Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls

Deficiency in the long-chain omega-3 fatty acid, docosahexaenoic acid (DHA) has been associated with increased corticotropin releasing hormone and may contribute to hypothalamic pituitary axis (HPA) hyperactivity. Elevated levels of the neuroactive steroids, allopregnanolone (3alpha,5alpha-THP) and 3alpha,5alpha-tetrahydrodeoxycorticosterone (THDOC) appear to counter-regulate HPA hyperactivity. Plasma essential fatty acids and neurosteroids were assessed among 18 male healthy controls and among 34 male psychiatric patients with DSM-III alcoholism, depression, or both. Among all subjects, lower plasma DHA was correlated with higher plasma THDOC (r = -0.3, P < 0.05) and dihydroprogesterone (DHP) (r = -0.52, P < 0.05). Among psychiatric patients lower DHA was correlated with higher DHP (r = -0.60, P < 0.01), and among healthy controls lower plasma DHA was correlated with higher THDOC (r = -0.83, P < 0.01) and higher isopregnanolone (3beta,5alpha-THP) (r = -0.55, P < 0.05). In this pilot observational study, lower long-chain omega-3 essential fatty acid status was associated with higher neuroactive steroid concentrations, possibly indicating increased feedback inhibition of the HPA axis.     

omega-6 and omega-3 fatty acids: monolayer packing and effects on bilayer permeability and cholesterol exchange.

It has been suggested that the polyunsaturated omega-3 fatty acid, docosahexaenoic acid (DHA), can adopt unique closely packed arrays in lipid bilayers (Glomset and Applegate. (1986) J. Lipid Res. 27, 658-680). These conformations are predicted on the basis of molecular dynamics calculations and are in contrast to the expanded conformations characteristic of omega-6 unsaturated fatty acids. It has also been suggested that close packing of omega-3 acyl chains could have a substantial affect on the physical properties of lipid bilayers (e.g. permeability). We report here some experimental tests of these predictions. Surface pressure-area experiments have been carried out on DHA and its mixtures with stearic and oleic acids. At low surface pressures DHA is more expanded than oleic acid. Extrapolation to the high surface pressures characteristic of lipid bilayers indicates that the area per molecule of DHA is only marginally less than that for oleic acid. Thus there is no compelling evidence to suggest that the average area per molecule of the omega-3 fatty acid is substantially different from the omega-6 fatty acid at high surface pressures. Experiments also show that the permeability of bilayers to glucose and the rates of dissociation of pyrenyl cholesterol from bilayers were similar for bilayers containing DHA compared to bilayers containing oleic acid or linoleic acid.     

Serotonin-induced endothelial cell proliferation is blocked by omega-3 fatty acids.

Serotonin (5HT) released from aggregating platelets at sites of vascular injury is a known mitogen for vascular endothelial cells. Recent studies have indicated that regenerating endothelial cells at sites of vessel wall injury may play a role in the development of restenosis by synthesizing and releasing growth factors for vascular smooth muscle cells, proliferation of which may result in the development of neointima. Diets rich in fish oils (omega-3 fatty acids) are associated with reduced risk of cardiovascular disease including atherosclerosis and restenosis. This study examined the effect of the omega-3 and other fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on 5HT induced endothelial cell proliferation. Among the fatty acids examined only EPA and DHA could reverse the mitogenic effect of 5HT on vascular endothelial cells, whereas oleic acid or palmitic acid did not have any effect. When added together, EPA and DHA potentiate each other in reversing the mitogenic effect of 5HT. EPA and DHA also inhibited the 5HT-induced increase in the 5HT2 receptor mRNA, without a change in the receptor density or affinity. This data suggests that one of the mechanisms by which omega-3 fatty acids may attenuate the development of atherosclerosis or restenosis is to inhibit the mitogen induced growth of vascular endothelial cells, which attenuates the release of growth factors for vascular smooth muscle cells.     

