Prostaglandins, Leukotrienes and Essential Fatty Acids - Articles in Press

Polyunsaturated fatty acids deficits are associated with psychotic state and negative symptoms in patients with schizophrenia - Corrected Proof

2010-07-28

Abstract: The study was aimed to examine membrane polyunsaturated fatty acids (PUFAs) profile in patients with schizophrenia (SZ) before and after antipsychotic medication and test their association with psychopathology. Erythrocyte membrane fatty acids were analysed by gas chromatography in 36 drug-free patients with SZ and 36 controls. Psychometric evaluation and blood sampling were achieved at baseline and after 3 months of antipsychotic treatment. At enrolment, levels of total PUFAs and arachidonic (AA) and docosahexaenoic (DHA) acids were significantly lower, but ω6/ω3 PUFAs ratio was higher in patients. AA and DHA were negatively related to the Andreason’s scale for assessment of negative symptoms (SANS) score. DHA was inversely related to “alogia”, “anhedonia”, “avolition”, and “blunted affect” subitems of SANS. After 3 months under typical antipsychotic drugs, fatty acid profile turned into comparable to controls in parallel with psychopathology improvement. Data indicate that PUFAs deficits are associated with psychotic state and negative symptoms of SZ.

Bioavailability of marine n-3 fatty acid formulations - Corrected Proof

J. Dyerberg, P. Madsen, J.M. Møller, I. Aardestrup, E.B. Schmidt — 2010-07-21

Abstract: The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations — ethyl esters, free fatty acids and re-esterified triglycerides — with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

Erythrocyte fatty acids and prostate cancer risk: A comparison of methods - Corrected Proof

J. Shannon, J. O’Malley, M. Mori, M. Garzotto, A.J. Palma, I.B. King — 2010-07-15

Abstract: The role of fatty acids (FA) in prostate carcinogenesis is unclear. Interest in the inter-relationship among different types of FA has resulted in new analytic approaches to FA and their role in cancer development.We evaluated the association between erythrocyte FA and prostate cancer in 127 prostate cancer patients and 183 screen negative controls. We present three approaches to the analyses of the FA and prostate cancer association; (1) individual or common groups of FA, (2) biologically meaningful FA ratios and (3) principal components analysis.Monounsaturated FA and the alpha-linolenic:eicosapentaenoic ratio were associated with reduced risk of prostate cancer. However, Factor 1, which was strongly correlated with some long chain saturated FA, was associated with an increased risk of prostate cancer.We provide an example of modeling FA and their inter-relationships on the risk of prostate cancer. Comparing three approaches suggests the importance of considering the impact of the entire fatty acid profile in disease prevention.

Is marine mammal fat or fish intake most strongly associated with omega-3 blood levels among the Nunavik Inuit? - Corrected Proof

M. Lucas, F. Proust, C. Blanchet, A. Ferland, S. Déry, B. Abdous, É. E. Dewailly — 2010-07-15

Abstract: Here we determined the relationship between red blood cell (RBC) omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) and usual dietary marine food product intake among 630 Nunavik Inuit adults.Marine food product intake was determined by a food frequency questionnaire (FFQ) and fatty acids were quantified in RBC membranes. Multiple linear regression was undertaken to determine the relationship between marine food product inatke and RBC n-3 LC-PUFAs (dependent variable).Mean RBC n-3 LC-PUFA level was 9.16±0.11% [SEM]. The highest correlations noted with RBC n-3 LC-PUFAs were for marine mammal fat (rs=0.41, P<0.0001) and fish (rs=0.35, P<0.0001). Age, total marine mammal fat and fish intakes were the variables that contributed the most to predicted RBC n-3 LC-PUFAs and explained 34%, 15% and 5%, respectively, of its variances.Our study indicates that marine mammal fat intake is more important than fish in accounting for RBC n-3 LC-PUFA levels among the Nunavik Inuit.

