Decrease In Docosahexaenoic Acid Research Articles

Enzyme-assisted aqueous extraction of fish oil from Baltic herring (Clupea harengus membras) with special reference to emulsion-formation, extraction efficiency, and composition of crude oil.

Enzyme-assisted aqueous extraction (EAAE) is a green, and scalable method to produce oil and protein hydrolysates from fish. This study investigated the role of different parameters on emulsion formation, oil recovery, and the composition of crude oil during EAAE of Baltic herring (Clupea harengus membras). Fatty acid compositions, lipid classes, tocopherols, and oxidation status of the EAAE crude oils were studied. Compared to solvent-extracted oil, EAAE resulted in a lower content of phospholipids accompanied by a 57% decrease in docosahexaenoic acid. Changing fish to water ratio from 1:1 to 2:1 (w/w) with ethanol addition led to the greatest reduction (72%) of emulsion, which resulted in an increase in oil recovery by 11%. The addition of ethanol alone, or reduction of enzyme concentration from 0.4% to 0.1% also reduced emulsion-formation significantly. Overall, emulsion reduction resulted in higher content of triacylglycerols and n-3 polyunsaturated fatty acids in the crude oil extracted.

The potential adverse effects of acrylamide on the oxidative stress response, fatty acids profile, and histopathological aspect of the Mediterranean Holothuria forskali respiratory tree.

Acrylamide (ACR), organic compound, has been widely used owing to its broad spectrum of chemical and industrial applications. This study aims at evaluating the response of the antioxidant defense system, fatty acid composition and histopathological aspect in the respiratory trees of Holothuria forskali against ACR exposure under laboratory conditions. Holothuries were exposed to 5, 10, and 20 mg L-1 ACR concentrations for 5 days. A significant increase in n-6 polyunsaturated fatty acids levels especially the arachidonic acid (ARA, C20:4n-6) and its precursor linoleic acid (LA, C18:2n-6) in ACR-treated organisms. Regarding the n-3 levels, eicosapentaenoic acid (EPA, C20:5n-3) levels were increased in treated groups despite an acute decrease in docosahexaenoic acid (DHA, C22:6n-3) levels was observed. Our results showed a significant increase in hydrogen peroxide, malondialdehyde, protein carbonyl, and metallothionein levels along with an alteration of the antioxidants status in all treated sea cucumbers. The exposure to ACR prompted the inhibition of Acetylcholinesterase activity in a concentration-dependent manner. The histopathological aspect was marked especially with the infiltration of coelomic cells which confirms our biochemical findings. Our study provided novel insights to create a link between redox status and fatty acid composition disruptions to better understand ACR-triggered toxicity.

A decrease of docosahexaenoic acid in testes of mice fed a high-fat diet is associated with impaired sperm acrosome reaction and fertility.

Obesity is a major worldwide health problem that is related to most chronic diseases, including male infertility. Owing to its wide impact on health, mechanisms underlying obesity-related infertility remain unknown. In this study, we report that mice fed a high-fat diet (HFD) for over 2 months showed reduced fertility rates and increased germ cell apoptosis, seminiferous tubule degeneration, and decreased intratesticular estradiol (E2) and E2-to-testosterone ratio. Interestingly, we also detected a decrease in testicular fatty acid levels, behenic acid (C22:0), and docosahexaenoic acid (DHA, 22:6n-3), which may be related to the production of dysfunctional spermatozoa. Overall, we did not detect any changes in the frequency of seminiferous tubule stages, sperm count, or rate of in vitro capacitation. However, there was an increase in spontaneous and progesterone-induced acrosomal exocytosis (acrosome reaction) in spermatozoa from HFD-fed mice. These data suggest that a decrease in E2 and fatty acid levels influences spermatogenesis and some steps of acrosome biogenesis that will have consequences for fertilization. Thus, our results add new evidence about the adverse effect of obesity in male reproduction and suggest that the acrosomal reaction can also be affected under this condition.

