, besides the activation of exogenous LCFA, in bacteria FadD plays a major role in the activation of endogenous fatty acids released from membrane lipids. Furthermore, expression analysis performed with S. meliloti revealed that a functional FadD is required for the upregulation of genes involved in fatty acid degradation and suggested that in the wild-type strain, the fatty acids released from membrane lipids are degraded by β-oxidation in the stationary phase of growth.

  9. Lipase catalyzed synthesis of epoxy-fatty acids

    Institute of Scientific and Technical Information of China (English)

    CHEN, Qian; LI, Zu-Yi

    2000-01-01

    Lipase catalyzed synthesis of epoxy-fatty acidas from unsaturated carboxylic acids was investigated.Under mild conditions unsaturated arboxylic acids were convcveed to peroxide,then the unsaturated peroxycarboxylic acids epoxidised the C=C bond of themselves

  10. The effect of short-chain fatty acids butyrate, propionate, and acetate on urothelial cell kinetics in vitro: potential therapy in augmentation cystoplasty.

    Science.gov (United States)

    Dyer, J P; Featherstone, J M; Solomon, L Z; Crook, T J; Cooper, A J; Malone, P S

    2005-07-01

    The intestinal element of enterocystoplasty is affected by chronic inflammatory changes, which lead to excess mucus production, urinary tract infections, and stone formation. There is also an increased risk of malignancy. These inflammatory changes may be due to diversion colitis, which affects colonic segments excluded from the faecal stream and likewise may respond to intraluminal short-chain fatty acid (SCFA) therapy. The SCFAs have interesting antiproliferative, differentiating, and pro-apoptotic effects, which are protective against colorectal cancer and may influence the risk of malignancy in enterocystoplasty. Before intravesical therapy can be considered, the effect on normal urothelium must be investigated. Primary urothelial cells cultured from biopsy specimens and transformed urothelial (RT112 and MGH-U1) and intestinal cell lines (HT29 and CaCo-2) were incubated with SCFAs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the residual viable biomass to assess cell proliferation. Proliferation of primary and transformed urothelial cells in culture was inhibited by all SCFAs in a similar time- and dose-dependent manner. The concentration of SCFA required to inhibit growth of primary cells by 50% (IC50) was 20 mM of butyrate, 120 mM of propionate, and 240 mM of acetate after incubation for 1 h. After 72 h the IC50 was 2 mM of butyrate, 4 mM of propionate, and 20 mM of acetate. Transformed urothelial and colon cancer cell lines demonstrated similar growth inhibition. Butyrate was the most potent inhibitor of cell proliferation, followed by propionate and then acetate. Growth inhibition is not an immediate cytotoxic effect, and urothelial cells show a degree of adaptation to butyrate and growth recovery after incubation with butyrate. In conclusion, butyrate- and propionate-induced growth inhibition is potentially clinically significant and may have therapeutically beneficial implications in vivo. PMID:15864601

  11. A radial glia gene marker, fatty acid binding protein 7 (FABP7, is involved in proliferation and invasion of glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Antonella De Rosa

    Full Text Available Glioblastoma multiforme (GBM is among the most deadly cancers. A number of studies suggest that a fraction of tumor cells with stem cell features (Glioma Stem-like Cells, GSC might be responsible for GBM recurrence and aggressiveness. GSC similarly to normal neural stem cells, can form neurospheres (NS in vitro, and seem to mirror the genetic features of the original tumor better than glioma cells growing adherently in the presence of serum. Using cDNA microarray analysis we identified a number of relevant genes for glioma biology that are differentially expressed in adherent cells and neurospheres derived from the same tumor. Fatty acid-binding protein 7 (FABP7 was identified as one of the most highly expressed genes in NS compared to their adherent counterpart. We found that down-regulation of FABP7 expression in NS by small interfering RNAs significantly reduced cell proliferation and migration. We also evaluated the potential involvement of FABP7 in response to radiotherapy, as this treatment may cause increased tumor infiltration. Migration of irradiated NS was associated to increased expression of FABP7. In agreement with this, in vivo reduced tumorigenicity of GBM cells with down-regulated expression of FABP7 was associated to decreased expression of the migration marker doublecortin. Notably, we observed that PPAR antagonists affect FABP7 expression and decrease the migration capability of NS after irradiation. As a whole, the data emphasize the role of FABP7 expression in GBM migration and provide translational hints on the timing of treatment with anti-FABP7 agents like PPAR antagonists during GBM evolution.

  12. Trans fatty acids in the Nordic countries

    OpenAIRE

    Aro, Antti; Becker, Wulf; Pederssen, Jan I.

    2006-01-01

    Trans fatty acids (TFA) comprise a variety of positional isomers, mainly with 18 carbon atoms and one double bond (C18:1). They are found in foods of ruminant animal origin and in partially hydrogenated vegetable oils. The isomeric composition of TFA in animal and vegetable foods differs, but no definite differences have been documented between the metabolic and health effects of the different isomers. In the Nordic countries the intake of TFA has declined during the past 10-15 years, mainly ...

  13. Metabolism of fatty acids in rat brain in microsomal membranes

    International Nuclear Information System (INIS)

    Using a technique in which substrate fatty acids are incorporated into microsomal membranes followd by comparison of their rates of desaturation or elongation with those of exogenous added fatty acids it has been found that the desaturation rate is more rapid for the membrane-bound substrate than for the added fatty acid. Moreover, the product of the membrane-bound substrate is incorporated into membrane phospholipid whereas the product of the exogenous substrate is found in di- and triacyl glycerols and in free fatty acids as well. These and other findings point to a normal sequence of reaction of membrane liqids with membrane-bound substrates involving transfer of fatty acid from phospholipid to the coupled enzyme systems without ready equilibration with the free fatty acid pool

  14. Adipose tissue Fatty Acid patterns and changes in antrhropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre;

    2011-01-01

    in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate...... the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WCBMI), adjusting for confounders. Results 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men....... Associations with patterns with high levels of n-3 LC-PUFA were dependent on the context of the rest of the fatty acid pattern. Conclusions Adipose tissue fatty acid patterns with high levels of TFA may be linked to weight gain, but patterns with high n-3 LC-PUFA did not appear to be linked to weight loss...

  15. Effect of antioxidants on polyunsaturated fatty acids – review

    Directory of Open Access Journals (Sweden)

    Ancuţa Elena Prisacaru

    2016-06-01

    Full Text Available This paper aims to review the available literature data and provide an overview regarding the efficiency of antioxidants to prevent peroxidation of polyunsaturated fatty acids. Lipid peroxidation is a serious problem that often leads to a loss of shelf-life, reduced consumer acceptability, poorer functionality, lower nutritional value, and poorer safety. It represents an oxidative degradation of polyunsaturated fatty acids incorporated in cell membrane lipids or in lipoproteins, but also in vegetables and food oils rich in PUFA n-3. It is a complex process that leads to the production of numerous highly reactive metabolites with consequences for food preservation and for the development of various diseases. The targets of lipid oxidation are polyunsaturated fatty acids. Lipid peroxidation can proceed by means of two different reactions that lead to the formation of hydroperoxides as primary products. Hydroperoxides decompose rapidly to give many secondary products, such as lipid free radicals, which contribute to increased oxidation of other molecules, such as proteins, nu- cleic acids and other lipids. Lipid peroxidation is a major problem for the food industry, as well as for human health, since it is associated with many diseases. The use of antioxidants reduces oxidative damage.

