Acids In Plasma Phospholipids Research Articles

The FADS1 Genotype Modifies Metabolic Responses to the Linoleic Acid and Alpha-linolenic Acid Containing Plant Oils-Genotype Based Randomized Trial FADSDIET2.

The article investigates the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha-linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and of markers of low-grade inflammation and glucose-insulin homeostasis. One-hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8-week intervention with either LA- or ALA-enriched diet (13 E% PUFA). The source of LA and ALA are 30-50mL of sunflower oil (SFO, 62-63% LA) and Camelina sativa oil (CSO, 30- are randomized to an 35% ALA), respectively. In the SFO arm, there is a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p < 0.001), disposition index (DI30 ) (p = 0.039), and for serum high-sensitive c-reactive protein (hs-CRP, p = 0.029) after excluding the participants with hs-CRP concentration of >10mg L-1 and users of statins or anti-inflammatory therapy. In the CSO arm, there are significant genotype x diet interactions for n-3 polyunsaturated fatty acids, but not for the clinical characteristics. The FADS1 genotype modifies the response to high PUFA diets, especially to high-LA diet. These findings suggest that approaches considering FADS variation may be useful in personalized dietary counseling.

Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?

Dietary polyphenols promote cardiometabolic health and are linked with long-chain polyunsaturated fatty acids in plasma phospholipids (LC-PUFA). The FADS2 polymorphisms are associated with LC-PUFA metabolism and overweight/obesity. This 4-week study examined the link between polyphenol intake, FADS2 variants (rs174593, rs174616, rs174576) and obesity in 62 overweight adults (BMI ≥ 25), allocated to consume 100 mL daily of either: Aronia juice, a rich source of polyphenols, with 1177.11 mg polyphenols (expressed as gallic acid equivalents)/100 mL (AJ, n = 22), Aronia juice with 294.28 mg polyphenols/100 mL (MJ, n = 20), or nutritionally matched polyphenol-lacking placebo as a control (PLB, n = 20). We analyzed LC-PUFA (% of total pool) by gas chromatography and FADS2 variants by real-time PCR. Four-week changes in LC-PUFA, BMI, and body weight were included in statistical models, controlling for gender and PUFA intake. Only upon AJ and MJ, the presence of FADS2 variant alleles affected changes in linoleic, arachidonic, and eicosapentaenoic acid (EPA). Upon MJ treatment, changes in EPA were inversely linked with changes in BMI (β= −0.73, p = 0.029) and weight gain (β= −2.17, p = 0.024). Only in subjects drinking AJ, the link between changes in EPA and anthropometric indices was modified by the rs174576 variant allele. Our results indicate the interaction between FADS2, fatty acid metabolism, and polyphenol intake in overweight subjects.

A rapid method for the separation of the phospholipids from the neutral lipids in plasma

The blood fraction most commonly used for the assessment of fatty acid status is the plasma or serum phospholipids, since these provide a measure of long term dietary intake. However, conventional assays of fatty acid status in human plasma and serum require labour intensive, multi-step approaches, which are impractical for high-throughput analyses. This study reports a system capable of selectively separating plasma phospholipids from other lipid classes in just a few minutes. We demonstrate that compositional analysis of the fatty acids in plasma phospholipids using our plasma spot method resulted in greater than 97% of neutral lipid standards had been eluted from the paper, whereas more than 96% of the PC remained on the paper. These results were almost identical to conventional methods involving liquid/liquid extraction and thin layer chromatography separation. Evaluation of our plasma spot fractionation and assay using plasma from 110 human subjects (75 males, 35 females), provides confirmation of significant correlations between the fatty acid measures and those obtained from conventional measures for all fatty acids (r > 0.97, P<0.0001), including the omega (n)-6 (r = 0.988, P<0.0001) and n-3 long chain polyunsaturated fatty acids (r = 0.997, P<0.0001). These results establish our newly developed plasma spot separation technique as a rapid and reliable method for the assessment of plasma phospholipid fatty acid composition.

