ABSTRACT
BACKGROUND: Maternal dietary docosahexaenoic acid (DHA) intake is thought to affect development in the offspring. OBJECTIVE: We assessed the impact of maternal dietary DHA on behavior, brain fatty acid (FA) profile, and sickness response of offspring in pigs, a pertinent model for human nutrition. METHODS: Sows (n = 24) were fed a diet with DHA-rich fish oil (FO) (20 g/kg) or high-oleic acid sunflower oil (HOSF) (20 g/kg) from day 61 of gestation through lactation. At 4 wk of age, 4 piglets per litter were weaned and mixed with piglets from other litters. Behavior was observed in 4- to 8-wk-old piglets, and brain FA composition was analyzed at 4 (n = 15) and 14 (n = 12) wk. Thirteen-week-old piglets (n = 48) were subjected to a lipopolysaccharide (LPS) challenge. Body temperature, plasma cytokines, and motivation to approach a familiar human, indicative of a sickness response, were measured. RESULTS: FO-fed pigs displayed more social activities (+262%, P = 0.02), played more (+61%, P = 0.03), and tended to show fewer oral manipulative behaviors directed at pen mates (-25%, P = 0.06) than did HOSF-fed pigs up to 4 wk after weaning. Brain DHA concentrations were higher in FO- than in HOSF-fed pigs up to 10 wk after supplementation (+10-50%, P < 0.001), although differences declined with age. Body temperature (P < 0.001) and tumor necrosis factor α and interferon γ concentrations (P < 0.05) increased after LPS injection, but no diet effect was found (P > 0.10). LPS-treated pigs were less likely to approach the human than saline-treated pigs in the HOSF-fed (-29%, P = 0.0003), but not in the FO-fed group (-13%, P = 0.11). CONCLUSIONS: Maternal DHA beneficially affected offspring social behavior after weaning and mildly attenuated sickness behavior after an inflammatory challenge in pigs. These behavioral changes may be mediated by increased brain DHA proportions.
Subject(s)
Brain/drug effects , Fatty Acids/chemistry , Fish Oils/administration & dosage , Maternal Nutritional Physiological Phenomena , Social Behavior , Animals , Brain Chemistry , Dietary Supplements , Docosahexaenoic Acids/administration & dosage , Female , Illness Behavior/drug effects , Lactation/drug effects , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/adverse effects , Male , Plant Oils/administration & dosage , Pregnancy , Sunflower Oil , Swine , WeaningABSTRACT
BACKGROUND: Intakes of n-3 polyunsaturated fatty acids (PUFAs), especially EPA (C20:5n-3) and DHA (C22:6n-3), are known to prevent fatal coronary heart disease (CHD). The effects of n-6 PUFAs including arachidonic acid (C20:4n-6), however, remain unclear. δ-5 and δ-6 desaturases are rate-limiting enzymes for synthesizing long-chain n-3 and n-6 PUFAs. C20:4n-6 to C20:3n-6 and C18:3n-6 to C18:2n-6 ratios are markers of endogenous δ-5 and δ-6 desaturase activities, but have never been studied in relation to incident CHD. Therefore, the aim of this study was to investigate the relation between these ratios as well as genotypes of FADS1 rs174547 and CHD incidence. METHODS: We applied a case-cohort design within the CAREMA cohort, a large prospective study among the general Dutch population followed up for a median of 12.1 years. Fatty acid profile in plasma cholesteryl esters and FADS1 genotype at baseline were measured in a random subcohort (nâ=â1323) and incident CHD cases (nâ=â537). Main outcome measures were hazard ratios (HRs) of incident CHD adjusted for major CHD risk factors. RESULTS: The AA genotype of rs174547 was associated with increased plasma levels of C204n-6, C20:5n-3 and C22:6n-3 and increased δ-5 and δ-6 desaturase activities, but not with CHD risk. In multivariable adjusted models, high baseline δ-5 desaturase activity was associated with reduced CHD risk (P for trendâ=â0.02), especially among those carrying the high desaturase activity genotype (AA): HR (95% CI)â=â0.35 (0.15-0.81) for comparing the extreme quintiles. High plasma DHA levels were also associated with reduced CHD risk. CONCLUSION: In this prospective cohort study, we observed a reduced CHD risk with an increased C20:4n-6 to C20:3n-6 ratio, suggesting that δ-5 desaturase activity plays a role in CHD etiology. This should be investigated further in other independent studies.
Subject(s)
Coronary Artery Disease/enzymology , Coronary Artery Disease/genetics , Fatty Acid Desaturases/genetics , Genetic Predisposition to Disease , Adult , Biomarkers/blood , Cholesterol Esters/blood , Cohort Studies , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Delta-5 Fatty Acid Desaturase , Fatty Acids, Unsaturated/metabolism , Female , Humans , Incidence , Male , Middle Aged , Netherlands/epidemiology , Polymorphism, Single Nucleotide/genetics , Risk FactorsABSTRACT
The effect of dietary conjugated linoleic acid (CLA) on body composition and energy metabolism was investigated in broiler chickens. Male broiler chicks were assigned to receive either a control diet (1 % sunflower oil) or a diet containing CLA (1 % of a 1:1 mixture of trans-10, cis-12 and cis-9, trans-11 isomers of octadecadienoic acid). The diets were fed ad libitum for 3 weeks and there were eight replicates per diet, each replicate including four chickens so that each treatment had thirty-two animals. The proportion of body fat was lower in the control group than in the CLA group. No significant differences as to the proportions of body water, ash and protein were observed. Feed and energy intake were significantly lower in CLA-fed birds. The percentage of ingested energy lost in excreta was higher after CLA feeding and heat expenditure as a percentage of ingested energy was lower in the CLA-fed group. The CLA-fed group showed a higher percentage of SFA and lower percentages of MUFA and PUFA in carcass fat. It is concluded that CLA stimulated de novo fatty acid synthesis and lowered desaturase activity.
