89 Background: The health effects of long chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) 90 are partly mediated by their oxidized metabolites, i.e. eicosanoids and other oxylipins. Some 91 intervention studies demonstrate that eicosapentaenoic acid (EPA) and docosahexaenoic acid 92 (DHA) increase systemic concentrations n-3 PUFA-derived oxylipins and moderately decrease 93 arachidonic acid-derived oxylipins. There is no information on the dose-response of oxylipin 94 concentrations following n-3 PUFA intake. 95 Objective: The objective was to quantify oxylipins in human plasma samples from an 96 intervention study in which participants were randomly assigned to different daily intakes of EPA 97 and DHA for 12 months. Design: Healthy adult men and women with low habitual fish consumption ( n = 121) were 99 randomized to receive capsules providing doses of n-3 PUFAs reflecting three patterns of 100 consumption of oily fish (i.e. 1, 2, or 4 portions/week with 3.27 g EPA+DHA (1:1.2, ( wt:wt )) per 101 portion) or placebo. Oxylipins were quantified in plasma after 3 and 12 months. Relative and 102 absolute changes of individual oxylipins were correlated with the dose and the content of EPA 103 and DHA in blood lipid pools. Results: 73 oxylipins, mostly hydroxy-, dihydroxy-, and epoxy-PUFAs were quantified in the 105 plasma samples. After 3 and 12 months a linear increase with dose was observed for all EPA- 106 and DHA-derived oxylipins. Cytochrome-P450-derived anti-inflammatory and cardio-protective 107 epoxy-PUFAs increased linearly with n-3 PUFA dose and showed low inter-individual variance 108 (r 2 >0.95). Similarly, 5, 12- and 15-lipoxygenase derived hydroxy-PUFAs as well as those formed 109 autoxidatively increased linearly. These include the precursors of so-called specialized pro- resolving mediators (SPMs), e.g. 17-hydroxy-DHA and 18-hydroxy-EPA. Conclusions: Plasma concentrations of biologically active oxylipins derived from n-3 PUFAs, 112 including epoxy-PUFAs and SPM-precursors, increase linearly with elevated intake of EPA and 113 DHA. Inter-individual differences in resulting plasma concentrations are low. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as of oxylipins follow a similar dose-response is not clear. However, because of the high biological activity of n-3 PUFA-derived oxylipins 2, 4), how these relate to intake and is fundamental n-3 This study was primarily designed to elucidate the effect of different doses of EPA and DHA on their incorporation into blood and tissue pools in healthy adult humans with low habitual consumption of fatty fish, as reported elsewhere (21). The current research extends this to investigate the dose-response effect of EPA+DHA intake on the plasma oxylipin pattern. Four dose groups were selected to reflect EPA+DHA intake on a Western diet poor in EPA+DHA (no additional EPA+DHA) and that reflecting intake of one, two or four servings of fatty cold water fish per week. Effects on oxylipins were quantified in plasma after 3 and 12 months of supplementation utilizing a state of the art comprehensive targeted oxylipin metabolomics 158 platform.

An abstract is not available for this content. As you have access to this content, full HTML content is provided on this page. A PDF of this content is also available in through the ‘Save PDF’ action button.

O. Mugridge, L. M. Browning, M. Chatfield, A. K. Dixon, A. M. Prentice and S. A. Jebb MRC Human Nutrition Research, Fulbourn Road, Cambridge CB1 9NL, UK, Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK and MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

Incorporation of n–3 polyunsaturated fatty acids into human peripheral blood mononuclear cells according to intakes representing consumption of oily fish one, two or four times per week over 12 months - Volume 69 Issue OCE3

(2010). Acute effects of hyperglycaemia on asymmetric dimethylarginine (ADMA), adiponectin and inflammatory markers (IL-6, hs-CRP) in overweight and obese women with metabolic syndrome. British Journal of Biomedical Science: Vol. 67, No. 4, pp. 216-218.

