Positive association between plasma antioxidant capacity and n-3 PUFA in red blood cells from women.

PUFA are susceptible to oxidation. However, the chain-reaction of lipid peroxidation can be interrupted by antioxidants. Whether an increased concentration of PUFA in the body leads to decreased antioxidant capacity and/or increased consumption of antioxidants is not known. To elucidate the relationship between plasma total antioxidant capacity (TAC), the concentration of antioxidant vitamins, and the proportion of PUFA in red blood cells (RBC), plasma TAC was measured by a Trolox equivalent antioxidant capacity assay in blood samples from 99 Icelandic women. Concentrations of tocopherols and carotenoids in the plasma were determined by HPLC, and the FA composition of RBC total lipids was analyzed by GC. Plasma TAC and the plasma concentration of alpha-tocopherol correlated positively with the proportion of total n-3 PUFA, 20:5n-3, and 22:6n-3 in RBC, whereas the plasma lycopene concentration correlated negatively with the proportion of total n-3 PUFA and 20:5n-3. On the other hand, plasma TAC correlated negatively with the proportion of n-6 PUFA in RBC. Plasma TAC also correlated positively with the plasma concentration of alpha-tocopherol, alcohol consumption, and age. Both the plasma concentration of alpha-tocopherol and age correlated positively with the proportion of n-3 PUFA in RBC; however, n-3 PUFA contributed independently to the correlation with plasma TAC. Because the proportion of n-3 PUFA in RBC reflects the consumption of n-3 PUFA, these results suggest that dietary n-3 PUFA do not have adverse effects on plasma TAC or the plasma concentration of most antioxidant vitamins.

Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

Study of a haploid yeast strain with an unusually high rDNA content. III. Unequal meiotic segregation of the gamma-DNA fraction.

DNA from different strains of Saccharomyces cerevisiae has been fractionated in preparative Ag+/Cs2-SO4 density gradients. The results show that there are real differences in amount of the nuclear satellite component, the gamma-DNA, from one strain to the other. The gamma-DNA forms a homogeneous dense band that contains all the rDNA, and the amount of gamma-DNA estimated from the gradients can be correlated to amount of rDNA derived from rRNA-DNA hybridizations. By various crossings and sporulations we have obtained diploid and haploid strains with gamma-DNA contents ranging from 7 to 20% of the nuclear DNA. During meiosis, the amount of gamma-DNA appears to segregate in a pattern that indicates unequal crossing over as a possible mechanism for differences in gamma-DNA contents.

Polyunsaturated fatty acids in heart muscle and alpha 1-adrenoceptor binding properties.

Modifications of membrane phospholipids and binding characteristics of adrenoceptors by hydrocortisone and epinephrine were examined in sarcolemmal preparation from rat heart muscle. The influence of hydrocortisone and epinephrine on the fatty acid composition of membrane phospholipids and the affinity (1/Kd) and number of binding sites (Bmax) of alpha 1- and beta-adrenoceptors was studied in male Wistar rats treated daily for 7 days with the hormones. The alpha 1- and beta-adrenoceptors were characterized by using the antagonist ligands [3H]prazosin and [3H]dihydroalprenolol, respectively. Administration of the hormones altered significantly the composition of fatty acids, decreased linoleic acid (18: 2(n-6)) level of both phosphatidylcholine and phosphatidylethanolamine, and increased arachidonic acid (20: 4(n-6)) level of phosphatidylcholine and docosahexaenoic acid (22: 6(n-3)) level in both phosphatidylcholine and phosphatidylethanolamine. The binding sites of alpha 1-adrenoceptors were of high affinity in the control group. Following administration of the hormones Kd of alpha 1-adrenoceptors increased markedly. The number of alpha 1-adrenoceptors binding sites did not change significantly due to the hormones. In contrast, while the hormone treatments did not alter the affinity of the beta-adrenoceptors the number of binding sites were significantly decreased by the hormones. The results indicate that the decrease in affinity of alpha 1-adrenoceptors and the down-regulation of beta-adrenoceptors is accompanied by alteration in percentage fatty acid compositions of phosphatidylethanolamine and phosphatidylcholine in cardiac muscle.

Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist.

1. We designed and synthesized several novel cyclic MSH analogues and tested their affinities for cells expressing the MC1, MC3, MC4 and MC5 receptors. 2. One of the substances HS028 (cyclic [AcCys11, dichloro-D-phenylalanine14, Cys18, Asp-NH2(22)]-beta-MSH11-22) showed high affinity (Ki of 0.95nM) and high (80 fold) MC4 receptor selectivity over the MC3 receptor. HS028 thus shows both higher affinity and higher selectivity for the MC4 receptor compared to the earlier first described MC4 receptor selective substance HS014. 3. HS028 antagonised a alpha-MSH induced increase in cyclic AMP production in transfected cells expressing the MC3 and MC4 receptors, whereas it seemed to be a partial agonist for the MC1 and MC5 receptors. 4. Chronic intracerebroventricularly (i.c.v.) administration of HS028 by osmotic minipumps significantly increased both food intake and body weight in a dose dependent manner without tachyphylaxis for a period of 7 days. 5. This is the first report demonstrating that an MC4 receptor antagonist can increase food intake and body weight during chronic administration providing further evidence that the MC4 receptor is an important mediator of long term weight homeostasis.

Food conversion is transiently affected during 4-week chronic administration of melanocortin agonist and antagonist in rats.

The central melanocortin system is involved in the regulation of food intake and body weight. In this study, we investigated the effect of a 4-week intracerebroventricular infusion of the melanocortin receptor agonist MT-II and the selective melanocortin-4 receptor antagonist HS024 on food intake and body weight homeostasis. The MT-II-treated rats ate less and lost considerably more weight than the control rats during the first week of treatment. During the second and third week, they gained weight and, by the end of the treatment period, the weight gain was similar to that of the control rats. The HS024 treatment caused hyperphagia and development of obesity during the entire period. Extensive accumulations of fat and a sixfold increase in leptin levels were observed in the HS024-treated rats, as compared with controls, after the 4-week period. Food conversion ratio, defined as body weight increase relative to weight of ingested food, was clearly increased in the HS024-treated rats, while it was lowered in the MT-II-treated rats compared with controls. The effect on food conversion ratio was transient, being greatest for both experimental groups during the first week and it was then attenuated to reach the level of controls at the end of the study. The results suggest that long-term injection of exogenous melanocortin receptor active substances may have an important transient effect on food conversion.

Melanocortin receptor agonist transiently increases oxygen consumption in rats.

Acute injections of melanocortin (MC) agonist and antagonist are highly effective in reducing or increasing food take, respectively. Much less is known about how injection of MC receptor active substances affects metabolism, in particular during long term administration. Here we investigated the effect of 8 days continuous i.c.v. infusion of either MC receptor agonist MTII or the selective MC4 receptor antagonist HS024 on oxygen consumption, food intake and body weight in rats. We observed significant increase in oxygen consumption 2 days after the start of the MTII infusion. However, this increase had disappeared by day 4 of the study. No difference was observed in the oxygen consumption after injection of HS024. MTII substantially decreased the food intake during the first days, but then the feeding recovered and the body weight stabilised at a new level. The immediate effect of the MC receptor agonist on both food intake and metabolism was thus transient, even though the weight loss was maintained. The HS024 treated rats were hyperphagic throughout the test period, continuously gaining weight, resulting in increased fat pads and high leptin levels. This is the first study that describes long term effects of MC receptor agonist and antagonist on metabolism and energy balance.

Effects of ageing and adrenergic stimulation on alpha 1- and beta-adrenoceptors and phospholipid fatty acids in rat heart.

