Erythrocyte Membrane Phospholipid Fatty Acid Research Articles

Fatty Acids as Useful Serological Markers for Crohn’s Disease

Background: We have previously reported that patients with Crohn’s disease (CD) have a very specific erythrocyte membrane phospholipid fatty acid profile. The findings of this study suggest that the activities of enzymes involved in the metabolism of linoleic acid (LA), that is, delta-6 desaturase, are higher in CD patients than in healthy individuals. Methods: We evaluated the utilities of various fatty acid compositions of the plasma (p-) as new serological markers for CD compared to those of erythrocyte membranes (e-). Results: Fifty CD patients and 50 healthy individuals were enrolled. In both plasma and erythrocyte membranes, the weight percentages of palmitic acid (PA) were significantly higher, while those of LA were significantly lower in CD patients than in controls. Fatty acids with high sensitivity and specificity were p-PA (0.86 and 0.74) and e-PA (0.80 and 0.74). With PA and LA as a CD fatty acid index (CDFAi), that is, CDFAi = (PA/LA), the sensitivity and specificity of plasma CDFAi (p-CDFAi) and e-CDFAi were 0.80 and 0.80; and 0.82 and 0.88 respectively. Conclusion: In CD patients, various fatty acids were specifically altered in both plasma and erythrocytes, and p-PA and p-CDFAi are potentially useful as new serological markers for CD.

The association of cardiovascular risk factors with saturated fatty acids and fatty acid desaturase indices in erythrocyte in middle-aged Korean adults.

BackgroundThe quality of dietary fats is associated with risk of cardiovascular diseases (CVD). We aimed to investigate the association between fatty acids in erythrocyte membrane phospholipids and CVD risk factors in middle-aged Korean adults.MethodsFifty-five middle-aged adults who underwent health examinations were included in this retrospective and cross-sectional study. Anthropometry, serum lipids, clinical parameters, and erythrocyte membrane phospholipid fatty acid data were obtained from a registry.ResultsThe proportion of C14:0 and C16:0 was greatly elevated in high quartile groups for triglyceride (TG) and systolic and diastolic blood pressure groups (SBP and DBP) (p = 0.042, p = 0.021, or p = 0.008 respectively) compared to low quartile groups. While C16:1n7 and/or C18:1n9 were positively associated with CVD risk factors, the delta 9 desaturase activity index (D9D) (C18:1n9/C18:0) was only significantly increased in high quartile groups for TG and blood pressures (p = 0.001, p = 0.002 or p = 0.003). Conversely, TG and blood pressures showed inverse relationships with C20:4n6 or D5D (C20:4n6/C20:3n6). C18:3n6 and/or D6D (C18:3n6/C18:2n6) were positively associated with insulin resistance and diabetic parameters. Particularly high D6D was detected in high quartile groups of FBS and insulin (p = 0.016 and p = 0.042). In linear regression analysis, D9D and/or C14:0 + C16:0 were significant contributors to serum TG and blood pressures. D6D was a contributing factor to FBS.ConclusionsThe indices of D9D and D6D from erythrocyte membrane phospholipids and the proportion of saturated fatty acids were increased as the cardiovascular risk factors, including serum TG, blood pressures, and FBS increased their levels (IRB number C2014199 (1396)).Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0135-x) contains supplementary material, which is available to authorized users.

Utility of Fatty Acid Profile of Erythrocyte Membrane in Identifying Diagnostic Markers of Crohnʼs Disease