In vitro mimicry of essential fatty acid deficiency in human endothelial cells by TNFalpha impact of omega-3 versus omega-6 fatty acids

Severe endothelial abnormalities are a prominent feature in sepsis with cytokines such as tumor necrosis factor (TNF)alpha being implicated in the pathogenesis. As mimic to inflammation, human umbilical vascular endothelial cells (HUVEC) were incubated with TNFalpha for 22 h, in the absence or presence of the omega-6 fatty acid (FA), arachidonic acid (AA), or the alternative omega-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). TNFalpha caused marked alterations in the PUFA profile and long chain PUFA content of total phospholipids (PL) decreased. In contrast, there was a compensatory increase in mead acid [MA, 20:3(omega-9)], the hallmark acid of the essential fatty acid deficiency (EFAD) syndrome. Corresponding changes were noted in phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, but not in the sphingomyelin fraction. Supplementation with AA, EPA, or DHA markedly increased the respective FA contents in the PL pools, suppressed the increase in MA, and resulted in a shift either toward further predominance of omega-6 or predominance of omega-3 FA. We conclude that short-term TNFalpha incubation of HUVEC causes an EFAD state hitherto only described for long-term malnutrition, and that endothelial cells are susceptible to differential influence by omega-3 versus omega-6 FA supplementation under these conditions.     

Docosahexaenoic acid transfer into human milk after dietary supplementation: a randomized clinical trial

Docosahexaenoic acid (DHA) is important for infant development. The DHA transfer from maternal diet into human milk has not been investigated in detail. We studied the effects of DHA supplementation on the fatty acid composition of human milk and the secretion of dietary (13)C-labeled fatty acids, including DHA, into human milk. Ten lactating women were randomized to consume, from 4 to 6 weeks postpartum, an oil rich in DHA (DHASCO, 200 mg of DHA/day) (n = 5) or a placebo oil (n = 5). Dietary intakes were followed by 7-day protocols. On study day 14 a single dose of [U-(13)C]DHASCO was given orally, milk samples were collected over 48 h, and milk production was recorded. Milk fatty acid composition was determined by gas-liquid chromatography and isotopic enrichment was determined by gas chromatography- combustion-isotope ratio mass spectrometry (GC-C-IRMS). Milk DHA content did not differ between the supplemented and placebo group at study entry (0.29 vs. 0.28 wt%, median). After 2 weeks of supplementation the milk DHA content was almost 2-fold higher in the supplemented versus placebo group (0.37 vs. 0.21 wt%, P = 0.003). Cumulative recovery of [(13)C]palmitic, [(13)C]oleic, and [(13)C]docosahexaenoic acids in human milk at 48 h was similar between supplemented and placebo groups (palmitic acid 7.40 vs. 8. 14%, oleic acid 9.14 vs. 9.97%, and docosahexaenoic acid 9.09 vs. 8. 03% of dose, respectively). Notable lower recovery was observed for [(13)C]myristic acid in both the supplemented and placebo groups, 0. 62 versus 0.77% of dose.Dietary DHA supplementation increases the DHA content in human milk. DHA transfer from the diet into human milk is comparable to palmitic and oleic acid transfer.     

Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance

Omega-3 fatty acids (FAs) reduce postprandial triacylglycerol (TG) concentrations. This study was undertaken to determine whether this effect was due to reduced production or increased clearance of chylomicrons. Healthy subjects (n = 33) began with a 4-week, olive oil placebo (4 g/d) run-in period. After a 4-week wash-out period, subjects were randomized to supplementation with 4 g/d of ethyl esters of either safflower oil (SAF), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) for 4 weeks. Results for EPA and DHA were similar, and therefore the data were combined into one omega-3 FA group. Omega-3 FA supplementation reduced the postprandial TG and apolipoprotein B (apo B)-48 and apoB-100 concentrations by 16% (P = 0.08), 28% (P < 0.001), and 24% (P < 0.01), respectively. Chylomicron TG half-lives in the fed state were reduced after omega-3 FA treatment (6.0 +/- 0.5 vs. 5.1 +/- 0.4 min; P < 0.05), but not after SAF (6.9 +/- 0.7 vs. 7.1 +/- 0.7 min). Omega-3 FA supplementation decreased chylomicron particle sizes (mean diameter; 293 +/- 44 vs. 175 +/- 25 nm; P < 0.01) and increased preheparin lipoprotein lipase (LPL; 0.6 +/- 0.1 vs. 0.9 +/- 0.1 micromol/h/ml; P < 0.05) activity during the fed state, but had no effect on postheparin LPL or hepatic lipase activities. The results suggest that omega-3 FA supplementation accelerates chylomicron TG clearance by increasing LPL activity, and that EPA and DHA are equally effective.     