Long-Chain Polyunsaturated Fatty Acids Are Associated with Blood Pressure and Hypertension over 10-Years in Black South African Adults Undergoing Nutritional Transition

Nutritional transition in Africa is linked with increased blood pressure (BP). We examined 10-year fatty acid status and longitudinal associations between individual long-chain polyunsaturated fatty acids (PUFA), BP and status of hypertension (≥140/90 mmHg and/or medication use) in black South Africans. We included 300 adults (>30 years) participating in the Prospective Urban Rural Epidemiology study, and analysed data from three consecutive examinations (2005, 2010 and 2015 study years). Fatty acids in plasma phospholipids were analysed by gas chromatography-mass spectrometry. We applied sequential linear mixed models for continuous outcomes and generalized mixed models for the hypertension outcome, in the complete sample and separately in urban and rural subjects. Mean baseline systolic/diastolic BP was 137/89 mmHg. Ten-year hypertension status increased among rural (48.6% to 68.6%, p = 0.001) and tended to decrease among urban subjects (67.5% to 61.9%, p = 0.253). Regardless of urbanisation, n-6 PUFA increased and eicosapentaenoic acid (EPA, C20:5 n-3) decreased over the 10-years. Subjects in the highest tertile of arachidonic acid (C20:4 n-6) had 3.81 mmHg lower systolic (95% confidence interval (CI): −7.07, −0.54) and 3.82 mmHg lower diastolic BP (DBP) (95% CI: −5.70, −1.95) compared to the reference tertile, irrespective of lifestyle and clinical confounders. Similarly, osbond acid (C22:5 n-6) was inversely associated with DBP. Over the 10-years, subjects in the highest EPA tertile presented with +2.92 and +1.94 mmHg higher SBP and DBP, respectively, and with 1.46 higher odds of being hypertensive. In black South African adults, individual plasma n-6 PUFA were inversely associated with BP, whereas EPA was adversely associated with hypertension, supporting implementation of dietary fat quality in national cardiovascular primary prevention strategies.

Camelina sativa Oil, Fatty Fish, and Lean Fish Do Not Markedly Affect Urinary Prostanoids in Subjects with Impaired Glucose Metabolism.

Dietary fatty acids are suggested to affect oxidative stress; however, results from interventions have been inconclusive. The aim was to examine if fatty fish, lean fish, and Camelina sativa oil (CSO) affect the urinary prostanoid levels in subjects with impaired glucose metabolism. Altogether 79 participants aged 43-72 years completed a randomized controlled study lasting 12 weeks. There were four parallel groups, fatty fish, lean fish (four fish meals/week in both), CSO providing 10 g/day alpha-linolenic acid (ALA), and control diet with limited fish and ALA containing oil consumption. Urinary prostanoids (prostaglandin F2α , 5-F2t -isoprostanes and 15-F2t -isoprostane metabolites, isofuran, 8-F3t -isoprostanes, and 4-(RS)-4-F4t -neuroprostane) of 72 participants (age: mean (±SD) 58.9 ± 6.5 years; body mass index: 29.3 ± 2.5 kg/m2 ) collected over 12-h were measured using liquid chromatography tandem-mass spectrometry. Plasma phospholipid fatty acids were determined using gas chromatography. Our study showed that the proportion of ALA in plasma phospholipids increased in the CSO group (overall difference among the groups p-value <0.001). In the fatty fish group, proportions of eicosapentaenoic and docosahexaenoic acids increased (overall p-value <0.001 for both). Prostaglandin F2α was higher in the CSO group than in the control group (p < 0.05), however, there were no other significant changes in urinary excretion of other prostanoids among the study groups. At baseline, arachidonic acid in plasma phospholipids was positively (r = 0.247, p < 0.05) and ALA negatively (r = -0.326, p < 0.05) associated with urinary total isoprostanes. In conclusion, CSO, fatty fish, and lean fish consumption do not cause major changes in oxidative stress markers in subjects with impaired glucose tolerance.

BLTR1 and CD36 Expressing Microvesicles in Atherosclerotic Patients and Healthy Individuals.

