Prostaglandins, Leukotrienes and Essential Fatty Acids

Editorial Board

2012-01-01

Tissue-specific LCPUFA accretion in fetal humans

Tom Brenna — 2011-11-11

DHA and other LCPUFA accrete in fetal tissues, and especially the brain, at an accelerating rate starting around 27 weeks of the normal human 40-week gestational period. Dramatic improvements in the neonatal intensive care nursery over recent decades have enabled high rates of survival among very low birth weight infants of gestational age above about 24 weeks. For the brain, the normal placental supply of LCPUFA is interrupted for these infants and they must obtain all PUFA from intake. Concerns over their ability to biosynthesize DHA specifically led to many studies starting in the mid-1980s on the need for dietary preformed DHA. For more than 10 years, DHA and AA have been included in infant formula to support brain accretion and growth. Moreover, recommendations for lactating women to consume DHA are, at least in part, motivated by a presumed need for breastmilk DHA at the median or higher end of global values. Mixed results of human studies and the limitation of extrapolation from animal studies leave room for discussion as to the absolute amount of DHA that might be required. Nearly all studies that show an effect are conducted with infants in the western world, where the now-normal linoleic acid-rich diet may well enhance the need for preformed DHA in infant feeds.

Radiation resistance, invasiveness and metastasis are inflammatory events that could be suppressed by lipoxin A4

Undurti N. Das — 2011-10-24

Abstract: Radiation induces overexpression and activity of the MET oncogene that, in turn, enhances the production of prostaglandin E2, a pro-inflammatory molecule. Prostaglandin E2 promotes tumor cell invasion, prevents apoptosis, enhances their metastasis and causes radioresistance. It is proposed that lipoxin A4, a potent endogenous anti-inflammatory molecule, opposes the actions of prostaglandin E2 and thus, could promote radiosensitivity, suppress tumor cell proliferation, invasiveness and suppress metastasis. Thus, methods designed to enhance endogenous lipoxin A4 formation or its synthetic analogs may be useful in the management of cancer.

Fetal intrauterine whole body linoleic, arachidonic and docosahexaenoic acid contents and accretion rates

2011-11-24

Abstract: Introduction: There is no information on the whole body fatty acid (FA) contents of preterm or term infants, although scattered information on the FA-composition of many organs is available.Material and methods: We collected data on the weights, lipid contents and FA-compositions of the quantitatively most important fetal organs of appropriate for gestational age (AGA) Western infants. From these we estimated the total body contents of linoleic (LA), arachidonic (AA) and docosahexaenoic (DHA) acids at 25, 35 and 40 weeks of gestation.Results: Western infants accrete FA in the order of LA>AA>DHA at all stages during pregnancy and the highest accretion rates are reached in the last 5 weeks of gestation, i.e. 342mg LA, 95mg AA and 42mg DHA/day. At term, most of the infant's LA, AA and DHA is located in adipose tissue (68, 44 and 50%, respectively), with substantial amounts of LA also located in skeletal muscle (17%) and skin (13%); of AA in skeletal muscle (40%) and brain (11%); and of DHA in brain (23%) and skeletal muscle (21%). The term AGA infant has accreted about 21g LA, 7.5g AA and 3g DHA, which constitutes a gap of 12g LA, 3.3g AA and 1.5g DHA compared to a 35 weeks old AGA infant.Conclusion: The current fetal LA, AA and DHA pool sizes and accretion rates may especially be useful to estimate the preterm infant's requirements and the maternal LCP needs during pregnancy. Since they derive from populations with typically Western diets they do not necessarily reflect ‘optimality’ or ‘health’.

Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats

2011-12-02

Abstract: A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B12. The vitamin B12 deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases Δ5 desaturase activity but decreases mRNA levels, decreases Δ6 desaturase activity but not mRNA levels as compared to control. mRNA level of Δ5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver.

Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients

W.S. An, S.M. Lee, Y.K. Son, S.E. Kim, K.H. Kim, J.Y. Han, H.R. Bae, Y. Park — 2011-11-09

Abstract: Erythrocyte membrane fatty acids (FA), such as oleic acid, are related to acute coronary syndrome. There is no report about the effect of omega-3 FA on oleic acid in peritoneal dialysis (PD) patients. We hypothesized that omega-3 FA can modify erythrocyte membrane FA, including oleic acid, in PD patients. In a double-blind, randomized, placebo-controlled study, 18 patients who were treated with PD for at least 6 months were randomized to treatment for 12 weeks with omega-3 FA or placebo. Erythrocyte membrane FA content was measured by gas chromatography at baseline and after 12 weeks. The erythrocyte membrane content of eicosapentaenoic acid and docosahexaenoic acid was significantly increased and saturated FA and oleic acid were significantly decreased in the omega-3 FA supplementation group after 12 weeks compared to baseline. In conclusion, erythrocyte membrane FA content, including oleic acid, was significantly modified by omega-3 FA supplementation for 12 weeks in PD patients.

