Maternal dietary 22 : 6n-3 is more effective than 18 : 3n-3 in increasing the 22 : 6n-3 content in phospholipids of glial cells from neonatal rat brain

One of the debates in infant nutrition concerns whether dietary 18 : 3n-3 (linolenic acid) can provide for the accretion of 22 : 6n-3 (docosahexaenoic acid, DHA) in neonatal tissues. The objective of the present study was to determine whether low or high 18 : 3n-3 v. preformed 22 : 6n-3 in the maternal diet enabled a similar 22 : 6n-3 content in the phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) of glial cells from whole brain (cerebrum and cerebellum) of 2-week-old rat pups. At parturition, the dams were fed semi-purified diets containing either increasing amounts of 18 : 3n-3 (18 : 2n-6 to 18 : 3n-3 fatty acid ratio of 7.8 : 1, 4.4 : 1 or 1 : 1), preformed DHA, or preformed 20 : 4n-6 (arachidonic acid)+DHA. During the first 2 weeks of life, the rat pups from the respective dams received only their dam's milk. The fatty acid composition of the pups' stomach contents (dam's milk) and phospholipids from glial cells were quantified. The 20 : 4n-6 and 22 : 6n-3 content in the stomach from rat pups at 2 weeks of age reflected the fatty acid composition of the dam's diet. The 20 : 4n-6 content of PE and PS in the glial cells was unaffected by maternal diet treatments. Preformed 22 : 6n-3 in the maternal diet increased the 22 : 6n-3 content of glial cell PE and PS compared with maternal diets providing an 18 : 2n-6 to 18 : 3 n-3 fatty acid ratio of 7.8 : 1, 4.4 : 1 or 1 : 1 (P<0.0001). There was no significant difference in the 20 : 4n-6 and 22 : 6n-3 content of glial cell PC and PI among maternal diet treatments. It was concluded that maternal dietary 22 : 6n-3 is more effective than low or high levels of maternal dietary 18 : 3n-3 at increasing the 22 : 6n-3 content in PE and PS of glial cells from the whole brain of rat pups at 2 weeks of age. The findings from the present study have important implications for human infants fed infant formulas that are devoid of 22 : 6n-3.     

Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in frontal cortex caused by a linoleic and alpha-linolenic acid deficient diet in formula-fed piglets.

This study examined the effects of diets deficient (D) in linoleic [18:2(n-6)] and linolenic acid [18:3(n-3)] at 0.8 and 0.05% energy, respectively, or adequate (C) in 18:2(n-6) and 18:3(n-3) at 8.3 and 0.8% energy, respectively, without (-) or with (+) 0.2% energy arachidonic [20:4(n-6)] and 0.16% energy docosahexaenoic [22:6(n-3)] acid in piglets fed from birth to 18 d. Frontal cortex dopaminergic and serotoninergic neurotransmitters and phospholipid fatty acids were measured. Piglets fed the D- diet had significantly lower frontal cortex dopamine, 3,4-dihydroxyphenylacetic (DOPAC), homovanillic acid (HVA), serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations than did piglets fed the C- diets. Frontal cortex dopamine, norepinephrine, DOPAC, HVA, serotonin and 5-HIAA were higher in piglets fed the D+ compared to those fed the D- diet (P < 0.05) and not different between piglets fed the D+ and those fed the C- diets or the C- and C+ diets. Piglets fed the D- diet had lower frontal cortex phosphatidylcholine (PC) and phosphatidylinositol (PI) 20:4(n-6) and PC and phosphatidylethanolamine (PE) 22:6(n-3) than did piglets fed the C- diet (P < 0.05). Piglets fed the D+ diet had higher frontal cortex PC and PI 20:4(n-6) and PC, PE, PS and PI 22:6(n-3) than did piglets fed the D- diet. These studies show that dietary essential fatty acid deficiency fed for 18 d from birth affects frontal cortex neurotransmitters in rapidly growing piglets and that these changes are specifically due to 20:4(n-6) and/or 22:6(n-3).     

Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain

The importance of maternal dietary fatty acids on arachidonic acid [AA; 20:4(n-6)] and docosahexaenoic acid [DHA; 22:6(n-3)] in fetal brain nerve growth cone membranes and monoaminergic neurotransmitters was investigated. Rats were fed purified diets containing 20 g/100 g safflower oil with 74.3% 18:2(n-6), 0.2% 18:3(n-3), soybean oil with 55.4% 18:2(n-6), 7.7% 18:3(n-3) or high fish oil with 24.6% 22:6(n-3) through gestation. Tissue for rats within a litter were pooled at birth, brain growth cone membranes prepared and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) fatty acids quantified by gas-liquid chromatography. Dopamine, serotonin, and the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxyindolacetic acid were quantified by HPLC. Growth cone membranes from offspring of rats fed safflower oil had significantly lower, and offspring of rats fed high 22:6(n-3) fish oil had significantly higher 22:6(n-3) in PE, PS and PI than the soybean oil group. The growth cone membrane PC, PE and PS 20:4(n-6) was significantly lower in the fish oil than in the soybean or safflower oil groups. Serotonin concentration was significantly higher in brain of offspring in the safflower oil compared with the soybean oil group. The newborn brain dopamine was inversely related to PE DHA and PS DHA (P < 0.001), but positively related to PC AA (P < 0.05). These studies show that maternal dietary fatty acids may alter fetal brain growth cone (n-6) and (n-3) fatty acids, and neurotransmitters involved in neurite extension, target finding and synaptogenesis. The functional importance, however, is not known at this time.     

Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*

The capacity for conversion of alpha-linolenic acid (ALNA) to n-3 long-chain polyunsaturated fatty acids was investigated in young men. Emulsified [U-13C]ALNA was administered orally with a mixed meal to six subjects consuming their habitual diet. Approximately 33 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h. [13C]ALNA was mobilised from enterocytes primarily as chylomicron triacylglycerol (TAG), while [13C]ALNA incorporation into plasma phosphatidylcholine (PC) occurred later, probably by the liver. The time scale of conversion of [13C]ALNA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) suggested that the liver was the principal site of ALNA desaturation and elongation, although there was some indication of EPA and DPA synthesis by enterocytes. [13C]EPA and [13C]DPA concentrations were greater in plasma PC than TAG, and were present in the circulation for up to 7 and 14 d, respectively. There was no apparent 13C enrichment of docosahexaenoic acid (DHA) in plasma PC, TAG or non-esterified fatty acids at any time point measured up to 21 d. This pattern of 13C n-3 fatty acid labelling suggests inhibition or restriction of DHA synthesis downstream of DPA. [13C]ALNA, [13C]EPA and [13C]DPA were incorporated into erythrocyte PC, but not phosphatidylethanolamine, suggesting uptake of intact plasma PC molecules from lipoproteins into erythrocyte membranes. Since the capacity of adult males to convert ALNA to DHA was either very low or absent, uptake of pre-formed DHA from the diet may be critical for maintaining adequate membrane DHA concentrations in these individuals.     

Testes of obese rats are highly responsive to n-3 long-chain fatty acids

The present study investigated whether fatty acid compositions of testes are affected by the obese condition and dietary n-3 long-chain fatty acid (LCFA) intake. Male lean and obese Zucker rats were fed a 15?% (w/w, total diet) fat diet containing either 0 or 5·0?% (w/w, total fatty acids) n-3 LCFA for 8 weeks. Reproductive organ weights, sperm morphology and fatty acid composition of phosphatidylcholine (PC), and phosphatidylethanolamine (PE) of testes were analysed. The obese rats had significantly (P?相似文献   

Depletion of delta 9 desaturase (EC 1.14.99.5) enzyme activity in growing rat during dietary protein restriction.

