PUFA Group Research Articles

Orally administered [14C]DPA and [14C]DHA are metabolised differently to [14C]EPA in rats

Previous studies have revealed that C20 PUFA are significantly less oxidised to CO₂ in whole-body studies compared with SFA, MUFA and C18 PUFA. The present study determined the extent to which three long-chain PUFA, namely 20:5n-3 EPA, 22:5n-3 docosapentaenoic acid (DPA) and 22:6n-3 DHA, were catabolised to CO₂ or, conversely, incorporated into tissue lipids. Rats were administered a single oral dose of 2·5 μCi [1-¹⁴C]DPA, [1-¹⁴C]EPA, [1-¹⁴C]DHA or [1-¹⁴C]oleic acid (18:1n-9; OA), and were placed in a metabolism chamber for 6 h where exhaled ¹⁴CO₂ was trapped and counted for radioactivity. Rats were euthanised after 24 h and tissues were removed for analysis of radioactivity in tissue lipids. The results showed that DPA and DHA were catabolised to CO₂ significantly less compared with EPA and OA (P<0·05). The phospholipid (PL) fraction was the most labelled for all three n-3 PUFA compared with OA in all tissues, and there was no difference between C20 and C22 n-3 PUFA in the proportion of label in the PL fraction. The DHA and DPA groups showed significantly more label than the EPA group in both skeletal muscle and heart. In the brain and heart tissue, there was significantly less label in the cholesterol fraction from the C22 n-3 PUFA group compared with the C20 n-3 PUFA group. The higher incorporation of DHA and DPA into the heart and skeletal muscle, compared with EPA, suggests that these C22 n-3 PUFA might play an important role in these tissues.

Abstract 462: Dose Matters: Omega-3 Polyunsaturated Fatty Acid Supplementation at 3600 mg/d but Not 900 mg/d Reduces Inflammatory Response to Evoked Endotoxemia in Healthy Volunteers

Inflammation is a key component in the pathogenesis of cardiometabolic disease. Certain anti-inflammatory compounds may improve atherosclerotic disease risk by modulating systemic and vascular inflammation. Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may represent a dietary mechanism for improving cardiometabolic health through reduction of inflammation. We hypothesized that n-3 PUFA supplementation would reduce the inflammatory response to evoked endotoxemia in healthy humans. In the Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia study (FFAME Study), we recruited healthy individuals (N=60; age 18-45; BMI 18-30; 43% Female; 65% Caucasian, 20% African, 15% Asian ancestry) randomized to one of three treatment groups; n-3 PUFA (Lovaza 465mg EPA/375mg DHA) supplemented at either 900mg per day or 3,600mg per day, or placebo. An additional arm of the study included a fenofibrate treatment group, not included here. Participants were treated for ∼8 weeks then admitted to the research center for an endotoxin challenge of lipopolysaccharide (LPS) 0.6ng/kg intravenously. Multiple clinical and biochemical variables were assessed throughout, and analyzed using RM-ANOVA with Bonferroni post-hoc tests for between group differences. Compared to placebo, high-dose (P&lt;0.01) but not low dose n-3 PUFA reduced peak temperature, but not heart rate or blood pressure, responses to endotoxin. Cytokines and inflammatory markers (IL-6, TNFα, IL-10, CRP, SAA) were decreased in high-dose n-3 PUFA vs. placebo . Interestingly, these inflammatory markers tended to be increased in low-dose n-3 PUFA vs. placebo, with a significant difference in the effect of low-dose vs. high-dose n-3 PUFA on peak IL-6 (P&lt;0.001), TNFα (P&lt;0.01) and IL-10 (P&lt;0.05). Plasma lipids tended to decrease in both n-3 PUFA groups compared with placebo, with equal lipid-lowering effect of 900 or 3,600 mg/day on cholesterol, ApoA-I, and triglycerides. The specific anti-inflammatory properties of n-3 PUFA appear to be dose-specific, with high doses (3,600mg/day) leading to attenuation of the inflammatory response to evoked endotoxemia, while lower doses (900mg/day) do not reduce the inflammatory response despite similar reductions in plasma lipids.