  16. Fe-Catalyzed Oxidative Cleavage of Unsaturated Fatty Acids

    OpenAIRE

    Spannring, P.

    2013-01-01

    The oxidative cleavage of unsaturated fatty acids into aldehydes or carboxylic acids gives access to valuable products. The products can be used as chemical building blocks, as emulsifiers or in the paint or polymer industry. Ozonolysis is applied industrially to cleave the fatty acid oleic acid into the aldehydes nonanal and 9-oxo-nonanoic acid or into pelargonic and azelaic acid. Considerable hazards, including explosion risks, are associated with the use of ozone, and alternative processes...

  17. Potential applications of antimicrobial fatty acids in medicine, agriculture and other industries.

    Science.gov (United States)

    Desbois, Andrew P

    2012-08-01

    The antimicrobial effects of free fatty acids are well recognised and these compounds can prevent the growth of or directly kill bacteria, fungi and other microbes by affecting multiple cellular targets, including the cell membrane and components found therein. Moreover, fatty acids exert detrimental effects on microbial pathogens by interfering with mechanisms of virulence, such as preventing biofilm formation and inhibiting the production of toxins and enzymes. The antimicrobial properties of free fatty acids can be exploited for the preservation of perishable products, such as food and cosmetics, and for the prevention and treatment of infections. These safe natural products are particularly useful in circumstances where antimicrobial activity is required but where the use of conventional antibiotics is undesirable or forbidden. This review focuses on the most promising prospects for exploiting the antimicrobial properties of free fatty acids for applications in various industries. The benefits of using fatty acids as antimicrobial agents are discussed and relevant recent patents are highlighted. PMID:22630821

  18. Fatty acid binding receptors in intestinal physiology and pathophysiology

    OpenAIRE

    Kaemmerer, Elke; Plum, Patrick; Klaus, Christina; Weiskirchen, Ralf; Liedtke, Christian; Adolf, Maximilian; Schippers, Angela; Wagner, Norbert; Reinartz, Andrea; Gassler, Nikolaus

    2010-01-01

    Free fatty acids are essential dietary components and recognized as important molecules in the maintenance of cellular homeostasis. In the last decade, the molecular pathways for free fatty acid sensing in the gastrointestinal tract have been further elucidated by molecular identification and functional characterization of fatty acid binding receptors. These sensing molecules belong to the family of G protein-coupled receptors. In the intestine, four important receptors have been described so...

  19. Fatty acids intake and immune parameters in the elderly

    OpenAIRE

    Sonia González; Patricia López; Abelardo Margolles; Ana Suárez; Patterson, Ángeles M.; Adriana Cuervo; de los Reyes-Gavilán, Clara G.; Miguel Gueimonde

    2013-01-01

    Introduction: The rapid increase on life-expectancy represents a major challenge and economic burden for modern societies. Several studies have focused on the effects of polyunsaturated fatty acids (PUFA) upon the immune system; however less attention has been paid to the effects of monounsaturated fatty acids (MUFA). In this work we investigated the relationship of habitual consumption of different types of fatty acids with different immune parameters in the elderly. Subjects and methods: 40...

  20. The clinical significance of fatty acid binding proteins

    Directory of Open Access Journals (Sweden)

    Barbara Choromańska

    2011-11-01

    Full Text Available Excessive levels of free fatty acids are toxic to cells. The human body has evolved a defense mechanism in the form of small cytoplasmic proteins called fatty acid binding proteins (FABPs that bind long-chain fatty acids (LCFA, and then refer them to appropriate intracellular disposal sites (oxidation in mitochondria and peroxisomes or storage in the endoplasmic reticulum. So far, nine types of these proteins have been described, and their name refers to the place in which they were first identified or where they can be found in the greatest concentration. The most important FABPs were isolated from the liver (L-FABP, heart (H-FABP, intestine (I-FABP, brain (B-FABP, epidermis (E-FABP and adipocytes (A-FABP. Determination of H-FABP is used in the diagnosis of myocardial infarction, and L-FABP in kidney lesions of different etiologies. It is postulated that FABPs play an important role in the pathogenesis of metabolic diseases. Elevated levels of A-FABP have been found in the pericardial fat tissue and were associated with cardiac dysfunction in obese people. A rise in A-FABP has been observed in patients with type II diabetes. I-FABP is known as a marker of cell damage in the small intestine. Increased concentration of B-FABP has been associated with human brain tumors such as glioblastoma and astrocytoma, as well as with neurodegenerative diseases (Alzheimer’s, Parkinson’s and other disorders of cognitive function. The aim of this work was to present current data on the clinical significance of fatty acid binding proteins.

  1. PPAR-γ activation increases insulin secretion through the up-regulation of the free fatty acid receptor GPR40 in pancreatic β-cells.

    Directory of Open Access Journals (Sweden)

    Hyo-Sup Kim

    Full Text Available BACKGROUND: It has been reported that peroxisome proliferator-activated receptor (PPAR-γ and their synthetic ligands have direct effects on pancreatic β-cells. We investigated whether PPAR-γ activation stimulates insulin secretion through the up-regulation of GPR40 in pancreatic β-cells. METHODS: Rat insulinoma INS-1 cells and primary rat islets were treated with rosiglitazone (RGZ and/or adenoviral PPAR-γ overexpression. OLETF rats were treated with RGZ. RESULTS: PPAR-γ activation with RGZ and/or adenoviral PPAR-γ overexpression increased free fatty acid (FFA receptor GPR40 expression, and increased insulin secretion and intracellular calcium mobilization, and was blocked by the PLC inhibitors, GPR40 RNA interference, and GLUT2 RNA interference. As a downstream signaling pathway of intracellular calcium mobilization, the phosphorylated levels of CaMKII and CREB, and the downstream IRS-2 and phospho-Akt were significantly increased. Despite of insulin receptor RNA interference, the levels of IRS-2 and phospho-Akt was still maintained with PPAR-γ activation. In addition, the β-cell specific gene expression, including Pdx-1 and FoxA2, increased in a GPR40- and GLUT2-dependent manner. The levels of GPR40, phosphorylated CaMKII and CREB, and β-cell specific genes induced by RGZ were blocked by GW9662, a PPAR-γ antagonist. Finally, PPAR-γ activation up-regulated β-cell gene expressions through FoxO1 nuclear exclusion, independent of the insulin signaling pathway. Based on immunohistochemical staining, the GLUT2, IRS-2, Pdx-1, and GPR40 were more strongly expressed in islets from RGZ-treated OLETF rats compared to control islets. CONCLUSION: These observations suggest that PPAR-γ activation with RGZ and/or adenoviral overexpression increased intracellular calcium mobilization, insulin secretion, and β-cell gene expression through GPR40 and GLUT2 gene up-regulation.