The purpose of this study was to examine the influence of ageing on the alterations in binding characteristics of adrenoceptors and membrane phospholipid fatty acids in rat heart following repeated administration of epinephrine. The maximal number of binding sites (Bmax) and dissociation constant (Kd) of [3H]prazosin and [3H]dihydroalprenolol binding to alpha 1- and beta-adrenoceptors, respectively, changed significantly during ageing. The downregulation of alpha 1- and beta-adrenoceptors after repeated epinephrine administration for one week, did not differ with age, but the response of the affinity (1/Kd) of both alpha 1- and beta-adrenoceptors to epinephrine treatment was age dependent. In 3-month-old rats the affinity of alpha 1-adrenoceptors was decreased after epinephrine treatment but the affinity of beta-adrenoceptors was unchanged. In 10- and 23-month-old rats the affinity of beta-adrenoceptors decreased after epinephrine treatment but the affinity of alpha 1-adrenoceptors did not change. During ageing the linoleic acid (18:2(n-6)) level decreased in phosphatidylcholine and the arachidonic acid (20:4(n-6)) level increased in phosphatidylcholine and phosphatidylethanolamine. After epinephrine administration the 18:2(n-6) level decreased and the docosahexaenoic acid (22:6(n-3)) level increased in phosphatidylcholine and phosphatidylethanolamine and those changes were not age dependent. The 20:4(n-6) level increased in phosphatidylcholine after epinephrine administration, but that increase was smaller in old than in young rats. The results show that both ageing and epinephrine administration simultaneously modify the fatty acid composition of membrane phospholipids and the binding properties of alpha 1- and beta-adrenoceptors in rat heart.

Plasma fatty acids and lipids in two separate, but genetically comparable, Icelandic populations.

Levels of serum lipids and lipoproteins, and the fatty acid composition of plasma phospholipids, were measured in two genetically comparable, but widely separated, populations. The 1975 mortality rates for ischemic heart disease were significantly higher in one of these populations, the Manitoban residents of pure Icelandic descent, than in the other, a rural population from Northeastern Iceland. Two study populations, Icelanders and Icelandic-Canadians, were drawn from these larger populations. The study populations were matched for age and sex and divided into three age groups, 20-39, 40-59, and 60-69 years. In comparison to the Icelandic-Canadians, the Icelanders exhibited significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but lower triglyceride levels. Their plasma phospholipids contained significantly lower levels of saturated fatty acids (SFA), monounsaturated fatty acids, and n-6 polyunsaturated fatty acids (PUFA); but their n-3 PUFA levels were three times as high. It was additionally found that fatty acid composition of plasma phospholipids differed among Icelanders of different ages. SFA levels were significantly lower, and n-6 PUFA levels significantly higher, in the 20-39 year group than in the 60-69 year group, possibly due to different dietary fat consumption patterns between generations. No corresponding age-related difference in the fatty acid composition of plasma phospholipids was found in the Icelandic-Canadian study population. As the Icelandic and Icelandic-Canadian groups are assumed to be genetically similar, the biochemical differences between them are evidently due to environmental, probably dietary, differences. The findings indicate that n-3 PUFA may be cardioprotective in the context of an otherwise atherogenic diet.

Effects of dietary oils and methyl ethyl ketone peroxide on in vivo lipid peroxidation and antioxidants in rat heart and liver.

Weanling male Sprague-Dawley rats were fed diets for four weeks which differed in their content of n-6 (corn oil; CO) and n-3 fatty acids (fish oil; FO), but were similar in their content of saturated and monounsaturated fatty acids and vitamin E. At the end of the four-week feeding period, each dietary group was subdivided into two groups. One group received a single placebo injection of alpha-tocopherol-stripped corn oil (TSCO); the other group received a single injection of the free radical generator; methyl ethyl ketone peroxide (MEKP), in TSCO. Twenty-four hours after injection, the effect of dietary oil and MEKP treatment on endogenous lipid peroxide (LPO) production (measured as methylene blue formed by the "Determiner LPO" assay), glutathione (GSH) and vitamin E content, and fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in heart and liver from unfasted animals were measured. FO-fed rats had significantly heavier hearts and livers, increased levels of n-3 fatty acids in membrane phospholipids, and higher liver LPO levels than CO-fed rats. MEKP treatment resulted in significantly lower body weights and liver GSH levels. The data indicate that dietary n-3 fatty acids increase lipid peroxidation in liver somewhat more than in heart. The study also demonstrates that the effect of induced oxidative stress due to a single dose of MEKP on lipid peroxide formation and antioxidant status in tissues from unfasted animals was independent of the dietary oils.