Background: Inflammation is strongly related to obesity and the risk of cardiovascular disease (CVD). The metabolic benefits of long chain (LC) n-3 polyunsaturated fatty acid (PUFA) may be attributable to its anti-inflammatory properties.Objective: To investigate whether an individual's habitual inflammatory status influences the impact of a LC n-3 PUFA intervention on CVD risk.Design: The study was a randomized crossover design. Subjects received LC n-3 PUFA capsules or a placebo for 12 weeks, with 4-week washout between phases. Thirty women, in the top and bottom tertiles of baseline sialic acid concentration, formed raised inflammatory status (top, n = 12) and reference (bottom, n = 18) groups. Baseline data were analysed using one-way ANOVA, differences between treatment phases were calculated at each timepoint and analysed using a random effects model.Results: At baseline, the raised inflammatory status group had significantly higher body mass index and area under the curve (AUC) insulin than the reference group. With LC n-3 PUFA supplementation, both groups showed significantly higher plasma eicosapentaenoic acid and docosahexaenoic acid at 4 and 12 weeks (p < 0.001), and lower triacylglycerols (4 weeks p < 0.01 and 12 weeks p < 0.05). The difference in AUC insulin between the two treatment phases at 12 weeks was significantly greater in the raised inflammatory status group compared to the reference group (p < 0.05). Inflammatory markers were significantly lower after 12 weeks LC n-3 PUFA supplementation compared to baseline (C-reactive protein p < 0.05 and interleukin-6 p < 0.01), but there was no significant group effect.Conclusions: Habitual inflammatory status influences the impact of LC n-3 PUFA supplementation, but it is not clear whether the effect of LC n-3 PUFA on AUC insulin is mediated through inflammatory mechanisms.

Background: Obesity, inflammation, insulin resistance and cardiovascular disease (CVD) risk are inter-related. Both weight-loss and long-chain n -3 polyunsaturated fatty acids (LC n -3 PUFA) are independently known to reduce metabolic risk, but the combined effects are unclear. Objective: This study examines whether addition of LC n -3 PUFA to a low fat/high carbohydrate weight-loss programme results in greater improvements in inflammation, insulin sensitivity and CVD risk, than weight-loss alone. Design: One hundred and sixteen overweight insulin-resistant women entered a 24-week randomised intervention study. Thirty-nine women were randomised to a weight-loss programme, with LC n -3 PUFA (WLFO), 38 to a weight-loss programme with placebo oil (WLPO), and 39 to receive placebo oil, with no weight-loss programme (control). Results: Ninety-three women completed the study (35 WLFO, 32 WLPO and 26 control), with significant weight-loss in WLFO (10.8±1.0%) and WLPO (12.4±1.0%) compared to the control group ( P <0.0001). The WLFO, but not WLPO or control group, showed significant increases in adipose tissue LC n -3 PUFA (0.34±0.20 vs 0.17±0.10 and 0.16±0.10 %DHA, P <0.0001). Weight-loss showed significant improvements in insulin sensitivity ( P <0.001), lipid profile (triglycerides P <0.05) and inflammation (sialic acid P <0.05). Time*group effects showed significant decreases in triglycerides ( P <0.05) and increases in adiponectin ( P <0.01) with LC n -3 PUFA, in the WLFO vs WLPO groups. Conclusions: Weight-loss improved risk factors associated with CVD, with some additional benefits of LC n -3 PUFA on triglycerides and adiponectin. Given the current low dietary intake of LC n -3 PUFA, greater attention should be given to increase these fatty acids in the treatment of obesity.