<p><strong>Compositional alterations in erythrocyte membranes in Type II diabetes</strong></p>

Loss of erythrocyte membrane deformability is one of the most crucial factors in developing complications associated with Type II diabetes. The observed loss of erythrocyte membrane deformability could be related to structural changes in the membrane. In this context, here, we have made an attempt at gaining a better insight (quantitative as well as qualitative) into the protein and lipid contents in erythrocyte membranes and their interrelationships in Type II diabetes. Age matched control (n=12) and Type II diabetic subjects (n=22) were selected for this study. Morphological characteristics were studied by atomic force microscopy (AFM). AFM study confirmed remarkable alterations in morphology of the diabetic erythrocytes. In diabetic erythrocytes following changes were noted: (i) Significant increase in membrane as well as cytosolic proteins with a marginal increase in phospholipids content; (ii) The membrane total lipids:protein, phospholipids:protein, cholesterol:protein and phospholipids:cholesterol (mole:mole) ratios decreased significantly; (iii). A reproducible decrease in docosahexaenoic acid (DHA) and Omega-3 index with increase in Omega-6:Omega-3 ratio in membrane fatty acids; and (iv) The SDS-PAGE analysis indicated that all membrane proteins increased in almost equal proportion leading to increased membrane protein content. The observed compositional and stochiometric changes in lipids, proteins and their ratios may underlie morphological alterations and loss of deformability.

Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta–brain axis

Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to trophoblast giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+ GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, a negative correlation existed between dopamine+ GCs and reductions in spongiotrophoblast to GC area ratio. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GCs within the junctional zone. Third, imbalances in neurotransmitter-positive GCs and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental-brain axis of the developing mouse fetus.

Next-Generation Sequencing Identifies Polyunsaturated Fatty Acid Responsive Genes in the Juvenile Rat Cerebellum.

Dietary n-3 polyunsaturated fatty acids (PUFA) influence postnatal brain growth and development. However, little data exist regarding the impacts of dietary n-3 PUFA in juvenile animals post weaning, which is a time of rapid growth. We tested the hypothesis that depleting dietary n-3 PUFA would result in modifications to the cerebellar transcriptome of juvenile rats. To test this hypothesis, three week old male rats (an age that roughly corresponds to an 11 month old child in brain development) were fed diets containing either soybean oil (SO) providing 1.1% energy from α-linolenic acid (ALA; 18:3n-3; ALA-sufficient) or corn oil (CO) providing 0.13% energy from ALA (ALA-deficient) for four weeks. Fatty acids (FAs) in the cerebellum were analyzed and revealed a 4-fold increase in n-6 docosapentaenoic acid (DPA; 22:5n-6), increases in arachidonic acid (AA; 20:4n-6) and docosatetraenoic acid (DTA; 22:4n-6), but no decrease in docosahexaenoic acid (DHA; 22:6n-3), in animals fed CO versus SO. Transcript abundance was then characterized to identify differentially expressed genes (DEGs) between the two diets. Upper quartile (UQ) scaling and transcripts per million (TPM) data normalization identified 100 and 107 DEGs, respectively. Comparison of DEGs from the two normalization methods identified 70 genes that overlapped, with 90% having abundance differences less than 2-fold. Nr4a3, a transcriptional activator that plays roles in neuroprotection and learning, was elevated over 2-fold from the CO diet. These data indicate that expression of Nr4a3 in the juvenile rat cerebellum is responsive to dietary n-3 PUFA, but additional studies are needed clarify the neurodevelopmental relationships between n-3 PUFA and Nr4a3 and the resulting impacts.