Gut bacteria profiles of Mus musculus at the phylum and family levels are influenced by saturation of dietary fatty acids

BackgroundMammalian gut microbiota have been implicated in a variety of functions including the breakdown of ingested nutrients, the regulation of energy intake and storage, the control of immune system development and activity, and the synthesis of novel chemicals. Previous studies have shown that feeding mammalian hosts a high-fat diet shifts gut bacteria at the phylum level to reduce the ratio of Bacteroidetes-to-Firmicutes, while feeding hosts a fat-restricted diet increases this ratio. However, few studies have investigated the differential effects of fatty acid type on gut bacterial profile. MethodsOver a 14-week period, Mus musculus were fed a diet rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), or saturated fatty acids (SFAs). Fecal pellets were collected before and after the treatment period from 12 randomly selected mice (4 per treatment group). Bacterial DNA was extracted from the pellets and characterized by analysis of the hypervariable V3 region of the 16S rRNA. Nominal logistic regression models were used to assess shifts in microbial profile at the phylum and family levels in response to diet. ResultsA significant decrease in the proportion of phylum Bacteroidetes species was observed for mice fed any of the three diets over time. However, the SFA-rich diet group showed a significantly greater decrease in Bacteroidetes proportion (−28%) than did either the n-3 PUFA group (−10%) or the n-6 PUFA group (−12%). At the family level, a significant decrease in proportion of Porphyromonadaceae was observed for mice fed the n-6 PUFA-rich diet, and a significant decrease in proportion of Lachnospiraceae was observed for mice fed the SFA-rich diet. There was no significant effect of diet type on body mass change. ConclusionOur results indicate that SFAs have stronger effects than PUFAs in shifting gut microbiota profiles toward those typical of obese individuals, and that dietary fatty acid saturation influences shifts in gut microbiota independently of changes in body mass.

The effects of n-3 PUFA and intestinal lymph drainage on high-mobility group box 1 and Toll-like receptor 4 mRNA in rats with intestinal ischaemia–reperfusion injury

The aim of the present study was to investigate the impacts of n-3 PUFA and lymph drainage (D) on intestinal ischaemia-reperfusion (I/R) injury in rats. A total of forty-eight Sprague-Dawley male rats were randomly divided into three groups (n 16): normal diet (N), enteral nutrition (EN) and EN plus n-3 PUFA. Each group was further divided into lymph drainage (I/R+D) and non-drainage (I/R) sub-groups (n 8). After 5d with different nutrition regimens, the rats were subjected to 60min ischaemia by clamping the superior mesenteric artery, followed by 120min reperfusion. At the same time, the rats in the I/R+D sub-groups were treated with intestinal lymph drainage for 180min. Organs were harvested and we detected the cytokine, endotoxin, and expression of Toll-like receptor (TLR) 4 mRNA and its endogenous ligand high-mobility group box 1 (HMGB1). We found that the serum levels of HMGB1, inflammatory cytokine and endotoxin in the three I/R+D sub-groups were significantly lower than those in the N (I/R) and EN (I/R) sub-groups (P<0·05). The activation of NF-κB and the expression of HMGB1 and TLR4 mRNA significantly increased in the jejunum, ileum, liver and lung after intestinal I/R injury, but notably lower in the I/R+D groups than those in I/R (P<0·05). The injury degree and HMGB1 expression were decreased in the n-3 PUFA group than in the N and EN groups. We preliminarily concluded that nutrition with n-3 PUFA and/or intestinal lymph drainage may reduce HMGB1 and inflammatory cytokine in serum and lymph and inhibit the expression and signal transmission of TLR4 mRNA, thereby alleviating intestinal I/R injury in rats.

Using omega-3 fatty acids to treat persistent atrial fibrillation: Time to fish or cut bait?

