Type 1 diabetes compromises plasma arachidonic and docosahexaenoic acids in newborn babies

The activity of Δ6- and Δ5-desaturase, enzymes required for the synthesis of AA and DHA, are impaired in human and experimental diabetes. We have investigated whether neonates of type 1 diabetic women have compromised plasma AA and DHA at birth. Cord blood was obtained from healthy babies born to mothers with (n=31) and without (n=59) type 1 diabetes. FA composition of plasma choline phosphoglycerides (CPG), TG, and cholesterol esters (CE) was assayed. The neonates of the diabetics had lower levels of AA (20∶4n−6, P<0.0001), adrenic acid (22∶4n−6, P<0.01), Σn−6 metabolites (P<0.0001), docosapentaenoic acid (22∶5n−3, P<0.0001), DHA (22∶6n−3, P<0.0001), Σn−3 (P<0.0001), and Σn−3 metabolites (P<0.0001) in CPG compared with the corresponding babies of the nondiabetic mothers. Similarly, they had lower levels of AA (P<0.05), Σn−6 metabolites (P<0.05), DHA (P<0.0001), and Σn−3 metabolites (P<0.01) in plasma CE. There was also a nonsignificant reduction of AA and DHA in TG in the babies of the diabetic group. The current investigation indicates that healthy neonates born to mothers with type 1 diabetes have highly compromised levels of AA and DHA. These nutrients are of critical importance for neurovisual and vascular system development. In poorly controlled maternal diabetes, it is conceivable that the relative “insufficiency” of AA and DHA may exacerbate speech and reading impairments, behavioral disorders, suboptimal performance on developmental tests, and lower IQ, which have been reported in some children born to mothers with type 1 diabetes mellitus. Further studies are needed to understand the underlying mechanism for this biochemical abnormality and its implications for fetal and infant development.     

Mice raised on milk transgenically enriched with n−3 PUFA have increased brain docosahexaenoic acid

The brain contains high levels of the long-chain n−3 FA DHA(22∶6n−3), mainly in the gray matter and synaptosomes. Adequate intake of DHA is crucial for optimal nervous system function, particularly in infants. Supplementation of infant formulas with DHA at levels similar to human breast milk is recommended for biochemical and functional benefits to neonates. We generated transgenic mice that produce elevated levels of n−3 PUFA in their milk by expressing the Caenorhabditis elegans n−3 FA desaturase under the control of a lactation-induced goat beta-casein promoter. To examine the postnatal effects of consuming the n−3-enriched milk, we compared the growth and brain and plasma FA composition of mouse pups raised on milk from transgenic dams with those observed for pups raised on milk from nontransgenic dams. A significant decrease in arachidonic acid (ARA, 20∶4n−6) and concomitant increases in n−3 PUFA were observed in the phospholipid fraction of transgenic mouse milk. The n−6∶n−3 FA ratios were 4.7 and 34.5 for the transgenic and control milk phospholipid fractions, respectively. DHA and DPA (22∶5n−6) comprised 15.1% and 2.8% of brain FA from weanling mice nursed on transgenic dams, as compared with 6.9% and 9.2% for weanling mice nursed on control dams, respectively. This transgenic mouse model offers a unique approach to disassociate the effects and fetal programming resulting from a high n−6∶n−3 FA ratio gestational environment from the postnatal nutritional effects of providing milk with differing n−6∶n−3 FA ratios.     

Supplementation and delivery of n−3 fatty acids through spray-dried milk reduce serum and liver lipids in rats