Unraveling the causes of arrhythmias in very-long chain acyl-CoA (VLCAD) deficiency through the combined use of non-targeted lipidomic and molecular analyses in a mouse model

VLCAD catalyses the first reaction of mitochondrial fatty acids (FA) β-oxidation. Inherited VLCAD deficiency predisposes to severe neonatal arrhythmias whose pathophysiology is not fully understood. We hypothesized that VLCAD deficiency disrupts cardiac lipid homeostasis, which could contribute to arrhythmia. Our study model is the VLCAD null mouse (VLCAD −/− ), which is known to develop a prolonged QT interval and ventricular arrhythmias. Mice were fed a chow or high fat (HF) diet, the latter being known to worsen the cardiac phenotype in VLCAD deficiency. Non-targeted lipidomic profiling of heart tissues was achieved using liquid chromatography-mass spectrometry (LC-QTOF). The expression of genes or proteins involved in polyunsaturated FA synthesis, phospholipid (PL) remodeling, endoplasmic reticulum (ER) stress and calcium handling were assessed using RT-qPCR or Western blotting. Compared to their littermate counterparts, VLCAD −/− mouse hearts displayed alterations in the FA composition of PL characterised by an increase in arachidonic acid and a decrease in docosahexaenoic acid, a profile that was worsened with the HF diet. These changes in PL composition were associated with diet-dependent increased expression of gene or protein markers for (1) PL remodeling, especially the calcium-dependent phospholipase A2 and the lysophosphatidylcholine-acyltransferase 2, (2) ER stress, namely CHOP and GRP78, and (3) calcium handling, namely SERCA2a and phospholamban (PLB). In contrast, the phosphorylated form of PLB (Ser16) and RyR2 (Ser2808) was decreased. Altogether, results from this study highlight perturbations in PL remodeling in VLCAD −/− mouse hearts, which are associated with ER stress and alterations in proteins involved in calcium handling and exacerbated by a HF diet. These perturbations represent novel potential mechanisms, which could contribute to the pathogenesis of arrhythmias in VLCAD −/− mice as well as in humans.

MJ4-M4 - Unraveling the causes of arrhythmias in very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency through the combined use of nontargeted lipidomic and molecular analyses in a mouse model

Background VLCAD catalyses the first reaction of mitochondrial fatty acids (FA) β-oxidation. Inherited VLCAD deficiency predisposes to severe neonatal arrhythmias whose pathophysiology is not fully understood. We hypothesized that VLCAD deficiency disrupts cardiac lipid homeostasis, which could contribute to arrhythmia. Methods Our study model is the VLCAD null mouse (VLCAD−/−), which is known to develop a prolonged QT interval and ventricular arrhythmias. Mice were fed a chow or high fat (HF) diet, the latter being known to worsen the cardiac phenotype in VLCAD deficiency. Non-targeted lipidomic profiling of heart tissues was achieved using liquid chromatography-mass spectrometry (LC-QTOF). The expression of genes or proteins involved in polyunsaturated FA synthesis, phospholipid (PL) remodeling, endoplasmic reticulum (ER) stress and calcium handling were assessed using RT-qPCR or Western blotting. Results Compared to their littermate counterparts, VLCAD−/− mouse hearts displayed alterations in the FA composition of PL characterised by an increase in arachidonic acid and a decrease in docosahexaenoic acid, a profile that was worsened with the HF diet. These changes in PL composition were associated with diet-dependent increased expression of gene or protein markers for (1) PL remodeling, especially the calcium-dependent phospholipase A2 and the lysophosphatidylcholine-acyltransferase 2, (2) ER stress, namely CHOP and GRP78, and (3) calcium handling, namely SERCA2a and phospholamban (PLB). In contrast, the phosphorylated form of PLB (Ser16) and RyR2 (Ser2808) was decreased. Conclusion Altogether, results from this study highlight perturbations in PL remodeling in VLCAD−/− mouse hearts, which are associated with ER stress and alterations in proteins involved in calcium handling and exacerbated by a HF diet. These perturbations represent novel potential mechanisms, which could contribute to the pathogenesis of arrhythmias in VLCAD−/− mice as well as in humans.

Protective effect of resveratrol against light-induced retinal degeneration in aged SAMP8 mice.