Selective retention of n-3 and n-6 fatty acids in human milk lipids in the face of increasing proportions of medium chain-length (C10-14) fatty acids

This paper reports the results of our analysis of the impact high levels of de novo fatty acids have on the proportions of essential and non-essential fatty acids in human milk lipids. The data for seven fatty acids (linoleic, alpha-linolenic, arachidonic (AA), docosahexaenoic (DHA), palmitic, stearic and oleic) were derived from several studies conducted in Nigeria. The proportion by weight of each of these fatty acids was plotted versus the proportion of C10-14 fatty acids. As the proportion of C10-14 fatty acids increased from 15 to 65%, there was not a proportional decrease in the percentages of all seven fatty acids, but, instead, preferential incorporation of the essential fatty acids, AA and DHA into the triacylglycerol component of the milk. At the same time, the proportions of stearic and oleic acid declined by 69% and 86%, respectively. However, the proportions of linoleic acid, palmitic acid, DHA, AA and alpha-linolenic acid, in milk lipids decreased by only 44%, 40%, 39%, 28% and 2.3%, respectively. These observations indicate that as the contribution of C10-14 fatty acids increases, essential fatty acids are preferentially incorporated into milk triacylglycerols at the expense of oleic acid and stearic acid.     

再投喂鱼油对瓦氏黄颡鱼肌肉脂肪酸组成的影响

为研究植物油替代鱼油对瓦氏黄颡鱼（Pelteobagrus vachelli）生长及肌肉脂肪组成的影响及重投喂鱼油对瓦氏黄颡鱼肌肉脂肪酸组成的影响,实验以大豆油分别替代饲料中的0（FO）、50（S1）、75（S2）和100%（SO）的鱼油配制等氮、等能的颗粒饲料,每组设置3个平行,养殖80d后,再投喂鱼油30d。结果表明,饲料中添加豆油不会显著影响瓦氏黄颡鱼的增重率、肝体指数和体成分（P>0.05）。随着饲料中大豆油含量的增加,S2和SO组肌肉中C18:1n-9、C18:2n-6和单不饱和脂肪酸比例显著增加（P < 0.05）,而C20:5n-3,C22:5n-3及n-3/n-6比例显著下降（P < 0.05）。再投喂鱼油30d后,SO组肌肉中C18:3n-6、C20:4n-6、Σ n-9、Σ n-6和S2组中C18:1n-9、Σ n-6比例显著下降（P < 0.05）,而S2和SO组肌肉中Σn-3多不饱和脂肪酸、C20:5n-3和C22:5n-3比例显著增加（P < 0.05）。在生产中,可采用先植物油饲料、后鱼油饲料的养殖方式提高瓦氏黄颡鱼肌肉品质（增加有益人类健康的多不饱和脂肪酸）。     

Regulation of intracellular lipid metabolism by the preparation of omega-3 phospholipids from marine organisms in deficiency of essential fatty acids in rats

It has been established that a deficit of essential fatty acids (EFA) in the animal organism induces specific modifications of composition of fatty acid (FA) of general phospholipids and plasmalogenic P1 in microsomal tissue membranes with various functions and affects the activity of phospholipase A2. It has been shown that arachidonic (AA), docosapentaenoic (DPA) and docosahexaenoic (DHA) acids in the composition of general phospholipids - phosphatidylcholine (PC), phosphatidylethanolamine (PEA) and plasmalogens PC and PEA react to EFA deficit in the organism. Quantitative redistribution of AA, DPA, DHA of FA in general phospholipids and plasmalogenic microsomal membranes depending on their functions was found under EFA deficit in the organism. Deficit of DHA and plasmalogenic phospholipids evidences that the status of cell plasmalogens affects the level of PUFA at EFA deficit in the organism. AA and DHA can be a selective target for plasmalogens. The drug of omega-3 phospholipids, considerable amount of DHA and eicosapentaenoic (EPA)FA being present in their structure, increases the amount of plasmalogens and decreases the amount of AA in the brain, heart and reproductive organs. It was also found that EFA deficit in the organism favours the increase of lisoPEA, lisoPC, free FA (FFA) connected with the increase of activity of endogenic phospholippase A2 and plasmalogen-selective phospholipase A2. The omega-3 phospholipase from marine organisms at EFA defecit decreases the amount of FFA, lisophospholipids and activity of phospholipase A2 in the microsomas of the studied tissues. The drug of omega-3 phospholipids normalizes the state and functions of the brain, liver, and heart tissues, reproductive organs against a background of EFA defecit and regulates the synthesis of biologocically active metabolites of AA in the organism.     