Genetic polymorphism of CYP2U1, a cytochrome P450 involved in fatty acids hydroxylation - Corrected Proof

2010-07-14

Abstract: The human cytochrome P450 2U1 (CYP2U1) has been described as a novel extrahepatic P450. CYP2U1 is a highly conserved gene mainly expressed in brain and thymus, but also at lower levels in kidney, lung or heart. This selective tissue distribution suggests important endogenous functions, in particular in the conversion of arachidonic acid into two bioactive compounds, the 19- and 20-HETE. To investigate the extent of CYP2U1 genetic polymorphism in 70 French individuals, a screening for sequence variations in the 5′-flanking and protein encoding regions was performed using PCR-SSCP and sequencing strategies. Four polymorphisms were identified and correspond to −204C>A and –241T>C in the 5′-flanking region, −37G>A in the 5′-untranslated region, and IVS2-17T>C in the intron 2. The most frequent mutations, –241T>C (59.7%) and IVS2-17T>C (66.0%), did not seem to alter CYP2U1 lung expression. These results suggest that CYP2U1 exhibits few genetic variations and support a probable role in endogenous processes.

Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women - Corrected Proof

2010-06-28

Abstract: Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose.

Age dependent incorporation of 14C-DHA into rat brain and body tissues after dosing various 14C-DHA-esters - Corrected Proof

2010-06-28

Abstract: Introduction: The omega-3 fatty acid docosahexaenoic acid (DHA) accounts for 10% of fatty acids in human brain and is critical for neuronal function and brain development. Mechanisms of transport, accumulation and conservation of DHA in the brain are unclear. The objective of the study was to quantify the age dependent DHA incorporation into the brain of 2-, 4- or 10-week-old rats after a bolus dose of different DHA-esters.Methods: Rats were gavaged with 14C-DHA-TAG, 14C-DHA-PL or 14C-DHA-TAG+PL at 2mgDHA/kg BW. After 24h the distribution of radioactivity in body and brain regions was determined using quantitative whole body autoradiography (QWBA). Radiolabeled compounds were extracted from the brains to determine the identity of the radiolabeled compounds.Results: Accumulation of orally ingested 14C-DHA in rat brain was less than 1% of the dose and decreased with age. Ester specific differences were seen only in 10-week-old rats, where oral 14C-DHA-PL delivered a 2-fold higher accretion of radioactivity in the brain.Conclusions: Less than 1% of a dietary achievable DHA dose reached the rat brain within 24h. Optimal efficacy of DHA-PL may occur in older age groups.

Omega-3 long chain fatty acid synthesis is regulated more by substrate levels than gene expression - Corrected Proof

W.C. Tu, R.J. Cook-Johnson, M.J. James, B.S. Mühlhäusler, R.A. Gibson — 2010-06-23

Abstract: The conversion of linoleic acid (LA) and alpha-linolenic acid (ALA) to long chain polyunsaturated fatty acids (LCPUFA) is known to involve desaturation and elongation steps. Although there is evidence that genes for these steps can be regulated by extremes of dietary PUFA, the degree to which there is meaningful regulation of LCPUFA levels in tissues by diet as a result of changes in expression of desaturase and elongase genes is unclear. In this study, we tested the effect of increasing ALA levels in diets of rats from 0.2% to 2.9% energy (en) against a constant LA level (1%en) on plasma and liver phospholipid LCPUFA content together with the expression of hepatic genes involved in PUFA metabolism, the desaturases FADS1 and FADS2, the elongases ELOV2 and ELOV5, and the transcription factors sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor alpha (PPARα). The levels of plasma and liver eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) increased in proportion to dietary ALA whereas docosahexaenoic acid (DHA) increased only up to 1%en ALA. A low PUFA (0.4%en) reference diet stimulated the expression of delta 6 desaturase (FADS2) and elongase 2 (ELOVL2) when compared to higher PUFA diets. There was, however, no difference in the expression of any of the genes in rats, which were fed diets containing between 0.2%en and 2.9%en ALA and mRNA expression was unrelated to tissue/plasma LCPUFA content. These data suggest that the endogenous synthesis of n−3 LCPUFA from the precursor ALA is regulated independently of changes in the expression of the synthetic enzymes or regulatory transcription factor, and provides evidence that n−3 LCPUFA synthesis is regulated more by substrate competition for existing enzymes than by an increase in their mRNA expression.