Introduction: We often experience cases of Crohn's disease (CD) that are hard to distinguish from other inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC) and indeterminate colitis, making diagnosis difficult. We have previously reported that the erythrocyte membrane phospholipid fatty acid profile is very specific in patients with initial IBD, particularly CD. This suggests that the activity of enzymes involved in the metabolism of linoleic acid (LA) and palmitic acid (PA), namely, delta 6 desaturase and elongase 6, is expected to be higher than that of healthy individuals. In this study, we evaluated the utility of delta 6 desaturation index (Δ6di), elongation index (EI), and various fatty acids as diagnostic markers of CD. Methods: Ninety-five IBD patients (70 with CD and 25 with UC) and controls (90 healthy individuals) were enrolled in this study. We analyzed the erythrocyte membrane phospholipid fatty acid concentrations in each of these groups. As indexes of enzyme activity, we calculated the Δ6di using the percentage weights of LA, dihomo-γ-linoleic acid (DGLA), and arachidonic acid (AA), i.e., Δ6di=(DGLA+AA)/LA, and EI using the percentage weights of PA, stearic acid (SA), and oleic acid (OA), i.e., EI=(SA+OA)/PA. Results: In CD patients, the percentage weights of SA, DGLA, and AA were significantly higher, and those of PA and LA were significantly lower (p < 0.001), in comparison with those of UC patients and controls. Similarly, Δ6di and EI were significantly higher (p < 0.001). The areas under the receiver operating characteristic curve of Δ6di and SA were the highest at 0.920 and 0.922, respectively. When cut-off values of 1.325 and 13.27 were chosen for Δ6di and SA, respectively, the sensitivity and specificity for CD patients versus UC patients and controls were 91.4 and 87.8% for Δ6di and 82.9 and 99.1% for SA, respectively. Conclusion: In CD patients, the percentage weights of LA and PA were significantly lower, and those of AA and SA were significantly higher as compared to those of UC patients and controls. In addition, Δ6di and SA could be excellent diagnostic markers of CD.Figure 1

Mo1138 Erythrocyte Membrane Phospholipid Fatty Acid Concentrations and Colorectal Adenomas: A Case Control in Tennessee

G A A b st ra ct s we reviewed patients > 18 years of age with rectal adenocarcinoma from 1991-2010. Continuous and categorical variables are reported using mean (SD), proportions, and percentages. Univariate analysis was done using T-test and Chi-square tests respectively. Multivariate Cox regression analysis was used to evaluate risk adjusted outcomes and to predict the hazard of dying. Kaplan Meier method was used to estimate the survival function. Results: We included 102,167 patients in our study. YPs with rectal carcinoma were more likely to be African American (11.9% vs 8.8%; p<0.001), Hispanic (13.3% vs 8.3%; p<0.001) and Asian (10.9% vs 8.3%; p<0.001) as compared to the older age group. YPs were more likely to present with distant metastasis (16.7% vs 13.4%; p<0.001) and had more poorly differentiated tumors (13.3 % vs 12.1%; p< 0.001). YPs also received more cancer directed surgery (84 % vs 80%; p<0.001) and post-operative radiation (52% vs 39.8; p<0.001) compared to their older counterpart. In contrast to previous studies the five year survival was better for younger patients (74.3% vs 70.7%; p<0.001{table 1}). After controlling for gender, race, marital status, grade, stage, cancer specific surgery and post-operative radiation, multivariate Cox regression analysis revealed that age is an independent predictor of death, and younger patients with rectal cancer had a lower risk of dying (HR 0.693; p<0.001) Conclusion: In previous studies younger patients with rectal cancer were found to have poorer or equivalent survival compared to older patients. In contrast, our study shows that young patients less than 50 years of age, have advanced stage rectal cancer at diagnosis but have better survival. Table 1: Five-year relative survival for rectal cancer patients

Erythrocyte Membrane Phospholipid Fatty Acid Concentrations and Risk of Colorectal Adenomas: A Case–Control Nested in the French E3N-EPIC Cohort Study

Although dietary fatty acids may influence colorectal carcinogenesis, few studies have examined the association with adenoma risk. We assessed the association between biomarkers of dietary fatty acids or metabolism of fatty acids and the risk of colorectal adenomas in a nested case-control study from the French E3N-EPIC cohort. Among 13,106 women without prevalent cancer who completed the diet history questionnaire and who provided blood samples, 328 cases of adenomatous polyp were identified during an average of 6.6-year follow-up and randomly matched to 619 polyp-free colonoscopy controls. Erythrocyte membrane phospholipid fatty acid concentrations were determined by gas chromatography. Adjusted ORs for risk of colorectal adenomas with increasing concentrations of fatty acids were calculated using conditional logistic regression, separately for advanced and nonadvanced adenomas. Associations were stronger with advanced than nonadvanced adenomas. High concentration of pentadecanoate plus heptadecanoate acids were inversely associated with the risk of advanced adenomas [highest vs. lowest tertile: OR(T3vsT1) = 0.40 (95% confidence interval (CI) 0.20-0.79); P(trend) = 0.009]. Oleic acid was associated with an increased risk of advanced adenomas [OR(T3vsT1) = 2.32 (1.16-4.64); P(trend) = 0.018]. Some polyunsaturated fatty acids were associated with the risk of advanced adenomas, either positively for di-homo-γ-linolenate [OR(T3vsT1) = 2.07 (1.15-3.72); P(trend) = 0.013], or negatively for eicosapentaenoic and docosahexaenoic acids [OR(T3vsT1) = 0.50 (0.27-0.93); P(trend) = 0.044 and OR(T3vsT1) = 0.50 (0.26-0.96); P(trend) = 0.028, respectively]. A specific erythrocyte membrane phospholipid fatty acid profile, presumably reflecting both a complex dietary pattern and altered fatty acid metabolism, is associated with advanced colorectal adenoma risk. Adenomas could be a target for primary prevention of colorectal cancer, using interventional strategy based on lipidomic profile of patients.

