Academic literature on the topic 'Delta 6 desaturase'

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Journal articles on the topic "Delta 6 desaturase"

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Hughes, S., and D. A. York. "Hepatic ∆6-desaturase activity in lean and genetically obese ob/ob mice." Biochemical Journal 225, no. 2 (January 15, 1985): 307–13. http://dx.doi.org/10.1042/bj2250307.

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Hepatic delta 6-desaturase activity is primarily located in the mitochondrial fraction in mice. Both delta 6- and delta 5-desaturase activities are increased in the liver of young (6-week-old) obese mice. The increase in hepatic delta 6-desaturase activity in obese mice does not occur until weaning. Neither restriction of food intake nor hyperinsulinaemia normalize hepatic delta 6-desaturase activity of obese mice. Both cold acclimation and tri-iodothyronine (30 micrograms/day per kg) decreased hepatic delta 6-desaturase activity of obese mice to levels observed in lean mice, whereas the increase in activity in obese mice was still maintained after the induction of hypothyroidism.
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Jones, A. L., D. Lloyd, and J. L. Harwood. "Rapid induction of microsomal Δ12(ω 6)-desaturase activity in chilled Acanthamoeba castellanii." Biochemical Journal 296, no. 1 (November 15, 1993): 183–88. http://dx.doi.org/10.1042/bj2960183.

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The activity of microsomal delta 12-desaturase in Acanthamoeba castellanii was increased after growing cultures were chilled from the optimal growth temperature (30 degrees C) to 15 degrees C. This increase was detectable in microsomes isolated from organisms subjected to only 10 min chilling. The mechanism of induction was investigated. The increase in activity on chilling was greatly reduced when protein synthesis was blocked before the temperature shift. Thus the major mechanism for the induction of delta 12-desaturase is increased protein synthesis. delta 12-Desaturase activity was higher when assayed at 20 degrees C than when assayed at 30 degrees C, but these changes were not due to the increased solubility of O2 at 20 degrees C. The major substrate of delta 12-desaturase was found to be 1-acyl-2-oleoyl phosphatidylcholine.
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Zhang, Lei, Yeeman Ramtohul, Sebastien Gagné, Angela Styhler, Hao Wang, Jocelyne Guay, and Zheng Huang. "A Multiplexed Cell Assay in HepG2 Cells for the Identification of Delta-5, Delta-6, and Delta-9 Desaturase and Elongase Inhibitors." Journal of Biomolecular Screening 15, no. 2 (January 19, 2010): 169–76. http://dx.doi.org/10.1177/1087057109356208.

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A multiplexed cell assay has been optimized to measure the activities of fatty acyl-CoA elongase, delta-5 desaturase (Δ5D), delta-6 desaturase (Δ6D), and delta-9 desaturase (Δ9D) together using 14C-labeled tracers in HepG2 cells, which express the human stearoyl-CoA desaturase-1 isoform (SCD1) exclusively. The Δ5 and Δ9 desaturase activities are indexed by the efficient conversion of [1-14C]-eicosatrienoic acid (C20:3, cis-8,11,14) to 14C-arachidonic acid (C20:4, cis-5,8,11,14) and the conversion of [1-14C]-stearic acid to 14C-oleic acid (C18:1, cis-9), respectively. CP-74006 potently blocks the Δ5D activity with an IC50 value of 20 nM and simplifies the metabolism of [1-14C]-α-linolenate (C18:3, cis-9,12,15) by accumulating 14C-eicosatetraenoic acid (C20:4, cis-8,11,14,17) as the major 14C-eicosatrienoic acid (C20:3, cis-11,14,17) and 14C-docosatetraenoic acid (C22:4, cis-10,13,16,19) as the minor metabolites through Δ6 desaturation and elongation. This simplified metabolite spectrum enables the delineation of the Δ6D activity by comparing the combined Δ6D/elongase activity index of the 14C-(C20:4/C18:3) ratio with the corresponding elongation index of the 14C-(C20:3/C18:3) ratio following compound treatment. SC-26196 and sterculic acid specifically inhibit the Δ6D and Δ9D activities with an IC50 value of 0.1 µM and 0.9 µM, respectively. This medium-throughput cell assay provides an efficient tool in the identification of specific desaturase and elongase inhibitors.
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Naval, J., M. J. Martínez-Lorenzo, I. Marzo, P. Desportes, and A. Piñeiro. "Alternative route for the biosynthesis of polyunsaturated fatty acids in K562 cells." Biochemical Journal 291, no. 3 (May 1, 1993): 841–45. http://dx.doi.org/10.1042/bj2910841.