Indian diets comprising staples such as cereals, millets, and pulses provide 4.8 energy % from linoleic acid (18∶2n−6) but fail to deliver adequate amounts of n−3 FA. Consumption of long-chain n−3 PUFA such as EPA (20∶5n−3) and DHA (22∶6n−3) is restricted to those who consume fish. The majority of the Indian population, however, are vegetarians needing additional dietary sources of n−3 PUFA. The present work was designed to use n−3 FA-enriched spray-dired milk powder to provide n−3 FA. Whole milk was supplemented with linseed oil to provide α-linolenic acid (LNA, 18∶3n−3), with fish oil to provide EPA and DHA, or with groundnut oil (GNO), which is devoid of n−3 PUFA, and then spray-dired. Male Wistar rats were fed the spray-dired milk formulations for 60 d. The rats given formulations containing n−3 FA showed significant increases (P<0.001) in the levels of LNA or EPA/DHA in the serum and in tissue as compared with those fed the GNO control formulation. Rats fed formulations containing n−3 FA had 30–35% lower levels of serum total cholesterol and 25–30% lower levels of serum TAG than control animals. Total cholesterol and TAG in the livers of rats fed the formulations containing n−3 FA were lower by 18–30% and 11–18%, respectively, compared with control animals. This study showed that spray-dried milk formulations supplemented with n−3 FA are an effective means of improving dietary n−3 FA intake, which may decrease the risk factors associated with cardiovascular disease.     

Relationships between the fatty acid composition of muscle and erythrocyte membrane phospholipid in young children and the effect of type of infant feeding

Muscle membrane fatty acid (FA) composition is linked to insulin action. The aims of this study were to compare the FA composition of muscle and erythrocyte membrane phospholipid in young children; to investigate the effect of diet on these lipid compositions; and to investigate differential incorporation of FA into muscle, erythrocyte and adipose tissue membrane phospholipid, and adipose tissue triglyceride. Skeletal muscle biopsies and fasting blood samples were taken from 61 normally nourished children (15 males and 16 females), less than 2 yr old (means ±SE, 0.80±0.06 yr), undergoing elective surgery. Adipose tissue samples were taken from 15 children. There were significant positive correlations between muscle and erythrocyte docosahexaenoic acid (DHA) (r=0.44, P<0.0001), total n−3 polyunsaturated fatty acids (PUFA) (r=0.39, P=0.002), and the n−6/n−3 PUFA ratio (r=0.39, P=0.002). Adipose tissue triglyceride had lower levels of long-chain PUFA, especially DHA, than muscle and erythrocytes (0.46±0.18% vs. 2.44±0.26% and 3.17±0.27%). Breast-fed infants had higher levels of DHA than an age-matched group of formulafed infants in both muscle (3.91±0.21% vs. 1.94±0.18%) and erythrocytes (3.81±0.10% vs. 2.65±0.23%). The results of this study show that (i) erythrocyte FA composition is a reasonable index of muscle DHA, total n−3 PUFA, and the n−6/n−3 PUFA ratio; (ii) breast feeding has a potent effect on the FA composition of all these tissues; and (iii) there is a wide range in long-chain PUFA levels in muscle, erythrocytes, and adipose tissue.     

Lipid and FA composition of the pearl oyster <Emphasis Type="Italic">Pinctada fucata martensii</Emphasis>: Influence of season and maturation

The lipid and FA composition of the total lipids of the pearl oyster Pinctada fucata martensii, in different seasons and in different areas, were analyzed to clarify its lipid physiology and to estimate the possible influence of its prey phytoplankton. TAG and sterols were the major components in the neutral lipids in all conditions, whereas high levels of phospholipids (PE and PC) were found in the polar lipids. The major FA in the TAG in all samples were 14∶0, 16∶0, and 18∶0 as saturated FA (saturates); 16∶1n−7, 18∶1n−9, and 18∶1n−7 as monoenoic FA (monoenes); and 20∶4n−6 (arachidonic acid: AA), 20∶5n−3 (EPA), and 22∶6n−3 (DHA) as PUFA. The major components found in the polar lipids were 16∶0 and 18∶0 as saturates; 22∶2n−9, 15 and 22∶2n−7, 15 as non-methylene-interrupted dienes (NMID), and AA, 22∶3n−6, 9, 15, EPA, and DHA as PUFA. Although it is a marine animal, characteristically high levels of AA were found in both the TAG and phospholipids. This result suggests that lipids of P. fucata may be influenced by those of its phytoplanktonic prey. The increase in levels of NMID from TAG to PE with a decrease in those of monoenes suggests that the tissues of this species are able to biosynthesize only the less unsaturated PUFA, such as NMID. In particular, NMID derivatives are considered to be biosynthesized in the PE; thus, they might play a particular role in the membrane, because NMID were characteristically localized only in the PE.     