Erythrocyte membrane fatty acid composition, serum lipids, and non-Hodgkin’s lymphoma risk in a nested case–control study: the multiethnic cohort

Composition of dietary fatty acid intake, which influences cytokine production, may contribute to the development of non-Hodgkin's lymphoma (NHL). Serum lipid levels may serve as biomarkers of inflammation associated with NHL risk. We conducted a case-control analysis (275 cases and 549 controls) nested within the Multiethnic Cohort Study (whites, Japanese Americans, Latinos, African Americans, and Native Hawaiians) to examine the association of prediagnostic, erythrocyte membrane phospholipid fatty acid composition, and serum cholesterol and triglyceride (TG) concentrations with the risk of NHL. Conditional logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) by tertiles of biomarker concentrations. Higher total saturated fatty acids (SFA) were associated with an increase in NHL risk (OR(T3 vs. T1) = 1.57 [95 % CI: 1.03-2.39]; p(trend) = 0.01), whereas no associations were detected for total n-3 or n-6 polyunsaturated fatty acids. Inverse associations were observed for total cholesterol (TC; OR (T3 vs. T1) = 0.51 [95 % CI: 0.35-0.74]; p(trend) < 0.0001) and high-density lipoprotein cholesterol (HDL-C; OR (T3 vs. T1) = 0.47 [95 % CI: 0.31-0.71]; p(trend) = 0.0001) but not for low-density lipoprotein cholesterol or TG. Adjustment for the use of lipid-lowering medication did not modify the results substantially. This prospective biomarker investigation offers supportive evidence for an adverse effect of higher erythrocyte membrane SFA levels on NHL risk, but preclinical effects cannot be excluded. Inverse relations between prediagnostic, circulating TC and HDL-C and NHL risk may be due to reverse causation or a result of protective actions of these lipids and lipoproteins.

Brain protection by rapeseed oil in magnesium-deficient mice

Diets given for 30 days with various mono-(MUFA) and poly-(PUFA) unsaturated fatty acid contents were evaluated for brain protection in magnesium-deficient mice: a commercial and three synthetic diets (n-6PUFA, n-3PUFA and MUFA-based chows enriched with 5% corn/sunflower oils 1:3, with 5% rapeseed oil and with 5% high oleic acid sunflower oil/sunflower oil 7:3, respectively). Unlike magnesium deprivation, they induced significant differences in brain and erythrocyte membrane phospholipid fatty acid compositions. n-3PUFA but not other diets protected magnesium-deficient mice against hyperactivity and moderately towards maximal electroshock- and NMDA-induced seizures. This diet also inhibited audiogenic seizures by 50%, preventing animal deaths. Because, like n-6PUFA diet, matched control MUFA diet failed to induce brain protections, alpha-linolenate (ALA) rather than reduced n-6 PUFA diet content is concluded to cause n-3PUFA neuroprotection. Present in vivo data also corroborate literature in vitro inhibition of T type calcium channels by n-3 PUFA, adding basis to ALA supplementation in human anti-epileptic/neuroprotective strategies.

Elevated concentrations of linoleic acid in erythrocyte membrane phospholipids in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is a disorder characterized by diffuse inflammation of the gastrointestinal tract. The immune response and inflammation are mediated by polyunsaturated fatty acids and influenced by dietary fats and lipid metabolism. This study examined the qualitative and quantitative fat intake of IBD patients and healthy controls on plasma phospholipid and erythrocyte membrane phospholipid (EMP) fatty acid content. Measurement of the fatty acid composition of plasma phospholipid and EMP were performed in 29 UC patients, 20 CD patients, and 31 healthy controls. Anthropometric characteristics and data on dietary intake were also collected. We observed significantly lower lipid intake in UC and CD patients vs controls. The UC and CD patients had significantly higher levels of linoleic acid in their EMP than did controls. There were no significant differences in the levels of n-3 polyunsaturated fatty acids, but there were significantly higher levels of the n-6 in the EMP of UC and CD patients compared with controls. The significant differences persisted after the data were adjusted for potential confounders and lipid intake. Higher levels of linoleic acids and n-6 fatty acids, which are involved in production of proinflammatory mediators, were found in IBD patients compared with controls, thereby implicating n-6 fatty acids in the pathophysiology of the disease.