The effects of protein restriction on delta 9 desaturase (EC 1.14.99.5) activity were studied in growing rats. A control group was fed on a balanced diet (200 g casein/kg; BD) for 28 d. The experimental group was fed on the low-protein diet (20 g casein/kg; LP) for 26 d, then refed the balanced diet (BD-R) for 2 d. Rats were born to and suckled from normally fed dams. The enzyme activity was measured after 2 and 14 d of LP, and 26 d of LP plus 2 d of BD-R, by incubations in vitro of hepatic microsomal pellets with [1-14C]steric acid. The results indicated a decreased delta 9 desaturase activity after 2 and 14 d of LP of -33 and -43% respectively. Refeeding for 2 d was sufficient to super-repair this activity (+66%). The fatty acid composition of total liver lipids and microsomal phosphatidylethanolamines (PE) and phosphatidylcholines (PC) were also investigated; 18:0 decreased in total liver lipids at 14 d of LP, when 18:1n-9 increased. Stearic acid (18:0) increased in PC at 2 d of LP and in PE at 14 d of LP; oleic acid (18:1n-9) did not change. Therefore, it is concluded that a defect occurred in the bioconversion of 18:0 into 18:1n-9 by delta 9 desaturation during protein depletion. As oleic acid is accumulated in total liver lipids during LP, we speculate that this is due to a decreased oxidation or transport of this fatty acid.     

Effects of casein and soy-protein on alpha-linolenic acid metabolism in rats.

In order to study the effects of different proteins on alpha-linolenic acid (alpha-LnA) metabolism, rats were given the diet added respectively with milk casein and soy-protein isolate (SPI) as sources of proteins and perilla oil as a source of lipid. The results obtained are as follows. The ratio of (C20:3 + C20:4)/C18:2 in liver microsomal PL, liver PE fraction, and kidney PE and PC fractions was significantly lowered by the SPI treatment when compared to the casein treatment, similarly to the already established results. In the liver microsomal PL and PE and PC fractions of liver and kidney in rats treated with SPI, there was also observed a significant decrease or a decrease tendency in the (C20:4 + C20:5)/C18:3 ratio. A similar tendency was again shown in the sigma (n-3)M/C18:3 ratio indicating metabolic conversion from C18:3(n-3) to C22:6. On the other hand, contrary to the ratios of (C20:3 + C20:4)/C18:2, sigma (n-3)M/C18:3, and (C20:3 + C20:5)/C18:3, the (C22:5 + C22:6)/C20:5 ratio which is the parameter for metabolic conversion of C20:5(n-3) was elevated in the PE and PC fraction of liver, heart and kidney in the SPI group compared to the casein group. Then, further analysis of the metabolic process from C20:5 to C22:6 showed that the C22:5/C20:5 ratio increased while the C22:6/C22:5 ratio decreased in the SPI group compared to the casein group. Based on these results, it is assumed that the metabolic process from C18:3(n-3) to C20:5(n-3) and from C22:5 to C22:6 is affected by SPI but that the elongation process from C20:5(n-3) to C22:5(n-3), on the contrary, is rather accelerated by SPI.     

Effects of different quantities of fat on serum and liver lipids, phospholipid class distribution and fatty acid composition in alcohol-treated rats

The present study investigated the quantitative effect of dietary fats and ingestion of alcohol on serum and liver lipids, fatty acid bound to phospholipids and their class distribution of male Wistar rats. The rats in C (control) and A (alcohol) groups were fed a standard laboratory diet, HFC (high fat-control) and HFA (high fat-alcohol) groups were fed a high fat diet (standard diet supplemented with 20 g%w/w, sunflower oil: lard mixture 1: 1) for 6 wk. Alcohol-treated rats consumed alcohol at the rate of 9 g/kgbw/d (15-20% energy). Liver phospholipid (PL) content was decreased, and phospholipid/cholesterol liver molar ratio increased in the alcohol treated rats. The proportion of serum sphingophospholipid (Sph) was significantly lower and proportion of phosphatidylcholin (PC) significantly higher in serum PL in alcohol-treated rats. Phospholipid class distribution was unaffected by alcohol feeding in liver. Significantly lower levels of 16:1n-7 and higher levels of 20:5n-3 and 22:4n-6 in the serum PL were observed in the alcohol-treated rats. The groups on the HF diet increased levels of 20:4n-6, 22:4n-6 and total n-6, polyunsaturated fatty acid (PUFA) and decreased levels of 18:1n-9 and total monounsaturated fatty acids (MUFA)in both liver and serum PL, but n-3 fatty acid increased in serum PL and decreased in liver PL compared to groups on the standard diet. Alcohol fat interaction was evident in MUFA and PUFA/SFA in serum PL and n-6, MUFA, PUFA and polyunsaturated/saturated fatty acid ratios (PUFA/SFA) in liver PL. This study showed that the high fat intake in alcohol-treated rats increased levels of 20:4n-6, 22:4n-6 and 20:4/18:2 ratio, and decreased level of 18:1n-9 in liver and serum phospholipids.     