Aims: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalization of oxLDL leads to activation of monocytes and subsequent release of microvesicles (MVs) derived from monocytes (MMVs). Further, pro-inflammatory leukotriene B4 (LTB4) derived from arachidonic acid promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes (CD14+ MVs) on the one hand, and arachidonic acid and eicosapentaenoic acid contents in different compartments including atherosclerotic plaques, plasma, and granulocytes on the other.Methods and Results: Samples from patients with femoral atherosclerosis and healthy controls were analyzed on an Apogee A60 Micro-PLUS flow cytometer. Platelet-poor plasma was labeled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE, and anti-BLTR1-AF700. Eicosapentaenoic acid and arachidonic acid content in different compartments in patients were analyzed using gas chromatography. Compared to controls, patients had lower levels of BLTR1+ MVs (p = 0.007), CD14+BLTR1+ MVs (p = 0.007), and CD14+BLTR1+CD36+ MVs (p = 0.001). Further, in patients CD14+ MVs and CD14+CD36+ MVs correlated inversely with arachidonic acid in granulocytes (r = −0.302, p = 0.039 and r = −0.322, p = 0.028, respectively). Moreover, CD14+CD36+ MVs correlated inversely with arachidonic acid in plasma phospholipids in patients (r = −0.315, p = 0.029), and positively with triglyceride in both patients (r = 0.33, p = 0.019) and controls (r = 0.46, p = 0.022).Conclusion: This is the first study of its kind and thus the results are explorative and only indicative. BLTR1+ MVs and CD14+CD36+ MVs has potential as markers of atherosclerosis pathophysiology, but this needs further investigation.

Low levels of linoleic acid and α-linolenic acid and high levels of arachidonic acid in plasma phospholipids are associated with hypertension.

Dietary fat is an important determinant in the development and progression of high blood pressure (BP), a major risk factor for cardiovascular diseases and mortality. The aim of the present study was to determine the association between plasma phospholipid fatty acids and hypertension in Japanese men. The plasma level of linoleic acid (LA) in the subjects with hypertension (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg) was identified to be significantly higher than that in the healthy controls. Following adjustment for age, body mass index, physical activity, smoking status, alcohol consumption, salt intake, and serum levels of glucose and hemoglobin A1c, higher plasma levels of LA and α-linolenic acid (ALA), and lower levels of arachidonic acid (AA) were significantly associated with a lower prevalence of hypertension. The odds ratio (OR) for the highest quartile (Q4) versus the lowest quartile (Q1) of LA was 0.17 (P=0.003), the OR for Q4 versus Q1 of ALA was 0.26 (P=0.042) and the OR for Q4 versus Q1 of AA was 2.04 (P=0.047). These results indicate that elevated levels of LA and ALA, and reduced levels of AA in the plasma prevent hypertension.

Inflammatory markers in dependence on the plasma concentration of 37 fatty acids after the coronary stent implantation

Using the regression model building the relationships between the concentration of 37 fatty acids of blood plasma phospholipids of 41 patients with coronary artery disease after coronary stent implantation, the inflammatory response and oxidative stress markers were estimated. The dynamics of the inflammatory response and the oxidative stress was indicated by measuring plasma concentrations of highly sensitive C-reactive protein, interleukin-6, serum amyloid A and malondialdehyde before, 24h after stent implantation. The multiple linear regression analysis was preceded by an exploratory data analysis, principal component analysis, factor analysis and cluster analysis, which proved a hidden internal relation of 37 fatty acids. The concentration of cerotic acid (C26:0) has been positively associated with an increase of malondialdehyde concentration after stent implantation, while the concentrations of tetracosatetraenoic (C24:4 N6) and nonadecanoic (C19:0) acids were associated with decrease of lipoperoxidation. The increase of interleukin-6 during the 24h after implantation was associated with higher levels of pentadecanoic acid (C15:0) and lower levels of α-linolenic acid (C18:3 N3). Regression models found several significant fatty acids at which the strength of the parameter β for each fatty acid on selected markers of C-reactive protein, malondialdehyde, interleukin-6 and serum amyloid A was estimated. Parameter β testifies to the power of the positive or negative relationship of the fatty acid concentration on the concentration of selected markers. The influencing effect of the cerotic acid (C26:0) concentration in plasma phospholipids exhibiting parameter β=140.4 is, for example, 3.5 times higher than this effect of n-3 tetracosapentaenoic acid (C24:5 N3) with β=40.0. Composition of fatty acids in plasma phospholipids shows spectrum of fatty acids available for intercellular communication in systemic inflammatory response of organism and should affect clinical outcomes.