Erythrocyte Membrane Phospholipid Composition as a Biomarker of Dietary Fat

Background/Aims: In a cross-sectional study, we investigated the relationship between erythrocyte membrane phospholipid fatty acid composition and dietary fat; we also investigated roles of menopausal status, age, body mass index (BMI) and waist-to-hip ratio (WHR) in interindividual variation of the biomarker. Methods: Study participants were 204 women, aged 39–65 years, drawn from the ORDET cohort and selected as controls in a study of breast cancer. Membrane composition was assessed using capillary gas chromatography. Dietary fat composition was evaluated using a food frequency questionnaire. Results: In pre- and postmenopausal women, erythrocyte membrane phospholipid levels of linoleic acid, oleic acid, and mono-unsaturated fatty acids were significantly associated with corresponding dietary measures (partial correlation coefficients: 0.23 and 0.39; 0.45 and 0.47; 0.40 and 0.48; respectively, in pre- and postmenopausal women). Among postmenopausal women, membrane poly-unsaturated fatty acids were correlated with the corresponding dietary measure (r = 0.39, p < 0.001). Membrane eicosapentanoic and docosahexanoic acid levels were significantly correlated with intake of fish/shell fish : r = 0.21 and r = 0.43 (premenopausal), and r = 0.41 and r = 0.44 (postmenopausal). Age, BMI and WHR had independent effects on membrane lipid composition. Age was associated with delta-6 desaturase activity in postmenopausal women (r = 0.25, p < 0.05). BMI was negatively associated with delta-9 desaturase activity in both pre- and postmenopausal women (r = –0.29, p = 0.01 and r = –0.22, p < 0.01, respectively). WHR was negatively associated with delta-5 desaturase activity in pre-menopausal women (r = –024, p < 0.05). Conclusions: Erythrocyte membrane levels of some specific fatty acids can be used as biomarkers of these fatty acids as proportions of dietary fat.

Long-chain conversion of [13C]linoleic acid and α-linolenic acid in response to marked changes in their dietary intake in men

We studied the long-chain conversion of [U-13C]alpha-linolenic acid (ALA) and linoleic acid (LA) and responses of erythrocyte phospholipid composition to variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in 38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil (FXO; 17 g/day ALA, n=21) or sunflower oil (SO; 17 g/day LA, n=17). The FXO diet induced increases in phospholipid ALA (>3-fold), 20:5n-3 [eicosapentaenoic acid (EPA), >2-fold], and 22:5n-3 [docosapentaenoic acid (DPA), 50%] but no change in 22:6n-3 [docosahexanoic acid (DHA)], LA, or 20:4n-6 [arachidonic acid (AA)]. The increases in EPA and DPA but not DHA were similar to those in subjects given the SO diet enriched with 3 g of EPA plus DHA from fish oil (n=19). The SO diet induced a small increase in LA but no change in AA. Long-chain conversion of [U-13C]ALA and [U-13C]LA, calculated from peak plasma 13C concentrations after simple modeling for tracer dilution in subsets from the FXO (n=6) and SO (n=5) diets, was similar but low for the two tracers (i.e., AA, 0.2%; EPA, 0.3%; and DPA, 0.02%) and varied directly with precursor concentrations and inversely with concentrations of fatty acids of the alternative series. [13C]DHA formation was very low (<0.01%) with no dietary influences.

Erythrocyte membrane phospholipid fatty acid changes in cerebral palsy patients during nutritional rehabilitation—A response

Erythrocyte membrane phospholipid fatty acid changes in cerebral palsy patients during nutritional rehabilitation—A response

Role of carnitine and carnitine palmitoyltransferase as integral components of the pathway for membrane phospholipid fatty acid turnover in intact human erythrocytes.