Dietary counseling to improve fat quality during pregnancy alters maternal fat intake and infant essential fatty acid status

To explore the effect of maternal dietary intervention on infant essential fatty acid (FA) status, we conducted a prospective, single-blind, randomized nutrition intervention study. At the first trimester of pregnancy, 90 women from families with a history of allergy were randomized either to receive intensive dietary counseling to modify dietary intake according to current recommendations or as controls. Infants' cord and 1-mo isolated serum phospholipid FA were identified and quantified by GC. Detectable levels of eicosatrienoic acid [ETA, 20:3(n-9)] were taken as a biochemical marker for essential FA deficiency, and the DHA sufficiency index [22:6(n-3):22:5(n-6)] and the DHA deficiency index [22:5(n-6):22:4(n-6)] were taken as markers for DHA [22:6(n-3)] status. The concentration of ETA was lower in cord blood in the intervention (I) group [median 0.64 (IQR 0.40-0.78) mg/L; 2.09 (1.31-2.54) μmol/L] than in the control (C) group [0.92 (0.54-1.20) mg/L; 3.00 (1.76-3.92) μmol/L] (P = 0.048). The proportion of ETA in total FA in the I group [0.73% (0.48-0.85%)] was lower than in the C group [0.93% (0.78-1.22%)] (P = 0.003). A higher DHA sufficiency index and lower DHA deficiency index were detected in cord blood in the I group than in the C group, although the groups did not differ in the DHA concentration or proportion of the total FA. There were no differences among groups at 1 mo for any of the variables measured. Our findings suggest a better supply of essential FA, particularly important during the period of rapid development, in infants whose mothers received dietary counseling. The results thus highlight the importance of maternal diet for child health, calling for dietary counseling for pregnant women in primary health care.     

Effect of dietary blackcurrant seed oil on mouse macrophage subclasses of choline and ethanolamine glycerophospholipids

There have been reports that dietary gamma-linolenic acid [18:3(n-6)] and alpha-linolenic acid [18:3(n-3)] are capable of regulating cellular eicosanoid biosynthesis and inflammation. Because the eicosanoid cascade is regulated in part by the distribution of arachidonic acid [20:4(n-6)] among phospholipid subclasses, the effects of feeding blackcurrant seed oil [containing 18:3(n-6) and 18:3(n-3)] on the fatty acid composition of diacyl, alkylacyl and alkenylacyl subclasses of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were studied in mouse peritoneal macrophages. After 4 wk of dietary treatment, the relative distribution (mol %) of macrophage phospholipid classes and subclasses was not altered in animals fed blackcurrant seed oil relative to those fed corn oil [containing linoleic acid, 18:2(n-6)]. Macrophages from blackcurrant seed oil-fed animals had reduced levels of PC diacyl 18:3(n-6), 18:3(n-3), 20:3(n-6), 22:5(n-3), and alkylacyl 20:3(n-6), 22:5(n-3) and 22:6(n-3). In general, dietary blackcurrant treatment produced fatty acid alterations in PE subclasses that were similar to those in PC. A major exception, however, was the reduction in 20:4(n-6) levels in all PE subclasses, whereas no effect in PC subclass 20:4(n-6) levels was noted. These findings indicate i) that pronounced differences in the polyunsaturated fatty acid (PUFA) compositions of macrophage PC and PE subclasses exist following dietary fat manipulation and ii) that 18:3(n-6) and 18:3(n-3) feeding can increase potential anti-flammatory precursor levels of 20:3(n-6) and (n-3) PUFA in the macrophage.     