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K562 human leukaemia cells lack a significant delta 6-desaturase activity. However, they synthesize long-chain polyunsaturated fatty acids (PUFA) from linoleic (C18:2(9,12)) and linolenic (C18:3(9,12,15)) acids, by reactions involving a C2 chain elongation followed by a delta 5-desaturation step and, to some extent, a further elongation. The main products formed were separated by argentation t.l.c. and identified by g.l.c. as the uncommon fatty acids C20:3(5,11,14) and C20:4(5,11,14,17) respectively. These acids were also produced when cells were supplemented with C20:2(11,14) or C20:3(11,14,17) respectively. The presence of a delta 5-desaturase was further confirmed by using its corresponding normal substrates, C20:3(8,11,14) and C20:4(8,11,14,17), which led to C20:4(5,8,11,14) and C20:5(5,8,11,14,17) respectively. On the other hand, a high delta 9-desaturase activity, but no significant delta 4-desaturase activity, were detected in K562 cells. These results indicate the existence of an alternative pathway, involving delta 5-desaturase, which is the only route for PUFA biosynthesis in K562 cells. This pathway may be relevant for the biosynthesis of PUFA in cells lacking delta 6-desaturase activity.
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Bonafini, Sara, Alice Giontella, Angela Tagetti, Irene Bresadola, Rossella Gaudino, Paolo Cavarzere, Diego Alberto Ramaroli, et al. "Fatty Acid Profile and Desaturase Activities in 7–10-Year-Old Children Attending Primary School in Verona South District: Association between Palmitoleic Acid, SCD-16, Indices of Adiposity, and Blood Pressure." International Journal of Molecular Sciences 21, no. 11 (May 30, 2020): 3899. http://dx.doi.org/10.3390/ijms21113899.

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In previous studies, dietary and circulating fatty acids (FA) and desaturases activity (delta-5 desaturase [D5D], delta-6 desaturase [D6D], and stearoyl-CoA desaturase [SCD-16]) involved in their metabolism were associated with metabolic and cardiovascular disorders. The aim of the study was to assess the association between different FAs and desaturases activity (estimated as product:precursor ratios) with individual cardiovascular risk factors (in particular, anthropometric measurements and blood pressure [BP]) in children. The FA profile was determined on a whole-blood drop in 243 children (age: 8.6 ± 0.72 years) participating in a school-based cross-sectional study. Docosahexaenoic acid (DHA) inversely correlated with indices of adiposity, glucose, and triglycerides. Palmitoleic acid and SCD-16 were directly associated with markers of adiposity and BP, even after adjustment for main confounders. D6D correlated directly with the waist/height ratio. Children with excess weight (>85th percentile; that is overweight plus obese ones) showed higher palmitic acid, palmitoleic acid, and higher SCD-16 activity as compared to normal-weight children. Most of the associations were confirmed in the excess-weight group. Omega-3 FAs, particularly DHA, but not omega-6 FA, showed a potentially beneficial association with metabolic parameters, whereas palmitoleic acid and SCD-16 showed a potentially harmful association with indices of adiposity and BP, especially in obese children.
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Tharuni, Boya, T. Sathish, G. Nadana Raja Vadivu, and K. Vasumathi. "IN SILICO ANALYSIS OF DELTA 6 DESATURASE - A KEY ENZYME FOR OMEGA €“3/6€“ FATTY ACID PRODUCTION." International Journal of Advanced Research 9, no. 02 (February 28, 2021): 818–23. http://dx.doi.org/10.21474/ijar01/12519.

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Delta 6 desaturase is a key enzyme involved in the production of omega 3/6 fatty acids and it is the rate-limiting step. The study aims to characterize the delta 6 desaturase enzyme and to find the binding affinity of various ligand with the protein by docking. It is found that delta 6 desaturase enzyme sequence is very unique and has less similarity with the other desaturase protein. The structural analysis was performed by Ramachandran plot and SCOPe structure prediction. Modeller is used to determine the DOPE score of the selected enzyme. The lowest DOPE score protein is chosen to determine the binding affinity of ligand molecules. Three different ligands were selected and its interaction was determined by the PyRX - Autodock Vina. These studies will give a better idea of the interaction of various molecules, which help to deduce its function by further experimentation.
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Nakamura, M. T., A. B. Tang, J. Villanueva, C. H. Halsted, and S. D. Phinney. "Selective reduction of delta 6 and delta 5 desaturase activities but not delta 9 desaturase in micropigs chronically fed ethanol." Journal of Clinical Investigation 93, no. 1 (January 1, 1994): 450–54. http://dx.doi.org/10.1172/jci116981.

