Effects of Prenatal Ethanol and Long-Chain n-3 Fatty Acid Supplementation on Development in Mice. 2. Fatty Acid Composition of Brain Membrane Phospholipids

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. The diet also contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Birth occurred on day 19, and the fatty acid composition of the brain membrane phospholipids was determined in the pups 3 days after birth (day 22 postconception) and again, 10 days later (day 32 postconception). On day 22 the polyunsaturated fatty acid (PUFA) composition of the brain phospholipids reflected dietary availability, with the n-3/n-6 ratio higher in the n-3 groups; this was decreased by ethanol in the phosphatidylcholine (PC) fraction. The dietary effect was still apparent on day 32; again ethanol reduced this in both the PC and phosphatidylethanolamine (PE) fractions. The n-3 oil, but not ethanol, increased the 20:3n-6/20:4n-6 ratio, indicative of an inhibition of the activity of delta-5 desaturase. With respect to the 22:C compounds, the n-3 oil decreased the levels of 22:5n-6, while increasing those of 22:6n-3, but generally the sum of these two fatty acids remained unchanged. Ethanol decreased levels of 22:5n-6, and, on day 32, also decreased those of 22:6n-3, resulting in a decrease in the sum of these 22:C PUFA.     

Comparative changes in the fatty-acid composition of rat cardiac phospholipids after long-term feeding of sunflower seed oil- or tuna fish oil-supplemented diets

The fatty-acid composition of rat heart phospholipids was examined after long-term, i.e. more than 12 months, feeding of diets supplemented with n-6 fatty acids as sunflower seed oil (SSO), or n-3 fatty acids as tuna fish oil (TFO) which is a particularly rich source of docosahexenoic acid (DHA). Although some small changes occurred in the relative proportions of palmitic and stearic acids and in the ratio of total saturates to total unsaturates, the most important changes were in the relative proportions of 18:2 n-6 and 20:4 n-6 to 20:5 n-3 and 22:6 n-3. In general, the n-6/n-3 ratio of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and diphosphatidyl glycerol (DPG) was altered in favour of the family of fatty acids administered, although the proportions of the individual long-chain polyunsaturated fatty acids which contributed to this ratio varied from one class of phospholipids to another. In cardiac PC and PE, feeding TFO supplements reduced the proportions of arachidonic acid (AA) and significantly elevated (p less than 0.01) the proportions of DHA but produced relatively little change in those of eicosapentenoic acid (EPA). In DPG, feeding TFO led to a significant increase in the proportion of AA as well as an increase in DHA. The level of EPA was relatively low in PC, PE and DPG even after TFO feeding and never reached comparable levels with that of either AA or DHA. Nevertheless the n-6/n-3 ratio in all these classes of major cardiac phospholipids was significantly reduced by feeding TFO compared to the SSO diet or the commercial rat chow (CC) reference group. In contrast to the reports of other workers who have studied the fatty-acid composition of platelet membranes after feeding various fish oil supplements, in the rat heart the major effect of tuna fish oil is an increase in the proportion of DHA rather than EPA in the cardiac phospholipids.     

The profile of polyunsaturated fatty acids in juvenile idiopathic arthritis and association with disease activity

We investigated the association between dietary intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs), serum profiles, and immune and inflammatory markers in juvenile idiopathic arthritis (JIA) in relation to onset, activity, and duration. A total of 66 JIA patients and 42 controls were included. Serum PUFA levels were assessed by gas-liquid chromatography-mass spectrometry, a dietary intake by 7-day dietary record method, and IL-6, IL-10, and IL-17A levels using ELISA. Dietary PUFA intake did not differ between the JIA group and controls. Intakes of n-6 and n-3 PUFA and serum levels were not associated. Levels of total n-6 PUFA and linoleic acid (LA) were higher in inactive JIA than in active JIA. Patients with active and short-lasting disease (less than 3 months from diagnosis) had significantly lower levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) than the control. Serum α-linolenic acid (ALA) levels were significantly higher in poly-JIA than in oligo-JIA and in controls. We found significantly higher serum IL-10 levels in JIA than in controls. Serum n-6 and n-3 levels were significantly negatively correlated with active joint count, erythrocyte sedimentation rate, and C-reactive protein and positively with platelet count. Our study presents the low levels of AA and DHA in the active phase of short-lasting JIA, particularly poly-JIA, and the relationship between n-6 and n-3 PUFA and classic markers of inflammation. PUFAs may contribute to the pathogenesis of JIA and support a necessity to identify new targets suitable for successful interventional studies in JIA patients.     