r t Recently, Kowey et al performed a controlled, prospecive, multicenter, randomized clinical trial comparing precription-grade omega-3 fatty acids (PUFAs) from fish oil o placebo to determine efficacy in preventing recurrent ymptomatic paroxysmal or persistent atrial fibrillation AF). Fish oil was ineffective when given at a dose of 8 g/d or a week followed by 4 g/d through week 24. For the 105 atients randomized with persistent AF, 33% (n 18) in the lacebo group and 50% (n 32) in the fish oil group had documented recurrent symptomatic AF. In a prior commentary, I (B.O.) stated: “It is safe to say, based on this wellcontrolled rather definitive randomized clinical trial, that PUFAs have no role in the management of recurrent symptomatic atrial fibrillation.” Similar results suggesting no enefit were found in another randomized trial and in a trial valuating the prevention of new-onset AF in the postopertive period, although data from an open-label study showed diametrically opposite results. A meta-analysis inicated no benefit from PUFAs to prevent AF. Since then, in contradistinction to these “rather definitive” data, Nodari et al reported results from a recent ouble-blind placebo-controlled study showing that PUFAs lus amiodarone conferred long-term benefit for patients ith persistent AF. Now, Kumar et al find that PUFA upplementation reduced recurrent persistent AF after carioversion. At 90 days, 38.5% of the PUFA group vs 77.5% f the control group had a recurrence of persistent AF. Not nly did more patients in the PUFA group have pharmacologic eversion to sinus rhythm compared with controls (12.1% vs .4%; P .05), but those who underwent electrical cardioverion did substantially better as well. The mean time to persisent AF recurrence was 190 days in the PUFA group vs 77 ays in the control group (P .001). The median time to ecurrence was 201 days in the PUFA group compared with 32 ays in the control group. This is nearly 7 times better. These ndings were strengthened by longer AF duration and lesser

Treatment with w-3 fatty acids reduces serum C-reactive protein concentration

Background: Studies have demonstrated that patients with diets high in w-3 fatty acids have a lower risk of adverse cardiovascular events. C-reactive protein (CRP), a marker of inflammation, is a strong predictor of future cardiovascular events. w-3 fatty acids have been shown to have anti-inflammatory properties. However, there is a paucity of data examining the effect of =-3 fatty acids on CRP levels. This randomized, double-blind, placebocontrolled trial tested the hypothesis that treatment with w-3 polyunsaturated fatty acids (n-3 PUFAs) would reduce serum high-sensitivity CRP levels. Materials & methods: Fifty three patients with elevated baseline CRP (?3 mg/l) were randomized to n-3 PUFA (27 patients) or placebo (26 patients). Patients with active infection, inflammatory disease, baseline CRP ?10 mg/l or those started on HMG-CoA reductase inhibitor therapy during the study period were excluded. The primary end point was CRP level following 8 weeks of treatment. Results: After 8 weeks of treatment with the study drug, the median CRP level in the n-3 PUFA group was 3.4 mg/l compared with 4.0 mg/l in the placebo group (p = 0.36). After controlling for baseline CRP, there was a significant percentage decrease in CRP from baseline in the n-3 PUFA group (-40.3%; p = 0.009) but not in the placebo group (-16.4%; p = 0.32) Conclusion: Treatment for 8 weeks with w-3 fatty acids resulted in a significant percentage reduction of CRP levels as compared with baseline, a finding not seen with placebo.

N-3 PUFA prevent metabolic disturbances associated with obesity and improve endothelial function in golden Syrian hamsters fed with a high-fat diet

Glucose intolerance and dyslipidaemia are independent risk factors for endothelium dysfunction and CVD. The aim of the present study was to analyse the preventive effect of n-3 PUFA (EPA and DHA) on lipid and carbohydrate disturbances and endothelial dysfunction. Three groups of adult hamsters were studied for 20 weeks: (1) control diet (Control); (2) high-fat diet (HF); (3) high-fat diet enriched with n-3 PUFA (HFn-3) groups. The increase in body weight and fat mass in the HF compared to the Control group (P < 0.05) was not found in the HFn-3 group. Muscle TAG content was similar in the Control and HF groups, but significantly lower in the HFn-3 group (P = 0.008). Glucose tolerance was impaired in the HF compared to the Control group, but this impairment was prevented by n-3 PUFA in the HFn-3 group (P < 0.001). Plasma TAG and cholesterol were higher in the HF group compared to the Control group (P < 0.001), but lower in the HFn-3 group compared to the HF group (P < 0.001). HDL-cholesterol was lower in the HFn-3 group compared to the Control and HF groups (P < 0.0005). Hepatic secretion of TAG was lower in the HFn-3 group compared to the HF group (P < 0.005), but did not differ from the Control group. Hepatic gene expression of sterol regulatory element-binding protein-1c, diacylglycerol O-acyltransferase 2 and stearyl CoA desaturase 1 was lower in the HFn-3 group, whereas carnitine palmitoyl transferase 1 and scavenger receptor class B type 1 expression was higher (P < 0.05). In adipocytes and adipose macrophages, PPARγ and TNFα expression was higher in the HF and HFn-3 groups compared to the Control group. Endothelium relaxation was higher in the HFn-3 (P < 0.001) than in the HF and Control groups, and was correlated with glucose intolerance (P = 0.03) and cholesterol (P = 0.0003). In conclusion, n-3 PUFA prevent some metabolic disturbances induced by high-fat diet and improve endothelial function in hamsters.