To understand the role of inflammation in chronic disease it is important to have a reliable measure of habitual inflammatory status. A number of acute-phase response markers have been used as measures of inflammatory status, but the ability of a single measure to appropriately reflect habitual inflammatory status has not been assessed. This study compares the ability of different inflammatory markers to characterize habitual inflammatory status in overweight women. A single fasting blood sample was taken from 86 overweight women (mean body mass index [BMI], 35.2 kg/m2; range, 26.2 to 47.6 kg/m2) and a number of inflammatory markers (both acute-phase response markers and cytokines) were measured. A randomly selected subpopulation of 15 women attended on 2 further occasions for further blood samples. Using the subpopulation, discrimination ratios (DRs) were calculated for each inflammatory marker to assess the within-subject variability. The DRs were then used to determine the relationship between these markers, adjusted for within-subject variability, in the whole population. In this highly controlled experimental environment, interleukin-6 (IL-6), with a DR of 3.71, was the cytokine with the greatest ability to discriminate between subjects, suggesting that it is best able to characterize habitual inflammatory status. Sialic acid was the acute-phase response marker with the highest DR (3.16), and showed stronger correlations with other inflammatory markers, including C-reactive protein (CRP), than IL-6. This study suggests that use of some inflammatory markers, such as CRP, with large within-individual variability, will underestimate the relationship between inflammation and disease, and thus relationships between inflammation and chronic disease may be stronger than previously appreciated. Future studies should consider IL-6 or sialic acid to provide a more robust measure of inflammatory status.

AIMS: C-reactive protein (CRP) is a predictor of many diseases including type II diabetes and cardiovascular disease. Fewer studies have similarly shown sialic acid (SA) to be a predictor of obesity-related diseases, but importantly SA shows less intra-individual variability than CRP and acts as an integrated marker of the activity of a number of acute-phase proteins. This study examines the association between both CRP and SA with individual and combined features of the metabolic syndrome. SUBJECTS: In all, 257 women with a body mass index (BMI) ranging from 25.1 to 54.5 kg/m 2 (geometric mean 33.1±5.8kg/m 2 ) and aged 19–71 y (mean 45.6±12.1 y) were studied. Subjects had no symptoms of intercurrent infection, known diabetes, treated dyslipidaemia, a chronic inflammatory condition, liver disease or malignancy. RESULTS: Linear regression demonstrates that both CRP and SA were positively associated with weight, BMI, insulin resistance, dyslipidaemia and hypertension. There was a highly significant ( P <0.0001) positive association of both SA and CRP with none, one, two, three or four features of the metabolic syndrome. For a 1 s.d. (4.0 mg/l) increase in CRP, there was a significant increased risk when comparing the odds of having metabolic syndrome (defined as three or more individual features) compared with the remainder of the population (odds ratio=1.7, P <0.0001), but this was not significant after adjustment for BMI. However, for a 1 s.d. (0.34 mmol/l) increase in SA, the odds of having metabolic syndrome compared with those without metabolic syndrome was 2.5 ( P <0.0001), and persisted after additional adjustment for BMI (adjusted odds ratio=1.9, P <0.0001). CONCLUSIONS: While SA and CRP are both univariately associated with individual features of the metabolic syndrome, SA, but not CRP, is significantly associated with the metabolic syndrome, independent of BMI. We conclude that SA identifies a subgroup of overweight individuals with an inflammatory phenotype, who are at the greatest risk of metabolic syndrome.

Obese individuals are at increased risk from a range of metabolic diseases, including insulin resistance, dyslipidaemia and hypertension. Adipose tissue is an important endocrine organ, secreting a range of inflammatory mediators, including tumour necrosis factor a and interleukin 6. Circulating concentrations of these cytokines are increased in obesity and may contribute to the pathogenesis of metabolic diseases. The present review considers the evidence linking inflammation and obesity-related disease. The data show that an inflammatory phenotype, measured by serum sialic acid concentration, identifies individuals with insulin resistance, dyslipidaemia and hypertension. Serum sialic acid concentration increases progressively in obese individuals with none, one or multiple features of the metabolic syndrome, independent of BMI. Supplementation with long-chain n-3 polyunsaturated fatty acids has shown anti-inflammatory effects in studies of both healthy populations and in models of chronic inflammatory conditions. The effect on insulin sensitivity has been varied, with both positive and negative effects. This variability may relate to the metabolic characteristics of the study population; individuals with high background inflammation may derive greater benefits from n-3 polyunsaturated fatty acid supplements, suggesting a possible interaction between diet and phenotype. Future research is needed to fully evaluate the role of anti-inflammatory strategies in the dietary management of obesity.