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Griffiths, G., A. K. Stobart, and S. Stymne. "Δ 6- and Δ12-desaturase activities and phosphatidic acid formation in microsomal preparations from the developing cotyledons of common borage (Borago officinalis)." Biochemical Journal 252, no. 3 (June 15, 1988): 641–47. http://dx.doi.org/10.1042/bj2520641.

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Microsomal membrane preparations from the maturing cotyledons of common borage (Borago officinalis) exhibit delta 12- and delta 6-desaturase activities, which resulted in the synthesis of linoleate and gamma-linolenate respectively. The desaturase enzymes utilized the complex lipid substrate phosphatidylcholine. The activity of these enzymes was sufficiently high to allow the monitoring of the mass changes in the endogenous oleate, linoleate and gamma-linolenate in the microsomal phosphatidylcholine in the presence of NADH (i.e. under desaturating conditions). The results illustrate that the delta 12-desaturase uses the oleate substrate at both the sn-1 and -2 positions of sn-phosphatidylcholine, whereas the delta 6-desaturase is almost totally restricted to the linoleate at position 2 of the complex lipid. Estimate of the acyl-substrate pool size at position 2 of sn-phosphatidylcholine for both desaturases indicated that some 50% of the oleate and linoleate was available to the enzymes. The microsomes (microsomal fractions) had a somewhat impaired Kennedy [(1961) Fed. Proc. Fed. Am. Soc. Exp. Biol. 20, 934-940] pathway for the formation of triacylglycerols when compared with other oil-rich plant species that have been studied [Stymne & Stobart (1987) The Biochemistry of Plants: a Comprehensive Treatise (Stumpf, P.K., ed.), vol. 10, chapter 8, pp. 175-214, Academic Press, New York]. In the presence of sn-glycerol 3-phosphate and acyl-CoA, large quantities of phosphatidic acid accumulated in the membranes. Acyl-selectivity studies on the glycerol-acylating enzymes showed that gamma-linolenate could be acylated to both the sn-1 and sn-2 positions of sn-glycerol 3-phosphate. However, stereochemical analysis of the acyl components of the sn-triacylglycerol obtained from mature seeds indicated that, whereas no gamma-linolenate was present at the sn-1 position, it accounted for over 50% of the fatty acids at position sn-3. The results indicate that the diacylglycerol acyltransferase (EC 2.3.1.20) may show a strong selectivity for gamma-linolenoyl-CoA and hence result in the efficient removal of this fatty acid from the acyl-CoA pool in vivo, leaving negligible substrate for utilization by the sn-glycerol 3-phosphate acyltransferase (EC 2.3.1.15).
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Wolters, Maike, Heike Schlenz, Claudia Börnhorst, Patrizia Risé, Claudio Galli, Luis A. Moreno, Valeria Pala, et al. "Desaturase Activity Is Associated With Weight Status and Metabolic Risk Markers in Young Children." Journal of Clinical Endocrinology & Metabolism 100, no. 10 (October 1, 2015): 3760–69. http://dx.doi.org/10.1210/jc.2015-2693.