Marine n-3 fatty acids, atrial fibrillation and QT interval in haemodialysis patients

Patients treated with haemodialysis are at high risk of sudden cardiac death (SCD) often caused by arrhythmias. Atrial fibrillation (AF) is frequent among haemodialysis patients and is associated with increased mortality. Prolonged QTc is a risk marker of ventricular arrhythmia and is thereby associated with SCD. Studies have suggested that n-3 PUFA may have an antiarrhythmic effect, but the exact mechanism is not clear. The aim of this study was to examine whether AF was associated with n-3 PUFA in plasma phospholipids and whether supplementation with n-3 PUFA would shorten the QTc interval in haemodialysis patients compared to placebo. In a double-blinded randomised, placebo-controlled intervention trial 206 haemodialysis patients with CVD were treated with 1·7 g n-3 PUFA or placebo (olive oil) daily for 3 months. Blood samples and electrocardiogram evaluations were carried out at baseline and after 3 months. The QT interval, PQ interval and heart rate were measured in all patients with sinus rhythm (SR). At baseline 13 % of patients had AF. The content of the n-3 PUFA, DHA, was significantly lower (P < 0·05) in serum of patients with AF compared with patients with SR. Thus, the DHA content was independently negatively associated with AF. Supplementation with n-3 PUFA did not shorten the QT interval significantly compared to the placebo group (P = 0·42), although subgroup analysis within the n-3 PUFA group revealed a shortening effects on QTc (P = 0·01). In conclusion, an inverse association was found between the presence of AF and the plasma DHA in haemodialysis patients. Intervention with n-3 PUFA did not shorten the QTc interval compared to placebo.

Effects of lymphatic drainage and omega-3 polyunsaturated fatty acids on intestinal ischemia-reperfusion injury in rats

To investigate the effects of lymphatic drainage and omega-3 polyunsaturated fatty acid (omega-3PUFA) on high mobility group box 1 (HMGB1), inflammatory cytokines and endotoxin in rats with intestinal ischemia-reperfusion (I/R) injury. A total of 72 SD rats were randomly divided into drainage-alone group, I/R group, ischemia-reperfusion plus drainage (I/R + D) group (n = 8 each) and 3 groups with 16 rats undergoing gastrostomy in each group: normal diet (N) group, enteral nutrition (EN) group and enteral nutrition & omega-3PUFA (PUFA) group. And they were further divided into 2 subgroups (n = 8). The rats in I/R and I/R + D groups were subjected to a 60-min ischemia follow by 120-min reperfusion injury of superior mesenteric artery. When the rats suffered I/R injury, intestinal lymph was drained for 180 min in the I/R + D group. The rats in the drainage-alone group received 180-min lymph drainage without I/R injury. After 5 days with different nutrition regimes, the models were established similarly. The rats in the I/R + D sub-groups were treated with intestinal lymph drainage for 180 min. The serum and lymph samples were collected post-operatively. Endotoxin was detected by a Limulus kit. The inflammatory cytokines and high mobility group box 1 (HMGB1) were analyzed by enzyme-linked immunosorbent assay (ELISA). Endotoxin, inflammatory cytokines and lymphatic HMGB1 of lymphatic in the I/R + D group were higher than those in the drainage-alone group [all P < 0.05, IL-6: (30 +/- 8) pg/ml vs (20 +/- 6) pg/ml, endotoxin: (0.029 +/- 0.011) U/ml vs (0.008 +/- 0.005) U/ml]. The serum levels of endotoxin and inflammatory cytokines in the I/R + D group were lower than those in the I/R group (P < 0.05). The lymphatic levels of TNF-alpha (tumor necrosis factor-alpha) and HMGB1 in the N and EN groups were higher than those in the PUFA group[ TNF-alpha: (46 +/- 17) pg/ml, (54 +/- 16) pg/ml vs (28 +/- 9) pg/ml, HMGB1: (4.8 +/- 1.6) ng/ml, (5.3 +/- 1.8) ng/ml, (3.0 +/- 1.0) ng/ml, all P < 0.05)]. The serum levels of endotoxin, inflammatory cytokines and HMGB1 in the PUFA (I/R) group were lower than those in the N (I/R) group (P < 0.05). The levels of TNF-alpha and HMGB1 were lower in the PUFA (I/R + D) group than those in the N (I/R + D) group (both P < 0.05). Lymphatic drainage may reduce the levels of endotoxin, inflammatory cytokines and HMGB1 so as to alleviate the intestinal I/R injury. The intervention of omega-3PUFA has some protective effect through relieving inflammation.