Enhanced prostaglandin F2α formation in human pregnancy and the effect of increased oily fish intake: Results from the Salmon in Pregnancy Study

2011-11-02

Abstract: Oily fish intake during pregnancy may reduce the risk of allergic diseases in infancy possibly by shifts in the fatty acid balance and subsequent altered prostaglandin (PG) formation. This intervention is the first study to evaluate if increased oily fish intake affects in vivo PGF2α formation during pregnancy. British pregnant women were randomised to two portions of farmed salmon weekly (n=47), or maintenance of their normal diet low in fish (n=41), from pregnancy week 20 until parturition. The concentrations of eicosapentaenoic and docosahexaenoic acids in plasma phosphatidylcholine (PC) were higher and the concentration of arachidonic acid in plasma PC was lower in the salmon group than the control group at weeks 34 and 38 of pregnancy. PGF2α formation was evaluated by urinary measurement of 15-keto-dihydro-PGF2α, a major PGF2α metabolite, at 20, 34 and 38 weeks. In both the salmon and control groups urinary 15-keto-dihydro-PGF2α concentrations increased significantly during pregnancy, which may be of physiological importance. Oily fish intervention altered fatty acid concentrations but did not affect urinary 15-keto-dihydro-PGF2α concentrations in pregnant women.

Gestational age dependent content, composition and intrauterine accretion rates of fatty acids in fetal white adipose tissue

2011-11-18

Abstract: Background: Little is known about the gestational age (GA) dependent content, composition and intrauterine accretion rates of fatty acids (FA) in fetal white adipose tissue (WAT).Objective & design: To acquire this information, we collected abdominal subcutaneous WAT samples from 40 preterm and term fetuses. Their GA ranged from 22 to 43 weeks. FA were expressed as mg/g wet WAT and g/100g FA (g%). Intrauterine WAT FA accretion rates were estimated for appropriate (AGA) and large (LGA) for gestational age infants.Results: From 25 to 40 weeks gestation, saturated-FA (SAFA) increased from 83 to 298mg/g WAT and monounsaturated-FA (MUFA) from 83 to 226mg/g WAT, while polyunsaturated-FA (PUFA) increased insignificantly from 18.0 to 23.2mg/g WAT. As percentages of total FA, SAFA increased from 46 to 55g%, MUFA decreased from 44 to 41g%, and PUFA from 10.3 to 4.26g%. Docosahexaenoic (DHA) and arachidonic acid (AA) accretion rates in WAT during the 3rd trimester for AGA infants were 88 and 193mg/week, respectively. Contemporaneous DHA and AA accretion rates for 4500g LGA infants were 184 and 402mg/week, respectively. Compared to the whole 3rd trimester, increment rates during the last 5 weeks of gestation were about 2-fold higher.Conclusion: FA accretion rates, notably those of DHA and AA, may be important for designing nutritional regiments for preterm infants. The current WAT-DHA and WAT-AA accretion rates are considerably lower than previously reported in the literature.

Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content

2011-11-07

Abstract: Objective: The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time.Methods: Healthy subjects (n=131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2g/d) or EPA (0.44, 1.3, or 2.7g/d) for 12 weeks. RBC fatty acids were analyzed biweekly.Results: RBC %EPA increased in all EPA and SDA groups (p<0.02 vs. control) except the 0.43g/d SDA group (p=0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32g/d (conversion efficiencies of 41%, 26%, and 17%), respectively.Conclusions: SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3g/d.

Maternal supplementation with dietary arachidonic and docosahexaenoic acids during lactation elevates bone mass in weanling rat and guinea pig offspring even if born small sized

2011-10-24

Abstract: Whether post-natal long chain polyunsaturated fatty acids (LCPUFA) elevates bone mineral content (BMC) of small and normal neonates was studied using pregnant rats and guinea pigs fed a control (C) diet or low protein (LP) diet to induce small neonates followed by C or LCPUFA diets during lactation. Measurements (days 3 and 21 post-partum) included BMC and density (BMD) plus bone metabolism. In rats LP reduced birth weight but at day 21 elevated weight and whole body BMC; LCPUFA enhanced spine BMC, tibia BMC and BMD and whole body BMD. In guinea pig pups, at days 3 and 21, LP reduced weight, whole body and regional BMC and BMD whereas LCPUFA reduced day 3 osteocalcin and elevated day 21 spine BMD. LCPUFA minimized loss of whole body BMC in dams and elevated osteocalcin in sows. LCPUFA during lactation enhances bone in normal and small neonates without compromising maternal bone.