Dietary n-3 and n-6 fatty acids alter avian metabolism: molecular-species composition of breast-muscle phospholipids

The effects of diets high in n-3 polyunsaturated fatty acids (PUFA; provided by fish oil), n-6 PUFA (sunflower oil) or in more-saturated fatty acids (tallow) on the distribution of subclasses of choline phospholipids (PC) and ethanolamine phospholipids (PE) from the breast muscle of broiler chickens were examined. Supplementation with the different fatty acids had no effect on the distribution of phospholipid subclasses. Feeding sunflower oil or tallow gave a molecular-species profile similar in both fatty acid subtype and proportion. In the diacyl PC phospholipids, 16 : 0-18 : 1n-9 and 16 : 0-18 : 2n-6 accounted for approximately 60 % of the total molecular species, whereas for the alkylenyl PC the predominant species were 16 : 0-18 : 1n-9 and 16 : 0-20 : 4n-6. Of the diacyl PE the dominant species was 18 : 0-20 : 4n-6 which accounted for 50 % of the molecular species, and of the alkylenyl PE the dominant species were 16 : 0-18 : 1n-9, 16 : 0-20 : 4n-6 and 18 : 0-20 : 4n-6. Supplementation with fish oil significantly increased levels of both eicosapentaenoic acid (20 : 5n-3) and docosahexaenoic acid (22 : 6n-3) in PC and PE when compared with either sunflower oil or tallow supplementation. The increase in the n-3 PUFA incorporation was associated with a corresponding decrease in the proportion of arachidonic acid (20 : 4n-6) in both PC and PE. Different dietary fats induce different patterns of fatty acid incorporation and substitution in the sn-2 position of the diacyl and alkylenyl PC and PE of avian breast muscle, and this finding is indicative of selective acyl remodelling in these two phospholipids.     

Dietary eritadenine and ethanolamine depress fatty acid desaturase activities by increasing liver microsomal phosphatidylethanolamine in rats

The effects of eritadenine, a constituent of the Lentinus edodes mushroom, and ethanolamine, the base constituent of phosphatidylethanolamine (PE), on fatty acid desaturase activities and lipid profiles were investigated comparatively in rats. Rats were fed a control diet or a diet supplemented with either eritadenine (0.05 g/kg) or ethanolamine (8 g/kg) for 14 d. Eritadenine and ethanolamine had marked hypocholesterolemic effects. The concentration of liver microsomal PE was significantly increased and the ratio of phosphatidylcholine (PC) to PE was significantly decreased by both eritadenine and ethanolamine. These changes in phospholipid profile were also observed in the mitochondria and plasma membranes in the liver. The activities of the Delta5-, Delta6- and Delta9-desaturases in liver microsomes were significantly decreased by eritadenine and ethanolamine; there was a significant correlation between the activity of Delta5- or Delta6-desaturase and the proportion of PE in the total phospholipids or the PC/PE ratio. Reflecting decreased Delta5- and Delta6-desaturase activities, the 20:4(n-6)/18:2(n-6) ratio was significantly decreased by eritadenine and ethanolamine in PC of the liver microsomes, mitochondria and plasma membranes. Although the 20:4(n-6)/18:2(n-6) ratio of liver microsomal PE was also significantly decreased by eritadenine and ethanolamine, the fatty acid composition of phosphatidylinositol and phosphatidylserine was less affected by these compounds. Eritadenine and ethanolamine increased the proportion of 16:0-18:2 and decreased the proportion of 18:0-20:4 in liver PC. The results suggest that dietary eritadenine and ethanolamine might lead to decreases in desaturase activities and changes in fatty acid and molecular species composition of PC through an increase in liver microsomal PE.     

Lipid profiles of Chinese soft-shell turtle eggs (Pelodiscus sinensis)

Studies have shown potential beneficial functions of turtle eggs, but the mechanism is not clear. The species and content of lipids have a significant impact on human health. The major lipid classes and fatty acids composition of dried Chinese soft-shell turtle eggs were characterized with the aim of clarifying the potential beneficial functions of turtle eggs from the perspective of lipid nutrition. 100 g dried turtle eggs power contained an average of 24.7 g of triacylglycerol (TAG), 1.24 g of phospholipid (PL) and 0.72 g of cholesterol. The striking feature of the lipid composition was the abundant n-3 polyunsaturated fatty acids, resulting in an excellent n-6/n-3 ratio (1.27) and low atherogenic index (AI) and thrombogenic index (TI) values, which were considered to be a healthier option for the human diet. A total of 85 TAG molecular species and 95 PL molecular species were obtained by lipidomics. ΣcisC18:1, C18:2n-6 and C18:3n-3 were preferentially esterified at sn-2 position of TAG. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accounted for more than 90 % of the PL, while no sphingomyelin (SM) was detected. C22:6n-3 and C20:5n-3 were preferentially bound to PE and lysophosphatidylcholine (LPC) respectively.     