N-3 Polyunsaturated fatty acid therapy improves endothelial function and affects adiponectin and resistin balance in the first month after myocardial infarction

IntroductionN-3 Polyunsaturated fatty acids (n-3 PUFA) exert clinical beneficial effects in patients after acute myocardial infarction (AMI). However, their exact mechanisms of action are not well recognized yet. Our aim was to evaluate effects of early introduced n-3 PUFA supplementation on endothelial function and serum adipokine concentrations in patients with AMI.Material and methodsThirty-eight patients with AMI and successful coronary stent implantation were randomized to the study group (PUFA group: n = 19; standard therapy + PUFA 1 g daily) and the control group (control group: n = 19; standard therapy). The study group patients were given n-3 PUFA (Omacor 1 g daily) starting from the 3rd day of AMI. Ultrasound vascular indexes (flow-mediated dilatation [FMD], nitroglycerine-mediated dilation [NMD]) and serum concentrations of adiponectin and resistin (ELISA) were evaluated before and after 30 days of pharmacotherapy.ResultsComparison of the mean delta values (baseline/after 30 days of therapy) between groups revealed significant differences for delta FMD (PUFA 7.6 ±12.4% vs. control –1.7 ±10.5%, p = 0.019) and delta resistin concentrations (PUFA 1.0 ±3.8pg/ml vs. control –1.6 ±2.9pg/ml, p = 0.028). Multiple linear regression analysis for all subjects revealed the n-3 PUFA supplementation (r = 10.933, p = 0.004) and waist circumference (r = –0.467, p = 0.01) as independent factors associated with delta FMD values (R-adjusted 0.29; p = 0.002).ConclusionsEarly and short-term n-3 PUFA supplementation in AMI with successful primary PCI and optimal pharmacotherapy improves endothelial function. However, increased resistin serum levels observed after 1-month n-3 PUFA supplementation merits further investigations.

Effects of Dietary Omega-3 Polyunsaturated Fatty Acids on the Skeletal-Muscle Blood-Flow Response to Exercise in Rats

The polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) affect vascular relaxation and involve factors (e.g., nitric oxide) that contribute to exercise-induced increases in skeletal-muscle blood flow (Q). The authors investigated whether DHA and EPA supplementation augments skeletal-muscle Q and vascular conductance (VC) and attenuates renal and splanchnic Q and VC in exercising rats. Rats were fed a diet of 5% lipids by weight, of which 20% was DHA and 30% EPA (PUFA group, n = 9), or 5% safflower oil (SO group, n = 8) for 6 wk. Heart rate (HR), blood pressure (MAP), and hind-limb, renal, and splanchnic Q were measured at rest and during moderate treadmill running. MAP, HR, and renal and splanchnic Q and VC were similar between the 2 groups at rest and during exercise. In the PUFA group, Q (158 ± 27 vs. 128 ± 28 ml × min⁻¹ × 100 g⁻¹) and VC (1.16 ± 0.21 vs. 0.92 ± 0.23 ml × min⁻¹ × 100 g⁻¹ × mm Hg⁻¹) were greater in the exercising hind-limb muscle. Q and VC were also higher in 8 of 28 and 11 of 28 muscles and muscle parts, respectively. These increases were positively correlated to the percent sum of Types I and IIa fibers. Results suggest that DHA+EPA (a) enhances Q and VC in active skeletal muscle (especially Type I and IIa fibers) and that the increase in Q is due to an increase in cardiac output secondary to increases in VC and (b) has no apparent influence on vasoconstriction in renal and splanchnic tissue.