U-shaped relationship between tissue docosahexaenoic acid and atrial fibrillation following cardiac surgery.

BACKGROUND/OBJECTIVES: Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF. SUBJECTS/METHODS: We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression. RESULTS: Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence. CONCLUSIONS: The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.

Inflammatory response following heart surgery and association with n-3 and n-6 long-chain polyunsaturated fatty acids in plasma and red blood cell membrane lipids.

BACKGROUND: Open heart surgery is associated with a systemic inflammatory response. The n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n-6 LC-PUFA arachidonic acid (AA) may contribute to modulation of the inflammatory response. OBJECTIVE: We investigated whether the preoperative levels of EPA, DHA and AA in plasma phospholipids (PL) and red blood cell (RBC) membrane lipids in patients (n=168) undergoing open heart surgery were associated with changes in the plasma concentration of selected inflammatory mediators in the immediate postoperative period. RESULTS AND CONCLUSIONS: The postoperative concentration of TNF-ß was lower (P<0.05) and those of hs-CRP, IL-6, IL-8, IL-18 and IL-10 higher (P<0.05) than the respective preoperative concentrations. We observed that the preoperative levels of EPA and AA in plasma PL and RBC membrane lipids were associated with changes in the concentration of pro-inflammatory and anti-inflammatory mediators, suggesting a complex role in the postoperative inflammatory process.

Lipid peroxidation in brain during aging in the senescence-accelerated mouse (SAM).

Accumulation of toxic amyloid-beta (Abeta)-peptide is suggested to cause oxidative stress in Alzheimer's disease (AD) brain, and decrease the content of polyunsaturated fatty acids (PUFA) in neuronal membrane lipids. The senescence accelerated prone mice (SAMP8) have age-related increases in the level of hippocampal Abeta-peptide, learning and memory deficits, and a shorter lifespan than their controls. The effects of age-related oxidative damage on PUFA content in membrane phospholipids (PL), and alpha-tocopherol concentration were investigated in hippocampus and amygdala of 2-, 4-, 12-, and 18-month-old SAMP8 mice. In comparison to the younger SAMP8 mice, the hippocampus of the 12-month-old mice contained lower proportions of docosahexaenoic acid (DHA) in phosphatidylserine (PS) and phosphatidylinositol (PI), and higher proportions of arachidonic acid (AA) in PS. Their amygdala contained a lower proportion of AA in phosphatidylcholine (PC). In the hippocampus of the oldest age group, the proportions of DHA in PS, and AA in PC and PI were higher than in the younger age groups. At 2 months of age, the amygdala contained a higher concentration of alpha-tocopherol than the hippocampus, but this difference between the two brain regions was lost with aging. The oldest age group contained the highest concentration of alpha-tocopherol, indicating a protection against oxidative damage of PUFA in brain membrane phospholipids.

Relationship between high consumption of marine fatty acids in early pregnancy and hypertensive disorders in pregnancy.