Dietary fish oil attenuates cardiac hypertrophy in lipotoxic cardiomyopathy due to systemic carnitine deficiency

OBJECTIVE: 1,2-Diacylglycerol (DAG), a lipid second messenger that activates protein kinase C (PKC), is increased with a distinct fatty acid composition in the heart of the juvenile visceral steatosis (JVS) mouse, which develops pathological cardiac hypertrophy with lipid accumulation induced by the perturbation of fatty acid beta-oxidation due to systemic carnitine deficiency. Fish oil (FO) may exert its beneficial effects on the cardiomyopathy in JVS mice by modifying the molecular species composition of myocardial DAG. To test this hypothesis, we investigated the effects of dietary FO on the hypertrophied hearts in JVS mice. METHODS: Both control and JVS mice were fed a FO diet (containing 10% FO) or a standard diet from 4 weeks of age. RESULTS: At 8 weeks of age, the ventricular-to-body weight ratio in JVS mice was 2.7-fold higher than that in controls (9.9 +/- 0.1 vs. 3.7 +/- 0.1 mg/g, P < 0.01) and was reduced by dietary FO (7.7 +/- 0.1 mg/g, P < 0.01 vs. JVS mice). In JVS mice, myocardial DAG levels were elevated by 2.3-fold with a distinct fatty acid composition with increases in C18:1n-7,9 and C18:2n-6 fatty acids compared with controls; dietary FO had no effects on the total DAG levels but significantly altered the fatty acid composition of DAG with reduction of both fatty acid species. Immunoblot analysis showed that dietary FO prevented the membrane translocation of cardiac PKCs alpha, beta2, and epsilon in JVS mice. Dietary FO did not affect the plasma and myocardial total carnitine levels in JVS mice. Furthermore, dietary FO significantly improved the progressive left ventricular dysfunction and survival rate in JVS mice. CONCLUSIONS: Dietary FO may attenuate cardiac hypertrophy with improvements in cardiac function and survival in JVS mice via modification of the molecular species composition of myocardial DAG and the consequent inhibition of PKC redistribution. These results suggest the implication of the molecular species composition of DAG in the pathogenesis of lipotoxic cardiomyopathy due to perturbations of fatty acid beta-oxidation.     

Long-term saturated fat supplementation in the rat causes an increase in PGI2/TXB2 ratio of platelet and vessel wall compared to n-3 and n-6 dietary fatty acids

The effect of long-term manipulation of dietary lipid intake on platelet and vessel wall lipid composition and eicosanoid synthesis was investigated. Rats were fed a standard diet (REF diet) supplemented (12% w/w) with either sheep fat (SF), sunflower seed oil (SSO) or tuna fish oil (TFO) for a period of 15 months. Significant compositional changes both in the aorta and platelets were observed following dietary lipid treatment and differences between these tissues were particularly apparent with regard to the incorporation and conversion of n-3 fatty acids. For example, platelets displayed a selective accumulation of eicosapentaenoic acid (EPA, 20:5 n-3) over docosahexaenoic acid (DHA, 22:6, n-3), but in the aorta the proportion of DHA was considerably higher than that of EPA. In both tissues, compared to REF diet, n-3 dietary fatty acids replaced the n-6 unsaturates 20:4 and 22:4, but did not affect the proportion of linoleic acid. In contrast to aorta, the unsaturation index for platelet membrane varied significantly between dietary groups. The capacity of aorta and platelets to generate PGI2-like activity and thromboxane was unaltered by the SSO diet. However, changes were seen following SF and TFO supplementation. Rats fed the SF diet displayed a greater synthetic capacity whilst in animals maintained on TFO diet the synthesis of these two eicosanoids was considerably suppressed. The SF group displayed the highest value for PGI2/TXB2 ratio whereas TFO diet fed rats showed the lowest which may partly be due to synthesis of TXA3. The reduction in eicosanoids following the tuna fish oil supplementation can be explained on the basis of concurrent compositional changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes.

