Fatty Acid Composition of Porcine Muscle and Adipose Tissue Lipids as Affected by Anatomical Location and Cod Liver Oil Supplementation of the Diet

In pigs fed a standard pig mash the contents of polyunsaturated fatty acids (PUFAs) of both the n-6 and n-3 series were significantly higher in the dark red mm adductores compared to the light coloured m longissimus lumborum. Perirenal fat had a higher concentration of saturated fatty acids (14:0,16:0, 18:0) than backfat, and a lower concentration of monounsaturated fatty acids, such as 16:ln-7 and 18:ln-9. Daily supplementation of 50 ml cod liver oil, rich in n-3 PUFAs, during the fourth and third week before slaughter led to a 1.4 to 1.7 times increase in the contents of n-3 PUFAs in muscles and fat depots. There was no difference between the incorporation of n-3 PUFAs in dark and light muscles. Perirenal fat contained more 20:5n-3 (EPA) and 22:6n-3 (DHA), but less 20:ln-9 (eicosenoic acid) than the backfat, after cod liver oil supplementation rich in these 3 fatty acids. Supplementation of cod liver oil reduced the n-6/n-3 fatty acid ratio in all anatomical locations examined.     

Fatty acid compositions of red blood cell phospholipids in children with autism

We compared the compositions of fatty acids including n-3, n-6 polyunsaturated fatty acids, trans- and cis-monounsaturated fatty acids, and saturated fatty acids in the red blood cell membranes of 40 children with autism (20 with early onset autism and 20 with developmental regression) and age-matched, 20 typically developing controls and 20 subjects with non-autistic developmental disabilities. The main findings include increased levels of eicosenoic acid (20:1n9) and erucic acid (22:1n9) in autistic subjects with developmental regression when compared with typically developing controls. In addition, an increase in 20:2n6 and a decrease in 16:1n7t were observed in children with clinical regression compared to those with early onset autism. Our results do not provide strong evidence for the hypothesis that abnormal fatty acid metabolism plays a role in the pathogenesis of autism spectrum disorder, although they suggest some metabolic or dietary abnormalities in the regressive form of autism.     

Role of dietary oleic acid from two different sources on fatty acid composition of erythrocyte membrane and blood pressure in healthy subjects

This study has been undertaken to determine the effect of a diet enriched with olive oil (OO) and high-oleic sunflower oil (HOSO) on fatty acid composition of erythrocyte membrane phospholipids and blood pressure in healthy women. OO and HOSO were used as natural sources of monounsaturated fatty acids (MUFAs) in a random-order sequence over two 4-week periods with a 4-week washout period between both MUFA diets. HOSO diet resulted in significant increases in oleic [(18:1n-9) 8.6%, P < 0.001], eicosenoic [(20:1n-9) 33.3%, P < 0.05], arachidonic [(20:4n-6) 6.2%, P < 0.05], and docosapentaenoic [(22:5n-6) 56.0%, P < 0.001] acids, whereas OO diet besides increased the content of stearic acid [(18:0) 13.6%, P < 0.01] and long-chain polyunsaturated fatty acids (PUFAs) of the n-3 family (22:5n-3 and 22:6n-3), when compared with the baseline [a diet high in saturated fatty acids (SFAs) and low in MUFAs]. In contrast, there was a significant decrease in linoleic acid [(18:2n-6) 21.8%, P < 0.001] for both MUFA diets. Consistent with these data, dietary intake of OO significantly raised total PUFAs (7.2%, P < 0.05), the n-3 fatty acids (22.2%, P < 0.01) and the PUFAs/SFAs ratio (9.3%, P < 0.01), as well as decreased the ratio of cholesterol to phospholipids (26,1%, P < 0.001) versus HOSO-based diet. Interestingly, dietary OO, but not HOSO, was able to significantly reduce the systolic (3%, P < 0.05) and diastolic (4%, P < 0.05) blood pressures. Although both vegetable oils provided a similar content of MUFAs (mainly oleic acid), our findings rather indicate that OO has important benefits to modulate the fatty acid composition of membranes and the mechanisms involved in the regulation of blood pressure in human.     