Blood phospholipid fatty acid analysis of adults with and without attention deficit/hyperactivity disorder

Several psychiatric disorders, including juvenile Attention Deficit/Hyperactivity Disorder (ADHD), have been associated with abnormalities of certain long-chain PUFA (LCPUFA). Despite this reported association, the FA levels of patients with the adult form of ADHD have not previously been evaluated. In this study we measured the total blood phospholipid FA concentrations in 35 control subjects and 37 adults with ADHD symptoms to determine whether adults with ADHD symptoms would show abnormalities of FA relative to control subjects. In the serum phospholipids, adults with ADHD symptoms had significantly lower levels of total saturated, total polyunsaturated, and total omega-6 (n−6) FA, as well as the omega-3 (n−3) LCPUFA DHA (22∶6n−3), and significantly higher levels of total monounsaturated FA and the n−3 LCPUFA docosapentaenoic acid (22∶5n−3). In the erythrocyte membrane phospholipids, adults with ADHD symptoms had significantly lower levels of total PUFA, total n−3 FA, and DHA, and significantly higher levels of total saturated FA. Neither serum nor erythrocyte membrane phospholipid DHA was related to ADHD symptom severity (as assessed by the Amen questionnaire) in ADHD subjects. Although the exact cause of these variations is unknown, both environmental and genetic factors may be involved.     

Specific modifications of phosphatidylinositol and nonesterified fatty acid fractions in cultured porcine cardiomyocytes supplemented with n-3 polyunsaturated fatty acids

Mechanisms for the antiarrhythmic effect of n−3 polyunsaturated fatty acids (PUFA) are currently being investigated using isolated cardiac myocytes. It is still not known whether the incorporation of n−3 PUFA into membrane phospholipids is a prerequisite for its protective action or if n−3 PUFA exert antiarrhythmic effects in their nonesterified form as demonstrated by recent studies. Adult porcine cardiomyocytes were grown in media supplemented with arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). After 24 h, analysis of total lipids showed that the myocytes were enriched with the respective fatty acids compared to control cells. Large proportions of all three fatty acids supplemented (69% AA, 72% DHA, and 66% EPA) remained unesterified. Fatty acid analysis of total phospholipids (PL) revealed that the incorporation of EPA and DHA, though small, was significantly different (P<0.05) from that of the control cells. The PL fraction was further separated into phosphatidylinositol (Pl), phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine to study the pattern of incorporation of the fatty acids in these fractions. It became apparent that EPA and DHA were selectively incorporated into the Pl fraction. This study demonstrates that in adult porcine cardiomyocytes, the n−3 PUFA supplementation selectively modulates two important lipid fractions, nonesterified fatty acid and Pl, which were implicated in the mechanisms of prevention of cardiac arrhythmias.     

Hepatic lipid characteristics and histopathology of laying hens fed CLA or n−3 fatty acids

The effect of dietary CLA and n−3 PUFA on hepatic TAG accumulation, histopathology, and FA incorporation in lipid classes by laying chickens was investigated. One hundred twenty 30-wk-old single-comb white leghorn laying hens were distributed randomly to four treatments (3 replications of 10 birds) and were fed diets containing CLA and animal fat (Diet I), 18∶3n−3 (Diet II), or long-chain n−3 FA (Diet III). A sunflower oil (n−6 FA)-based diet was the control. Feeding Diet I resulted in an increase in hepatic total lipids (P<0.05). The liver TAG content was 32.2, 18.9, 29.4, and 18.7 mg/g for hens fed Diet I, Diet II, Diet III, and the control diet, respectively (P<0.05). The serum TAG was lowest in bilds fed Diet II (P<0.05). Diet I resulted in an increase in the total number of fat vacuoles and lipid infiltration in hepatocytes (P<0.05). The number of cells with 75% or higher lipid vacuolation was observed only in birds fed Diet I. Feeding diets containing CLA resulted in an increase in the content of the c9,t11 CLA isomer in liver TAG and PC (P<0.05). No difference was observed in the CLA concentration of hepatic PE fractions. The content of DHA (22∶6n−3) was higher in the TAG, PC, and PE of hens fed Diet II and Diet III than Diet I and the control (P<0.05). Feeding CLA resulted in an increase in total saturated FA in the TAG and PC fractions (P<0.05). Long-term feeding of CLA in laying birds leads to an increase in liver TAG and may predispose birds to fatty liver hemorrhagic syndrome.     