Subject(s)
Animal Feed , Animal Nutritional Physiological Phenomena , Chickens/metabolism , Diet , Linoleic Acids, Conjugated/administration & dosage , Animals , Body Composition , Body Weight , Calorimetry , Energy Metabolism , Male , Plant Oils/administration & dosage , Random Allocation , Sunflower OilABSTRACT
OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.
Subject(s)
Arrhythmias, Cardiac/chemically induced , Fatty Acids, Omega-3/administration & dosage , Animals , Arrhythmias, Cardiac/physiopathology , Dietary Supplements , Docosahexaenoic Acids/analysis , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/analysis , Eicosapentaenoic Acid/blood , Electrocardiography , Heart/physiopathology , Male , Myocardial Ischemia/metabolism , Myocardial Ischemia/physiopathology , Perfusion , Plant Oils/administration & dosage , Sunflower Oil , SwineABSTRACT
BACKGROUND: Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil reduce the risk of sudden death presumably by preventing life-threatening arrhythmias. Acutely administered omega3-PUFAs modulate the activity of several cardiac ion channels, but the chronic effects of a diet enriched with fish oil leading to omega3-PUFA-incorporation into the sarcolemma on membrane currents are unknown. METHODS: Pigs received a diet either rich in omega3-PUFAs or in omega9-fatty acids for 8 weeks. Ventricular myocytes (VMs) were isolated and used for patch-clamp studies. RESULTS: omega3-VMs contained higher amounts of omega3-PUFAs and had a shorter action potential (AP) with a more negative plateau than control VM. In omega3 VMs, L-type Ca(2+) current (I(Ca,L)) and Na(+)-Ca(2+) exchange current (I(NCX)) were reduced by approximately 20% and 60%, respectively, and inward rectifier K(+) current (I(K1)) and slow delayed rectifier K(+) current (I(Ks)) were increased by approximately 50% and 70%, respectively, compared to control. Densities of rapid delayed rectifier K(+) current, Ca(2+)-activated Cl(-) current, and Na(+) current (I(Na)) were unchanged, although voltage-dependence of I(Na) inactivation was more negative in omega3 VMs. CONCLUSIONS: A fish oil diet increases omega3-PUFA content in the ventricular sarcolemma, decreases I(Ca,L) and I(NCX), and increases I(K1) and I(Ks), resulting in AP shortening. Incorporation of omega3-PUFAs in the sarcolemma may have consequences for arrhythmias independent of circulating omega3-PUFAs.
Subject(s)
Action Potentials/physiology , Diet , Fatty Acids, Omega-3/administration & dosage , Fish Oils , Myocytes, Cardiac/physiology , Sarcolemma/physiology , 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid , Animals , Antioxidants/pharmacology , Arrhythmias, Cardiac/metabolism , Calcium Channel Blockers/pharmacology , Calcium Channels/metabolism , Chromans/pharmacology , Heart Ventricles , Male , Membrane Potentials/physiology , Myocytes, Cardiac/metabolism , Nifedipine/pharmacology , Patch-Clamp Techniques , Sarcolemma/metabolism , Sodium Channels/metabolism , Sodium-Calcium Exchanger/physiology , Swine , Time FactorsABSTRACT
Feeding mice conjugated linoleic acid (9 cis,11 trans/9 trans,11 cis-and 10 trans,12 cis-CLA in equal amounts) resulted in triacylglycerol accumulation in the liver. The objective of this study was to examine whether this steatosis is associated with changes in hepatic fatty acid synthesis and oxidation. Therefore, we measured the activities of key enzymes of fatty acid synthesis, i.e., acetyl-CoA carboxylase and fatty acid synthase and of fatty acid oxidation, i.e., 3-hydroxy-acyl-CoA dehydrogenase and citrate synthase in livers of mice fed a diet with 0.5% (w/w) CLA. CLA (a 1:1 mixture of the 10 trans, 12 cis and 9 cis, 11 trans isomers of octadecadenoic acid) was administered for 3 and 12 weeks with high-oleic sunflower oil fed as control. The proportion of body fat was significantly lower on the CLA than on the control diet and this effect was already significant after 3 weeks. The specific activites of 3-hydroxy-acyl-CoA dehydrogenase and citrate synthase were unaffected by CLA both after 3 and 12 weeks. The specific activity of fatty acid synthase was nonsignificantly raised (by 12%) after 3 weeks on the CLA diet but had increased significantly (by 34%) after 12 weeks of feeding. The specific activity of acetyl-CoA carboxylase had also increased both after 3 weeks (by 53%) and 12 weeks (by 23%) on the CLA diet, but this effect did not reach statistical significance. Due to CLA-induced hepatomegaly, the overall capacity for both fatty acid oxidation and synthesis-as evidenced by the total hepatic activities of 3-hydroxy-acyl-CoA dehydrogenase, citrate synthase, acetyl-CoA carboxylase, and fatty acid synthase-was significantly greater in the CLA-fed group after 12 weeks, although the overall capacity for fatty acid synthesis had increased more than that for fatty acid oxidation. Thus, this study indicates that prolonged, but not short-term, feeding mice with CLA increased hepatic fatty acid synthesis relative to oxidation, despite the decrease in body fat and the increase in liver weight seen earlier. It is concluded that the observed CLA-induced changes in hepatic fatty acid synthesis and oxidation are the result, rather than the cause, of the lowering of body fat.