  2. Effect of dietary fatty acids on the postprandial fatty acid composition of triacylglycerol-rich lipoproteins in healthy male subjects

    DEFF Research Database (Denmark)

    Bysted, Anette; Holmer, G.; Lund, Pia;

    2005-01-01

    interesterified test fats with equal amounts of palmitic acid ( P fat), stearic acid (S fat), trans-18: 1 isomers (T fat), oleic acid (O fat), or linoleic acid (L fat) were tested. Subjects: A total of 16 healthy, normolipidaemic males ( age 23 +/- 2 y) were recruited. Interventions: The participants ingested fat......Objective: The aim of the present study was to investigate the effect of trans-18: 1 isomers compared to other fatty acids, especially saturates, on the postprandial fatty acid composition of triacylglycerols ( TAG) in chylomicrons and VLDL. Design: A randomised crossover experiment where five......-rich test meals ( 1 g fat per kg body weight) and the fatty acid profiles of chylomicron and VLDL TAG were followed for 8 h. Results: The postprandial fatty acid composition of chylomicron TAG resembled that of the ingested fats. The fatty acids in chylomicron TAG were randomly distributed among the three...

  3. Role and significance of polyunsaturated fatty acids in nutrition in prevention and treatment of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ristić Vanja I.

    2003-01-01

    Full Text Available Introduction Hyperlipoproteinemia is a key factor in development of atherosclerosis, whereas regression of atherosclerosis mostly depends on decreasing the plasma level of total and LDL-cholesterol. Many studies have reported the hypocholesterolemic effect of linolenic acid. Types of polyunsaturated fatty acids (PUFA Linoleic and α-linolenic acids are essential fatty acids. The main sources of linoleic acid are vegetable seeds and of α-linolenic acid - green parts of plants. α-linolenic acid is converted to eicosapentaenoic and docosahexaenoic acid. Linoleic acid is converted into arachidonic acid competing with eicosapentaenoic acid in the starting point for synthesis of eicosanoids, which are strong regulators of cell functions and as such, very important in physiology and pathophysiology of cardiovascular system. Eicosanoids derived from eicosapentaenoic acid have different biological properties in regard to those derived from arachidonic acid, i.e. their global effects result in decreased vasoconstriction platelet aggregation and leukocyte toxicity. Role and significant of PUFA The n-6 to n-3 ratio of polyunsaturated fatty acids in the food is very important, and an optimal ratio 4 to 1 in diet is a major issue. Traditional western diets present absolute or relative deficiency of n-3 polyunsaturated fatty acids, and a ratio 15-20 to 1. In our diet fish and fish oil are sources of eicosapentaenoic and docosahexaenoic acid. Refined and processed vegetable oils change the nature of polyunsaturated fatty acids and obtained derivates have atherogenic properties.

  4. Echinococcus granulosus fatty acid binding proteins subcellular localization.

    Science.gov (United States)

    Alvite, Gabriela; Esteves, Adriana

    2016-05-01

    Two fatty acid binding proteins, EgFABP1 and EgFABP2, were isolated from the parasitic platyhelminth Echinococcus granulosus. These proteins bind fatty acids and have particular relevance in flatworms since de novo fatty acids synthesis is absent. Therefore platyhelminthes depend on the capture and intracellular distribution of host's lipids and fatty acid binding proteins could participate in lipid distribution. To elucidate EgFABP's roles, we investigated their intracellular distribution in the larval stage by a proteomic approach. Our results demonstrated the presence of EgFABP1 isoforms in cytosolic, nuclear, mitochondrial and microsomal fractions, suggesting that these molecules could be involved in several cellular processes.

  5. Effects of soya fatty acids on cassava ethanol fermentation.

    Science.gov (United States)

    Xiao, Dongguang; Wu, Shuai; Zhu, Xudong; Chen, Yefu; Guo, Xuewu

    2010-01-01

    Ethanol tolerance is a key trait of microbes in bioethanol production. Previous studies have shown that soya flour contributed to the increase of ethanol tolerance of yeast cells. In this paper, the mechanism of this ethanol tolerance improvement was investigated in cassava ethanol fermentation supplemented with soya flour or defatted soya flour, respectively. Experiment results showed that ethanol tolerance of cells from soya flour supplemented medium increased by 4-6% (v/v) than the control with defatted soya flour. Microscopic observation found that soya flour can retain the cell shape while dramatic elongations of cells were observed with the defatted soya flour supplemented medium. Unsaturated fatty acids (UFAs) compositions of cell membrane were analyzed and the UFAs amounts increased significantly in all tested strains grown in soya flour supplemented medium. Growth study also showed that soya flour stimulated the cell growth rate by approximately tenfolds at 72-h fermentation. All these results suggested that soya fatty acids play an important role to protect yeast cells from ethanol stress during fermentation process.

  6. Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

    OpenAIRE

    P.C. Calder

    1998-01-01

    1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, a-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune...

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

    Directory of Open Access Journals (Sweden)

    James P. Hardwick

    2009-01-01

    Full Text Available 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 -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -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 HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. 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 -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 CYP4F -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

  8. Effects of fatty acid activation on photosynthetic production of fatty acid-based biofuels in Synechocystis sp. PCC6803

    Directory of Open Access Journals (Sweden)

    Gao Qianqian

    2012-03-01

    Full Text Available Abstract Background Direct conversion of solar energy and carbon dioxide to drop in fuel molecules in a single biological system can be achieved from fatty acid-based biofuels such as fatty alcohols and alkanes. These molecules have similar properties to fossil fuels but can be produced by photosynthetic cyanobacteria. Results Synechocystis sp. PCC6803 mutant strains containing either overexpression or deletion of the slr1609 gene, which encodes an acyl-ACP synthetase (AAS, have been constructed. The complete segregation and deletion in all mutant strains was confirmed by PCR analysis. Blocking fatty acid activation by deleting slr1609 gene in wild-type Synechocystis sp. PCC6803 led to a doubling of the amount of free fatty acids and a decrease of alkane production by up to 90 percent. Overexpression of slr1609 gene in the wild-type Synechocystis sp. PCC6803 had no effect on the production of either free fatty acids or alkanes. Overexpression or deletion of slr1609 gene in the Synechocystis sp. PCC6803 mutant strain with the capability of making fatty alcohols by genetically introducing fatty acyl-CoA reductase respectively enhanced or reduced fatty alcohol production by 60 percent. Conclusions Fatty acid activation functionalized by the slr1609 gene is metabolically crucial for biosynthesis of fatty acid derivatives in Synechocystis sp. PCC6803. It is necessary but not sufficient for efficient production of alkanes. Fatty alcohol production can be significantly improved by the overexpression of slr1609 gene.

  9. The effect of chronic exposure to fatty acids

    DEFF Research Database (Denmark)

    Xiao, J.; Gregersen, S.; Kruhøffer, Mogens;

    2001-01-01

    . In conclusion, chronic exposure to low palmitate alters insulin secretion as well as gene expression. The number of genes that changed expression was palmitate dose and exposure time dependent. Randle's fatty acid-glucose cycle seems to be operative on the gene transcription level. A modification of expression...... found that basal insulin secretion increased in cells exposed to palmitate. The response to glucose stimulation declined on d 44 in cells cultured at 200 microM palmitate. In response to 50 and 200 microM palmitate exposure, expression was changed in 11 and 99 genes on d 2 and 134 and in 159 genes on d...