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Context: Activity of delta-9, delta-6, and delta-5 desaturases (D9D, D6D, D5D) are associated with obesity, insulin resistance, and dyslipidemia. Objective: To investigate the association of estimated desaturase activities with weight status, insulin resistance, and dyslipidemia in children, cross-sectionally and longitudinally. Design: The IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort study was used, with examinations at baseline (T0) and after 2 years (T1). Setting and Participants: Children aged 2 to less than 10 years from eight European countries were recruited in kindergartens/primary schools. Children with available data on fatty acids, outcome, and covariate information were included in the analyses. Methods: Whole blood fatty acids were analyzed in 2600 children at baseline. D9D (16:1n-7/16:0), D6D (20:3n-6/18:2n-6), and D5D (20:4n-6/20:3n-6) activities were estimated from product-precursor fatty acids ratios. Body mass index (BMI), Homeostatic Model Assessment index, and high-density lipoprotein cholesterol (HDL), and triglycerides (TG) served as outcomes for weight status, insulin resistance, and dyslipidemia, respectively. Linear and logistic regression and repeated measures models were used to assess the cross-sectional and longitudinal associations between desaturase activity and outcomes. Results: In the cross-sectional analysis, D9D and D6D were positively associated with BMI and TG z-scores and inversely with HDL z-scores. D5D was inversely associated with BMI and TG z-scores (ie, a D5D increase of 1 unit is associated with a BMI z-score decrease of 0.07 and a 28% lower odds ratio for TG ≥75th percentile). Longitudinally, similar associations were found for T0 desaturase activities with BMI and for T0 D6D with HDL at follow-up (T1). Baseline D6D and D5D were positively associated with the change of HDL z-score from T0 to T1, and D6D with the change of Homeostatic Model Assessment index z-score. Conclusion: Desaturase activities are associated with metabolic risk markers already in young children and appear to predict the metabolic risk.
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Zietemann, Vera, Janine Kröger, Cornelia Enzenbach, Eugene Jansen, Andreas Fritsche, Cornelia Weikert, Heiner Boeing, and Matthias B. Schulze. "Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition-Potsdam study." British Journal of Nutrition 104, no. 12 (August 9, 2010): 1748–59. http://dx.doi.org/10.1017/s0007114510002916.

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Delta-5 (D5D) and delta-6 (D6D) desaturases are key enzymes in PUFA metabolism. Several factors (e.g. hyperglycaemia, hypertension, blood lipids, statins and fatty acids in diet and biological tissues) may influence desaturase activity. The goals were to evaluate the associations between variation in genes encoding these desaturases (FADS1 and FADS2) and blood concentrations of n-6 PUFA and estimated D5D and D6D activities (evaluated as product/precursor ratio), and to investigate whether other factors influencing the activity of desaturases modify these associations. A random sample of 2066 participants from the European Prospective Investigation into Cancer and Nutrition-Potsdam study (n 27 548) was utilised in the analyses. Crude and adjusted associations between rs174546 genotypes (reflecting genetic variation in the FADS1FADS2 gene cluster), n-6 PUFA in erythrocytes and estimated desaturase activities were evaluated using multiple linear regression. Potential effect modification was determined by performing stratified analyses and evaluating interaction terms. We found rs174546 genotypes to be related to linoleic (r2 0·060), γ-linolenic (r2 0·041), eicosadienoic (r2 0·034), arachidonic (r2 0·026), docosatetraenoic acids (r2 0·028), estimated D6D activity (r2 0·052) and particularly strongly to dihomo-γ-linolenic acid (DGLA, r2 0·182) and D5D activity (r2 0·231). We did not observe effect modifications with regard to the estimated D5D activity, DGLA and arachidonic acid (AA) for most of the factors evaluated; however, the genetic effect on D5D activity and DGLA may be modified by the dietary n-6:n-3-ratio (P-values for interaction: 0·008 and 0·002), and the genetic effect on DGLA and AA may be modified by lipid-lowering medication (P-values for interaction: 0·0004 and 0·006). In conclusion, genetic variation in the FADS1 FADS2 gene cluster affects n-6 PUFA profiles in erythrocytes reflecting altered D5D activity.
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Dissertations / Theses on the topic "Delta 6 desaturase"

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Callamand, Pierre. "Etude des desaturases delta 6 et delta 5 hepatiques en periode perinatale." Montpellier 1, 1991. http://www.theses.fr/1991MON11223.

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Warensjö, Eva. "Fatty Acid Desaturase Activities in Metabolic Syndrome and Cardiovascular Disease : Special Reference to Stearoyl-CoA-Desaturase and Biomarkers of Dietary Fat." Doctoral thesis, Uppsala University, Clinical Nutrition and Metabolism, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8312.

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The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios.

In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice.

This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.

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Portolesi, Roxanne, and roxanne portolesi@flinders edu au. "Fatty acid metabolism in HepG2 cells: Limitations in the accumulation of docosahexaenoic acid in cell membranes." Flinders University. Medicine, 2007. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20070802.103146.