Role of omega-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma

Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that omega-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of omega-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor-alpha upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in omega-6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel invasion. Taken together, these results indicate that omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.     

The effect of arginine vasopressin on the excitability and fatty acid content of the brain structures in rats with a neurosis

Experiments on rats with chronic bipolar electrodes implanted into the frontal cortex (FC), dorsal hippocampus (DH) and midbrain reticular formation (RF) established that the neurotic state (model "conflict of afferent excitation") was characterised by the increase in structure excitability: FC--15.4% (P less than 0.01), DH--12.4% (P = 0.05) and RF--17.5% (P less than 0.001). The presence of free fatty acids (FFA) revealed by chromatograph Schimadzu in brain cortex (BC), hippocampus (H) and midbrain (MB) in acute experiments evidenced the increase in the level of linolinic acid in all matters within the limits of 64-162% (P less than 0.05) and also different changes in arachidonic acid in BC and subcortical structures. The level of arachidonic acid increased by 120% (P less than 0.01) in BC but it decreased in H and MB within the limits of 34-56%. AVP (1 micrograms/kg) decreased excitability of FC by 6% (P less than 0.001), of H--by 8% (P less than 0.01) and RF--by 6%. In this case FFA, especially arachidonic acid, was increased in H and MB (by 2.5-6 times). The quantity of palmitic, stearic and oleic acids increased.     

In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation

There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.     

Omega- and (omega-1)-hydroxylation of lauric acid and arachidonic acid by rat renal cytochrome P-450

We resolved four cytochrome P-450s, designated as P450 K-2, K-3, K-4, and K-5, from the renal microsomes of untreated male rats by high-performance liquid chromatography (HPLC) and investigated the lauric acid and arachidonic acid hydroxylation activities of these fractions. P450 K-4 and K-5 had high omega- and (omega-1)-hydroxylation activities toward lauric acid. The ratio of the omega-/(omega-1)-hydroxylation activity of P450 K-4 and K-5 was 3 and 6, respectively. Also, P450 K-4 and K-5 effectively catalyzed the omega- and (omega-1)-hydroxylation of arachidonic acid. P450 K-3 was not efficient in the hydroxylation of either lauric acid or arachidonic acid. P450 K-2 had low omega- and (omega-1)-hydroxylation activities toward arachidonic acid, and efficiently catalyzed the hydroxylation of lauric acid at the (omega-1)-position only, not at the omega-position.     

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept EPA and DHA to yield more potent vasodilatory and potentially anti-arrhythmic metabolites, suggesting that the endogenous CYP-eicosanoid profile can be favorably shifted by dietary omega-3 fatty acids. To test this hypothesis, 20 healthy volunteers were treated with an EPA/DHA supplement and analyzed for concomitant changes in the circulatory and urinary levels of AA-, EPA-, and DHA-derived metabolites produced by the cyclooxygenase-, lipoxygenase (LOX)-, and CYP-dependent pathways. Raising the Omega-3 Index from about four to eight primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA- and DHA-derived LOX-dependent monohydroxy-metabolites including the precursors of the resolvin E and D families; resolvins themselves were not detected. The metabolite/precursor fatty acid ratios indicated that CYP epoxygenases metabolized EPA with an 8.6-fold higher efficiency and DHA with a 2.2-fold higher efficiency than AA. Effects on leukotriene, prostaglandin E, prostacyclin, and thromboxane formation remained rather weak. We propose that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA supplementation.     

Fatty acid contents and profiles of 16 macroalgae collected from the Irish Coast at two seasons