  10. TRPA1 is a polyunsaturated fatty acid sensor in mammals.

    Directory of Open Access Journals (Sweden)

    Arianne L Motter

    Full Text Available Fatty acids can act as important signaling molecules regulating diverse physiological processes. Our understanding, however, of fatty acid signaling mechanisms and receptor targets remains incomplete. Here we show that Transient Receptor Potential Ankyrin 1 (TRPA1, a cation channel expressed in sensory neurons and gut tissues, functions as a sensor of polyunsaturated fatty acids (PUFAs in vitro and in vivo. PUFAs, containing at least 18 carbon atoms and three unsaturated bonds, activate TRPA1 to excite primary sensory neurons and enteroendocrine cells. Moreover, behavioral aversion to PUFAs is absent in TRPA1-null mice. Further, sustained or repeated agonism with PUFAs leads to TRPA1 desensitization. PUFAs activate TRPA1 non-covalently and independently of known ligand binding domains located in the N-terminus and 5(th transmembrane region. PUFA sensitivity is restricted to mammalian (rodent and human TRPA1 channels, as the drosophila and zebrafish TRPA1 orthologs do not respond to DHA. We propose that PUFA-sensing by mammalian TRPA1 may regulate pain and gastrointestinal functions.

  11. Pseudo catalytic transformation of volatile fatty acids into fatty acid methyl esters.

    Science.gov (United States)

    Jung, Jong-Min; Cho, Jinwoo; Kim, Ki-Hyun; Kwon, Eilhann E

    2016-03-01

    Instead of anaerobic digestion of biodegradable wastes for producing methane, this work introduced the transformation of acidogenesis products (VFAs) into fatty acid methyl esters (FAMEs) to validate the feasible production of short-chained fatty alcohols via hydrogenation of FAMEs. In particular, among VFAs, this work mainly described the mechanistic explanations for transforming butyric acid into butyric acid methyl ester as a case study. Unlike the conventional esterification process (conversion efficiency of ∼94%), the newly introduced esterification under the presence of porous materials via the thermo-chemical process reached up to ∼99.5%. Furthermore, the newly introduced esterification via the thermo-chemical pathway in this work showed extremely high tolerance of impurities: the conversion efficiency under the presence of impurities reached up to ∼99±0.3%; thus, the inhibition behaviors attributed from the impurities used for the experimental work were negligible. PMID:26720136

  12. The metastasis inducer CCN1 (CYR61) activates the fatty acid synthase (FASN)-driven lipogenic phenotype in breast cancer cells

    Science.gov (United States)

    Menendez, Javier A.; Vellon, Luciano; Espinoza, Ingrid; Lupu, Ruth

    2016-01-01

    The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation. Pharmacological blockade of MAPK or PI-3'K activation similarly prevented the ability of CCN1 to induce FASN gene activation. Pharmacological inhibition of FASN activity with the mycotoxin cerulenin or the small compound C75 reversed CCN1-induced acquisition of estrogen independence and resistance to hormone therapies such as tamoxifen and fulvestrant in anchorage-independent growth assays. This study uncovers FASNdependent endogenous lipogenesis as a new mechanism controlling the metastatic phenotype promoted by CCN1. Because estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer, this previously unrecognized CCN1-driven lipogenic phenotype represents a novel metabolic target to clinically manage metastatic disease progression.

  13. Morphology and Structure of Amino-fatty Acid Intercalated Montmorillonite

    Science.gov (United States)

    Reyes, Larry; Sumera, Florentino

    2015-04-01

    amino fatty acid, but decreased with increasing surfactant loading. This suggested that the amino fatty acid may be tethered to the clay structure via ionic interaction and/or ion-dipole attraction. Significant changes in the clay morphology, particle size and surface charge were observed after organo-modification. Scanning electron microscopy (SEM) revealed that the organo-clays have a disordered and flaky morphology, while the unmodified MMT appeared to be dispersed spherical grains. The effective (Z) diameter of Na+-MMT was found to be ~520 nm, but increased up to ~937 nm upon intercalation of 12-ALA. The zeta potential (ξ) of the clay materials, on the other hand, ranged from -33 mV for undmodified MMT to -16 mv (200CEC-AMMT clay). The possible occupational hazards of working with nanoclays should also be explored. Presently, the MTT-dye reduction assay was performed to determine cell viability of mouse monocyte-macrophages (J774A.1) after direct exposure to the clays. The cytotoxicity of the clays exhibited a chemistry and dose dependent response, with unmodified Na+-MMT as the most cytotoxic while the organo-clays exhibited low toxicity. These results demonstrated the successful intercalation of the surfactant for the production of organophilic clay materials for a wide range of applications.

  14. Effect of acetate formation pathway and long chain fatty acid CoA-ligase on the free fatty acid production in E. coli expressing acy-ACP thioesterase from Ricinus communis.

    Science.gov (United States)

    Li, Mai; Zhang, Xiujun; Agrawal, Arpita; San, Ka-Yiu

    2012-07-01

    Microbial biosynthesis of fatty acid like chemicals from renewable carbon sources has attracted significant attention in recent years. Free fatty acids can be used as precursors for the production of fuels or chemicals. Wild type E. coli strains produce fatty acids mainly for the biosynthesis of lipids and cell membranes and do not accumulate free fatty acids as intermediates in lipid biosynthesis. However, free fatty acids can be produced by breaking the fatty acid elongation through the overexpression of an acyl-ACP thioesterase. Since acetyl-CoA might be an important factor for fatty acid synthesis (acetate formation pathways are the main competitive pathways in consuming acetyl-CoA or pyruvate, a precursor of acetyl-CoA), and the long chain fatty acid CoA-ligase (FadD) plays a pivotal role in the transport and activation of exogenous fatty acids prior to their subsequent degradation, we examined the composition and the secretion of the free fatty acids in four different strains including the wild type MG1655, a mutant strain with inactivation of the fatty acid beta-oxidation pathway (fadD mutant (ML103)), and mutant strains with inactivation of the two major acetate production pathways (an ack-pta (acetate kinase/phosphotransacetylase), poxB (pyruvate oxidase) double mutant (ML112)) and a fadD, ack-pta, poxB triple mutant (ML115). The engineered E. coli cells expressing acyl-ACP thioesterase with glucose yield is higher than 40% of theoretical yield. Compared to MG1655(pXZ18) and ML103(pXZ18), acetate forming pathway deletion strains such as ML112(pXZ18) and ML115(pXZ18) produced similar quantity of total free fatty acids, which indicated that acetyl-CoA availability does not appear to be limiting factor for fatty acid production in these strains. However, these strains did show significant differences in the composition of free fatty acids. Different from MG1655(pXZ18) and ML103(pXZ18), acetate formation pathway deletion strains such as ML112(pXZ18) and ML115