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The current dietary recommendations for optimal health are designed to increase our intake of two bioactive omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), abundant naturally in fatty fish such as salmon. Health authorities recommend that the general population consume two to three fatty fish meals per week (1) for optimal health and for the prevention of cardiovascular disease. However, some modern Western societies consume only modest amounts of fish and seafood (2;3). Land based vegetable oils may provide an alternative to meet these needs. Linseed and canola oils are rich in alpha-linolenic acid (ALA, 18:3n-3) (4). ALA can be converted endogenously to EPA and DHA and suggests that increasing the dietary intake of ALA may increase the conversion and accumulation of DHA in tissues and plasma. However, elevated dietary intakes of ALA in animals and humans results in an increased level of EPA in tissues yet there is little or no change in the level of DHA (5-7). The current consensus is that the synthesis of DHA from ALA in humans is limited yet the mechanisms involved in regulating the accumulation of DHA in tissues are poorly understood. The reputed rate-limiting enzyme in the conversion of fatty acids is delta 6 desaturase (D6D). ALA is a substrate for D6D and undergoes a series of desaturation and elongation reactions to yield n-3 long chain polyunsaturated fatty acids (LCPUFA). The final step in the synthesis of DHA from ALA involves translocation of its immediate fatty acid precursor, 24:6n-3 from the endoplasmic reticulum to the peroxisome to be partially beta-oxidised to yield DHA. The involvement of multiple enzymes in the desaturation-elongation pathway, and the integration of other pathways, such as phospholipid biosynthesis, suggests there are various steps that may regulate the accumulation of DHA in cell membranes. This thesis aimed to examine the possible regulatory steps in the conversion of fatty acids to LCPUFA, particularly in the synthesis of DHA from n-3 fatty acid precursors. The human hepatoma cell line, HepG2, was used as an in vitro cell system to examine the accumulation of individual fatty acids and their metabolites in isolation from other competing fatty acid substrates. The accumulation of linoleic acid (LA, 18:2n-6) and ALA in HepG2 cell phospholipids following supplementation with increasing concentrations of each respective fatty acid correlated with that described in vivo, as was the accumulation of their conversion products. The accumulation of DHA in cells supplemented with ALA reached a plateau at concentrations above 5 micro g/ml and paralleled the accumulation of 24:6n-3 in cell phospholipids, suggesting that the delta 6 desaturation of 24:6n-3 was prevented by increasing concentrations of ALA, thereby limiting the accumulation of DHA. The accumulation of DHA in cells supplemented with eicosapentaenoic acid (EPA, 20:5n-3) or docosapentaenoic acid (DPA, 22:5n-3) was significantly greater than the level of DHA that accumulated in cells supplemented with ALA. However, regardless of substrate, the level of DHA in cell membranes reached a plateau at substrate concentrations above 5 micro g/ml. This thesis further aimed to examine the effect of fatty acid supplementation on the mRNA expression of D6D in HepG2 cells. The expression and activity of D6D mRNA is subject to nutritional and hormonal regulation. The mRNA expression of D6D in HepG2 cells following supplementation with oleic acid (OA, 18:1n-9), LA, ALA, arachidonic acid (AA, 20:4n-6) or EPA was examined by real time RT PCR. The expression of D6D mRNA was reduced by up to 50% in cells supplemented with OA, LA, ALA , AA or EPA compared with control cells and suggests that fatty acids modulate the expression of the key enzyme involved in the conversion of fatty acids. The effect of fatty acid co-supplementation on the fatty acid composition of HepG2 cell phospholipids was also examined in an attempt to gain insights into the role of D6D and the enzymes involved in peroxisomal beta-oxidation on the accumulation of DHA from n-3 fatty acid precursors. The reduction in the accumulation of DHA in cells co-supplemented with DPA and docosatetraenoic acid (DTA, 22:4n-6) was greater than in cells co-supplemented with DPA and LA, suggesting that peroxisomal beta-oxidation may have a greater role in determining the accumulation of DHA from DPA than the activity of D6D. Further investigation should be directed towards understanding the role that peroxisomal beta-oxidation may play in the synthesis of DHA from precursor fatty acids. The fatty acid composition of cell membranes in vivo is a result of several physiological processes including dietary intake, phospholipids biosynthesis and fatty acid conversion as well as catabolic processes. This thesis demonstrates that a greater understanding of the regulation of the conversion of fatty acids will help to define dietary approaches that enhance the synthesis of n-3 LCPUFA from n-3 fatty acid precursors to lead to improved outcomes for health.
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Henchiri, Chérifa. "Contribution à l'étude des delta-6 et -5 désaturations par les microsomes hépatiques de rat : effets de l'obésité et des acides gras trans (présents dans les huiles chauffées)." Dijon, 1987. http://www.theses.fr/1987DIJOS034.