Dietary fish oil reduces skeletal muscle oxygen consumption, provides fatigue resistance and improves contractile recovery in the rat in vivo hindlimb

Dietary fish oil modulates skeletal muscle membrane fatty acid composition. Similar changes in heart membrane composition modulate myocardial oxygen consumption and enhance mechanical performance. The rat in vivo autologous perfused hindlimb was used to investigate the influence of membrane composition on skeletal muscle function. Male Wistar rats were fed either saturated fat (SF), n-6 PUFA (linoleic acid rich) or n-3 PUFA (fish oil) diets for 8 weeks. Hindlimb skeletal muscle perfused using the animal's own blood was stimulated via the sciatic nerve (1 Hz, 6-12 V, 0·05 ms) to contract in repeated 10 min bouts. The n-3 PUFA diet markedly increased 22 : 6n-3 DHA, total n-3 PUFA and decreased the n-6:n-3 PUFA ratio (P < 0·05) in red and white skeletal muscle membranes. There was no difference in initial twitch tension but the n-3 PUFA group maintained greater twitch tension within all contraction bouts and recovered better during rest to produce greater twitch tension throughout the final contraction bout (P < 0·05). Hindlimb oxygen consumption during contraction was significantly lower in the n-3 PUFA group compared with the SF group, producing a significantly higher O₂ efficiency index compared with both SF and n-6 PUFA groups (P < 0·05). Resting oxygen consumption was increased in recovery in the SF group (P < 0·05) but did not change in the n-3 PUFA group. Membrane incorporation of n-3 PUFA DHA following fish oil feeding was associated with increased efficiency of muscle O₂ consumption and promoted resistance to muscle fatigue.

Betaine Protects Chronic Alcohol and ω‐3 PUFA‐Mediated Down‐Regulations of PON1 Gene, Serum PON1 and Homocysteine Thiolactonase Activities With Restoration of Liver GSH

Paraoxonase (PON1) is an antioxidant enzyme that prevents LDL oxidation as well as detoxifies homocysteine thiolactone (HCTL), both of which can cause atherosclerosis. Chronic alcohol (ETOH) and high omega-3 polyunsaturated fatty acids (omega-3 PUFA) consumption may affect PON1 status presumably via reactive oxygen species by depleting liver glutathione (GSH), whereas betaine may counter their effects. Therefore, we investigated the influence of ETOH, omega-3 PUFA, and betaine on liver GSH, PON1 expression, lipid score, as well as serum PON1 and HCTLase activities. Experimental rats belonging to various dietary groups were pair-fed with Lieber-DeCarli low (2.8% the dietary calories as omega3-fatty acids) and high (13.8% the dietary calories as omega3-fatty acids) menhaden fish alcohol-liquid diets with and without betaine (10 g/l diet) for 8 weeks after which liver PON1 mRNA, GSH, lipid score, and serum PON1, HCTLase, and ALT activities were measured. High omega-3 PUFA decreased liver PON1 mRNA expression, serum PON1, and HCTLase activity by 23% (p < 0.01), 20% (p < 0.05), and 28% (p < 0.05), respectively compared to the low omega-3 PUFA group. ETOH decreased PON1 mRNA expression by 25 and 30% (p < 0.01) with concomitant 27% (p < 0.05) and 38% (p < 0.01), decrease in liver GSH levels in low and high omega-3 PUFA groups, respectively. Correspondingly, serum PON1 activity decreased by 23% (p < 0.05) and 58% (p < 0.01) while serum HCTLase activity decreased by 25% (p < 0.05) and 59% (p < 0.01) in the low and high omega-3 PUFA ETOH groups, respectively. Betaine restored liver PON1 mRNA expressions in low and high omega-3 PUFA ETOH groups with parallel restorations of PON1 activity and liver GSH. Concomitantly, betaine reduced hepatosteatosis accompanied by alleviation of liver injury caused by chronic alcohol and high omega-3 PUFA. Based on these results, we conclude that dietary betaine not only atheroprotective by restoring liver GSH that quenches free radicals, but also may alleviate liver injury by reducing hepatosteatosis.

Omega-3 Fatty Acid Supplementation Does Not Reduce Risk of Atrial Fibrillation After Coronary Artery Bypass Surgery