  15. Increased Brain Fatty Acid Uptake in Metabolic Syndrome

    Science.gov (United States)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti; Hirvonen, Jussi; Fielding, Barbara A.; Virtanen, Kirsi; Oikonen, Vesa; Kemppainen, Jukka; Viljanen, Tapio; Guiducci, Letizia; Haaparanta-Solin, Merja; Någren, Kjell; Solin, Olof; Nuutila, Pirjo

    2010-01-01

    OBJECTIVE To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS At baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction. PMID:20566663

  16. The development of radioiodinated fatty acids for myocardial imaging

    International Nuclear Information System (INIS)

    Since free fatty acids are the principal energy source for the normally oxygenated myocardium, the use of iodine-123-labeled fatty acid analogues is an attractive approach for myocardial imaging. Interest in the use of these substances results from divergent fatty acid metabolic pathways in ischemic (triglyceride storage) versus normoxic tissue (β-oxidative clearance), following flow-dependent delivery. Iodine-123-labeled fatty acids may offer a unique opportunity to identity myocardial viability using single photon emission tomography. The development of structurally-modified fatty acids became of interest because of the relatively long acquisition periods required for SPECT. The significant time required by early generation single- or dual-head SPECT systems for data acquisition requires minimal redistribution during the acquisition period to ensure accurate evaluation of the regional fatty acid distribution pattern after re-construction. Research has focussed on the evaluation of structural modifications which can be introduced into the fatty acid chain which would inhibit the subsequent β-oxidative catabolism which normally results in rapid myocardial clearance. Introduction of a methyl group in position-3 of the fatty acid carbon chain has been shown to significantly delay myocardial clearance and iodine-123-labeled 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) is a new tracer based on this strategy

  17. Genetic variability of fatty acids in bovine milk

    Directory of Open Access Journals (Sweden)

    Soyeurt H.

    2008-01-01

    Full Text Available Fatty acids composition of bovine milk influences the technological properties of butterfat and also presents some potential benefits for human health. Impact of feeding on fat composition is well described in the literature; less information is available about the impact of genetics. Based on few studies, essentially conducted to isolate some feeding effect, the breed seemed to influence the fatty acids composition. The variation in the activity of δ-9 desaturase, key enzyme in the production of monounsaturated fatty acids and conjugated linoleic acids in milk, could explain these differences. Very few studies have been focussing on the estimation of genetic parameters of fatty acids composition. However, the moderate heritability estimates observed by these studies for the major fatty acids could suggest a potential genetic effect.

  18. Omega-3 Fatty Acids in the Management of Epilepsy.

    Science.gov (United States)

    Tejada, Silvia; Martorell, Miquel; Capó, Xavier; Tur, Josep A; Pons, Antoni; Sureda, Antoni

    2016-01-01

    Omega-3 and omega-6 fatty acids are polyunsaturated fatty acids (PUFAs) with multiple double bonds. Linolenic and alpha-linolenic acids are omega-6 and omega-3 PUFAs, precursors for the synthesis of long-chain PUFAs (LC-PUFAs), such as arachidonic acid (omega-6 PUFA), and eicosapentaenoic and docosahexaenoic acids (omega-3 PUFAs). The three most important omega-3 fatty acids are alpha-linolenic, eicosapentaenoic and docosahexaenoic acids, which cannot be synthesized in enough amounts by the body, and therefore they must be supplied by the diet. Omega-3 fatty acids are essential for the correct functioning of the organism and participate in many physiological processes in the brain. Epilepsy is a common and heterogeneous chronic brain disorder characterized by recurrent epileptic seizures leading to neuropsychiatric disabilities. The prevalence of epilepsy is high achieving about 1% of the general population. There is evidence suggesting that omega-3 fatty acids may have neuroprotective and anticonvulsant effects and, accordingly, may have a potential use in the treatment of epilepsy. In the present review, the potential use of omega-3 fatty acids in the treatment of epilepsy, and the possible proposed mechanisms of action are discussed. The present article summarizes the recent knowledge of the potential protective role of dietary omega-3 fatty acids in epilepsy.

  19. N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function.

    Directory of Open Access Journals (Sweden)

    Maria Tikhonenko

    Full Text Available OBJECTIVE: The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs. We propose that n-3 polyunsaturated fatty acid (PUFA deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs. RESEARCH DESIGN AND METHODS: Type 2 diabetic rats on control or docosahexaenoic acid (DHA-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL-1β, IL-6, intracellular adhesion molecule (ICAM-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined. RESULTS: DHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation. CONCLUSIONS: In a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function.

  20. Mechanisms involved in the selective transfer of long chain polyunsaturted fatty acids to the fetus

    Directory of Open Access Journals (Sweden)

    Alfonso eGil-Sánchez

    2011-09-01

    Full Text Available The concentration of long chain polyunsaturated fatty acid (LCPUFA in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA during gestation and development of the cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is that of maternal origin. Both in vitro and human in vivo studies using labelled fatty acids have shown the preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts and even re-esterified and stored in lipid droplets (LD. Although trophoblast cells are not specialized in lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA synthetases and adipophilin or other enzymes related with lipolysis, modifying their rate of placental transfer and metabolization. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge on the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process.

  1. Red Blood Cell Docosapentaenoic Acid (DPA n-3 is Inversely Associated with Triglycerides and C-reactive Protein (CRP in Healthy Adults and Dose-Dependently Increases Following n-3 Fatty Acid Supplementation

    Directory of Open Access Journals (Sweden)

    Ann C. Skulas-Ray

    2015-08-01

    Full Text Available The role of the long-chain omega-3 (n-3 fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3 and inflammation and triglycerides (TG. We evaluated whether n-3 DPA content of red blood cells (RBC was associated with markers of inflammation (interleukin-6 (IL-6, tumor necrosis factor α (TNF-α, and C-reactive protein (CRP and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 20–44 years, body mass index (BMI 20–30 kg/m2, TG = 34–176 mg/dL; Study 2: n = 28, aged 22–65 years, BMI 24–37 kg/m2, TG = 141–339 mg/dL. We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA. In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001 and with fasting TG (r = −0.30, p = 0.001. The latter finding was replicated in Study 2 (r = −0.33, p = 0.04. In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%–61% vs. 14%–26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study.

  2. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  3. Pentadecanoic and Heptadecanoic Acids: Multifaceted Odd-Chain Fatty Acids.