Composition and seasonal variation of fatty acids of <Emphasis Type="Italic">Diplodus vulgaris</Emphasis> L. from the Adriatic Sea

Muscle tissue from the common two-banded sea bream Diplodus vulgaris L. originating from the Adriatic Sea, Croatia, was analyzed. The FA composition of neutral (TAG) and polar (PE, PC, PI/PS) lipid classes was determined, as well as the lipid and water contents during winter and summer periods. Both the total lipid and water contents were higher in the winter period. We identified 16 different FA. The major constituents of the total FA in both seasons were saturates: palmitic (16∶0) and stearic acids (18∶0); monoenes: oleic (18∶1n−9) and palmitoleic acids (16∶1n−7); and polyunsaturates: arachidonic acid (20∶4n−6), EPA (20∶5n−3), and DHA (22∶6n−3), but their amounts and ratios differed significantly between the two seasons and between lipid fractions. The FA composition showed a noticeable pattern of seasonality that reflected fluctuations mainly in TAG. The diminution of the monounsaturated FA content in the summer was clearly followed by an increase in PUFA content. Diplodus vulgaris is a good source of natural n−3 PUFA and would therefore be suitable for inclusion in highly unsaturated low-fat diets.     

n-3 long-chain FA decrease serum levels of TG and remnant-like particle-cholesterol in humans

A large number of papers have reported that administration of n−3 FA reduced serum TG concentrations in hypertriglyceridemic patients. However, few studies have examined the effect of n−3 FA on serum concentrations of remnant-like particle (RLP) cholesterol. Volunteers (n=41) whose serum TG concentrations were 100–300 mg/dL were recruited and randomly assigned to either an n−3 FA group or a control group with stratification by sex, age, and serum TG level in a double-blind manner. The subjects in the n−3 FA group were administered 125 ml of fermented soybean milk with fish oil containing 600 mg of EPA and 260 mg of DHA/d for 12 wk. The controls consumed control soybean milk with olive oil. Fasting blood samples were obtained before the start of administration and at 4, 8 and 12 wk. EPA concentrations in red blood cells increased significantly in all but one subject in the n−3 FA group, with no significant changes in the control group. TG levels decreased more in the n−3 FA group than in the control group at weeks 4 (P<0.05), 8 (P<0.01), and 12 (P<0.05) with their baseline as covariate. RLP cholesterol levels decreased more in the n−3 FA group than in the control at weeks 8 (P<0.01) and 12 (P<0.05) with their baseline as covariate. The groups did not differ in the other lipid levels. It is likely that n−3 long-chain FA may exert anti-atherosclerotic effects by lowering serum TG and RLP-cholesterol levels even at the dose of 860 mg/d.     

Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids

Fourteen healthy male volunteers were given two separate high-saturated-fat meals with and without the addition of 4 g highly purified ethyl esters of either eicosapentaenoic acid (EPA) (95% pure, n=7) or docosahexaenoic acid (DHA) (90% pure, n=7) supplied as 1-g capsules each containing 3.4 mg vitamin F. The chylomicrons were isolated 6 h after the meals, at peak concentrations of n−3 fatty acids (FA). Addition of n−3 FA with the meal caused a 10.4-fold increase in the concentration of n−3 FA in chylomicrons compared to the saturated fat meal without addition of n−3 FA. After the saturated-fat meal, the concentration of thiobarbituric acid-reactive substances (TBARS) was 327.6±34.6 nmol/mmol triacylglycerol (TAG), which increased to 1015.8±212.0 nmol/mmol TAG (P<0.0001, n=14) after EPA and DHA were added to the meal. There was no significant correlation between the concentrations of TBARS and vitamin E in the chylomicrons collected 6 h after the test meal. The present findings demonstrate an immediate increase in chylomicron peroxidation ex vivo provided by intake of highly purified n−3 FA. The capsular content of vitamin E was absorbed into chylomicrons, but the amount of vitamin E was apparently not sufficient to protect chylomicrons against lipid peroxidation ex vivo. Daily intake of 4 g n−3 FA either as EPA or DHA for 5 wk did not change the plasma concentration of TBARS. Although not significantly different between groups, DHA supplementation decreased total glutathione in plasma (P<0.05) and EPA supplementation increased plasma concentration of vitamin E (P<0.05). The other lipid-soluble and polar antioxidants in plasma remained unchanged during 5 wk of intervention with highly purified n−3 FA.     

Blood fatty acid composition of pregnant and nonpregnant Korean women: Red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus

Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n=40) and nonpregnant, nonlactating (n=40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P<0.05) and palmitic and oleic acids higher (P<0.0001) in plasma CPG of the pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA and DHA (P<0.05) and higher palmitic and oleic acids (P<0.01). The reduction in DHA and total n−3 fatty acids in plasma CPG of the pregnant women was paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA) acids of the n−6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and EPG) of the pregnant women, DTA and DPA acids of the n−6 series and DPA/DTA ratio did not increase with the decrease of the n−3 metabolites (eicosapentaenoic acid, DPA, and DHA) and total n−3. Since pregnancy was the main identifiable variable between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the pregnant women suggest that the mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.     

Maternal dietary FA modulate the long-chain n−3 PUFA status of chick cardiac tissue

The effect that egg yolk or maternal n−3 FA have on the cardiac tissue long-chain n−3 FA status of chicks during growth was investigated. Fggs with low, medium, and high levels of n−3 PUFA were obtained by feeding breeder hens a wheat/soybean meal-based diet containing 5% sunflower oil (Low n−3), 2.5% sunflower oil plus 2.5% fish oil (Medium n−3), or 5% fish oil (High n−3). The chicks hatched from Low, Medium, and High n−3 eggs were fed a diet containing 18∶3n−3, but devoid of long-chain n−3 FA. The FA composition of cardiac tissue was determined on days 0, 14, 28, and 42. At day 0, the cardiac FA reflected maternal diet. With time, the level of all the long-chain n−3 FA decreased compared with day 0, and this was true especially by day 14. These data show that dietary 18∶3n−3 fed to the chicks did not sustain high levels of EPA and DHA in cardiac tissue, despite the high content of long-chain n−3 FA in the maternal diet. At days 0 and 14, the chicks hatched from High and Medium n−3 eggs had higher 20∶5n−3, 22∶5n−3, and 22∶6n−3 contents with a concomitant reduction in 20∶4n−6 in the cardiac tissue compared with the Low n−3 egg group. Cardiac tissue of birds hatched from Medium n−3 eggs retained higher levels of 20∶5n−3 up to day 42 of growth when compared with other treatments (P<0.05). None of the treatments was effective in maintaining DHA levels after day 14 of growth.     