Alteration of plasma phospholipid fatty acid profile in patients with septic shock

In septic shock patients, alterations of plasma phospholipid fatty acid profile have never been described. The purpose of this monocentric, non-interventional, observational prospective study was to describe this fatty acid profile in the early phase of septic shock in intensive care unit. Thirty-seven adult patients with septic shock were included after the first day of stay in intensive care unit, before any form of artificial nutritional support. Plasma phospholipid fatty acid composition was determined by gas chromatography. All biological data from patients with septic shock were compared with laboratory reference values. Patients presented hypocholesterolemia and hypertriglyceridemia. They had low concentrations of phospholipid fatty acids specifically n-6 and n-3 polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma phospholipid PUFA concentrations were strongly correlated with cholesterolemia. PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids) ratios were low because of low percentage of n-6 and n-3 PUFAs and high percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (≥20 carbons) were significantly associated with mortality at 28th day. In conclusion, plasma phospholipid FA profile of septic patients is very characteristic, close to that of acute respiratory distress syndrome and mortality is associated with long chain PUFA decrease. This profile could be explained by numerous non-exclusive physio-pathological processes 1) an activation of hepatic de novo lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress, 4) an over-production of inflammatory lipid mediators.     

The high-level accumulation of n-3 polyunsaturated fatty acids in transgenic pigs harboring the n-3 fatty acid desaturase gene from Caenorhabditis briggsae

Livestock meat is generally low in n-3 polyunsaturated fatty acids (PUFAs), which are beneficial to human health. An alternative approach to increasing the levels of n-3 PUFAs in meat is to generate transgenic livestock animals. In this study, we describe the generation of cloned pigs that express the cbr-fat-1 gene from Caenorhabditis briggsae, encoding an n-3 fatty acid desaturase. Analysis of fatty acids demonstrated that the cbr-fat-1 transgenic pigs produced high levels of n-3 fatty acids from n-6 analogs; consequently, a significantly reduced ratio of n-6/n-3 fatty acids was observed. We demonstrated that the n-3 desaturase gene from C. briggsae was functionally expressed, and had a significant effect on the fatty acid composition of the transgenic pigs, which may allow the production of pork enriched in n-3 PUFAs.     

Plasma fatty acid levels in patients with acquired immune deficiency syndrome and in controls

Polyunsaturated fatty acids (PUFAs) are known to modulate the immune system in vivo and to inactivate envelope viruses in vitro. Patients with AIDS had low total plasma lipid levels and low levels of a number of individual fatty acids. However, the C20 and C22 essential fatty acids of the n-3 series were selectively and highly significantly reduced. Normalization of these fatty acid levels in AIDS patients may be a worthwhile therapeutic aim.     

C19 odd-chain polyunsaturated fatty acids (PUfas) are metabolized to C21-PUfas in a rat liver cell line, and curcumin, gallic acid, and their related compounds inhibit their desaturation

It was demonstrated that the rat liver cell line BRL-3A converted exogenous C19 odd chain-polyunsaturated fatty acids (PUFAs) into the corresponding C21- and C23-PUFAs as follows: 21:3n-8, 21:4n-8, 23:3n-8, and 23:4n-8 (from 19:3n-8); 21:4n-5, 21:5n-5, 23:4n-5, and 23:5n-5 (from 19:4n-5); 21:5n-2, 21:6n-2, 23:5n-2, and 23:6n-2 (from 19:5n-2). It presumed that these C19 PUFAs were converted through the mimic route to docosahexaenoic acid (22:6n-3) from eicosapentaenoic acid (20:5n-3). In addition, the characterization of the change of fatty acid composition of cellular lipids in rat liver cells were examined, using 19:4n-5 and several fatty acid desaturation inhibitors. Curcumin related compounds, curcumin, capsaicin, isoeugenol, 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one, and gallic acid esters with near five carbon numbered alcohol had great changes of fatty acid composition of cellular lipids based on inhibition of the A6 desaturation of C24-PUFAs in rat liver cells.     