    Science.gov (United States)

    Pfeuffer, Maria; Jaudszus, Anke

    2016-07-01

    The odd-chain fatty acids (OCFAs) pentadecanoic acid (15:0) and heptadecanoic acid (17:0), which account for only a small proportion of total saturated fatty acids in milk fat and ruminant meat, are accepted biomarkers of dairy fat intake. However, they can also be synthesized endogenously, for example, from gut-derived propionic acid (3:0). A number of studies have shown an inverse association between OCFA concentrations in human plasma phospholipids or RBCs and risk of type 2 diabetes and cardiovascular disease. We propose a possible involvement in metabolic regulation from the assumption that there is a link between 15:0 and 17:0 and the metabolism of other short-chain, medium-chain, and longer-chain OCFAs. The OCFAs 15:0 and 17:0 can be elongated to very-long-chain FAs (VLCFAs) such as tricosanoic acid (23:0) and pentacosanoic acid (25:0) in glycosphingolipids, particularly found in brain tissue, or can be derived from these VLCFAs. Their chains can be shortened, yielding propionyl-coenzyme A (CoA). Propionyl-CoA, by succinyl-CoA, can replenish the citric acid cycle (CAC) with anaplerotic intermediates and, thus, improve mitochondrial energy metabolism. Mitochondrial function is compromised in a number of disorders and may be impaired with increasing age. Optimizing anaplerotic intermediate availability for the CAC may help to cope with demands in times of increased metabolic stress and with aging. OCFAs may serve as substrates for synthesis of both odd-numbered VLCFAs and propionyl-CoA or store away excess propionic acid.

  4. Pentadecanoic and Heptadecanoic Acids: Multifaceted Odd-Chain Fatty Acids.

    Science.gov (United States)

    Pfeuffer, Maria; Jaudszus, Anke

    2016-07-01

    The odd-chain fatty acids (OCFAs) pentadecanoic acid (15:0) and heptadecanoic acid (17:0), which account for only a small proportion of total saturated fatty acids in milk fat and ruminant meat, are accepted biomarkers of dairy fat intake. However, they can also be synthesized endogenously, for example, from gut-derived propionic acid (3:0). A number of studies have shown an inverse association between OCFA concentrations in human plasma phospholipids or RBCs and risk of type 2 diabetes and cardiovascular disease. We propose a possible involvement in metabolic regulation from the assumption that there is a link between 15:0 and 17:0 and the metabolism of other short-chain, medium-chain, and longer-chain OCFAs. The OCFAs 15:0 and 17:0 can be elongated to very-long-chain FAs (VLCFAs) such as tricosanoic acid (23:0) and pentacosanoic acid (25:0) in glycosphingolipids, particularly found in brain tissue, or can be derived from these VLCFAs. Their chains can be shortened, yielding propionyl-coenzyme A (CoA). Propionyl-CoA, by succinyl-CoA, can replenish the citric acid cycle (CAC) with anaplerotic intermediates and, thus, improve mitochondrial energy metabolism. Mitochondrial function is compromised in a number of disorders and may be impaired with increasing age. Optimizing anaplerotic intermediate availability for the CAC may help to cope with demands in times of increased metabolic stress and with aging. OCFAs may serve as substrates for synthesis of both odd-numbered VLCFAs and propionyl-CoA or store away excess propionic acid. PMID:27422507

  5. Interaction between fatty acid salts and the elastin network.

    NARCIS (Netherlands)

    Vreeswijk, van J.

    1995-01-01

    The aim of the present study was to investigate the interaction between salts of fatty acids (FAS) and elastin. Absorption of fatty acids in elastin may affect the elasticity of elastin-containing tissue. Such phenomena could, for instance, be of relevance for the understanding of the formation of a

  6. Polyunsaturated fatty acid status of Dutch vegans and omnivores

    NARCIS (Netherlands)

    Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Hettema, Y; Bemelmans, W J; Muskiet, F A

    2000-01-01

    We compared the polyunsaturated fatty acid (PUFA) status of Dutch vegans and omnivores to investigate whether disparities can be explained by different diets and long chain PUFA (LCP) synthesis rates. Dietary intakes and fatty acid compositions of erythrocytes (RBC), platelets (PLT), plasma choleste

  7. Fatty acid profile of 25 alternative lipid feedstocks

    Science.gov (United States)

    This study reports the fatty acid profiles of 25 alternative lipid feedstocks for the production of bio-based fuels and chemicals. Lipids were extracted using hexane from oil-bearing seeds using a standard Soxhlet apparatus. Fatty acid profiles were measured using gas chromatography-flame ionization...

  8. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti;

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  9. The rationale for preventing cancer cachexia: targeting excessive fatty acid oxidation.

    Science.gov (United States)

    Qian, Chao-Nan

    2016-07-21

    Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms. A recent study published in Nature Medicine, entitled "Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia," reveals that cachectic cancer cells can secrete multiple cytokines that induce excessive fatty acid oxidation, which is responsible for muscle loss in cancer cachexia. Inhibition of fatty acid oxidation using etomoxir can increase muscle mass and body weight in cancer cachexia animal models. The usage of stable cachexia animal models is also discussed in this research highlight.

  10. Membrane Disruption by Antimicrobial Fatty Acids Releases Low-Molecular-Weight Proteins from Staphylococcus aureus

    OpenAIRE

    Parsons, Joshua B; Yao, Jiangwei; Frank, Matthew W.; Jackson, Pamela; Rock, Charles O

    2012-01-01

    The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward Gram-positive bacteria. A screen of fatty acids as growth inhibitors of Staphylococcus aureus revealed structure-specific antibacterial activity. Fatty acids like oleate (18:1Δ9) were nontoxic, whereas palmitoleate (16:1Δ9) was a potent growth inhibitor. Cells treated with 16:1Δ9 exhibited rapid membrane depolarization, the disruption of all major branches of macromolecular synthes...

  11. Dietary omega-3 fatty acids and ionizing irradiation on human breast cancer xenograft growth and angiogenesis

    OpenAIRE

    Cameron Ivan L; Short Nicholas; Sun LuZhe; Hardman W Elaine

    2005-01-01

    Abstract Background The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acid...

  12. Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids

    OpenAIRE

    Khalifeh-Soltani, Amin; McKleroy, William; Sakuma, Stephen; Cheung, Yuk Yin; Tharp, Kevin; Qiu, Yifu; Turner, Scott M; Chawla, Ajay; Stahl, Andreas; Atabai, Kamran

    2014-01-01

    Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8−/−) mice are protected from diet-induce...

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

    Science.gov (United States)

    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.

  14. Chlorophyll-derived fatty acids regulate expression of lipid metabolizing enzymes in liver - a nutritional opportunity

    Directory of Open Access Journals (Sweden)

    Wolfrum Christian

    2001-01-01

    Full Text Available Nutritional values of fatty acid classes are normally discussed on the basis of their saturated, monounsaturated and polyunsaturated structures with implicit understanding that they are straight-chain. Here we focus on chlorophyll-derived phytanic and pristanic acids that are minor isoprenoid branched-chain lipid constituents in food, but of unknown nutritional value. After describing the enzyme machinery that degrades these nutrient fatty acids in the peroxisome, we show by the criteria of a mouse model and of a human cell culture model that they induce with high potency expression of enzymes responsible for beta-oxidation of straight-chain fatty acids in the peroxisome. We summarize present mechanistic knowledge on fatty acid signaling to the nucleus, which involves protein/protein contacts between peroxisome proliferator activated receptor (PPAR and fatty acid binding protein (FABP. In this signaling event the branched-chain fatty acids are the most effective ones. Finally, on the basis of this nutrient-gene interaction we discuss nutritional opportunities and therapeutic aspects of the chlorophyll-derived fatty acids.