Lipids and delta6-desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B1

Alterations in the membrane structure and function of hepatocyte membranes by fumonisin B₁ (FB₁) have been proposed to play an important role in the disruption of growth regulatory effects and hence in the cancer-promoting ability of the mycotoxin. Detailed analyses of lipids in liver microsomal fractions of rats exposed to different dietary levels of FB₁ over a period of 21 d indicated an increase in PC, PE, PI, and cholesterol (Chol). These changes decreased the PC/PE and increased the total phospholipid/Chol ratios. When considering FA content, the quantities of total FA increased (P<0.05) in the major phospholipid fractions as a result of the increased phospholipid levels. However, when considering the relative levels (mg/100 mg of the total FA) of specific FA, the monounsaturated FA (16∶1n−7 and 18∶1n−9) and 18∶2n−6 increased (P<0.05), whereas the long-chain PUFA decreased (P<0.05) in the main phospholipid fractions. Enzyme analyses indicated that the activity of the Δ6-desaturase was significantly reduced in liver microsomal preparations in a dose-dependent manner. An increase in the 20∶3n−6/20∶4n−6 ratio also suggested a decrease in the activity of the Δ5-desaturase. Disruption of microsomal lipid metabolism at different levels by FB₁ could play an important role in the alteration of growth regulatory effects in the liver.     

Gestational age and birth weight in relation to n−3 fatty acids among inuit (Canada)

Seafood consumption during pregnancy carries both benefits (high n−3 FA intake) and risks (exposure to environmental contaminants) for the developing fetus. We determined the impacts of marine n−3 FA and environmental contaminants on gestational age (GA) of Nunavik women and the anthropometric characteristics of their newborns. FA and contaminant (polychlorinated biphenyls and mercury) concentrations were measured in cord plasma of Nuvavik newborns (n=454) and compared with those of a group of newborns (n=29) from southern Québec. Data were collected from hospital records and birth certificates. In Nunavik newborns, arachidonic acid (AA) was two times lower (P<0.0001), whereas DHA concentration, the Σn−3/Σn−6 ratio, and the percentage of n−3 highly unsaturated FA (HUFA) (of the total HUFA) were three times higher (P<0.0001) compared with southern Québec newborns. After controlling for confounders, GA and birth weight were higher by 5.4 d [95% confidence interval (CI): 0.7–10.1] and 77 g (95% CI: −64 to 217) in the third tertile of percentage of n−3 HUFA (of the total HUFA) as compared with the first tertile. There was no evidence that contaminants had negative effects on GA or birth weight. In this seafood-eating population, an increase in the proportion of n−3 HUFA (of the total HUFA), measured in umbilical cord plasma phospholipids, was associated with a significantly longer GA.     

Dietary menhaden, seal, and corn oils differentially affect lipid and Ex vivo eicosanoid and thiobarbituric acid-reactive substances generation in the guinea pig

This investigation was carried out to characterize the effects of specific dietary marine oils on tissue and plasma fatty acids and their capacity to generate metabolites (prostanoids, lipid peroxides). Young male guinea pigs were fed nonpurified diet (NP), or NP supplemented (10%, w/w) with menhaden fish oil (MO), harp seal oil (SLO), or corn oil (CO, control diet) for 23 to 28 d. Only the plasma showed significant n−3 polyunsaturated fatty acid (PUFA)-induced reductions in triacylglycerol (TAG) or total cholesterol concentration. Proportions of total n−3 PUFA in organs and plasma were elevated significantly in both MO and SLO dietary groups (relative to CO), and in all TAG fractions levels were significantly higher in MO-than SLO-fed animals. The two marine oil groups differed in their patterns of incorporation of eicosapentaenoic acid (EPA). In guinea pigs fed MO, the highest levels of EPA were in the plasma TAG, whereas in SLO-fed animals, maximal incorporation of EPA was in the heart polar lipids (PL). In both marine oil groups, the greatest increases in both docosahexaenoic acid (22∶6n−3, DHA) and docosapentaenoic acid (22∶5n−3, DPA) relative to the CO group, were in plasma TAG, although the highest proportions of DHA and DPA were in liver PL and heart TAG, respectively. In comparing the MO and SLO groups, the greatest difference in levels of DHA was in heart TAG (MO>SLO, P<0.005), and in levels of DPA was in heart PL (SLO>MO, P<0.0001). The only significant reduction in proportions of the major n−6 PUFA, arachidonic acid (AA), was in the heart PL of the SLO group (SLO>MO=CO, P<0.005). Marine oil feeding altered ex vivo generation of several prostanoid metabolites of AA, significantly decreasing thromboxane A₂ synthesis in homogenates of hearts and livers of guinea pigs fed MO and SLO, respectively (P<0.04 for both, relative to CO). Lipid peroxides were elevated to similar levels in MO- and SLO-fed animals in plasma, liver, and adipose tissue, but not in heart preparations. This study has shown that guinea pigs respond to dietary marine oils with increased organ and plasma n−3 PUFA, and changes in potential synthesis of metabolites. They also appear to respond to n−3 PUFA-enriched diets in a manner that is different from that of rats.     