PurposeThe purpose of this study was to determine the protective effects of Resveratrol (RESV) on acute bright light-induced retinal degeneration in aged senescence accelerated mouse strain.MethodsTen three-month-old male SAMP8 mice (prone to aging) were randomly assigned to two experimental dietary groups: one untreated group and one RESV treatment group (n=20 eyes for each group). After 30 days of treatment, mice were exposed to intense bright light. Ten male SAMR1 mice (resistant to aging) served as control (n=20 eyes). The protective effects of RESV administration on light-induced retinal degeneration in SAMP8 strain as well as the effect of bright light damage in the retinas of SAMP8 mice were analyzed by electroretinography (ERG), retinal histology, mRNA, protein and lipid profile.Results68%-85% of a-wave amplitude and 72%-92% of b-wave amplitude were persevered by RESV in SAMP8 mice that were exposed to light damage. Also, RESV preserved their photoreceptor nuclei. mRNA expression of neuroprotective factors leukemia inhibitory factor (LIF), brain derived neurotrophic factor (BDNF), oncostatin M (OSM), cardiotrophin 1(CT-1) and cardiotrophin-like cytokine (CLC) were up-regulated 28, 8, 7, 5 and 9-fold in SAMP8 mice after RESV treatment. In addition, RESV could suppress the NF-κB pathway by down-regulating the expression of pIκB. Light damage led to increase of saturated FA, monoenoic FA, n6 PUFA and n6/n3 ratio and decrease of Docosahexaenoic acid (DHA). There was no significant difference on DHA and the ratio of n6/n3-FA between the untreated and RESV treated SAMP8 mice.ConclusionsCollectively, our study provides evidence that RESV prevents light-induced retinal damage associated with aging.

Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo.

Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR), whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR).TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities. Cardiotoxicity is very rare in patients treated with erlotinib, but considerably more common after sunitinib treatment. We hypothesized that the deleterious effects of TKIs on the heart were related to their impact on cardiac metabolism. Methods: Female FVB/N mice (10/group) were treated with therapeutic doses of sunitinib (40 mg/kg), erlotinib (50 mg/kg), or vehicle daily for two weeks. Echocardiographic assessment of the heart in vivo was performed at baseline and on Day 14. Heart, skeletal muscle, liver and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Results: Compared to vehicle-treated controls, sunitinib-treated mice had significant decreases in systolic function, whereas erlotinib-treated mice did not. Non-targeted metabolomics analysis of heart identified significant decreases in docosahexaenoic acid (DHA), arachidonic acid (AA)/ eicosapentaenoic acid (EPA), O-phosphocolamine, and 6-hydroxynicotinic acid after sunitinib treatment. DHA was significantly decreased in skeletal muscle (quadriceps femoris), while elevated cholesterol was identified in liver and elevated ethanolamine identified in serum. In contrast, erlotinib affected only one metabolite (spermidine significantly increased). Conclusions: Mice treated with sunitinib exhibited systolic dysfunction within two weeks, with significantly lower heart and skeletal muscle levels of long chain omega-3 fatty acids docosahexaenoic acid (DHA), arachidonic acid (AA)/eicosapentaenoic acid (EPA) and increased serum O-phosphocholine phospholipid. This is the first link between sunitinib-induced cardiotoxicity and depletion of the polyunsaturated fatty acids (PUFAs) and inflammatory mediators DHA and AA/EPA in the heart. These compounds have important roles in maintaining mitochondrial function, and their loss may contribute to cardiac dysfunction.

Influence of protein deficient diet, vitamin B[sub]2[/sub] supplementation and physical training on serum composition of polyunsaturated fatty acids (PUFAs) in rats.