  15. Prevalent mutations in fatty acid oxidation disorders

    DEFF Research Database (Denmark)

    Gregersen, N; Andresen, B S; Bross, P

    2000-01-01

    UNLABELLED: The mutational spectrum in a given disease-associated gene is often comprised of a large number of different mutations, of which a single or a few are present in a large proportion of diseased individuals. Such prevalent mutations are known in four genes of the fatty acid oxidation...... carrying the prevalent 985A > G mutation are at risk of developing life-threatening attacks. In SCAD/ethylmalonic aciduria, on the other hand, the presence of the prevalent susceptibility variations, 625A and 511T, in the SCAD gene seems to require additional genetic and cellular factors to be present...... in order to result in a phenotype. For the prevalent mutations in the LCHAD and CPT II genes further data are needed to evaluate the penetrance and risk of manifest disease when carrying these mutations. CONCLUSION: Assessment of the prevalence of a prevalent mutation in the mutation spectrum...

  16. Fatty acid-induced insulin resistance

    DEFF Research Database (Denmark)

    Le Marchand-Brustel, Y; Gual, P; Grémeaux, T;

    2003-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterized by a decrease in the insulin effect on glucose transport in muscle and adipose tissue. Tyrosine phosphorylation of IRS-1 (insulin receptor...... substrate 1) and its binding to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Various studies have implicated lipids as a cause of insulin resistance in muscle. Elevated plasma fatty acid concentrations...... are associated with reduced insulin-stimulated glucose transport activity as a consequence of altered insulin signalling through PI 3-kinase. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose...

  17. Complex Pharmacology of Free Fatty Acid Receptors

    DEFF Research Database (Denmark)

    Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond;

    2016-01-01

    G protein-coupled receptors (GPCRs) are historically the most successful family of drug targets. In recent times it has become clear that the pharmacology of these receptors is far more complex than previously imagined. Understanding of the pharmacological regulation of GPCRs now extends beyond...... pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or "free" fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets...... for the treatment of metabolic and inflammatory diseases. Further understanding of the complex pharmacology of these receptors will be critical to unlocking their ultimate therapeutic potential....

  18. Determination of free fatty acids in beer.

    Science.gov (United States)

    Bravi, Elisabetta; Marconi, Ombretta; Sileoni, Valeria; Perretti, Giuseppe

    2017-01-15

    Free fatty acids (FFA) content of beer affects the ability to form a stable head of foam and plays an important role in beer staling. Moreover, the presence of saturated FAs is related sometimes to gushing problems in beer. The aim of this research was to validate an analytical method for the determination of FFAs in beer. The extraction of FFAs in beer was achieved via Liquid-Liquid Cartridge Extraction (LLCE), the FFAs extract was purified by Solid Phase Extraction (SPE), methylated by boron trifluoride in methanol, and injected into GC-FID system. The performance criteria demonstrate that this method is suitable for the analysis of medium and long chain FFAs in beer. The proposed method was tested on four experimental beers. PMID:27542484

  19. Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Horn, T;

    2000-01-01

    Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate...... oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage...

  20. G-CSF Protects Human Brain Vascular Endothelial Cells Injury Induced by High Glucose, Free Fatty Acids and Hypoxia through MAPK and Akt Signaling

    Science.gov (United States)

    Tao, Yinghong; Guo, Jingchun; Guo, Zhuangli; Zhang, Shuo; Zhang, Yu; Huang, Yanyan; Tang, Yuping; Dong, Qiang; Hu, Renming

    2015-01-01

    Granulocyte-colony stimulating factor (G-CSF) has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of G-CSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA) and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM) revealed that G-CSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt, and deactivation of c-Jun N terminal kinase (JNK) and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogen-activated protein kinases (MAPK) and Akt signaling

  1. Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5.

    Science.gov (United States)

    Levi, Liraz; Wang, Zeneng; Doud, Mary Kathryn; Hazen, Stanley L; Noy, Noa

    2015-01-01

    Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes and precursors for signalling molecules. Here we show that these biological compounds also regulate gene expression and that they do so by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARβ/δ. The data indicate that these activities of LCFA are mediated by FABP5, which delivers ligands from the cytosol to nuclear PPARβ/δ. Both saturated and unsaturated LCFA (SLCFA, ULCFA) bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARβ/δ pathway. We show further that, by concomitantly promoting the activation of RAR and inhibiting the activation of PPARβ/δ, SLCFA suppress the oncogenic properties of FABP5-expressing carcinoma cells in cultured cells and in vivo. The observations suggest that compounds that inhibit FABP5 may constitute a new class of drugs for therapy of certain types of cancer. PMID:26592976

  2. Desaturation and chain elongation of essential fatty acids in isolated liver cells from rat and rainbow trout

    Energy Technology Data Exchange (ETDEWEB)

    Hagve, T.A.; Christophersen, B.O.; Dannevig, B.H.

    1986-03-01

    Isolated hepatocytes from rainbow trout and rat were incubated with /sup 14/C-labeled linoleic acid, linolenic acid, dihomogammalinolenic acid or eicosapentaenoic acid. The most striking difference in the desaturase activity was the lower level of delta 5 desaturase in trout than in rat. No delta 4 desaturation of 22:4(n-6) to 22:5(n-6) was observed in either of the two species, while the conversion of 22:5(n-3) to 22:6(n-3) was significant in both groups and highest in rainbow trout. The chain-elongating activity was remarkably similar in the two species, except for the dead-end elongation which was distinctly more important in fish.

  3. Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

    Energy Technology Data Exchange (ETDEWEB)

    Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.; Culley, David E.; Deng, Shuang; Collett, James R.; Umemura, Myco; Koike, Hideaki; Baker, Scott E.; Machida, Masa

    2013-01-01

    Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes we successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.

  4. Important bioactive properties of omega-3 fatty acids

    Directory of Open Access Journals (Sweden)

    Rui Xu

    2015-06-01

    Full Text Available Good health has been linked with healthy diet. N-3 fatty acids are required for proper functioning of many physiological systems. There is a large body of evidence documenting the effects of polyunsaturated fatty acids with the first double bond at the third position from methyl-terminal on health benefits. Scientific evidence is accumulating to substantiate the role omega-3 fatty acids play in conditions such as cardiovascular disease, certain cancers and other diseases. The availability of n-3 fatty acids to various tissues is of major importance to health and depends on dietary intake for both normal development and in the prevention and management of chronic diseases.In this review we will summarize the biological properties of omega-3 fatty acids.