The deacylation and reacylation process of phospholipids is the major pathway of turnover and repair in erythrocyte membranes. In this paper, we have investigated the role of carnitine palmitoyltransferase in erythrocyte membrane phospholipid fatty acid turnover. The role of acyl-L-carnitine as a reservoir of activated acyl groups, the buffer function of carnitine, and the importance of the acyl-CoA/free CoA ratio in the reacylation process of erythrocyte membrane phospholipids have also been addressed. In intact erythrocytes, the incorporation of [1-14C]palmitic acid into acyl-L-carnitine, phosphatidylcholine, and phosphatidylethanolamine was linear with time for at least 3 h. The greatest proportion of the radioactivity was found in acyl-L-carnitine. Competition experiments using [1-14C]palmitic and [9,10-3H]oleic acid demonstrated that [9,10-3H]oleic acid was incorporated preferentially into the phospholipids and less into acyl-L-carnitine. When an erythrocyte suspension was incubated with [1-14C]palmitoyl-L-carnitine, radiolabeled palmitate was recovered in the phospholipid fraction, and the carnitine palmitoyltransferase inhibitor, 2-tetradecylglycidic acid, completely abolished the incorporation. ATP depletion decreased incorporation of [1-14C]palmitic and/or [9,10-3H]oleic acid into acyl-L-carnitine, but the incorporation into phosphatidylcholine and phosphatidylethanolamine was unaffected. In contrast, ATP depletion enhanced the incorporation into phosphatidylcholine and phosphatidylethanolamine of the radiolabeled fatty acid from [1-14C]palmitoyl-L-carnitine. These data are suggestive of the existence of an acyl-L-carnitine pool, in equilibrium with the acyl-CoA pool, which serves as a reservoir of activated acyl groups. The carnitine palmitoyltransferase inhibition by 2-tetradecylglycidic acid or palmitoyl-D-carnitine caused a significant reduction of radiolabeled fatty acid incorporation into membrane phospholipids, only when intact erythrocytes were incubated with [9,10-3H]oleic acid. These latter data may be explained by the differences in rates and substrates specificities between acyl-CoA synthetase and the reacylating enzymes for palmitate and oleate, which support the importance of carnitine palmitoyltransferase in modulating the optimal acyl-CoA/free CoA ratio for the physiological expression of the membrane phospholipids fatty acid turnover.

Insulin binding to erythrocytes and fatty acid composition of erythrocyte membrane phospholipids in healthy men

The relationship between specific insulin binding to insulin receptors on erythrocytes and erythrocyte membrane phospholipid fatty acid pattern was evaluated in 11 healthy men. A significant negative correlation between insulin binding and the proportion of w-6 family essential fatty acids, especially linoleic acid ( r = -0.82, p < 0.01) and arachidonic acid ( r = -0.73, p < 0.05) in erythrocyte membrane was found. On the other hand significant positive correlation between insulin binding and the content of nonessential fatty acids ( r = +0.65, p < 0.05) was seen. Data presented support the hypothesis that the fatty acid composition of membrane phospholipids may modify properties of insulin receptors.

Selective stimulation of erythrocyte membrane phospholipid fatty acid turnover associated with decreased cell volume.

Treatment of erythrocytes with the divalent cation ionophore A23187 results in net uptake of calcium and a calcium-dependent decrease in cellular potassium content and cell volume. These changes in membrane properties are associated with a selective stimulation of fatty acid incorporation into membrane phosphatidylethanolamine (PE). In this study the relationship between this selective stimulation of phospholipid fatty acid turnover and changes in calcium uptake, cellular potassium content, and cell volume has been examined by 1) preventing the calcium-dependent loss of potassium without abolishing calcium uptake and 2) altering cellular potassium content and cell volume without increasing net uptake of calcium by utilizing the monovalent cation inonophore nigericin or increasing the osmolarity of the buffer. It has been shown that treatment of erythrocytes with A23187, nigericin, or hypertonic buffer results in a selective stimulation of fatty acid incorporation into PE. These results suggest that a mechanical or conformational change in the membrane is associated with a selective stimulation of fatty acid turnover in phosphatidylethanolamine.

Calcium-dependent stimulation of erythrocyte membrane phospholipid fatty acid incorporation by the ionophore A23187.

Treatment of human erythrocytes with A23187, a divalent cation ionophore, results in a calcium-dependent increase in the rate of incorporation of palmitic, oleic, and linoleic acids into phosphatidylethanolamine. Incorporation of fatty acids into phosphatidylcholine is unaffected by A23187. This calcium-dependent stimulation of membrane phosphatidylethanolamine fatty acid turnover by A23187 may be related to the changes in erythrocyte membrane function induced by A23187 that have been observed previously.