Omega-3 fatty acid deficiency increases stearoyl-CoA desaturase expression and activity indices in rat liver: Positive association with non-fasting plasma triglyceride levels

2011-11-03

Abstract: Although omega-3 (n−3) fatty acids negatively regulate triglyceride biosynthesis, the mechanisms mediating this effect are poorly understood, and emerging evidence suggests that stearoyl-CoA desaturase (Scd1) is required for de novo triglyceride biosynthesis. To investigate this mechanism, we determined the effects of perinatal n−3 deficiency and postnatal repletion on rat liver Scd1 mRNA expression and activity indices (liver 16:1/16:0 and 18:1/18:0 ratios), and determined relationships with postprandial (non-fasting) plasma triglyceride levels. Rats were fed conventional diets with or without the n−3 fatty acid precursor α-linolenic acid (ALA, 18:3n−3) during perinatal development (E0-P100), and a subset of rats fed the ALA− diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). Compared with controls, rats fed the ALA− diet exhibited significantly lower liver long-chain n−3 fatty acid compositions and elevations in monounsaturated fatty acid composition, both of which were normalized in repleted rats. Liver Scd1 mRNA expression and activity indices (16:1/16:0 and 18:1/18:0 ratios) were significantly greater in n−3 deficient rats compared with controls and repleted rats. Among all rats, liver Scd1 mRNA expression was positively correlated with liver 18:1/18:0 and 16:1/16:0 ratios. Plasma triglyceride levels, but not glucose or insulin levels, were significantly greater in n−3 deficient rats compared with controls and repleted rats. Liver Scd1 mRNA expression and activity indices were positively correlated with plasma triglyceride levels. These preclinical findings demonstrate that n−3 fatty acid status is an important determinant of liver Scd1 mRNA expression and activity, and suggest that down-regulation of Scd1 is a mechanism by which n−3 fatty acids repress constitutive triglyceride biosynthesis.

Preeclampsia activates 15-lipoxygenase and its metabolite 15-hydroxyeicosatetraenoic acid enhances constriction in umbilical arteries

Yuguang Wang, Daling Zhu, Yuan An, Jingxia Sun, Liying Cai, Jianhua Zheng — 2011-11-14

Abstract: Objective: To compare the differential expression of 15-lipoxygenase (15-LO) isoenzymes, 15-LO-1 and 15-LO-2 in preeclampsia (PE), and normal pregnancy and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) on the vasoconstriction of human umbilical artery (HUA) rings.Study design: We performed western blotting and isometric tension studies and t-test analysis on data from 6 women with normal pregnancy and 8 women with PE.Results: Expressions of 15-LO-1 and 15-LO-2 in placentas and HUA rings in PE increased more than that in normal groups (P<0.01). 15-HETE increased HUA rings tension in a dose-dependence manner, which were significantly greater in PE than in normal pregnant controls (P<0.01). However, the constriction of HUA rings was completely eliminated by 2-aminoethoxydiphenyl borate (2-APB) in both normal pregnancy and PE (P<0.01) and attenuated partly by nifedipine in dose-dependence in normal pregnancy (10−8mol/L P>0.05; 10−7, 10−6mol/L P<0.05) and in PE (P<0.01).Conclusion: PE upregulates 15-LO pathway via 15-HETE, which increased intercellular calcium level to cause constriction of HUA rings.

Hypoxia promotes rabbit pulmonary artery smooth muscle cells proliferation through a 15-LOX-2 product 15(S)-hydroxyeicosatetraenoic acid

Ruihui Shan, Li Chen, Xinyu Li, Hong Wu, Qingcheng Liang, Xiaobo Tang — 2011-10-24

Abstract: The initial event of hypoxic pulmonary hypertension is acute hypoxic pulmonary vasoconstriction followed by remodeling of pulmonary arteries. Although 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] is found to be able to induce hypoxic pulmonary vasoconstriction, role of 15(S)-HETE in pulmonary artery smooth muscle cells (PASMCs) proliferation has been studied less. We sought evidence for a role of 15(S)-HETE in the development of hypoxia-induced pulmonary hypertension. We found that hypoxia enhances 15-lipoxygenase-2 (15-LOX-2) expression and stimulates cultured rabbit PASMCs proliferation. 15(S)-HETE at concentration 0.1μM stimulated proliferation of PASMCs and induced ERK 1/ERK 2 phosphorylation but had no effect on p38 kinase expression as assessed by Western blotting. 15(S)-HETE-stimulated PASMC proliferation was blocked by the MEK inhibitors PD-98059. Hypoxia (3% O2)-stimulated PASMC proliferation was blocked by U0126, a MEK inhibitor, as well as by NDGA and CDC, inhibitors of 15-LOX, but not by the p38 MAPK inhibitor SB-202190. We conclude that 15-LOX-2 and its product, 15(S)-HETE, are important intermediates in hypoxia-induced rabbit PASMC proliferation and may participate in hypoxia-induced pulmonary hypertension.