  5. Short-Chain Fatty Acids Inhibit Growth Hormone and Prolactin Gene Transcription via cAMP/PKA/CREB Signaling Pathway in Dairy Cow Anterior Pituitary Cells

    Directory of Open Access Journals (Sweden)

    Jian-Fa Wang

    2013-10-01

    Full Text Available Short-chain fatty acids (SCFAs play a key role in altering carbohydrate and lipid metabolism, influence endocrine pancreas activity, and as a precursor of ruminant milk fat. However, the effect and detailed mechanisms by which SCFAs mediate bovine growth hormone (GH and prolactin (PRL gene transcription remain unclear. In this study, we detected the effects of SCFAs (acetate, propionate, and butyrate on the activity of the cAMP/PKA/CREB signaling pathway, GH, PRL, and Pit-1 gene transcription in dairy cow anterior pituitary cells (DCAPCs. The results showed that SCFAs decreased intracellular cAMP levels and a subsequent reduction in PKA activity. Inhibition of PKA activity decreased CREB phosphorylation, thereby inhibiting GH and PRL gene transcription. Furthermore, PTX blocked SCFAs- inhibited cAMP/PKA/CREB signaling pathway. These data showed that the inhibition of GH and PRL gene transcription induced by SCFAs is mediated by Gi activation and that propionate is more potent than acetate and butyrate in inhibiting GH and PRL gene transcription. In conclusion, this study identifies a biochemical mechanism for the regulation of SCFAs on bovine GH and PRL gene transcription in DCAPCs, which may serve as one of the factors that regulate pituitary function in accordance with dietary intake.

  6. Omega-3 fatty acids in health and disease and in growth and development.

    Science.gov (United States)

    Simopoulos, A P

    1991-09-01

    elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because omega 3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and omega 6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake.(ABSTRACT TRUNCATED AT 400 WORDS)

  7. Short branched-chain C6 carboxylic acids result in increased growth, novel 'unnatural' fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant.

    Science.gov (United States)

    Sen, Suranjana; Sirobhushanam, Sirisha; Hantak, Michael P; Lawrence, Peter; Brenna, J Thomas; Gatto, Craig; Wilkinson, Brian J

    2015-10-01

    Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique 'unnatural' fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant. PMID:26225744

  8. Profile of Fatty Acids, Amino Acids, Carotenoid Total, and α-Tocopherol from Flying Fish Eggs

    Directory of Open Access Journals (Sweden)

    Aulia Azka

    2015-12-01

    Full Text Available Flying fish are found in waters of eastern Indonesia, which until now is still limited information about nutritional content. The purpose of this research was determine the composition of fatty acids, amino acids, total carotenoids, α-tocopherol flying fish eggs (Hyrundicthys sp.. The composition of fatty acid was measured by gas chromatography (GC, while amino acids, total carotenoids, α-tocopherol was measured by High performanced Liquid Chromatography (HPLC. Egg contained 22 fatty acids such as saturated fatty acid 29.71%, monounsaturated fatty acid 7.86%, and polysaturated fatty acid 13.64%. The result showed that eggs flying fish contained 17 amino acids, such as essential amino acid 14.96% and non-essential amino acids 20.27%. Eggs contained a total carotenoid of 245.37 ppm. α-tocopherol content of flying fish eggs by 1.06 ppm.

  9. Handmade cloned transgenic sheep rich in omega-3 Fatty acids.

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    Full Text Available Technology of somatic cell nuclear transfer (SCNT has been adapted worldwide to generate transgenic animals, although the traditional procedure relies largely on instrumental micromanipulation. In this study, we used the modified handmade cloning (HMC established in cattle and pig to produce transgenic sheep with elevated levels of omega-3 (n-3 fatty acids. Codon-optimized nematode mfat-1 was inserted into a eukaryotic expression vector and was transferred into the genome of primary ovine fibroblast cells from a male Chinese merino sheep. Reverse transcriptase PCR, gas chromatography, and chromosome analyses were performed to select nuclear donor cells capable of converting omega-6 (n-6 into n-3 fatty acids. Blastocysts developed after 7 days of in vitro culture were surgically transplanted into the uterus of female ovine recipients of a local sheep breed in Xinjiang. For the HMC, approximately 8.9% (n  =925 of reconstructed embryos developed to the blastocyst stage. Four recipients became pregnant after 53 blastocysts were transplanted into 29 naturally cycling females, and a total of 3 live transgenic lambs were produced. Detailed analyses on one of the transgenic lambs revealed a single integration of the modified nematode mfat-1 gene at sheep chromosome 5. The transgenic sheep expressed functional n-3 fatty acid desaturase, accompanied by more than 2-folds reduction of n-6/n-3 ratio in the muscle (p<0.01 and other major organs/tissues (p<0.05. To our knowledge, this is the first report of transgenic sheep produced by the HMC. Compared to the traditional SCNT method, HMC showed an equivalent efficiency but proved cheaper and easier in operation.

  10. Fat-1 transgenic cattle as a model to study the function of ω-3 fatty acids

    Directory of Open Access Journals (Sweden)

    Guo Tao

    2011-12-01

    Full Text Available Abstract ω-3 polyunsaturated fatty acids have been shown to play an important role in health. Enriched with ω-3 polyunsaturated fatty acids modulate expression of a number of genes with such broad functions as cell proliferation, growth and apoptosis and cell signaling and transduction, these effects, seem to regulate coronary artery disease, hypertension, atherosclerosis, psychiatric disorders and various cancer. In this context, fat-1 transgenic cattle was designed to convert ω-6 to ω-3 fatty acids could form an ideal model to study the effect of ω-3 fatty acids on the above functions. This study focuses on the total genomic difference of gene expression between fat-1 transgenic cattle and wild-type using cDNA microarrays, several genes were found to be overexpressed or suppressed in transgenic cattle relative to wild-type, these discrepancy genes related with lipid metabolism, immunity, inflammation nervous development and fertility.

  11. Overexpression of Fatty-Acid-β-Oxidation-Related Genes Extends the Lifespan of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Shin-Hae Lee

    2012-01-01

    Full Text Available A better understanding of the aging process is necessary to ensure that the healthcare needs of an aging population are met. With the trend toward increased human life expectancies, identification of candidate genes affecting the regulation of lifespan and its relationship to environmental factors is essential. Through misexpression screening of EP mutant lines, we previously isolated several genes extending lifespan when ubiquitously overexpressed, including the two genes encoding the fatty-acid-binding protein and dodecenoyl-CoA delta-isomerase involved in fatty-acid β-oxidation, which is the main energy resource pathway in eukaryotic cells. In this study, we analyzed flies overexpressing the two main components of fatty-acid β-oxidation, and found that overexpression of fatty-acid-β-oxidation-related genes extended the Drosophila lifespan. Furthermore, we found that the ability of dietary restriction to extend lifespan was reduced by the overexpression of fatty-acid-β-oxidation-related genes. Moreover, the overexpression of fatty-acid-β-oxidation-related genes enhanced stress tolerance to oxidative and starvation stresses and activated the dFOXO signal, indicating translocation to the nucleus and transcriptional activation of the dFOXO target genes. Overall, the results of this study suggest that overexpression of fatty-acid-β-oxidation-related genes extends lifespan in a dietary-restriction-related manner, and that the mechanism of this process may be related to FOXO activation.

  12. Engineering the fatty acid metabolic pathway in Saccharomyces cerevisiae for advanced biofuel production

    Directory of Open Access Journals (Sweden)

    Xiaoling Tang

    2015-12-01

    Full Text Available Fatty acid-derived fuels and chemicals have attracted a great deal of attention in recent decades, due to their following properties of high compat