Maternal dietary fat intake during gestation and lactation alters tissue fatty acid composition in the adult offspring of C57Bl/6 mice - Corrected Proof

Kanta Chechi, Gene R. Herzberg, Sukhinder K. Cheema — 2010-06-18

Abstract: We investigated the effects of maternal dietary fat intake during gestation and lactation on the tissue fatty acid composition of the adult offspring. Female C57Bl/6 mice were fed high fat diets enriched with lard or safflower oil or chow during mating, gestation and lactation. The offspring obtained from each group of mothers were continued on diets rich in lard, safflower oil or chow post-weaning until 11 weeks of age. Livers and hearts were collected for fatty acid analysis. A maternal diet rich in safflower oil was associated with enrichment of hepatic tissue with n-3 polyunsaturated fatty acids in the offspring fed chow post-weaning compared to the offspring fed chow throughout. However, a continuous exposure to a safflower oil- as well as lard-rich diet during the pre- and post-weaning time periods was associated with reduced content of docosahexaenoic acid in both liver and heart tissues compared to the offspring fed chow throughout. In conclusion, this study demonstrated lasting effects of maternal dietary fat intake, as well as an interaction between pre- and post-weaning diets, on the tissue fatty composition in adult offspring.

Cide-a and Cide-c are induced in the progression of hepatic steatosis and inhibited by eicosapentaenoic acid - Corrected Proof

2010-06-14

Abstract: Cide-a and Cide-c belong to the cell death-inducing DNA fragmentation factor-α-like effector family. Recent evidences suggest that these proteins may be involved in lipid accumulation in liver and adipose tissues. We confirmed that in the high-fat/high-sucrose diet-induced murine model of hepatic steatosis, the expression levels of the Cide-a and Cide-c genes were markedly and time-dependently increased, but returned to normal levels following improvement of hepatic steatosis by eicosapentaenoic acid (EPA) administration. Levels of expression of the Cide-a and Cide-c genes correlated well with plasma ALT. EPA inhibited the promoter activity of the Cide-a gene in vitro. Sterol regulatory element-binding protein-1 (SREBP-1) markedly enhanced the promoter activity of Cide-a, and EPA inhibited the expression of Cide-a mRNA. SREBP-1 and EPA did not affect those of Cide-c. These findings indicate that Cide-a and Cide-c are closely involved in the progression of hepatic steatosis, and that EPA inhibits Cide-a gene expression through SREBP-1 regulation.

Eicosapentanoic acid prolongs survival and attenuates inflammatory response in an experimental model of lethal trauma - Corrected Proof

2010-06-10

Summary: In an attempt to define the efficacy of intravenously administered n-3 polyunsaturated fatty acids (PUFAs) in an animal model of lethal trauma following femur fracture, an intravenous solution of eicosapentanoic acid (EPA) – one n-3 PUFA – was administered in 25 rabbits; 13 were controls and 12 were treated with EPA 30min after fracture. Vital signs were recorded and serum concentrations of tumor necrosis factor-alpha (TNFα) and respiratory burst of neutrophils were assessed. Survival of controls was 7.7% and of animals treated with EPA 50% (log-rank: 5.162; p: 0.023). Vital signs of both groups did not differ. Oxidative burst of neutrophils was greater among EPA-treated animals compared with controls at 48h (p: 0.010). Serum levels of TNFα of the former group were decreased compared with the latter at 48h (p: 0.019). Bacterial growth of enterobacteriaceae from liver and spleen after death or euthanasia was lower among EPA-treated rabbits than controls. These results suggest that EPA possesses considerable immunomodulatory activities improving survival in a model of lethal trauma. Restoration of oxidative burst conferring efficient phagocytosis of evading bacteria seems the most probable mechanism of action.

WITHDRAWN: Prostaglandin E1 attenuate hydrogen peroxide-induced stress injury in human umbilical vein endothelial cells - Corrected Proof

Wentong Fang, Hongjian Li, Liaosheng Zhou — 2010-04-09

This article has been withdrawn at the request of the author(s). The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.