Dietary long-chain fatty acids and visual response in malnourished nursing infants

Polyunsaturated fatty acids (PUFAs) derived from essential fatty acids (EFAs) play an important role in prenatal visual and neural development. Protein-energy malnutrition affects PUFA supply, and hence the synthesis of structural lipids during growth. Recently, some physiological studies reported abnormalities in the visual function of formula-fed infants relative to breast-fed infants. The purpose of our study was to assess whether fatty acid composition of the malnourished infant diet modifies the visual function and erythrocyte phospholipid fatty acid composition. Three groups of full-term malnourished infants were selected. Two groups received commercial formulas. One of them supplied linoleic and alpha -linolenic acid: Formula I (FI), and the other supplied, in addition, long-chain PUFAs from n-3 and n-6 series: Formula II (FII). A reference group of breast-fed infants was also enrolled. Visual function was assessed using full-field flash electroretinography, and the erythrocyte phospholipid fatty acid composition was determined by gas-liquid chromatography. Those infants receiving the supplemented formula (FII) exhibited a similar retinal function to that of breast-fed infants. However, normal results were not achieved when infants were fed on the FI formula. In all groups, the results were correlated with the proportion of docosahexaenoic acid in erythrocyte phospholipid fatty acid composition. We conclude that in malnourished infants a nutrient formula enriched with long-chain fatty acids of n-6 and n-3 series could be helpful to achieve an erythrocyte fatty acid pattern and a visual function similar to that obtained in breast-fed infants.     

Gene transfer of the Caenorhabditis elegans n-3 fatty acid desaturase inhibits neuronal apoptosis

Previous studies have shown that n-3 polyunsaturated fatty acids (PUFAs) can exert an antiapoptotic effect on neurons. The present study was designed to investigate whether the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase (an enzyme that converts n-6 PUFAs to corresponding n-3 PUFAs) can be expressed functionally in rat cortical neurons and whether its expression can change the ratio of n-6 : n-3 fatty acids in the cell membrane and exert an effect on neuronal apoptosis. Infection of primary rat cortical cultures with Ad-fat-1 resulted in high expression of the fat-1 gene. Lipid analysis indicated a decrease in the ratio of n-6 : n-3 PUFAs from 5.9 : 1 in control cells, to 1.45 : 1 in cells expressing the n-3 fatty acid desaturase. Accordingly, the levels of prostaglandin E2, an eicosanoid derived from n-6 PUFA, were significantly lower in cells infected with Ad-fat-1 when compared with control cells. Finally, there was a significant inhibition of growth factor withdrawal-induced apoptotic cell death in neurons expressing the fat-1 gene. These results demonstrate that expression of the fat-1 gene can inhibit apoptotic cell death in neurons and suggest that the change in the n-6 : n-3 fatty acid ratio may play a key role in this protective effect.     

Dietary unsaturated fatty acids: interactions and possible needs in relation to eicosanoid synthesis

In addition to providing energy and essential fatty acids, dietary fatty acids can affect numerous biochemical and physiologic reactions related to secretory, cardiovascular, and immune functions. The major dietary unsaturated fatty acid, linoleic acid, affects tissue arachidonic acid and can influence eicosanoid-mediated reactions. Chronic, excess, or imbalanced eicosanoid synthesis may be conductive to excessive inflammation, thrombotic tendencies, atherosclerosis, and immune suppression. Dietary n-3 polyunsaturated fatty acids (PUFAs) may ameliorate eicosanoid-related phenomena by reducing tissue arachidonic acid and by inhibiting eicosanoid synthesis. This review summarizes information concerning the metabolism of unsaturated fatty acids, with emphasis on tissue arachidonic acid levels and eicosanoids, and discusses the need for data concerning the appropriate intake of dietary n-6 and n-3 PUFAs to modulate arachidonic acid and eicosanoid synthesis and to minimize possible adverse reactions.     

A modified <Emphasis Type="Italic">n</Emphasis>–3 fatty acid desaturase gene from <Emphasis Type="Italic">Caenorhabditis briggsae</Emphasis> produced high proportion of DHA and DPA in transgenic mice