Effects of geographic source, rearing system, and season on the nutritional quality of wild and farmed Perca fluviatilis

The effects of season, geographic source (Lake Geneva, Rhine River), and rearing system (extensive, semiextensive, and intensive systems) on the lipid content and FA composition of fillets of Perca fluviatilis were studied. Significant differences in the total lipid content were found between fish coming from the Rhine River and Lake Geneva (1.21 and 1.48%, respectively). Seasonal effects were investigated quarterly for perch sampled in the Rhine River. Intensively reared perch displayed a higher lipid content (1.48%) than the other farmed perch, i.e., 1.26% for a semiextensive system and 1.16% for an extensive system. No significant difference in lipid content was found (i) between lacustrine fish and intensively reared fish or (ii) among fish from the Rhine River and the semiextensive or extensive rearing systems. The main FA were 22∶6n−3 (DHA, 21.3–37.1% of total FA), 16∶0 (17.7–20.2%), 20∶5n−3 (EPA, 9.2–13.2%), 18∶1 (8.0–11.5%), 20∶4n−6 [arachidonic acid (ARA), 1.9–10.7%], 16∶1 (4.3–6.0%), and 18∶2n−6 (2.1–6.0%). In comparison with perch coming from the Rhine River, the lacustrine fish were characterized by higher total n−6 PUFA and a lower proportion of both total monounsaturated FA (MUFA) and total n−3 PUFA. Among rearing systems, extensively farmed fish had higher n−6 PUFA and lower n−3 PUFA contents. Wild fish showed higher ARA and 18∶2n−6 than farmed fish. They also had significantly more EPA (12.5–13.2%) than farmed perch (9.2–10.9%). For DHA no difference existed between (i) the lacustrine fish (31.9% of total FA) and the intensively reared fish (33.0%) and (ii) the Rhine (37.1%) and semiextensively reared fish (36%). Effects of size, diet composition, and environmental conditions on the total lipid contents and FA composition are discussed.     

Incorporation of polyunsaturated fatty acids into CT-26, a transplantable murine colonic adenocarcinoma

Previous studies in our laboratory have shown that marine oils, with high levels of eicosapentaenoic (EPA, 20∶5n−3) and docosahexaenoic acids (DHA, 22∶6n−3), inhibit the growth of CT-26, a murine colon carcinoma cell line, when implanted into the colons of male BALB/c mice. Anin vitro model was developed to study the incorporation of polyunsaturated fatty acids (PUFA) into CT-26 cells in culture. PUFA-induced changes in the phospholipid fatty acid composition and the affinity with which different fatty acids enter the various phospholipid species and subspecies were examined. We found that supplementation of cultured CT-26 cells with either 50 μM linoleic acid (LIN, 18∶2n−6), arachidonic acid (AA, 20∶4n−6), EPA, or DHA significantly alters the fatty acid composition of CT-26 cells. Incorporation of these fatty acids resulted in decreased levels of monounsaturated fatty acids, while EPA and DHA also resulted in lower levels of AA. While significant elongation of both AA and EPA occurred, LIN remained relatively unmodified. Incorporation of radiolabeled fatty acids into different phospholipid species varied significantly. LIN was incorporated predominantly into phosphatidylcholine and had a much lower affinity for the ethanolamine phospholipids. DHA had a higher affinity for plasmenylethanolamine (1-O-alk-1′-enyl-2-acyl-sn-glycero-3-phosphoethanolamine) than the other fatty acids, while EPA had the highest affinity for phosphatidylethanol-amine (1,2-diacyl-sn-glycero-3-phosphoethanolamine). These results demonstrate that,in vitro, significant differences are seen between the various PUFA in CT-26 cells with respect to metabolism and distribution, and these may help to explain differences observed with respect to their effects on tumor growth and metastasis in the transplantable model.     