[b]Introduction[/b]. Prolonged shortages of protein in the diet significantly alter the composition and content of polyunsaturated fatty acids (PUFA) in tissues and body fluids. One of nutritional factors which may reduce negative effects of protein malnutrition might be vitamin B[sub]2[/sub] due to its influence on lipids metabolism. [b]Objective. [/b]The aim of the study was to investigate the influence of low protein (LP) diet enriched with vitamin B[sub]2[/sub] on the content and composition of PUFA in the blood serum of rats treated with dosed physical exercise. [b]Materials and method. [/b]The experiment was carried out for 3 months on 72 growing male Wistar rats divided into 5 groups. Animals were fed ad libitum on a diet with an energy value of 350 kcal/100 g, in which 4.5% of the energy was provided by protein. In the control diet, 20% of the energy was provided by protein. Two groups were fed the diet enriched with vitamin B2. The two groups of tested animals were trained for 5 days a week. [b]Results.[/b] LP diet caused a decrease in α-linolenic acid (ALA) after 30 days, and a decrease in docosahexaenoic acid (DHA) after 60 days of experiment, compared with rats fed the control diet. After 60 and 90 days of the experiment, a significant decrease was noted in arachidonic acid (AA) in serum of trained rats, compared with sedentary rats fed the LP diet. Physical activity increased LA (mainly on day 30), EPA (on day 90) and reduced AA content (on day 90) in serum of rats fed the LP diet. B2 supplementation in the trained LP group did not change the EPA and AA dependence; however, there was a decrease in LA content in comparison to the non-supplemented trained group. [b]Conclusions. [/b] Results of this study suggest that all investigated factors (protein deficiency, physical exercise and supplementation of vitamin B2) have significant impact on PUFA composition of serum in rats.

Loss of human disease protein retinitis pigmentosa GTPase regulator (RPGR) differentially affects rod or cone-enriched retina.

It is unclear how genes, such as RPGR (retinitis pigmentosa guanine triphosphatase regulator) that are expressed in both rods and cones, cause variable disease pathogenesis. Using transcriptomic analysis, we show that loss of RPGR in a rod-dominant mouse retina (Rpgr(ko)) results in predominant alterations in genes involved in actin cytoskeletal dynamics, prior to onset of degeneration. We validated these findings and found an increase in activated RhoA-GTP levels and polymerized F-actin in the Rpgr(ko) mouse retina. To assess the effect of the loss of RPGR in the all-cone region of the human retina, we used Nrl(-/-) (neural retina leucine zipper) mice, to generate Rpgr(ko)::Nrl(-/-) double-knock-out (Rpgr-DKO) mice. These mice exhibited supranormal cone response to light and substantially retained retinal architecture. Transcriptomic analysis revealed predominant up-regulation of retinal pigmented epithelium (RPE)-specific genes associated with visual cycle, whereas fatty acid analysis showed mild decrease in docosahexaenoic acid in the retina of the Rpgr-DKO mice when compared with the Nrl(-/-) mice. Our data reveal new insights into distinct intracellular pathways that are involved in RPGR-associated rod and cone dysfunction and provide a platform to design new treatment modalities.

Basal ganglia vulnerability to oxidative stress.

Basal ganglia vulnerability to oxidative stress.

Deregulated Balance of Omega-6 and Omega-3 Polyunsaturated Fatty Acids following Infection by the Zoonotic Pathogen Streptococcus suis

Streptococcus suis is an important swine pathogen and an emergent zoonotic pathogen. Excessive inflammation caused by S. suis is responsible for early high mortality in septic shock-like syndrome cases. Polyunsaturated fatty acids (PUFAs) may contribute to regulating inflammatory processes. This study shows that mouse infection by S. suis is accompanied by an increase of arachidonic acid, a proinflammatory omega-6 (ω-6) PUFA, and by a decrease of docosahexaenoic acid, an anti-inflammatory ω-3 PUFA. Macrophages infected with S. suis showed activation of mitogen-activated protein kinase pathways and cyclooxygenase-2 upregulation. Fenretinide, a synthetic vitamin A analog, reduced in vitro expression of inflammatory mediators. Pretreatment of mice with fenretinide significantly improved their survival by reducing systemic proinflammatory cytokines during the acute phase of an S. suis infection. These findings indicate a beneficial effect of fenretinide in diminishing the expression of inflammation and improving survival during an acute infection by a virulent S. suis strain.

Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyunsaturated fatty acids in liver and brain of growing pigs

Studies suggested that in human adults, linoleic acid (LA) inhibits the biosynthesis of n-3 long-chain polyunsaturated fatty acids (LC-PUFA), but their effects in growing subjects are largely unknown. We used growing pigs as a model to investigate whether high LA intake affects the conversion of n-3 LC-PUFA by determining fatty acid composition and mRNA levels of Δ5- and Δ6 desaturase and elongase 2 and -5 in liver and brain. In a 2 × 2 factorial arrangement, 32 gilts from eight litters were assigned to one of the four dietary treatments, varying in LA and α-linolenic acid (ALA) intakes. Low ALA and LA intakes were 0.15 and 1.31, and high ALA and LA intakes were 1.48 and 2.65 g/kg BW0.75 per day, respectively. LA intake increased arachidonic acid (ARA) in liver. ALA intake increased eicosapentaenoic acid (EPA) concentrations, but decreased docosahexaenoic acid (DHA) (all P < 0.01) in liver. Competition between the n-3 and n-6 LC-PUFA biosynthetic pathways was evidenced by reductions of ARA (>40%) at high ALA intakes. Concentration of EPA (>35%) and DHA (>20%) was decreased by high LA intake (all P < 0.001). Liver mRNA levels of Δ5- and Δ6 desaturase were increased by LA, and that of elongase 2 by both ALA and LA intakes. In contrast, brain DHA was virtually unaffected by dietary LA and ALA. Generally, dietary LA inhibited the biosynthesis of n-3 LC-PUFA in liver. ALA strongly affects the conversion of both hepatic n-3 and n-6 LC-PUFA. DHA levels in brain were irresponsive to these diets. Apart from Δ6 desaturase, elongase 2 may be a rate-limiting enzyme in the formation of DHA.

Visualization of decreased docosahexaenoic acid in the hippocampus of rats fed an n – 3 fatty acid-deficient diet by imaging mass spectrometry

The present study employed an imaging mass spectrometry (IMS) method to evaluate the effect of dietary n – 3 fatty acids on the fatty acid composition in rat brain. Rats were divided into two groups and fed either an n – 3 fatty acid-deficient or adequate diet. We determined the decreased n – 3 fatty acids in the hippocampus of rats fed an n – 3 fatty acid-deficient diet compared to the control. IMS visualization was achieved at a resolution of 100 m in rat brain, and showed decreased docosahexaenoic acid (DHA)-containing phosphatidyl choline (PC) or phosphatidyl ethanolamine (PE) in the hippocampus of rats fed an n – 3 fatty acid-deficient diet.

Enteral Feeding Therapy for Newly Diagnosed Pediatric Crohnʼs Disease: A Double-Blind Randomized Controlled Trial with Two Years Follow-Up§

This study compared the efficacy of an elemental formula (EF) to a polymeric formula (PF) in inducing remission for pediatric Crohn's disease (CD). Newly diagnosed CD children were randomized to EF or PF for 6 weeks. Change in the Pediatric Crohn's Disease Activity Index (PCDAI), fecal calprotectin, and plasma fatty acids were measured at 0 and 6 weeks. Patients were followed up for 2 years. Time and treatment choice for first relapse were documented. Thirty-four children completed the study; EF: 15 (7 M, 8 F), PF: 19 (13 M, 6 F). The mean age was (years) EF: 12.6, PF: 11.7. Ninety-three percent of children (14/15) achieved remission in the EF group and 79% (15/19) in the PF group. One-third of patients maintained remission for 2 years. Mean time to relapse (days); EF: 183 (63-286), PF: 162 (53-301). Most children who relapsed used feed as a treatment for that relapse (EF: 9/10 and PF: 8/13). With PF, an increase of eicosapentanoic acid (EPA) and alpha linolenic acid was found with a reciprocal decrease in arachidonic acid (AA). With EF, AA and EPA levels were reduced with a significant decrease in docosahexaenoic acid. Fecal calprotectin measurements decreased significantly but did not normalize at the end of week 6. There was no significant difference between EF and PF in inducing remission. One-third of children maintained remission. Changes in plasma polyunsaturated fatty acid status were subtle and may be relevant; however, further evaluation is recommended.