Background— Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported to reduce the risk of sudden cardiac death presumed to be due to fatal ventricular arrhythmias, but their effect on atrial arrhythmias is unclear. Methods and Results— Patients (n=108) undergoing coronary artery bypass graft surgery were randomly assigned to receive 2 g/d n-3 PUFA or placebo (olive oil) for at least 5 days before surgery (median, 16 days; range, 12 to 21 days). Phospholipid n-3 PUFA were measured in serum at study entry and at surgery and in right atrial appendage tissue at surgery. Echocardiography was used to assess left ventricular function and left atrial dimensions. Postoperative continuous ECG monitoring (Lifecard CF) for 5 days or until discharge, if earlier, was performed with a daily 12-lead ECG and clinical review if patients remained in the hospital beyond 5 days. Lifecard recordings were analyzed for episodes of atrial fibrillation (AF) ≥30 seconds (primary outcome). Clinical AF, AF burden (% time in AF), hospital stay, and intensive care/high dependency care stay were measured as secondary outcomes. One hundred three patients completed the study (51 in the placebo group and 52 in the n-3 PUFA group). There were no clinically relevant differences in baseline characteristics between groups. n-3 PUFA levels were higher in serum and right atrial tissue in the active treatment group. There was no significant difference between groups in the primary outcome of AF (95% confidence interval [CI], −6% to 30%, P =0.28) in any of the secondary outcomes or in AF-free survival. Conclusions— Omega-3 PUFA do not reduce the risk of AF after coronary artery bypass graft surgery. Clinical Trial Registration— www.ukcrn.org.uk. Identifier: 4437.

N-3 Fatty acids prevent whereas trans-fatty acids induce vascular inflammation and sudden cardiac death

n-3 PUFA have well-recognised cardio-beneficial effects. In contrast, premature coronary deaths are associated with consumption of high levels of trans-fatty acids (TFA). The present study determined the effects of n-3 PUFA and TFA on sudden cardiac death and vascular inflammation. A rat coronary ligation model was used to study the effect of fatty acids on sudden cardiac death, whereas a mouse femoral artery ligation model was used to study compensatory vascular remodelling. Human aortic endothelial cells (HAEC) were utilised for the in vitro studies to investigate expression of inflammatory molecules. Feeding animals an n-3 PUFA-enriched diet caused a sevenfold increase in plasma n-3 PUFA compared with that of the TFA-fed group, whereas a TFA-enriched diet caused a 2.5-fold increase in plasma TFA compared with the n-3 PUFA group. Animals on a TFA diet had a lower survival rate due to sudden cardiac death and exhibited variable degrees of aortic atherosclerotic lesions. Animals on a TFA diet had diminished hindlimb collateral growth, whereas animals on the n-3 PUFA diet exhibited extensive collateral growth about ligated regions. HAEC treated with TFA (trans-18 : 2) showed significantly increased expression of intracellular adhesion molecule-1 and nitrosylation of cellular proteins than those treated with DHA (n-3 PUFA, 22 : 6). The in vivo study demonstrates that, in contrast to TFA, n-3 PUFA improve animal survival after myocardial infarction, prevent development of atherosclerotic lesions and stimulate compensatory vascular remodelling. The in vitro study demonstrates that TFA induce, while n-3 PUFA prevent, vascular inflammation.

N-3 Polyunsaturated Fatty Acids Do Not Alter Immune and Inflammation Measures in Endurance Athletes

The purpose of this study was to test the influence of 2.4 g/d fish oil n-3 polyunsaturated fatty acids (n-3 PUFA) over 6 wk on exercise performance, inflammation, and immune measures in 23 trained cyclists before and after a 3-d period of intense exercise. Participants were randomized to n-3 PUFA (n = 11; 2,000 mg eicosapentaenoic acid [EPA], 400 mg docosahexaenoic acid [DHA]) or placebo (n = 12) groups. They ingested supplements under double-blind methods for 6 wk before and during a 3-d period in which they cycled for 3 hr/d at ~57% W(max) with 10-km time trials inserted during the final 15 min of each 3-hr bout. Blood and saliva samples were collected before and after the 6-wk supplementation period, immediately after the 3-hr exercise bout on the third day, and 14 hr postexercise and analyzed for various immune-function and inflammation parameters. Supplementation with n-3 PUFA resulted in a significant increase in plasma EPA and DHA but had no effect on 10-km time-trial performance; preexercise outcome measures; exercise-induced increases in plasma cytokines, myeloperoxidase, blood total leukocytes, serum C-reactive protein, and creatine kinase; or the decrease in the salivary IgA:protein ratio. In conclusion, 6 wk supplementation with a large daily dose of n-3 PUFAs increased plasma EPA and DHA but had no effect on exercise performance or in countering measures of inflammation and immunity before or after a 3-d period of 9 hr of heavy exertion.