Effects of n-3 polyunsaturated fatty acids on coronary heart disease

The purpose of this paper is to discuss the role of n-6 and n-3 polyunsaturated fatty acids in coronary heart disease (CHD). The level of n-6 and n-3 fatty acids in plasma and cardiac phospholipids was examined in relation to CHD in man. The fatty acid profile of cardiac phospholipids was also examined in relation to various risk factors of CHD, such as the composition of dietary fat, aging and stress. Life expectancy in Iceland is higher than in other Nordic countries, and the cardiovascular diseases mortality is lower in Iceland in the older age groups. There is a positive correlation between the level of arachidonic acid (AA) in plasma phospholipids (PL) in the normal population and cardiovascular disease mortality in Nordic countries. The level of AA in plasma PL is significantly higher in patients with CHD than in normal subjects. Dietary intake of fish or fish oil lowers cellular levels of AA and favorably influences eicosanoid metabolism in platelets and leukocytes. The roles of n-6 and n-3 fatty acids in heart muscle are less well understood. Rats fed diets containing either 10% butter, corn oil or cod liver oil showed markedly different fatty acid composition of individual phospholipids in sarcolemma. Dietary cod liver oil lowered the AA level in sarcolemmal phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) by 50% compared to butter or corn oil fed rats, replacing AA with docosahexaenoic acid (DHA). Adaptation to moderate to severe stress induced by repeated administration of catecholamines for 15 days resulted in marked but reversible alterations in the fatty acid profile of cardiac phospholipids. During severe stress the level of AA increased by 50% in PC replacing linoleic acid (LA), whereas in PE the DHA increased markedly replacing LA. Aging was accompanied by similar alterations in cardiac phospholipids, increased levels of AA in PC and increased DHA in PE. The incidence of ventricular fibrillation (VF) and sudden cardiac death induced by isoproterenol in adult rats fed different dietary fat was lowest in rats fed cod liver oil, with a low ratio of AA/DHA in cardiac phospholipids. Mortality due to VF was highest in rats fed corn oil with the highest ratio of AA/DHA. Sudden cardiac death in man was frequently associated with a higher ratio of AA/DHA than observed in people of the same age who died in accidents. The balance between n-6 and n-3 fatty acids in cellular phospholipids seems to play an important role in stress tolerance and survival.     

Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects

OBJECTIVE: To compare the effects of alpha-linolenic acid (ALA, C18:3n-3) to those of eicosapentaenoic acid (EPA, C20:5n-3) plus docosahexaenoic acid (DHA, C22:6n-3) on cardiovascular risk markers in healthy elderly subjects. DESIGN: A randomized double-blind nutritional intervention study. SETTING: Department of Human Biology, Maastricht University, the Netherlands. SUBJECTS: Thirty-seven mildly hypercholesterolemic subjects, 14 men and 23 women aged between 60 and 78 years. INTERVENTIONS: During a run-in period of 3 weeks, subjects consumed an oleic acid-rich diet. The following 6 weeks, 10 subjects remained on the control diet, 13 subjects consumed an ALA-rich diet (6.8 g/day) and 14 subjects an EPA/DHA-rich diet (1.05 g EPA/day + 0.55 g DHA/day). RESULTS: Both n-3 fatty acid diets did not change concentrations of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerol and apoA-1 when compared with the oleic acid-rich diet. However, after the EPA/DHA-rich diet, LDL-cholesterol increased by 0.39 mmol/l (P = 0.0323, 95% CI (0.030, 0.780 mmol/l)) when compared with the ALA-rich diet. Intake of EPA/DHA also increased apoB concentrations by 14 mg/dl (P = 0.0031, 95% CI (4, 23 mg/dl)) and 12 mg/dl (P = 0.005, 95% CI (3, 21 mg/dl)) versus the oleic acid and ALA-rich diet, respectively. Except for an EPA/DHA-induced increase in tissue factor pathway inhibitor (TFPI) of 14.6% (P = 0.0184 versus ALA diet, 95% CI (1.5, 18.3%)), changes in markers of hemostasis and endothelial integrity did not reach statistical significance following consumption of the two n-3 fatty acid diets. CONCLUSIONS: In healthy elderly subjects, ALA might affect concentrations of LDL-cholesterol and apoB more favorably than EPA/DHA, whereas EPA/DHA seems to affect TFPI more beneficially.     