Dietary fish oil dose- and time-response effects on cardiac phospholipid fatty acid composition

Fish consumption is associated with reduced cardiovascular mortality, and elevated myocardial long-chain n−3 polyunsaturated FA (PUFA) content is implicated in this cardioprotection. This study examined the dose and time responses for incorporation of n−3 PUFA into cellular membranes in rats fed fish oil (FO)-containing diets. For the time course study, rats were fed a 10% FO diet for periods ranging from 0 to 42 d, after which myocardial and erythrocyte membrane fatty acid composition was determined. For the dose response study, rats (n=3) were fed 0, 1.25, 2.5, 5, or 10% FO for 4 wk, with myocardial, erythrocyte, and skeletal muscle membrane FA determined. Myocardial DHA (22∶6n−3) levels doubled in 2 d, stabilizing at levels ≈200% higher than control after 28 d feeding with 10% FO. By comparison, DHA levels doubled after 4 wk of 1.25% FO feeding. In myocardium and skeletal muscle, EPA (20∶5n−3) levels remained low, but in erythrocytes EPA levels reached 50% of DHA levels. The n−3 PUFA were incorporated at the expense of n−6 PUFA in myocardium and skeletal muscle, whereas erythrocytes maintained arachidonic acid levels, and total n−3 PUFA incorporation was lower. This study shows that low doses of FO produce marked changes in myocardial DHA levels; maximal incorporation takes up to 28 d to occur; and while erythrocytes are a good indicator of tissue n−3 incorporation in stable diets, they vary greatly in their time course and pattern of incorporation.     

Alteration in mouse splenic phospholipid fatty acid composition and lymphoid cell populations by dietary fat

The fatty acid composition of diacyl- and alkylacylglycerophosphocholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), alkenylacyl-glycerophosphoethanolamine (aPE), and diacyl- and alkylacyl-glycerophosphoethanolamine (dPE) was assessed in isolated splenocytes from C3H/Hen mice fed one of four purified isocaloric diets for six weeks. Diets contained 20% by weight of either a high-linoleate sunflower oil (Hi 18∶2), a high-oleate sunflower oil (Hi 18∶1), a mixture of 17% menhaden fish oil and 3% high-linoleate sunflower oil (Hi n−3), or a mixture of 17% coconut oil and 3% high-linoleate sunflower oil (Hi SFA). Spleen weight and immune cell yield were significantly higher (P<0.05) in mice fed the Hi 18∶1 or the Hi n−3 diets compared with those fed the Hi 18∶2 and Hi SFA diets. Distinctive patterns of fatty acids were observed for each phospholipid in response to dietary fatty acids. Dietary fat significantly affected (P<0.05) total polyunsaturated fatty acids (PUFA) in PC and dPE, total saturated fatty acids (SFA) in PC, total monounsaturated fatty acids (MUFA), and n−3 PUFA in all phospholipid classes examined. In mice fed the Hi n−3 diet, n−3 PUFA were significantly elevated, whereas n−6 PUFA decreased in all of the phospholipids. In these mice, eicosapentaenoic acid (EPA) was the predominant n−3 PUFA in PC and PI, whereas docosahexaenoic acid (DHA) was the major n−3 PUFA in aPE and PS. Interestingly, the ratios of n−3/n−6 PUFA in the phospholipids from these mice were 3.2, 2.4, 1.8, 0.8 and 0.8 for aPE, PS, dPE, PC and PI, respectively. These data suggest a preferential incorporation of n−3 PUFA into aPE, PS and dPE over PC and PI.