Short term effects of energy restriction and dietary fat sub-type on weight loss and disease risk factors

Background and aims Decreasing energy intake relative to energy expenditure is the indisputable tenet of weight loss. In addition to caloric restriction modification of the type of dietary fat may provide further benefits. The aim of the present study was to examine the effect of energy restriction alone and with dietary fat modification on weight loss and adiposity, as well as on risk factors for obesity related disease. Methods and results One-hundred and fifty overweight men and women were randomized into a 3 month controlled trial with four low fat (30% energy) dietary arms: (1) isocaloric (LF); (2) isocaloric with 10% polyunsaturated fatty acids (LF-PUFA); (3) low calorie (LF-LC) (−2 MJ); (4) low calorie with 10% PUFA (LF-PUFA-LC). Primary outcomes were changes in body weight and body fat and secondary outcomes were changes in fasting levels of leptin, insulin, glucose, lipids and erythrocyte fatty acids. Changes in dietary intake were assessed using 3 day food records. One-hundred and twenty-two participants entered the study and 95 completed the study. All groups lost weight and body fat ( P < 0.0001 time effect for both), but the LC groups lost more weight ( P = 0.026 for diet effect). All groups reduced total cholesterol levels ( P < 0.0001 time effect and P = 0.017 intervention effect), but the LC and PUFA groups were better at reducing triacylglycerol levels ( P = 0.056 diet effect). HDL increased with LF-LC and LF-PUFA but not with LF-PUFA-LC (0.042 diet effect). The LF and LF-LC groups reported greater dietary fat reductions than the two PUFA groups ( P = 0.043). Conclusion Energy restriction has the most potent effect on weight loss and lipids, but fat modification is also beneficial when energy restriction is more modest.

T1610 Follow-Up Study of the Progression of Non-Alcoholic Steatohepatitis (NASH) in An Inducible Nitric Oxide Synthase (iNOS)-Knockout Mouse Model

A S L D A b st ra ct s PUFA group. Conclusions: An 8 week course of omega-3 PUFA did not result in a significant decrease in the degree of hepatic steatosis as determined by MRS. However subjects in the PUFA group also had an increased body fat mass which may have contributed to their lack of decreased steatosis. PUFA therapy was associatedwith an improvement in restingmetabolic rate and insulin response. Further studies are needed to the mechanism for this.

T1020 Dysfunctional VLDL Synthesis and Release Is a Key Factor in Non-Alcoholic Steatohepatitis(NASH) Progression

A S L D A b st ra ct s PUFA group. Conclusions: An 8 week course of omega-3 PUFA did not result in a significant decrease in the degree of hepatic steatosis as determined by MRS. However subjects in the PUFA group also had an increased body fat mass which may have contributed to their lack of decreased steatosis. PUFA therapy was associatedwith an improvement in restingmetabolic rate and insulin response. Further studies are needed to the mechanism for this.

Dietary supplementation with arachidonic acid but not eicosapentaenoic or docosahexaenoic acids alter lipids metabolism in C57BL/6J mice

In order to investigate the effects of dietary supplementation rich in omega 3 and omega 6 fatty acids, we set up an experiment of twenty four C57BL/6J male mice segregated into 3 groups: normal diet (ND), omega 3 polyunsaturated fatty acid (n-3 PUFA,) and omega 6 (n-6 PUFA). At the end of the experiment that lasted for 1 month, food consumption of ND and n-3 PUFA were similar while it decreased in n-6 PUFA group. Total cholesterol, triglycerides, free fatty acids, and phospholipids profiles were increased in n-6 PUFA. LDL decreased in n-3 PUFA while increased in n-6 PUFA fed mice comparing to control group. On the other hand, there was no difference between treatments in HDL and glucose levels. Expression of leptin (ob) gene transcripts in epididymal fat were significantly elevated in n-6 PUFA mice compared to ND and n-3 PUFA groups while hypothalamic ob receptor A (obRa) mRNA did not changed in response to diet regimes. Transmission and scanning electron microscopy showed different degrees in fatty changes in the liver of both PUFA groups including lipid droplet infiltration and Ito cells with over accumulated lipids. In conclusion, under PUFA dietary supplementation, the hyperlipidemic status and elevated ob expression of n-6 PUFA but not n-3 PUFA fed mice suggests altered lipid metabolism between PUFA groups and/or different endocrine involvement. Moreover, the coincidently structural changes observed in liver of this group direct us to call for further studies to investigate the anti-obesity effect and safety of these PUFA under high supplementation condition.