Associations between Proportion of Plasma Phospholipid Fatty Acids, Depressive Symptoms and Major Depressive Disorder. Cross-Sectional Analyses from the AGES Reykjavik Study.

Deficits in n-3 fatty acids may be associated with depression. However, data are scarce from older adults who are at greater risk of poor dietary intake and of developing depression. To investigate proportion of plasma phospholipid fatty acids with respect to depressive symptoms and major depressive disorder in community dwelling older adults. Cross-sectional analyses of 1571 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study aged 67-93 years. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15). Major depressive disorder was assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria using the Mini-International Neuropsychiatric Interview (MINI). Depressive symptoms were observed in 195 (12.4%) subjects and there were 27 (1.7%) cases of major depressive disorder. Participants with depressive symptoms were less educated, more likely to be smokers, less physically active and consumed cod liver oil less frequently. Difference in GDS-15 scores by tertiles of n-3 fatty acid proportion was not significant. Proportion of long chain n-3 fatty acids (Eicosapentaenoic- + Docosahexaenoic acid) were inversely related to major depressive disorder, (tertile 2 vs. tertile 1) OR: 0.31 (95% CI: 0.11, 0.86); tertile 3 vs. tertile 1, OR: 0.45 (95% CI: 0.17, 1.21). In our cross sectional analyses low proportions of long chain n-3 fatty acids in plasma phospholipids appear to be associated with increased risk of major depressive disorder. However, the results from this study warrant further investigation in prospective setting with sufficiently long follow-up.

Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study

SummaryBackgroundConflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants.MethodsThe EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis.FindingsSFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09–1·22], palmitic acid 1·26 [1·15–1·37], and stearic acid 1·06 [1·00–1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73–0·85] for pentadecanoic acid and 0·67 [0·63–0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses.InterpretationDifferent individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed.FundingEU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative.

Obesity is associated with increased dihomo‐λ‐linolenic and with decreased nervonic and n‐3 fatty acids in plasma phospholipids (643.8)

Obesity and blood fatty acid (FA) levels are associated with inflammation and chronic disease risk. The purpose of this study was to identify associations between FA in plasma phospholipids (PPL) and body mass index (BMI). 126 Caucasian males (48‐65 years old) were categorized: lean (BMI&lt;25), overweight (25蠄BMI&lt;30), or obese (BMI蠅30). PPL were extracted and analyzed using a modified Rosen‐Folch method and gas chromatography. PPL from obese men were less likely to contain n‐3 FA compared to those from lean (OR 0.72). Specifically, PPL from obese men had lower content of linoleic acid (OR 0.79), docosahexaenoic acid (DHA) (OR 0.68), eicosapentaenoic acid (EPA) (OR 0.45), and EPA+DHA (OR 0.74). Nervonic acid (NA), an n‐9 FA, was less abundant in PPL from overweight (OR 0.24) and obese men (OR 0.13), while dihomo λ‐linolenic acid (DGLA), an n‐6 FA, was more abundant in PPL from overweight (OR 3.02) and obese (OR 3.70) men. DGLA was positively correlated and NA was negatively correlated with serum C‐peptide, an indicator of insulin resistance. Similar associations were observed when participants were stratified by waist circumference. Future studies should examine the potential role of NA and DGLA in obesity‐associated diseases.Grant Funding Source: Research Support: NIH R03CA142000 and MSU CTSI

Serum concentrations of perfluorinated alkyl acids and their associations with diet and personal characteristics among Swedish adults