Because of the ability of certain long-chain polyunsaturated fatty acids (PUFAs) to prevent lethal cardiac arrhythmias, we have examined the effects of various long-chain fatty acids on the contraction of spontaneously beating, isolated, neonatal rat cardiac myocytes. The omega 3 PUFA from fish oils, eicosapentaenoic acid [EPA; C20:5 (n-3)] and docosahexaenoic acid [DHA; C22:6 (n-3)], at 2-10 microM profoundly reduced the contraction rate of the cells without a significant change in the amplitude of the contractions. The fatty acid-induced reduction in the beating rate could be readily reversed by cell perfusion with fatty acid-free bovine serum albumin. Addition of either oxygenase inhibitors or antioxidants did not alter the effect of the fatty acids. Arachidonic acid [AA; C20:4 (n-6)] produced two different effects on the beating rate, an increase or a decrease, or it produced no change. In the case of the increased or unchanged beating rate in the presence of AA, addition of AA oxygenase inhibitors subsequently reduced the contraction rate. The nonmetabolizable AA analog eicosatetraynoic acid (ETYA) always reduced the beating rate, as did EPA or DHA. Two other PUFAs, linoleic acid [C18:2 (n-6)] and linolenic acid [C18:3 (n-3)] also exhibited similar but less potent effects compared with EPA or ETYA. In contrast, neither the monounsaturated fatty acid oleic acid [C18:1 (n-9)] nor the saturated fatty acids stearic acid (C18:0), myristic acid (C14:0), and lauric acid (C12:0) affected the contraction rate. The inhibitory effect of these PUFAs on the contraction rate was similar to that produced by the class I antiarrhythmic drug lidocaine. The fatty acids that are able to reduce the beating rate, particularly EPA and DHA, could effectively prevent and terminate lethal tachyarrhythmias (contracture/fibrillation) induced by high extracellular calcium concentrations or ouabain. These results suggest that free PUFAs can suppress the automaticity of cardiac contraction and thereby exert their antiarrhythmic effects.     

Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats

The aim of this study was to estimate the contributions of dietary n-3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n-6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n-3 PUFA (n-3 diet) and the other an n-6 PUFA (n-6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor alpha in the rats fed the n-3 diet, compared with rats fed the n-6 diet. NK cell activity was reduced by consumption of the n-3 diet. This study suggests that consumption of n-3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.     

Altered levels of n-6/n-3 fatty acids in rat heart and storage fat following variable dietary intake of linoleic acid

Fat-supplemented dies enriched with linoleic acid by the addition of 12% w/w sunflower seed oil or proportionally reduced in linoleic acid by addition of 12% mutton fat were fed to rats for 18 months before the fatty acid composition of perirenal storage fat and myocardial membranes (phospholipids) was determined. Although the fatty acid composition of perirenal fat generally reflected that of the diet, there was an inverse relationship between the consumption of n-6 and the deposition of n-9 fatty acids. In addition, enhanced deposition of oleic acid (18:1, n-9) appears to be related to the dietary intake of stearic acid (18:0). In contrast, in myocardial membranes the n-3 polyunsaturated fatty acids are found to be increased when the intake of n-6 polyunsaturated fatty acids is reduced. This is particularly evident for docosahexaenoic acid (22:6, n-3) which is significantly increased in phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol fractions of myocardial membranes, when the mutton fat diet was fed. After feeding the sunflower seed oil diet, the increased consumption of linoleic acid produced only small changes in the 18:2, n-6 content of cardiac phosphatidylcholine and phosphatidylethanolamine. These major classes of membrane phospholipids also showed only small increases in 20:4, n-6. In diphosphatidylglycerol, increased 18:2, n-6 also followed increased dietary intake, but this was not accompanied by increased 20:4, n-6. These changes in myocardial phospholipid fatty acid composition are similar to those observed after short-term feeding reported previously and confirm that changes in dietary n-6/n-3 fatty acid intake affect the fatty acid composition of both myocardial membranes and storage fat. These changes persist for the duration of the feeding period.     