Due to the established health benefits of omega-3 long-chain polyunsaturated fatty acids (LC-PUFA), there is a globally increasing demand for alternative natural resources with appropriate fatty acid profiles. To assess the suitability of macroalgae as a source, 16 species (nine Phaeophyceae, five Rhodophyta and two Chlorophyta) were collected at two seasons (June and November) from the Irish west Coast, and total fatty acid contents and specific profiles were determined. Total fatty acid contents, expressed per percentage of dry weight, ranged from 6.4 %?±?0.3 (Pelvetia canaliculata, Phaeophyceae) to 0.8 %?±?0.2 (Porphyra dioica, Rhodophyta). Most common fatty acids were palmitic (16:0), oleic (OLE, 18:1 n-9), α-linolenic (ALA, 18:3 n-3), arachidonic (ARA, 20:4 n-6) and eicosapentaenoic (EPA, 20:5 n-3) acids. Fatty acid profiles were highly variable between and within algal groups; red and brown seaweeds were generally richer in LC-PUFA (e.g. 20:4 n-6 and 20:5 n-3), while high levels of saturated fatty acids such as palmitic acid (16:0) were observed in green species. Most omega-3 PUFA-rich species investigated had a omega-6/omega-3 fatty acid ratio close to 1, which is favourable for human health. The two seasonal sampling times revealed significant differences in total fatty acid and 20:5 n-3 (EPA) contents, with changes depending on species, thus implying varying suitability as potential target species for EPA production. At both times of the year, Palmaria palmata was identified as most promising species as a source of 20:5 n-3 (EPA) amongst all species investigated, with levels ranging from 0.44 to 0.58 % of dry weight in June and November, respectively.     

Effect of long-chain fatty acids in the culture medium on fatty acid composition of WEHI-3 and J774A.1 cells

As a first step in determining the mechanism of action of specific fatty acids on immunological function of macrophages, a comparative study of the effect of long-chain polyunsaturated fatty acids (PUFA) in the medium was conducted in two macrophage cell lines, J774A.1 and WEHI-3. The baseline fatty-acid profiles of the two cell lines differed in the % distribution of saturated (SFA) and unsaturated fatty acids (UFA). J774A.1 cells had a higher % of SFA (primarily palmitic acid) than WEHI-3 cells. Conversely, WEHI-3 cells had a higher % of UFA (primarily oleic acid) than J774A.1 cells. Neither cell line had detectable amounts of alpha-linolenic acid (ALA) or eicosapentaenoic acid (EPA). The most abundant polyunsaturated fatty acid in both cells lines was arachidonic acid (AA). The efficiency of transport of fatty acids from the medium to the macrophages by two delivery vehicles (BSA complexes and ethanolic suspensions) was compared. Overall, fatty acids were transported satisfactorily by both delivery systems. Alpha-linolenic acid and doscosahexenoic acid (DHA) were transported more efficiently by the ethanolic suspension system. Linoleic acid (LA) was taken up more completely than ALA, and DHA was taken up more completely than EPA by both cell cultures and delivery systems. A dose-response effect was demonstrated for LA, ALA, EPA and DHA in both J774A.1 and WEHI-3 cells. Addition of polyunsaturated fatty acids (PUFA) to the cell cultures modified the total lipid fatty acid composition of the cells. The presence of ALA in the culture medium resulted in a significant decrease in AA in both cell lines. The omega-3/omega-6 fatty acid ratio (omega-3/omega-6), polyunsaturated/saturated fatty acid ratio (P/S), and unsaturation index (UI) increased directly with the amount of PUFA and omega-3 fatty acid provided in the medium. The results indicate that the macrophage cell lines have similar, but not identical, fatty acid profiles that may be the result of differences in fatty acid metabolism. These distinctions could in turn produce differences in immunological function. The ethanol fatty-acid delivery system, when compared with the fatty acid-BSA complex system, is preferable for measurement of dose-response effects, because the cellular fatty acid content increased in proportion to the amount of fatty acid provided in the medium. Similar dose-response results were observed in a previous in vivo study using flaxseed, rich in ALA, as a source of PUFA.     

Exploring potential use of Australian thraustochytrids for the bioconversion of glycerol to omega-3 and carotenoids production

Marine microbes have the potential for accumulating large quantities of lipids and are therefore suitable candidate as feedstock in unsaturated fatty acid production. The efficient utilisation of glycerol as an alternative carbon source to glucose was demonstrated in the fermentation of newly isolated thraustochytrid strains from the Queenscliff, Victoria, Australia. The isolates exhibited the presence of omega-3 and omega-6 polyunsaturated fatty acids, with the major fatty acids for all isolates being (as percent total fatty acid), palmitic acid (25.1–40.78%), stearic acid (4.24–13.2%), eicosapentaenoic acid EPA (2.31–8.5%) and docosapentaenoic acid (7.24–10.9%). Glycerol as a carbon source gave promising biomass growth with significant lipid and DHA productivity. An approximate three-fold increase in carotenoid content in all isolates was achieved when glycerol was used as a carbon source in the production medium.     