Metabolism of arachidonic, eicosapentaenoic, and docosahexaenoic acids in HepG2 cells and rat hepatocytes.

The metabolism of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) was examined in HepG2 cells, a human hepatoma cell line, and rat hepatocytes. The AA level in HepG2 cells was lower than in rat hepatocytes and incorporation of AA into HepG2 was also smaller than into rat hepatocytes. Both cells could not increase the level of cellular DHA by the addition of exogenous 22:5 (n-3); whereas, rat hepatocytes, but not HepG2 cells, increased the levels of AA from 20:3 (n-6) and EPA from 20:4 (n-3). In both cells, retroconversion of AA to 20:3 (n-6) occurred, but EPA was not retroconverted to 20:4 (n-3). These results suggested that the levels of AA and DHA in both types of cells, were regulated more severely than EPA and that the activity of fatty acid desaturation might be different between n-6 and n-3 families.     

Neonatal dietary zinc deficiency in artificially reared rat pups retards behavioral development and interacts with essential fatty acid deficiency to alter liver and brain fatty acid composition.

The objective of this study was to investigate whether short-term zinc deficiency in the early neonatal period would exacerbate the effects of essential fatty acid (EFA) deficiency on liver and brain long-chain polyunsaturated fatty acid (LCPUFA) composition, as well as on behavioral development in artificially reared rat pups. Using a 2 x 2 factorial design, male Long-Evans rat pups were reared artificially from postnatal d 5 to 16; pups were fed through gastrostomy tubes with rat formula deficient in zinc and/or EFA. As expected, EFA deficiency significantly reduced levels of arachidonic acid [AA, 20:4(n-6)] and docosahexanoic acid [DHA, 22:6(n-3)] in liver phosphatidylcholine (PC) and brain phosphaditylethanolamine (PE), and increased 22:5(n-6) levels in liver and brain PC and PE. There were significant interactions between zinc and EFA in liver such that zinc deficiency reduced AA and DHA in the EFA-adequate groups, but significantly increased AA in the EFA-deficient groups. Contrary to the hypothesis, short-term zinc deficiency did not exacerbate the effects of EFA deficiency in liver phospholipids. In brain PE, a significant interaction between EFA and zinc was observed such that zinc deficiency increased 22:5(n-6) concentrations in EFA-adequate but not in EFA-deficient groups. Regardless of their EFA status, zinc-deficient rats were growth retarded and demonstrated deficits in locomotor skills. Possible effects of long-term zinc and EFA deficiency on brain function should be investigated in future studies.     

Behavioral responses are altered in piglets with decreased frontal cortex docosahexaenoic acid