The amount of dietary cholesterol changes the mode of effects of (n-3) polyunsaturated fatty acid on lipoprotein cholesterol in hamsters

This study was designed to investigate the effects of the interaction between dietary (n-3) polyunsaturated fatty acids (PUFA) and different dietary cholesterol content on plasma and liver cholesterol in hamsters. Male Syrian hamsters consumed diets containing an incremental increase in dietary cholesterol content (0, 0.025, 0.05, 0.1 and 0.2%, w/w) with either (n-3) PUFA (21 g/100 g fatty acids) or (n-6) PUFA (37.4 g/100 g fatty acids) fat for 6 weeks. In hamsters fed the nonatherogenic diet (0 or 0.025% dietary cholesterol), very low density lipoprotein (VLDL)-cholesterol levels in the (n-3) PUFA group were not significantly different from those in the (n-6) PUFA group, and low density lipoprotein (LDL)-cholesterol levels in the (n-3) PUFA group were significantly lower than those in the (n-6) PUFA group. In contrast, in hamsters fed the atherogenic diet (0.1 or 0.2% dietary cholesterol), VLDL- and LDL-cholesterol levels in the (n-3) PUFA group were significantly higher than those in the (n-6) PUFA group, in a dose-dependent manner. When the hamsters were fed with 0, 0.025, 0.05, 0.1 or 0.2% (w/w) dietary cholesterol, high density lipoprotein (HDL) cholesterol concentration was significantly lower in the (n-3) PUFA group than those in the (n-6) PUFA group. Hepatic cholesteryl esters were significantly lower, while hepatic microsomal acyl-coenzyme A:cholesterol acyltransferase activity and VLDL-cholesteryl esters were significantly higher in hamsters fed (n-3) PUFA with the atherogenic diet (0.1 or 0.2% dietary cholesterol) than in those fed (n-6) PUFA with the atherogenic diet. Our results demonstrate that the amount of dietary cholesterol is an important factor in determining the mode and extent of effects of dietary (n-3) PUFA, especially on VLDL- and LDL-cholesterol levels. When dietary cholesterol intake was above 0.1% (w/w), the plasma cholesterol-lowering effect of (n-3) PUFA disappeared, and instead, it showed a cholesterol-increasing effect. However, the effects of dietary (n-3) PUFA on HDL-cholesterol are independent of dietary cholesterol content.     

Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil

The effect of dietary docosahexaenoic acid (DHA, 22:6n-3) oil with different lipid types on lipid peroxidation was studied in rats. Each group of male Sprague-Dawley rats was pair fed 15% (w/w) of either DHA-triglycerides (DHA-TG), DHA-ethyl esters (DHA-EE) or DHA-phospholipids (DHA-PL) for up to 3 weeks. The palm oil (supplemented with 20% soybean oil) diet without DHA was fed as the control. Dietary DHA oils lowered plasma triglyceride concentrations in rats fed DHA-TG (by 30%), DHA-EE (by 45%) and DHA-PL (by 27%), compared to control. The incorporation of dietary DHA into plasma and liver phospholipids was more pronounced in the DHA-TG and DHA-EE group than in the DHA-PL group. However, DHA oil intake negatively influenced lipid peroxidation in both plasma and liver. Phospholipid peroxidation in plasma and liver was significantly higher than control in rats fed DHA-TG or DHA-EE, but not DHA-PL. These results are consistent with increased thiobarbituric acid reactive substances (TBARS) and decreased alpha-tocopherol levels in plasma and liver. In addition, liver microsomes from rats of each group were exposed to a mixture of chelated iron (Fe(3+)/ADP) and NADPH to determine the rate of peroxidative damage. During NADPH-dependent peroxidation of microsomes, the accumulation of phospholipid hydroperoxides, as well as TBARS, were elevated and alpha-tocopherol levels were significantly exhausted in DHA-TG and DHA-EE groups. During microsomal lipid peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n-6 fatty acids, including arachidonic acid (20:4n-6). These results indicate that polyunsaturation of n-3 fatty acids is the most important target for lipid peroxidation. This suggests that the ingestion of large amounts of DHA oil enhances lipid peroxidation in the target membranes where greater amounts of n-3 fatty acids are incorporated, thereby increasing the peroxidizability and possibly accelerating the atherosclerotic process.     