Maternal High Fat Diet Is Associated with Decreased Plasma n–3 Fatty Acids and Fetal Hepatic Apoptosis in Nonhuman Primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6∶n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6∶n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

Changes in the fatty acid composition of blood cell membranes in children with inflammatory diseases

Fatty acid composition of erythrocyte and leukocyte membranes has been studied in children (with normal body mass and obesity) with inflammatory diseases of the gastrointestinal tract and children with bronchial asthma in comparison with basically healthy children. Fifty seven children aged from 7 to 14 years were examined: 13 with inflammatory diseases of the gastrointestinal tract (IDGIT) (eosophagitis, gastroduodenitis, stomach ulcer), 25 with obesity stages (I-III) complicated by IDGIT, 9 with bronchial asthma and 10 basically healthy children. The study revealed that both IDGIT and bronchial asthma caused significant and similar changes in fatty acid composition of cell membranes. These included accumulation of omega3-eicosapentaenoic acid (EPA) and the decrease of docosahexaenoic acid (DHA); this phenomenon observed in both erythrocyte and leukocyte membranes suggests a common feature of the detected changes in fatty acid composition of cell membranes in inflammation. There was a significant decrease in the level of membrane omega6 polyunsaturated fatty acids (PUFA), first of all arachidonic acid and total omega6 PUFA. Consequently, EPA accumulation in membranes may be a compensatory response to low dietary arachidonic acid supply and/or its increased synthesis of pro-inflammatory eicosanoids (prostaglandins, leukotriens, thromboxans) during inflammatory process.

Effect of acute administration of dietary Pistacia lentiscus L. essential oil on the ischemia-reperfusion-induced changes in rat frontal cortex and plasma

In this study Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, was tested for its protective effects in cerebral ischemia/reperfusion-induced injury in Wistar rat frontal cortex and plasma. Cerebral ischemia was produced by a 20 min bilateral common carotid artery occlusion followed by 30 min reperfusion. Pistacia lentiscus L. essential oil (E.O.) (200 mg/0, 45 ml of sunflower oil as vehicle) was administered via gavage 6 hours prior to ischemia. Rats were randomly assigned to four groups, ischemic/reperfused (I/R) and sham-operated rats treated with the vehicle or with E.O.. Different brain areas were analysed for fatty acid changes and expression of the enzyme cyclooxygenase-2 (COX-2). Ischemia/reperfusion triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid (HPUFA) most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of COX-2, as assessed by Western Blot. In plasma of ischemic/reperfused rats, E.O. administration increased both the DHA-to-eicosapentaenoic acid (EPA) ratio and levels of the endocannabinoid congeners palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). The results obtained suggest that ischemia/reperfusion triggers a cerebral insult sufficient to cause a a region specific lipid peroxidation as evidenced by the detectable, significant decrease in the tissue level of DHA, the most abundant essential fatty acid of neuronal membrane phospholipids. Acute dietary pre-treatment with E.O. triggers modifications both in the frontal cortex, where COX-2 expression decreases and the decrease of DHA is apparently prevented, and in plasma, where PEA and OEA levels increase. We suggest that the activity of PEA and OEA, as endogenous ligands of the peroxisome proliferator-activated receptor (PPAR)-alpha, by inducing the peroxisomal beta oxidation, may explain the observed increase in the DHA/EPA ratio. The latter, in fact, might account for an increased metabolism of n-3 aimed at restoring DHA within damaged brain tissue. The possibility that changes in fatty acid metabolism and plasmatic availability of PEA and OEA are correlated events represents an issue worth future investigations.