Upregulated mRNA expression of desaturase and elongase,two enzymes involved in highly unsaturated fatty acids biosynthesis pathways during follicle maturation in zebrafish

Background  

Although unsaturated fatty acids such as eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (ARA, C20:4n-6), collectively known as the highly unsaturated fatty acids (HUFA), play pivotal roles in vertebrate reproduction, very little is known about their synthesis in the ovary. The zebrafish (Danio rerio) display capability to synthesize all three HUFA via pathways involving desaturation and elongation of two precursors, the linoleic acid (LA, C18:2n-6) and linolenic acid (LNA, C18:3n-3). As a prerequisite to gain full understanding on the importance and regulation of ovarian HUFA synthesis, we described here the mRNA expression pattern of two enzymes; desaturase (fadsd6) and elongase (elovl5), involved in HUFA biosynthesis pathway, in different zebrafish ovarian follicle stages. Concurrently, the fatty acid profile of each follicle stage was also analyzed.     

Oxygenation of omega-3 fatty acids by human cytochrome P450 4F3B: effect on 20-hydroxyeicosatetraenoic acid production

Cytochrome P450 (CYP) omega-oxidases convert arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a lipid mediator that modulates vascular tone. We observed that a microsomal preparation containing recombinant human CYP4F3B, which converts AA to 20-HETE, converted eicosapentaenoic acid (EPA) to 20-OH-EPA. Likewise, docosahexaenoic acid (DHA) was converted to 22-OH-DHA, indicating that human CYP4F3B also can oxidize 22-carbon omega-3 fatty acids. Consistent with these findings, addition of 0.5-5 microM EPA, DHA or omega-3 docosapentaenoic acid (DPA) to incubations containing 0.5 microM [3H]AA inhibited [3H]20-HETE production by 15-65%. [3H]20-OH-EPA was rapidly taken up by COS-7 cells, and almost all of the incorporated radioactivity remained as unmodified 20-OH-EPA. The 20-OH-EPA stimulated luciferase activity in COS-7 cells that express peroxisome proliferator-activated receptor alpha, indicating that this EPA metabolite may function as a lipid mediator. These findings suggest that some functional effects of omega-3 fatty acid supplementation may be due to inhibition of 20-HETE formation or the conversion of EPA to the corresponding omega-oxidized product.     

Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR.

The effects of dietary docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, on blood pressure and some pressure-regulating systems were measured in young spontaneously hypertensive rats (SHR). Plasma aldosterone and corticosterone levels, adrenal aldosterone production in vitro, and characteristics of adrenal angiotensin receptors were measured after 6 weeks of diet. Renal cytochrome P450 (CYP) 4A gene expression and arachidonic acid metabolism by renal microsomes were also investigated. Plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diets contained either corn/soybean oil alone (CSO), or oil enriched with DHA. After 6 weeks, rats fed DHA had systolic blood pressures averaging 34 mmHg less than controls (P < 0.001). Plasma aldosterone levels were 33% lower in the DHA-fed animals than in controls (22 +/- 3 vs. 33 +/- 3.7 ng/dl, P < 0.05). Plasma levels of corticosterone were 18% lower in animals fed DHA than in controls, but this difference was not statistically significant. Adrenal glomerulosa cells from DHA-fed rats produced less aldosterone in vitro in response to angiotensin II, ACTH, or potassium. The difference was less marked when aldosterone production was stimulated by supplying exogenous corticosterone, suggesting an effect of DHA on postreceptor steps in signal transduction or the early pathway of aldosteronogenesis. We found no significant differences in angiotensin receptor subtype, number, or affinity. Production of arachidonic epoxides by renal microsomes was 17% lower in DHA-fed animals than in controls (P < 0.05). Renal cortical mRNA levels of CYP4A genes and formation of 19- and 20-hydroxyeicosatetraenoic acid (HETE) did not differ between dietary groups. Plasma total cholesterol and high-density-lipoprotein (HDL) levels were significantly reduced in SHR fed the DHA supplement, but triglyceride levels were not significantly different. The effects of DHA on steroid and eicosanoid metabolism may be part of the mechanism by which this fatty acid prevents some of the hypertension in growing SHR.