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Liu, Yi-Wen. "Obesity, non-insulin-dependent diabetes mellitus and age, but not estrogen, were associated with changes of (delta)6 and (delta)5 desaturase enzyme activity in female shhf/mcc-facp rats and humans /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487936356159799.

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Vagner, Marie. "Orientation des processus métaboliques du bar européen (Dicentrarchus labrax) par un conditionnement nutritionnel au stade larvaire." Brest, 2008. http://www.theses.fr/2008BRES2009.

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Le but était de voir s’il est possible de stimuler les capacités de désaturation des acides gras pour la synthèse d’HUFA n-3 des juvéniles de bar par un conditionnement précoce. Lors d’une expérience 1 (F1), quatre groupes de larves ont reçu deux régimes de J6 à J45: LH (0,8% EPA+DHA) et HH (2,2%) à 16 ou 22°C. Après une période intermédiaire (2,7%, 19°C), la capacité des juvéniles à s’adapter à un régime carencé (0,5%) à été testée pendant 60 jours (19°C). L’expérience 2 (E2) avait pour but d’amplifier la réponse obtenue (une seul température d’élevage (19°C) et une gamme plus étendue de teneur en HUFA n-3 dans quatre régimes larvaires: XH (3,7%), HH (1,7%), LH (0,7%) et XLH (0,5%)). Après une période intermédiaire (2,7%, 19°C), les juvéniles ont reçu un régime à 0,35% pendant 35 jours. Les deux phases larvaires ont montré que les régimes carencés (0,8, 0,7 et 0,5%) stimulaient la transcription du gène de la delta-6 désaturase (∆6D, responsable de la première étape de synthèse des HUFA n-3) à J45. Mais une déficience en DHA dans les phospholipides (PL) et des retards de croissance ont été observés chez ces individus. Le conditionnement larvaire n’a pas affecté les performances de croissance des juvéniles mais E1 a montré une augmentation du niveau d’ARN de la (∆6D transitoire et une teneur en DHA des PL supérieure chez les juvéniles pré-conditionnés avec un régime carencé. F2 a mis en évidence une augmentation du niveau d’ARN tout au long de l’expérience mais une teneur en DHA similaire dans les PL. Il est possible de stimuler les capacités de désaturation des acides gras pour la synthèse d’HUFA n-3 des juvéniles de bar par un conditionnement précoce
The aim was to know if it is possible to apply a metabolic programming using nutritional conditioning during early larval stages to stimulate the fatty acid (FA) desaturation pathways of n-3 HUFA synthesis in marine fish. For the experience 1 (E1), four replicated groups of larvae were fed a diet with a Iow (LH) or high (HH) HUFA content from day 6 post-hatching to d-45 at 16 or 22°C: 0. 8 and 22% FPA÷DHA. After an intermediate period (19°C, 2. 7%), the capacity of juveniles to adapt to a HUFA-deprived diet (0. 5%) was tested during 60 days (19°C)- For the experience 2 (F2), four replicated groups of sea bass larvae were fed XH (3. 7% EPA+DHA), HH (1. 7%), LH (0. 7%) or XLH (0. 5%) diets from d-6 to d-45 at 19°C. After a period feeding a commercial diet (2. 7%, 19°C), the capacity of ail groups to adapt to an n-3 HUFA-Restricted diet (0. 3%) was tested for 35 days. The two larval periods indicated a positive modulation of the delta-6 desaturase (∆6D, rate-limiting enzyme responsible of the first step of the FA desaturation pathways for the n-3 HUFA synthesis) gene transcription by low dietary n-3 HUFA levels in larvae fed a low dietary HUFA n-3 content (0,8, 0,7 et 0. 5% EPA+DHA) than in others. Buta deficiency in DHA in phospholipides (PL) and a ower growth rate were observed, No significant effect of larval nutritional conditioning was observed in juveniles, but Fi showed a transient increase in mRNA level and an increase in DHA content in PL. F2 showed a persistent mRNA increase in pre-conditioned flsh, but similar DHA content in PL. T was possible to influence fatty acid desaturation pathways for HUFA synthesis, using a nutritional conditioning during larval stage
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Yang, Xiaoyu. "Knockdown of Delta-5 Desaturase to Elicit Anti-Cancer Effect of Dihomo-?-Linolenic Acid: Development of an ?-6 Fatty Acid-Based Therapeutic Strategy for Pancreatic Cancer." Diss., North Dakota State University, 2017. https://hdl.handle.net/10365/28361.