In this study, food is suggested as a major source of human exposure to perfluorinated alkyl acids (PFAA). We investigated relations between serum levels of PFAA in adults and diet/lifestyle factors nationwide in Sweden. In 2010-2011, adults (18-80 years, N = 270) recorded their diet for 4 days and answered a food frequency questionnaire. PFAA were measured in blood serum as well as v-3 fatty acids in plasma phospholipids as a biomarker for fish consumption. Higher levels of PFAA were associated with male sex, increased age, and higher education. Women reporting full breastfeeding for ≥12 months had 32-44% lower levels of perfluorooctane sulfonate, perfluorooctanoic acid, and perfluorohexane sulfonate than women who never nursed their infants full-time. Serum perfluorooctane sulfonate, perfluorononanoic acid, perfluorodecanoic acid, and perfluoroundecanoic acid were positively related to n-3 fatty acids in plasma (partial r = 0.19-0.34, p ≤ 0.05). The relatively strong correlations between biomarkers of fish consumption and certain PFAA suggest that PFAA exposure should be taken into account in health risk and benefit assessment of fish consumption. Breastfeeding appears to be a major source of elimination of certain PFAA among women, and consequently PFAA exposure of nursed infants could be significant.

Plasma Phospholipid Fatty Acid Content Is Related to Disease Activity in Ankylosing Spondylitis

To investigate fatty acid composition in the diet, plasma phospholipids, and adipose tissue in a cohort of patients with ankylosing spondylitis (AS), and to determine their correlations to disease activity and blood lipids in a cross-sectional study. Diet was assessed using a food frequency questionnaire in 66 patients with AS. Polyunsaturated fatty acids in plasma phospholipids and gluteal adipose tissue were measured using gas chromatography. Disease status was quantified using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein, and proinflammatory cytokines. Diet did not correlate with disease activity assessed by the BASDAI, but there were negative correlations between the dietary intake of long-chain omega-3 fatty acids and ESR (r(s) = -0.27, p < 0.05). The plasma phospholipid content of arachidonic acid correlated significantly with the BASDAI score (r(s) = 0.39, p < 0.01). There were correlations between the intake of long-chain omega-3 fatty acids and high-density lipoproteins and serum triglycerides (r(s) = 0.26 and r(s) = -0.25, respectively, p < 0.05). There was a positive correlation between levels of arachidonic acid in plasma phospholipids and disease activity assessed by BASDAI in patients with AS. A Western diet does not appear to influence this correlation, but seems to affect blood lipids involved in atherogenic processes.

Plasma n-3 and n-6 fatty acids and the incidence of atrial fibrillation following coronary artery bypass graft surgery

The anti-inflammatory or anti-arrhythmic effects of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) may decrease the risk of postoperative atrial fibrillation (POAF), but interventional studies have yielded conflicting results. We examined the association between n-3 LC-PUFA and n-6 LC-PUFA in plasma phospholipids (PL) and POAF in patients undergoing coronary artery bypass grafting (CABG). A total of 125 patients undergoing CABG were enrolled in the study. The levels of fatty acids in PL were measured preoperatively and on the third postoperative day. The endpoint was defined as POAF lasting ≥5 min. The incidence of POAF was compared between quartiles of the level of each fatty acid in plasma PL by univariate and multivariable analysis. The incidence of POAF was 49·6%. By univariate analysis, the incidence of POAF increased significantly with each higher quartile of pre- and postoperative docosahexaenoic acid (DHA) and diminished significantly with each higher quartile of pre- and postoperative arachidonic acid (AA). For postoperative total n-3 LC-PUFA, there was a significant U-curve relationship where the second quartile had the lowest incidence of POAF or 25·8%. In multivariable analysis, this U-curve relationship between n-3 LC-PUFA levels and POAF risk was not significant, whereas the association between POAF and DHA or AA remained statistically significant. This study suggests that n-3 LC-PUFA supplements might prevent POAF in CABG patients with low baseline levels of these fatty acids in plasma PL, but may be harmful in those with high levels. AA may play an important role in electrophysiological processes.