OBJECTIVE: To investigate whether there is a relationship between maternal intake of cod-liver oil in early and late pregnancy and hypertensive disorders in pregnancy. DESIGN: An observational prospective study. SETTING: Free-living conditions in a community with traditional fish and cod-liver oil consumption. POPULATION: Four hundred and eighty-eight low-risk pregnant Icelandic women. METHODS: Maternal use of cod-liver oil, foods and other supplements was estimated with a semiquantitative food frequency questionnaire covering food intake together with lifestyle factors for the previous 3 months. Questionnaires were filled out twice, between 11 and 15 weeks of gestation and between 34 and 37 weeks of gestation. Supplements related to hypertensive disorders in pregnancy, i.e. gestational hypertension and pre-eclampsia, were presented, with logistic regression controlling for potential confounding. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, cod-liver oil and multivitamins. RESULTS: The odds ratio for developing hypertensive disorders in pregnancy for women consuming liquid cod-liver oil was 4.7 (95% CI 1.8-12.6, P= 0.002), after adjusting for confounding factors. By dividing the amount of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) into centiles, the odds ratio for hypertensive disorders across groups for n-3 LCPUFA suggested a u-shaped curve (P = 0.008). Similar results were found for gestational hypertension alone. Further, the use of multivitamin supplements without vitamins A and D in late pregnancy doubled the odds of hypertensive disorders (OR 2.4, 95% CI 1.0-5.4, P= 0.044). CONCLUSIONS: Consumption of high doses of n-3 LCPUFA in early pregnancy, or other nutrients found in liquid cod-liver oil, may increase the risk of developing hypertensive disorders in pregnancy.

Maternal diet in early and late pregnancy in relation to weight gain.

OBJECTIVE: To identify dietary factors related to the risk of gaining weight outside recommendations for pregnancy weight gain and birth outcome. DESIGN: An observational study with free-living conditions. SUBJECTS: Four hundred and ninety five healthy pregnant Icelandic women. METHODS: The dietary intake of the women was estimated with a semiquantitative food frequency questionnaire covering food intake together with lifestyle factors for the previous 3 months. Questionnaires were filled out at between 11 and 15 weeks and between 34 and 37 weeks gestation. Comparison of birth outcome between the three weight gain groups was made with ANOVA and Bonferroni post hoc tests. Dietary factors related to at least optimal and excessive weight gain during pregnancy were represented with logistic regression controlling for potential confounding. RESULTS: Of the women, 26% gained suboptimal and 34% excessive weight during pregnancy. Women in late pregnancy with at least optimal, compared with women with suboptimal, weight gain were eating more (OR = 3.32, confidence interval (CI)=1.81-6.09, P < 0.001) and drinking more milk (OR = 3.10, CI = 1.57-6.13, P = 0.001). The same dietary factors were related to excessive, compared with optimal, weight gain. Furthermore, eating more sweets early in pregnancy increased the risk of gaining excessive weight (OR=2.52, CI=1.10-5.77, P=0.029). Women with a body mass index of 25.0-29.9 kg/m(2) before pregnancy were most likely to gain excessive weight (OR = 7.37, CI 4.13-13.14, P < 0.001). Women gaining suboptimal weight gave birth to lighter children (P < 0.001) and had shorter gestation (P = 0.008) than women gaining optimal or excessive weight. CONCLUSION: Women who are overweight before pregnancy should get special attention regarding lifestyle modifications affecting consequent weight gain during pregnancy. They are most likely to gain excessive weight and therefore most likely to suffer pregnancy and delivery complications and struggle with increasing overweight and obesity after giving birth.

Combined effects of maternal smoking status and dietary intake related to weight gain and birth size parameters.