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Pancreatic cancer is one of the most common causes of cancer death in the United States. Unlike ?-3 fatty acids, which have been commonly used as complementary therapy to treat pancreatic cancer, ?-6s (more abundant fatty acids in the human diet) have received much less attention in cancer treatment due to generation of deleterious metabolites from cyclooxygenase (COX)-catalyzed peroxidation of arachidonic acid, a downstream ?-6. However, dihomo-?-linolenic acid (DGLA), the immediate precursor of arachidonic acid, has been recently reported to be associated with some anti-cancer effects on various types of cancer cells. Recent studies from Dr. Qian?s lab have shown that the exclusive free radical byproduct 8-hydroxyoctanoic acid (8-HOA) formed from DGLA peroxidation catalyzed by COX-2 may actually account for DGLA?s anti-cancer activities. However, the generation of 8-HOA can be readily limited by the conversion from DGLA to arachidonic acid mediated by delta-5 desaturase (D5D). Here, we hypothesized that the high COX-2 expression in cancer cells and tumors can be exploited to promote formation of 8-HOA from COX-catalyzed DGLA peroxidation, and knockdown of D5D can reserve more DGLA to form 8-HOA which thus inhibits pancreatic cancer cell growth and migration. Clonogenic assay, apoptosis assay, transwell assay, immunofluorescence, and western blot were used to assess cancer cell and tumor viability, apoptosis, migration, invasion, and the associated molecular mechanisms. Our study showed that 8-HOA can inhibit pancreatic cancer cell growth and migration by acting as a histone deacetylase inhibitor to alter the expression of proteins involved in cancer growth and metastasis. We observed that knockdown of D5D (via siRNA/shRNA transfection) can promote formation of 8-HOA from COX-catalyzed DGLA peroxidation to a threshold level, leading to inhibition of pancreatic cancer cell growth and migration as well as subcutaneous tumor xenografts. Knockdown of D5D and DGLA treatment improved the efficacy of many chemotherapy drugs. We demonstrated that we could take advantage of the commonly overexpressed COX-2 level in cancers to control pancreatic cancer cell and tumor growth and metastasis. With this shifting paradigm of COX-2 biology in cancer treatment, the research outcome may provide us a ?-6s-based diet care strategy to supplement current chemotherapy.
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8

Cedernaes, Jonathan. "Intestinal Gene Expression Profiling and Fatty Acid Responses to a High-fat Diet." Doctoral thesis, Uppsala universitet, Funktionell farmakologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-196207.

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The gastrointestinal tract (GIT) regulates nutrient uptake, secretes hormones and has a crucial gut flora and enteric nervous system. Of relevance for these functions are the G protein-coupled receptors (GPCRs) and the solute carriers (SLCs). The Adhesion GPCR subfamily is known to mediate neural development and immune system functioning, whereas SLCs transport e.g. amino acids, fatty acids (FAs) and drugs over membranes. We aimed to comprehensively characterize Adhesion GPCR and SLC gene expression along the rat GIT. Using qPCR we measured expression of 78 SLCs as well as all 30 Adhesion GPCRs in a twelve-segment GIT model. 21 of the Adhesion GPCRs had a widespread (≥5 segments) or ubiquitous (≥11 segments) expression. Restricted expression patterns were characteristic for most group VII members. Of the SLCs, we found the majority (56 %) of these transcripts to be expressed in all GIT segments. SLCs were predominantly found in the absorption-responsible gut regions. Both Adhesion GPCRs and SLCs were widely expressed in the rat GIT, suggesting important roles. The distribution of Adhesion GPCRs defines them as a potential pharmacological target. FAs constitute an important energy source and have been implicated in the worldwide obesity increase. FAs and their ratios – indices for activities of e.g. the desaturase enzymes SCD-1 (SCD-16, 16:1n-7/16:0), D6D (18:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6) – have been associated with e.g. overall mortality and BMI. We examined whether differences in FAs and their indices in five lipid fractions contributed to obesity susceptibility in rats fed a high fat diet (HFD), and the associations of desaturase indices between lipid fractions in animals on different diets. We found that on a HFD, obesity-prone (OP) rats had a higher SCD-16 index and a lower linoleic acid (LA) proportions in subcutaneous adipose tissue (SAT) than obesity-resistant rats. Desaturase indices were significantly correlated between many of the lipid fractions. The higher SCD-16 may indicate higher SCD-1 activity in SAT in OP rats, and combined with lower LA proportions may provide novel insights into HFD-induced obesity. The associations between desaturase indices show that plasma measurements can serve as proxies for some lipid fractions, but the correlations seem to be affected by diet and weight gain.
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Xu, Yi. "Development of a Novel Omega-6 Fatty Acid Based Treatment Strategy for Colon Cancer by Knocking Down Delta-5-Desaturase and Exploiting High COX-2 Levels in Cancer CellsTumors." Diss., North Dakota State University, 2017. http://hdl.handle.net/10365/25947.