Marine phospholipids—a promising new dietary approach to tumor-associated weight loss

Advanced tumor disease very often evokes excessive loss of body weight. Among others, fish oil or marine fatty acid ethyl esters were investigated for treatment of cancer cachexia with controversial results. In this study, a new formulation of marine fatty acids was investigated, the marine phospholipids, with more than 50% of phospholipid-bound fatty acids being eicosapentaenoic and docosahexaenoic acid. Thirty-one tumor patients with various tumor entities suffering from weight loss were asked to take marine phospholipids (1.5 g/day) as softgel capsules for a period of 6 weeks. Compliance, body weight, appetite, and quality of life as well as the fatty acid profile in plasma and blood cells were monitored; 17 patients could be analyzed. Marine phospholipids were very well accepted; low-dose supplementation resulted in a significant increase of eicosapentaenoic and docosahexaenoic acid in plasma phospholipids; therefore, significantly reducing the n-6 to n-3 fatty acid ratio. A stabilization of body weight was achieved (median weight change of +0.6% after 6 weeks), while appetite and quality of life improved. These promising first results encourage further investigation of marine phospholipids in cancer care.

Long-chain polyunsaturated fatty acids in a diabetic teenager during and after nine repeated episodes of diabetic ketoacidosis

Type 1 diabetes is often accompanied with acute hypoinsulinemia that may theoretically inhibit the conversion of essential fatty acids to their longer-chain metabolites. Previously, we found significant reduction in plasma arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) acid values in a group of diabetic children during diabetic ketoacidosis. Here we report data on the changes of fatty acids in plasma phospholipids in a diabetic teenager during and after nine subsequent episodes of diabetic ketoacidosis (DKA). Plasma phospholipid linoleic acid (C18:2n-6) values significantly decreased [23.05 (1.05) versus 19.22 (3.22), % w/w, median (IQR), p < 0.01], while values of dihomo-gamma-linolenic acid (C20:3n-6) and docosatetraenoic acid (C22:4n-6) significantly increased [1.72 (0.44) versus 1.80 (0.63) and 0.40 (0.01) versus 0.45 (0.07), respectively, p < 0.05]. Values of alpha-linolenic acid (C18:3n-3) did not change, while values of docosahexaenoic acid were significantly higher after than during the ketoacidosis [1.57 (0.67) versus 1.87 (0.32), p < 0.05). These data obtained in the same patient during repeated episodes of diabetic ketoacidosis support the concept that hypoinsulinemia plays an important role in disturbances of essential fatty acid metabolism in diabetes.

Influence of Plasma Lipid Composition on Activity of Factors V, VII and X in Single Comb White Leghorn and Fatty Liver Haemorrhagic Syndrome-Susceptible Laying Hens

1. Plasma lipids were investigated to determine whether they influence the biological activities of specific coagulation proteins Factors V, VII and X. 2. Factor activities decreased when lipids were depleted from the plasma of Single Comb White Leghorn (SCWL) and Fatty Liver Haemorrhagic Syndrome-susceptible (FLHS) laying hens. 3. Addition of lipids removed from SCWL laying hens and FLHS-susceptible laying hens into lipid-depleted plasma of both bird strains caused an increase and decrease, respectively, in Factors V and X activities. 4. Omega-3 fatty acids were negatively correlated to Factors V, VII and X activities. When bird strain was considered, it was significant for Factor X in SCWL laying hens. Omega-6 fatty acids were positively correlated with Factors VII and X for FLHS-susceptible laying hens. 5. The results suggest that the type of fatty acid in plasma phospholipids influences the activities of Factors V, VII and X and by altering lipid composition in the plasma, activities of coagulation factors may be affected.

The influence of polymorphism of −493G/T MTP gene promoter and metabolic syndrome on lipids, fatty acids and oxidative stress