Plasma polyunsaturated fatty acid profile and delta-5 desaturase activity are altered in patients with type 2 diabetes

Objective

The association between imbalance of polyunsaturated fatty acids (PUFAs), especially low plasma n-3 to n-6 PUFA ratio, and risk of cardiovascular diseases is well known. A balance of plasma PUFAs is determined not only by dietary fatty acid intake, but also by the endogenous fatty acid metabolism, which could be dysregulated by diabetes. In this study, we investigated the plasma n-3 and n-6 PUFA profile and fatty acid desaturase activity in patients with type 2 diabetes (T2D).

Materials/Methods

The subjects were 396 patients with T2D and 122 healthy controls. Plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA) levels were measured by capillary gas chromatography.

Results

Plasma DHA, AA, and DGLA levels were significantly higher, and EPA levels tended to be lower in patients with T2D than in the controls. Patients with T2D also exhibited significantly lower EPA/AA, DHA/AA, and (EPA + DHA)/AA ratios, and a higher AA/DGLA ratio than the controls. Multiple regression analyses, including age, sex, body mass index, and metabolic parameters in the total population, revealed that the presence of T2D was independently associated with elevated plasma DHA, AA, and DGLA levels and decreased EPA/AA, DHA/AA, and (EPA + DHA)/AA ratios. Furthermore, T2D was independently and positively related to the AA/DGLA ratio, which serves as an estimate of delta (Δ)-5 desaturase activity.

Conclusions

Elevated plasma AA levels and decreased n-3 PUFA/AA ratios in T2D are attributable, at least partly, to Δ5 desaturase activation.     

Influence of different dietary fatty acid sources on erythrocyte lipids and plasma and liver essential fatty acids in hamsters fed ethanol

Hamsters fed ethanol were given three different dietary sources of essential fatty acids; safflower oil, evening primrose oil (both mainly n-6 fatty acids) or linseed oil (mainly n-3 fatty acids). After 7 weeks, plasma, erythrocyte and liver lipids and fatty acids were analyzed. Plasma and liver lipids were not significantly different in the ethanol-fed hamsters compared to the controls. Erythrocyte total phospholipid was increased only in the ethanol-fed groups given n-6 but not n-3 fatty acids. Some fatty acid changes induced by ethanol were predictable, e.g. lower 20:4 n-6 in hamsters fed n-6 fatty acids, but others were not predictable, e.g. higher 22:6 n-3 in all the ethanol-fed groups. The effect of ethanol on hamster lipids and fatty acid composition appears dependent on the predominant class of dietary fatty acids.     

A high-cholesterol, n-3 polyunsaturated fatty acid diet causes different responses in rats and hamsters

This study was designed to investigate the response to a high-cholesterol, n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA diet in rats and hamsters. Animals were fed n-3 or n-6 PUFA with a cholesterol-free diet, or with a diet enriched with cholesterol (0.5%, w/w) for 2 weeks. In rats and hamsters fed a cholesterol-free diet, plasma cholesterol, triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels in n-3 PUFA group were significantly lower than those in n-6 PUFA group. In contrast, when diets were supplemented with 0.5% cholesterol, the plasma cholesterol- and triglyceride-lowering effect of dietary n-3 PUFA disappeared. In hamsters fed with the atherogenic diet (0.5% dietary cholesterol) for 2 weeks, n-3 PUFA induced hypercholesterolemia more than n-6 PUFA, the increase being in the VLDL and low-density lipoprotein (LDL) fractions. Our data thus indicate that elevation of VLDL- and LDL-cholesterol in hamsters by n-3 PUFA, compared with n-6 PUFA, is dependent on 0.5% dietary cholesterol supplementation. In rats, on the other hand, dietary n-3 PUFA did not induce hypercholesterolemia more than n-6 PUFA when 0.5% cholesterol was supplemented. Although the effects of n-3 PUFA on plasma cholesterol, triglycerides and VLDL-triglycerides were similar in hamsters and rats, the interactive effects of n-3 PUFA and cholesterol on plasma and lipoprotein cholesterol levels differed in the two species. It was also found that plasma triglycerides, cholesterol and lipoprotein cholesterol levels in hamsters are higher than in rats in the presence and absence of dietary cholesterol. In addition, cholesterol feeding induces hypertriglyceridemia and hypercholesterolemia only in hamsters. Moreover, liver triglyceride concentrations increased in rats fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed rats were significantly lower than those in the n-6 PUFA-fed rats in the presence and absence of dietary cholesterol. However, triglycerides did not accumulate in the liver in hamsters fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed hamsters were not significantly different from those in the n-6 PUFA-fed hamsters in the presence and absence of dietary cholesterol. Therefore, these studies confirm marked species differences in response to the interactive effects of dietary n-3 PUFA and cholesterol.     

Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Docosahexaenoic acid (DHA, 22:6n-3), an n-3 polyunsaturated fatty acid (PUFA) found at high concentrations in brain and retina and critical to their function, can be obtained from fish products or be synthesized from circulating α-linolenic acid (α-LNA, 18:3n-3) mainly in the liver. With aging, liver synthetic enzymes are reported reduced or unchanged in the rat. To test whether liver synthesis-secretion of DHA from α-LNA changes with age, we measured whole-body DHA conversion coefficients and rates in unanesthetized adult male Fischer-344 rats aged 10, 20, or 30 months, fed an eicosapentaenoic acid (EPA, 20:5n-3)- and DHA-containing diet. Unesterified [U- ¹³?C]α-LNA bound to albumin was infused intravenously for 2 h, while [¹³?C]-esterified n-3 PUFAs were measured in arterial plasma, as were unlabeled unesterified and esterified PUFA concentrations. Plasma unesterified n-3 PUFA concentrations declined with age, but esterified n-3 PUFA concentrations did not change significantly. Calculated conversion coefficients were not changed significantly with age, whereas synthesis-secretion rates (product of conversion coefficient and unesterified plasma α-LNA concentration) of esterified DHA and n-3 DPA were reduced. Turnovers of esterified n-3 PUFAs in plasma decreased with age, whereas half-lives increased. The results suggest that hepatic capacity to synthesize DHA and other n-3 PUFAs from circulating α-LNA is maintained with age in the rat, but that reduced plasma α-LNA availability reduces net synthesis-secretion. As unesterified plasma DHA is the form that is incorporated preferentially into brain phospholipid, its reduced synthesis may be deleterious to brain function in aged rats.     

Fatty acid and enzymatic compositional changes in the pancreas of rats fed dietary n-3 and n-6 polyunsaturated fatty acids

The influence of n-3 and n-6 PUFA on the fatty acid composition and the enzyme content of zymogen granules of the normal exocrine pancreas was tested on rats. The animals were fed on different diets comprising 5% fish oil (FO), safflower oil (SFO), and evening primrose oil (EPO) used singly or in combination as dietary fats. The results were compared with those from animals fed 5% hydrogenated beef tallow (HBT). The fatty acid composition and digestive enzyme content were analyzed after a 6-wk feeding period. Differences in the pancreatic fatty acid profiles were related to the fatty acid composition of the ingested fats. Equivalent levels of n-3 fatty acids and 20:3n-6 were obtained with either EPO or FO fed singly or in combination. Similar results were observed with SFO/FO. Higher C20:3n-6/C20:4n-6 ratios were obtained with the oil mixtures. An increase in amylase levels, but a decrease in serine protease (Band 21 kdalton) levels, was associated with EPO. An elevation in procarboxypeptidase levels paralleled an increase in 18:0 levels, whereas the proportion of lipase (Band 49 kdalton) varied inversely with the proportion of C20:3n-6. The SFO/FO mixture elevated the proportions of protease II and proelastase. These results suggest that specific fatty acids influence the proportion of specific digestive enzymes in the zymogen granules.     

Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets

Endogenous ligands of cannabinoid receptors have been discovered recently and include some N-acylethanolamines (NAEs; e.g., N-arachidonoylethanolamine) and some 2-acylglycerols (e.g., sn-2-arachidonoylglycerol). Previously, we found these compounds to be active biologically when administered per os in large quantities to mice. In the present work, piglets were fed diets with and without 20:4n-6 and 22:6n-3 fatty acid precursors of NAEs, in levels similar to those found in porcine milk, during the first 18 days of life, and corresponding brain NAEs were assessed. In piglets fed diets containing 20:4n-6 and 22:6n-3, there were increases in several biologically active NAEs in brain homogenates-20:4n-6 NAE (4-fold), 20:5n-3 NAE (5-fold), and 22:5n-3 and 22:6n-3 NAE (9- to 10-fold). These results support a mechanism we propose for dietary long-chain polyunsaturated fatty acids influences on brain biochemistry with presumed functional sequelae. This paradigm will enable targeted investigations to determine whether and why specific populations such as infants, elderly, or persons suffering from certain clinical conditions may benefit from dietary long-chain polyunsaturated fatty acids.     

Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Prevents Trans-10, Cis-12 Conjugated Linoleic Acid (CLA)-Induced Insulin Resistance in Mice

Background: The objective of this study was to investigate if eicosapentaenoic acid (20:5n-3, EPA) or docosahexaenoic acid (22:6n-3, DHA) or both would prevent conjugated linoleic acid (CLA)-induced insulin resistance and fatty liver. Methods: Eight-week-old, pathogen-free C57BL/6N female mice (10 per group) were fed either a control diet or diets containing t10, c12-CLA (0.5 wt %), CLA + DHA (0.5% + 1.5 wt %), or CLA + EPA (0.5% + 1.5 wt %) for 8 weeks prior to sacrifice and tissue collection. Results: CLA supplementation caused an 8.9-fold increase in circulating insulin, a 2.6-fold increase in liver weight, and a 6.2-fold increase in the weight of total lipids in the liver as compared with the corresponding values in the control group. DHA prevented the CLA-induced insulin resistance, while EPA was ineffective. Both EPA and DHA prevented CLA-induced fatty liver and reduced weights of total liver lipids to the levels of the control group. CLA also reduced the plasma leptin and adiponectin concentrations to approximately 15% of those in the control group. Both EPA and DHA partially restored the CLA-induced decrease in leptin, but only DHA partially restored the plasma adiponectin. Conclusions: Our results suggest that DHA but not EPA in fish oils may reduce insulin resistance which may be mediated through an increase in circulating adiponectin. These findings may have clinical implications in the dietary management of patients at risk of insulin resistance and diabetes.     

Relation of long chain n-3 polyunsaturated fatty acid intake to serum high density lipoprotein cholesterol among Japanese men in Japan and Japanese-American men in Hawaii: the INTERLIPID study

Epidemiologic evidence shows an inverse relationship between fish consumption and coronary heart disease (CHD) mortality. Associations between dietary intake of long chain n-3 polyunsaturated fatty acids (PUFA) and serum high density lipoprotein (HDL) cholesterol concentration are unknown. In this study, the association between n-3 PUFA (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)) intake and serum HDL cholesterol among Japanese men and women in Japan and Hawaii was examined. The study population consisted of Japanese ancestries from five research centers of the International Study of Macronutrients and Blood Pressure (INTERMAP) study, in Japan and Hawaii (672 men and 676 women), surveyed between 1996 and 1998. Four 24-h dietary recalls and one set of serum lipid measurements were performed. For men, n-3 PUFA intake and HDL cholesterol were higher in Japan than in Hawaii (n-3 PUFA: 1.32 g/day versus 0.47 g/day, p<0.001). For women, n-3 PUFA intake was higher in Japan than in Hawaii (p<0.001) but HDL cholesterol was not significantly different (p=0.752). After adjustment for age, body mass index, physical activity, number of cigarettes per day, alcohol intake, and hormone replacement therapy (for women), n-3 PUFA intake was positively associated with serum HDL cholesterol in men (4.6 mg/dl higher HDL cholesterol with 1%kcal higher n-3 PUFA intake, p=0.011). This association was not observed in women. This positive association of dietary n-3 PUFA with serum HDL cholesterol may partially explain the low mortality from CHD among Japanese men.     

Contribution of Diet and Genes to Polyunsaturated Fatty Acid Composition

Dietary recommendations for polyunsaturated fatty acids (PUFA) are based in part on results from epidemiologic studies to determine the level of dietary PUFA required to maintain optimal health. There are many challenges to estimating consumption of fatty acids through dietary surveys. PUFA measured in different biological samples have been used as biomarkers of fatty acid consumption. In addition to diet, variability in blood or tissue PUFA composition is explained in part by genetics. In particular, genetic variations in enzymes involved in the n-3/n-6 metabolic pathway have shown consistent and robust association with PUFA concentrations. Understanding the genetic architecture of fatty acid homeostasis and their relationship to the etiology of complex diseases may shed light on the mechanisms for the protective effects of fatty acids in humans.