The functions of polyunsaturated fatty acids (PUFAs) have been widely investigated. In mammals, levels of n-3 PUFAs are relatively low compared to those of n-6 PUFAs. Either a lack of n-3 PUFAs or an excess of n-6 PUFAs could potentially cause health problems in humans. Hence, methods to increase the amount of n-3 PUFAs in diet have been intensely sought. In this study, we demonstrated that the n-3 fatty acid desaturase gene (sFat-1) synthesized from revised and optimized codons based on roundworm Caenorhabditis briggsae genomic gene for enhanced expression in mammals was successfully expressed in Chinese hamster ovary (CHO) cells and significantly elevated cellular n-3 PUFA contents. We generated sFat-1 transgenic mice by introducing mammal expression vector DNAs containing the sFat-1 gene into regular mice through the method of microinjection. Fatty acid compositions were then altered and the levels of docosahexaenoic acid (DHA, 22:6n-3) and docosapentaenoic acid (DPA, 22:5n-3) were greatly increased in these transgenic mice. Various types of tissues in the transgenic mice produced many types of n-3 PUFAs, such as alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), DPA, and DHA, for example, muscle tissues of the transgenic mice contained 12.2% DHA, 2.0% DPA, and 23.1% total n-3 PUFAs. These research results demonstrated that the synthesized sFat-1 gene with modified and optimized codons from C. briggsae possess functional activity and greater capability of producing n-3 PUFAs, especially DHA and DPA, in transgenic mice.     

The opposing effects of n-3 and n-6 fatty acids

Polyunsaturated fatty acids (PUFAs) can be classified in n-3 fatty acids and n-6 fatty acids, and in westernized diet the predominant dietary PUFAs are n-6 fatty acids. Both types of fatty acids are precursors of signaling molecules with opposing effects, that modulate membrane microdomain composition, receptor signaling and gene expression. The predominant n-6 fatty acid is arachidonic acid, which is converted to prostaglandins, leukotrienes and other lipoxygenase or cyclooxygenase products. These products are important regulators of cellular functions with inflammatory, atherogenic and prothrombotic effects. Typical n-3 fatty acids are docosahexaenoic acid and eicosapentaenoic acid, which are competitive substrates for the enzymes and products of arachidonic acid metabolism. Docosahexaenoic acid- and eicosapentaenoic acid-derived eicosanoids antagonize the pro-inflammatory effects of n-6 fatty acids. n-3 and n-6 fatty acids are ligands/modulators for the nuclear receptors NFkappaB, PPAR and SREBP-1c, which control various genes of inflammatory signaling and lipid metabolism. n-3 Fatty acids down-regulate inflammatory genes and lipid synthesis, and stimulate fatty acid degradation. In addition, the n-3/n-6 PUFA content of cell and organelle membranes, as well as membrane microdomains strongly influences membrane function and numerous cellular processes such as cell death and survival.     

BIOCHEMICAL COMPOSITION AND FATTY ACID CONTENT OF FILAMENTOUS NITROGEN-FIXING CYANOBACTERIA

The biochemical composition and fatty acid content of twelve strains of filamentous, heterocystous, nitrogen-fixing cyanobacteria have been determined. When grown under diazotrophic conditions, protein, carbohydrate, lipid, and nucleic acids comprised 37–52%, 16–38%, 8–13%, and 8–11% of the dry weight, respectively. The presence of a combined nitrogen source resulted in an increase in the protein content of the cells and a decrease in the levels of lipids and carbohydrates, although biomass productivity was not affected significantly. Biochemical composition also changed during culture growth, with the highest levels of proteins and lipids occurring as the culture entered stationary phase, whereas the highest levels of carbohydrate and nucleic acids were found during the exponential phase. Total fatty acid levels in the strains assayed ranged between 3 and 5.7% of the dry weight. With regard to fatty acid composition, all strains showed high levels of polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SAFAs), with values of 24–45% and 31–52% of total fatty acids, respectively, whereas the levels of monounsaturated fatty acids (MUFAs) were in general lower (11– 32%). Palmitic acid (16:0) was the most prevalent SAFA, whereas palmitoleic (16:1n- 7) and oleic acid (18:1n-9) were the most abundant MUFAs in all the strains. Among PUFAs, γ-linolenic acid (GLA, 18:3n-6) was present at high levels (18% of total fatty acids) in Nostoc sp. (Chile) and at lower levels (3.6% of total fatty acids) in Anabaenopsis sp. The presence of GLA has not been previously reported in these genera of cyanobacteria. The rest of the strains exhibited high levels (12–35% of total fatty acids) of α-linolenic acid (ALA, 18:3n-3). Linoleic acid (18:2n-6) was also present at a substantial level in most of the strains. Eicosapentaenoic acid (EPA, 20:5n-3) was also detected in Nostoc sp. (Albufera). Some filamentous nitrogen-fixing cyanobacteria therefore represent potential sources of commercially interesting fatty acids.     