The aim of this study was to investigate the effect of the microsomal triglyceride transfer protein (MTP) −493G/T polymorphism on clinical and biochemical parameters in relation to the presence of metabolic syndrome (MS). A group of 270 participants, 143 men and 127 women [50 men/36 women fulfilled the International Diabetes Federation (IDF) criteria of MS], was categorized on the basis of the MTP −493G/T polymorphism: GG homozygotes (Group GG) and carriers of the T allele (Group TT+TG). In men with MS, the presence of the T allele was associated with elevated concentrations of plasma insulin (by 48%, P<.01) and nonesterified fatty acids (by 49%, P<.05); homeostasis model assessment for insulin resistance index was higher by 64% ( P<.05). Carriers of the T allele were further characterized by elevated plasma concentrations of total cholesterol (by 14%, P<.05) and by increased triglycerides in plasma (by 95%, P<.01) and in very low-density lipoprotein (by 106%, P<.01). They also had lower concentrations of n-6 polyunsaturated fatty acids in plasma phospholipids (by 3.5%, P<.05), lower Δ5-desaturase activities (by 18%, P<.05) and elevated concentrations of conjugated dienes in low-density lipoprotein (by 29%, P<.01). No significant differences between Groups GG and TT+TG were found in men without MS and in women with and without MS. Our results imply evidence for interactive effects of genetic, metabolic and gender-specific factors on several components of metabolic syndrome, which can increase the risk for cardiovascular disease.

Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man

Background Dietary intake of fish rich in omega-3 fatty acids is associated with a reduction in cardiovascular events. The mechanisms for this are uncertain and previous studies investigating effects on platelet function have produced inconsistent results. Platelet-monocyte aggregation is a sensitive marker of platelet activation and may contribute to the initiation and progression of atherothrombosis. This study assessed the effect of dietary intervention with oily fish on platelet-monocyte aggregation in healthy subjects. Methods Fourteen subjects had their diet supplemented with 500 g of oil-rich fish per week for 4 weeks. A control group of 14 subjects received no dietary intervention over a 4-week period. Platelet-monocyte aggregates were assessed with flow cytometry. Results Dietary intervention with fish led to an increase in omega-3 fatty acids in plasma phospholipids (14.2 ± 3.4% versus 5.8 ± 1.3%, P < 0.001). In contrast to the control group, platelet-monocyte aggregates were reduced by 35% following dietary intervention with oily fish (16.0 ± 9.0% versus 24.8 ± 10.9%, P < 0.01), and returned to basal levels 4 weeks after discontinuation of supplementation. There was an inverse correlation between platelet-monocyte aggregation and plasma omega-3 fatty acid concentrations ( r = −0.421, P = 0.006). There were no changes in the plasma markers of platelet activation, soluble P-selectin or soluble CD40 ligand. Conclusions We have demonstrated, for the first time, that dietary intervention with oil-rich fish reduces platelet-monocyte aggregation in man. Our results suggest that reduced platelet activation provides a potential mechanism through which fish oils confer their cardiovascular preventative benefits.

Decreasing Linoleic Acid with Constant α-Linolenic Acid in Dietary Fats Increases (n-3) Eicosapentaenoic Acid in Plasma Phospholipids in Healthy Men1

High linoleic acid (LA) intakes have been suggested to reduce α-linolenic acid [ALA, 18:3(n-3)] metabolism to eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)], and favor high arachidonic acid [ARA, 20:4(n-6)]. We used a randomized cross-over study with men (n = 22) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods, while maintaining constant ALA, for 4 wk each, on plasma (n-3) fatty acids. Nonvegetable sources of fat, except fish and seafoods, were unrestricted. We determined plasma phospholipid fatty acids at wk 0, 2, 4, 6, and 8, and triglycerides, cholesterol, serum CRP, and IL-6, and platelet aggregation at wk 0, 4, and 8. LA and ALA intakes were 3.8 ± 0.12% and 1.0 ± 0.05%, and 10.5 ± 0.53% and 1.1 ± 0.06% energy with LA:ALA ratios of 4:0 and 10:1 during the low and high LA diets, respectively. The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period (P < 0.001), but DHA declined over the 8-wk period (r = −0.425, P < 0.001). The plasma phospholipid ARA:EPA ratios were (mean ± SEM) 20.7 ± 1.52 and 12.9 ± 1.01 after 4 wk consuming the high or low LA diets, respectively (P < 0.001); LA was inversely associated with EPA (r = −0.729, P < 0.001) but positively associated with ARA:EPA (r = 0.432, P < 0.001). LA intake did not influence ALA, ARA, DPA, DHA, or total, LDL or HDL cholesterol, CRP or IL-6, or platelet aggregation. In conclusion, high LA intakes decrease plasma phospholipid EPA and increase the ARA:EPA ratio, but do not favor higher ARA.