OBJECTIVE: To investigate the interaction of smoking status and dietary intake during pregnancy and its relationship to maternal weight gain and birth size parameters. DESIGN: An observational prospective study. SETTING: Free-living conditions. POPULATION: Four hundred and eight healthy pregnant Icelandic women. METHODS: Maternal smoking status, lifestyle factors and dietary habits were evaluated with questionnaires. Intake of foods and supplements was also estimated with a semiquantitative food frequency questionnaire for the previous 3 months. All questionnaires were filled out between 11 and 15 weeks and between 34 and 37 weeks of gestation. Smoking status in relation to optimal and/or excessive weight gain during pregnancy was represented with logistic regression controlling for potential confounding factors. MAIN OUTCOME MEASURES: Maternal weight gain, smoking status, dietary intake and birthweight. RESULTS: Women who smoked throughout pregnancy were unlikely to gain optimal weight or more (OR 0.51, 95% CI 0.27-0.97), whereas smoking cessation in connection with pregnancy ('former smokers') doubled the risk of excessive weight gain (OR 2.03, 95% CI 1.24-3.35). The latter association was no longer significant after adjustment for dietary factors and other confounding factors. Former smokers ate the least amount of fruit and vegetables (fruit: 129 versus 180 and 144 g/day (median), P= 0.038; vegetables: 53 versus 76 and 72 g/day, P= 0.026 for former smokers, nonsmokers and smokers, respectively). Birthweight was lowest among infants born to smokers, but birthweight was similar for former smokers and nonsmokers (3583 +/- 491 g versus 3791 +/- 461 g and 3826 +/- 466 g, respectively; P= 0.003). CONCLUSIONS: Smoking cessation in early pregnancy or pre-pregnancy is not associated with low birthweight. It is, however, associated with excessive maternal weight gain and a low fruit and vegetable intake.

Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions.

Vernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection.

Inotropic response of rat heart papillary muscle to alpha 1- and beta-adrenoceptor stimulation in relation to dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) and age.

The effect of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) and age on inotropic responses of heart papillary muscle to alpha 1-or beta-adrenoceptor stimulation was examined in young (4 months), middle-aged (12 months) and senescent (27 months) male Wistar rats. From the age of two months the rats were fed a diet containing 2% or 12% of fat by weight varying in PUFA type: a) standard low-fat n-6 PUFA diet, b) high-fat n-6 PUFA diet or c) high-fat n-3 PUFA diet. The inotropic responses to alpha 1-adrenoceptor stimulation with phenylephrine were triphasic (positive, negative, then positive). Young, high-fat n-3 PUFA-fed rats exhibited significantly lower negative and higher positive responses to phenylephrine stimulation, and higher positive responses to isoprenaline stimulation than young, high-fat n-6 PUFA-fed rats. On the other hand, no such dietary-related difference was found between young rats fed a high-fat n-3 PUFA diet and a standard low-fat n-6 PUFA diet. The young high-fat n-6 PUFA-fed rats exhibited inotropic responses similar to those of the middle-aged and senescent rats within the three dietary groups. The time to peak force and the time of half relaxation did not differ within dietary and age groups. The findings indicate that dietary n-6 PUFA-rich supplementation at a young age induces changes resembling the effects of age, as evidenced by decreasing cardiac responses to adrenoceptor agonists, such as phenylephrine or isoprenaline.

Influence of dietary cod liver oil on fatty acid composition of plasma lipids in human male subjects after myocardial infarction.

A randomized crossover study was carried out to investigate the fatty acid profile and concentrations of plasma lipids in male patients with myocardial infarction (MI) who supplemented their diet with 20 ml cod liver oil daily for 6 weeks. Subjects were divided into two groups, A and B. Group A received cod liver oil daily for 6 weeks after hospital discharge, but none for the subsequent 6 weeks. Group B did not start taking cod liver oil until 6 weeks after hospital discharge, and they then took cod liver oil for 6 weeks. Diet, medication or smoking habits were kept as constant as possible during the study. During the period of cod liver oil intake, eicosapentaenoic acid (20:5 (n-3), EPA) and docosahexaenoic acid (22:6 (n-3), DHA) increased significantly in phospholipids (PL), triglycerides (TG) and cholesterol esters (CE), whereas linoleic acid (18:2 (n-6), LA), dihomo-gamma-linolenic acid (20:3 (n-6), DHGLA) and arachidonic acid (20:4 (n-6), AA) were significantly decreased in phospholipids. The plasma level of TG was significantly decreased during the cod liver oil intake. Total cholesterol, high density lipoprotein (HDL) cholesterol, and levels of apolipoproteins A1 and B were not affected by cod liver oil in these MI patients.