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Colon cancer is the third most commonly diagnosed cancer in the world. Research showed that arachidonic acid, a downstream ?-6 fatty acid (?-6), plays a role in colon cancer development by producing deleterious metabolites from its COX-2 catalyzed peroxidation. On the other hand, dihomo-?-linolenic acid (DGLA), the immediate precursor of arachidonic acid, may represent an exceptional ?-6 associated with anti-cancer activities. However, the mechanism of DGLA?s anti-cancer effect still remains unclear, and the rapid conversion of DGLA to arachidonic acid in human body by delta-5 desaturase (D5D) greatly restricts DGLA?s availability. Recent work from Dr. Qian?s group demonstrated that DGLA can undergo a unique pathway during COX-2-catalyzed peroxidation and produce distinct free radical byproducts. Here we proposed that (1) DGLA?s anti-cancer activity is derived from its distinct byproduct, e.g., 8-hydroxyoctanoic acid (8-HOA), from COX-2-catalyzed peroxidation, and (2) by knocking down cellular D5D expression, we can take advantage of the commonly overexpressed COX-2 in cancer cells to promote 8-HOA formation, inhibit colon cancer growth and migration, and develop a novel cancer therapy and a paradigm shift concept in contrast to classic COX-2 inhibition strategy in cancer treatment. Our results showed that 8-HOA, at physiological concentrations, could suppress human colon cancer cell growth and migration, by serving as a histone deacetylase inhibitor and DNA damage agents. Data also showed that knocking down D5D in colon cancer cells promoted endogenous formation of 8-HOA to a threshold level which then inhibited cancer cell growth and migration. Consistent with the in vitro data, knocking down D5D in human colon cancer cell-derived mice xenograft tumors along with DGLA supplementation promoted endogenous formation of 8-HOA in vivo and significantly suppressed tumor growth. In addition, direct supplementation and endogenous formation of 8-HOA from COX-2 catalyzed DGLA peroxidation were found to enhance the efficacies of various chemotherapeutic drugs. In conclusion, we demonstrated that by taking advantage of commonly overexpressed COX-2 in cancer, D5D knockdown can promote the formation of 8-HOA from DGLA peroxidation to inhibit cancer growth and migration. Results from this work will lead us to develop a novel ?-6 based treatment strategy for colon cancer.
NCI/NIH: R15CA140833
National Institutes of Health (NIH)
Sanford Health-NDSU Collaborative Research Seed Grant
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10

Cho, Hye-kyung. "Cloning, expression, and fatty acid regulation of mammalian [delta]-5 and [delta]-6 desaturases /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.

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Thesis (Ph. D.)--University of Texas at Austin, 1999.
Vita. Greek alphabet delta in title. Includes bibliographical references (leaves 136-155). Available also in a digital version from Dissertation Abstracts.
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Book chapters on the topic "Delta 6 desaturase"

1

Miyazaki, M., F. E. Gomez, and J. M. Ntambi. "Presence of a Palmitoyl-CoA Delta 6-Desaturase in the Preputial Gland of the Mouse." In Advanced Research on Plant Lipids, 95–99. Dordrecht: Springer Netherlands, 2003. http://dx.doi.org/10.1007/978-94-017-0159-4_21.

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2

Sato, M., Y. Adan, K. Shibata, Y. Shoji, H. Sato, and K. Imaizumi. "Cloning of Rat Δ6-Desaturase and Its Regulation by Dietary Eicosapentaenoic or Docosahexaenoic Acid." In Fatty Acids and Lipids - New Findings, 196–99. Basel: KARGER, 2000. http://dx.doi.org/10.1159/000059780.

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3

Tosi, Federica, Filippo Sartori, Patrizia Guarini, Oliviero Olivieri, and Nicola Martinelli. "Delta-5 and Delta-6 Desaturases: Crucial Enzymes in Polyunsaturated Fatty Acid-Related Pathways with Pleiotropic Influences in Health and Disease." In Advances in Experimental Medicine and Biology, 61–81. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-07320-0_7.

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