ELOVL2 controls the level of n-6 28:5 and 30:5 fatty acids in testis, a prerequisite for male fertility and sperm maturation in mice

ELOVL2 is a member of the mammalian microsomal ELOVL fatty acid enzyme family, involved in the elongation of very long-chain fatty acids including PUFAs required for various cellular functions in mammals. Here, we used ELOVL2-ablated (Elovl2(-/-)) mice to show that the PUFAs with 24-30 carbon atoms of the ω-6 family in testis are indispensable for normal sperm formation and fertility in male mice. The lack of Elovl2 was associated with a complete arrest of spermatogenesis, with seminiferous tubules displaying only spermatogonia and primary spermatocytes without further germinal cells. Furthermore, based on acyl-CoA profiling, heterozygous Elovl2(+/-) male mice exhibited haploinsufficiency, with reduced levels of C28:5 and C30:5n-6 PUFAs, which gave rise to impaired formation and function of haploid spermatides. These new insights reveal a novel mechanism involving ELOVL2-derived PUFAs in mammals and previously unrecognized roles for C28 and C30 n-6 PUFAs in male fertility. In accordance with the function suggested for ELOVL2, the Elovl2(-/-) mice show distorted levels of serum C20 and C22 PUFAs from both the n-3 and the n-6 series. However, dietary supplementation with C22:6n-3 could not restore male fertility to Elovl2(+/-) mice, suggesting that the changes in n-6 fatty acid composition seen in the testis of the Elovl2(+/-) mice, cannot be compensated by increased C22:6n-3 content.     

Statin treatment alters serum n-3 and n-6 fatty acids in hypercholesterolemic patients

Statins are highly effective cholesterol-lowering drugs but may have broader effects on metabolism. This investigation examined effects of simvastatin on serum levels of n-6 and n-3 polyunsaturated fatty acids (PUFAs). Subjects were 106 healthy adults with hypercholesterolemia randomly assigned to receive placebo or 40 mg simvastatin daily for 24 weeks. Serum fatty acids were analyzed by gas chromatography. Total fatty acid concentration fell 22% in subjects receiving simvastatin (P<.001), with similar declines across most fatty acids. However, concentrations of arachidonic acid (AA, 20:4n-6), eicosapentanoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were unchanged. Relative percentages of linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (LNA, 18:3n-3), decreased while AA and DHA increased (P's < or = .007). In addition, simvastatin increased the AA:EPA ratio from 15.5 to 18.8 (P<.01), and tended to increase the AA:DHA ratio (P=.053). Thus, simvastatin lowered serum fatty acid concentrations while also altering the relative percentages of important PUFAs.     

Adaptive branchial mechanisms in the sturgeon Acipenser naccarii during acclimation to saltwater

Variations of Na(+)/K(+)-ATPase activity and fatty-acid composition in the gills of the sturgeon Acipenser naccarii subjected to progressive acclimation to full seawater (35 ppt) were determined in relation to the hypo-osmoregulatory capacity of this species in the hyperosmotic medium. Blood samples were taken and gills arches were removed at intermediate salinity levels between 0 and 35 ppt and after 20 days at constant salinity (35 ppt). Plasma osmolality and Na(+)/K(+)-ATPase activity increased significantly with growing environmental salinity. Total saturated fatty acids (SFAs) decreased, while total polyunsaturated fatty acids (PUFAs) increased significantly with increasing salinity due mainly to changes in n-3 PUFAs (20:5n-3 and 22:6n-3). The n-3/n-6 ratio increased significantly during the acclimation process. The results show a direct relationship between salinity, increased gill Na(+)/K(+)-ATPase activity and ultrastructural changes of the gill chloride cells. Changes in the fatty-acid composition in gills of A. naccarii during progressive acclimation to full seawater suggest that variations of gill fatty acids may also have a role in osmoregulatory mechanisms.     

Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease

We have recently identified a neuroprotective role for omega-3 polyunsaturated fatty acids (n-3 PUFAs) in a toxin-induced mouse model of Parkinson's disease (PD). Combined with epidemiological data, these observations suggest that low n-3 PUFA intake is a modifiable environmental risk factor for PD. In order to strengthen these preclinical findings as prerequisite to clinical trials, we further investigated the neuroprotective role of n-3 PUFAs in Fat-1 mice, a transgenic model expressing an n-3 fatty acid desaturase converting n-6 PUFAs into n-3 PUFAs. Here, we report that the expression of the fat-1 transgene increased cortical n-3:n-6 PUFA ratio (+28%), but to a lesser extent than dietary supplementation (92%). Such a limited endogenous production of n-3 PUFAs in the Fat-1 mouse was insufficient to confer neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity as assessed by dopamine levels, tyrosine hydroxylase (TH)-positive neurons and fibers, as well as nigral Nurr1 and dopamine transporter (DAT) mRNA expression. Nevertheless, higher cortical docosahexaenoic acid (DHA) concentrations were positively correlated with markers of nigral dopaminergic neurons such as the number of TH-positive cells, in addition to Nurr1 and DAT mRNA levels. These associations are consistent with the protective role of DHA in a mouse model of PD. Taken together, these data suggest that dietary intake of a preformed DHA supplement is more effective in reaching the brain and achieving neuroprotection in an animal model of PD.     

Fat-1基因在n-3多不饱和脂肪酸功能研究中的应用

n-3多不饱和脂肪酸是机体脂肪酸成分之一,维持体内合理的n-3多不饱和脂肪酸比例具有重要的生理意义。但n-3多不饱和脂肪酸在大多数动物体内不能合成,只能从食物中补充。fat-1基因的出现改变了这一现状,它可以将多不饱和脂肪酸从n-6形式转化为n-3形式。文章综述了n-3多不饱和脂肪酸的功能,并介绍了fat-1基因的功能及转fat-1基因动物在n-3多不饱和脂肪酸功能研究上的应用。     

Fatty-Acid Profile of Total and Polar Lipids in Cultured Rainbow Trout (Oncorhynchus mykiss) Raised in Freshwater and Seawater (Croatia) Determined by Transmethylation Method

Fatty acids from total lipids and polar lipids in cultured rainbow trout (Oncorhynchus mykiss) raised in seawater (SW) and freshwater (FW) were identified and quantified from the muscle samples in January, April, and July. The highest total lipid and polar lipid amounts were found in April. July contents of total lipids were low, but percent of the polyunsaturated fatty acids (PUFAs) was high in SW and FW environment (particularly n-3 PUFAs). Variety of 17 fatty acids was identified by GC-FID after transmethylation. The predominant fatty acids in rainbow trout from SW and FW were: docosahexaenoic acid among n-3 PUFAs, palmitic acid among saturated fatty acids (SFAs), and oleic acid among monounsaturated fatty acids (MUFAs). Appreciably higher n-3/n-6 ratio was found in total lipids in April (6.40, FW fish) and in polar lipids in July (18.76; SW fish). High n-3/n-6 ratio in total lipids and polar lipids of rainbow trout from SW and FW, besides beneficial n-3/n-6 ratio in the commercial fish food, could be characteristic for the local environmental conditions (Croatia).     

Docosahexaenoic acid induces ciap1 mRNA and protects human endothelial cells from stress-induced apoptosis

Induction of apoptosis represents a potential reaction of endothelial cells (ECs) after injury of the vascular endothelium. Beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) in vascular diseases are widely recognized although the responsible mechanisms are not fully understood. Because it is not known whether PUFAs modulate EC apoptosis, we investigated the effects of n-3 and n-6 PUFAs on 4-hydroxynonenal (HNE)-induced EC apoptosis by annexin V staining and caspase-3 activation assays. Pretreatment with the n-3 fatty acid docosahexaenoic acid (DHA) reduced HNE-induced EC apoptosis. DHA-treated cells did not show the pronounced drop in intracellular GSH after HNE exposure seen in vehicle- or n-6 arachidonic acid-treated cells. This is most likely due to increased GSH levels in DHA-treated cells. Furthermore, DHA pretreatment increased ciap1 mRNA levels and transfection of cIAP1 small interfering RNA abolished the protective effect of DHA in HNE-induced apoptosis in HUVECs. Thus pretreatment of HUVECs with DHA reduces HNE-induced oxidative stress and apoptosis, and the protective effects of DHA seem to be dependent on cIAP1. The results provide a possible new mechanism for the atheroprotective effects of n-3 fatty acids in vascular disease.