Docosahexaenoic acid [22:6(n-3)] is required in large amounts for membrane lipid synthesis during brain growth. The functional importance of differences in dietary fatty acid intakes that alter brain 22:6(n-3), however, is not well understood. We used a dietary approach to manipulate 22:6(n-3) in piglet brain and assessed the effects on behavior and change in behavior on an elevated plus maze after administration of L-dihydroxyphenylalanine (L-Dopa) or sulperide, a dopamine D2 receptor blocker. Piglets were fed 1.2% energy 18:2(n-6) and 0.05% energy 18:3(n-3) (low PUFA), or 10.7% energy 18:2(n-6), 1.1% energy 18:3(n-3), 0.3% energy 20:4(n-6) and 0.3% energy 22:6(n-3) (high PUFA) from 1 d of age and behavior assessed at 18-22 d of age. At 30 d of age, frontal cortex dopamine, and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidyethanolamine (PE) and phosphatidylinositol (PI) fatty acids were quantified. Piglets fed the low PUFA diet had fewer arm entries on the maze than piglets fed the high PUFA diet, P = 0.02. L-Dopa increased the open (P = 0.005) and closed (P = 0.04) arm entries by piglets fed the low PUFA diet. Behavior did not differ between piglets fed the low and high PUFA diets when given L-Dopa. Frontal cortex PC, PS and PE 22:6(n-3) was lower and 22:5(n-6) was higher in piglets fed the low compared with the high PUFA diet, P < 0.01. Our work establishes the neonatal piglet as a model with which to study the behavioral effects of diet-induced changes in brain 22:6(n-3), and provides functional evidence that brain 22:6(n-3) is important in central dopamine metabolism.     

Preterm infant formula supplementation with alpha linolenic acid and docosahexaenoic acid

OBJECTIVES: To investigate if supplementation of preterm infant formula with a high docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio together with alpha-linolenic acid (ALA) was able to maintain plasma and red blood cell DHA levels similar to that obtained with breast milk feeding without altering n-6 fatty acid status. DESIGN AND SUBJECTS: Preterm infants of mothers who elected not to breast feed (n=13) were assigned to ALA- and DHA-enriched formula (DHA group: DHA/EPA=5/l). Infants fed breast milk (n=25) constituted a reference group (BM group). Anthropometric and fatty acid parameters (plasma phospholipids, cholesterol esters, triglycerides and red blood cell phosphatidylethanolamine, PL, CE, TG, RBC-PE, respectively) were obtained after 2 days (D2) and 15 days (D15) of enteral feeding and at the 37th week (W37) of post-conception age and 1 month later (W37+30) in the DHA group. Mean DHA intake ranged between 16.5+/-1.6 and 17.9+/-2.9 mg/kg/day between D2 and W37+30. RESULTS: At W37, infant weights, heights, and head circumferences were similar in DHA and BM groups. PL DHA was maintained in the DHA group at the same level as in the BM group and the same for DHA in PE at W37. In RBC-PE and at W37, AA status was the same in both groups. In PL, AA levels remained very stable throughout the study; however, in the DHA group AA levels in PL remained in the range observed with standard formulas. CONCLUSION: The combined 18:3 n-3 and DHA supplementation of infant formula with DHA/EPA ratio 5/l is compatible with growth and n-3 fatty acid metabolism similar to that of preterm infants fed human milk.     

Using a fingertip whole blood sample for rapid fatty acid measurement: method validation and correlation with erythrocyte polar lipid compositions in UK subjects

It is well accepted that n-3 long-chain PUFA intake is positively associated with a range of health benefits. However, while benefits have been clearly shown, especially for CVD, the mechanisms for prevention/benefit are less understood. Analysis of plasma and erythrocyte phospholipids (PL) have been used to measure the status of the highly unsaturated fatty acids (HUFA), especially EPA (20 : 5n-3) and DHA (22 : 6n-3), although the time and complexity of the process places limitations on the sample numbers analysed. An assay has been developed using whole blood, collected by finger prick, and stored on absorbant paper, subjected to direct methylation and fatty acids quantified by automated GC. Tests on fatty acid stability show that blood samples are stable when stored at - 20°C for 1 month although some loss of HUFA was seen at 4°C. A total of fifty-one patients, including twenty-seven who consumed no fatty acid supplements, provided a blood sample for analysis. Concentrations of all major fatty acids were measured in erythrocyte PL and whole blood. The major HUFA, including EPA, DHA and arachidonic acid (ARA; 20 : 4n-6), as well as the ARA:EPA ratio and the percentage n-3 HUFA/total HUFA all showed good correlations, between erythrocyte PL and whole blood. Values of r2 ranged from 0.48 for ARA to 0.95 for the percentage of n-3 HUFA/total HUFA. This assay provides a non-invasive, rapid and reliable method of HUFA quantification with the percentage of n-3 HUFA value providing a potential blood biomarker for large-scale nutritional trials.