Erythrocyte Membrane Fatty Acid Research Articles

Abnormal erythrocyte fatty acid composition in first-diagnosed, drug-naïve patients with depression

Background & aimsThe correlation between fatty acids (FAs) and depression is not yet conclusive. This study examined the relationship of FAs composition with the presence and clinical characteristics of first-diagnosed, drug-naïve patients with depression. MethodsA total of 139 first-diagnosed, drug-naïve patients with depression and 55 healthy controls (HCs) were included in the cross-sectional study. The levels of erythrocyte membrane FAs were compared and then the correlation between clinical symptoms and fatty acid levels in depression was investigated. ResultsCompared to HCs, patients with depression had higher C18:1n9t (z = −2.033, p = 0.042), C20:4n6 (z = −2.104, p = 0.035), C20:3n6 (z = −2.104, p = 0.035) and n-6 polyunsaturated fatty acids (PUFAs) (z = −2.127, p = 0.033), whereas the levels of C18:1n9c (z = −3.348, p = 0.001) were significantly lower. Higher C20:3n6, C20:4n6, C18:1n9t and n-6 PUFAs levels were associated with higher severity of depressive and anxiety symptoms in patients with depression, and the correlation remained after adjusting for the related confounding factors (p < 0.05). ConclusionsPatients with first-diagnosed, drug-naïve depression show abnormal erythrocyte fatty acid composition. Trans fatty acids (TFAs) and n-6 PUFAs levels are closely related to clinical characteristics of depression. This study indicated that increased n-6 PUFAs and TFAs are characteristic changes of first-diagnosed, drug-naïve depression.

Eicosapentaenoic acid loaded silica nanoemulsion attenuates hepatic inflammation through the enhancement of cell membrane components

BackgroundLiver inflammation is a multistep process that is linked with cell membrane fatty acids composition. The effectiveness of eicosapentaenoic acid (EPA) undergoes an irreversible change during processing due to their unsaturated nature; so the formation of nanocarrier for EPA is crucial for improving EPA’s bioavailability and pharmacological properties.ObjectiveIn this study we aimed to evaluate the efficiency of EPA alone or loaded silica nanoemulsion on the management of hepatic inflammation induced by diethyl nitrosamine (DEN) through the enhancement of the cell membrane structure and functions.MethodsThe new formula of EPA was prepared to modify the properties of EPA. Forty-eight male Wistar albino rats were classified into: control, EPA, EPA loaded silica nanoemulsion (EPA–NE), DEN induced hepatic inflammation; DEN induced hepatic inflammation treated with EPA or EPA –NE groups. Plasma tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), liver hydroxyproline (Hyp) content, and liver oxidant and anti-oxidants were estimated. Urinary 8- hydroxyguanozine (8- OHdG) and erythrocyte membrane fatty acids fractions were estimated by High-performance liquid chromatography (HPLC). Also, histopathology studies were done to verify our hypothesis.ResultsIt was appeared that administration of EPA, in particular EPA loaded silica nanoemulsion, ameliorated the inflammatory response, increased the activity of the anti-oxidants, reduced levels of oxidants, and improved cell membrane structure compared to hepatic inflammation induced by DEN group. Histopathological examination confirmed these results.ConclusionEPA and notably EPA loaded silica nanoemulsion strongly recommended as a promising supplement in the management of hepatic inflammation.

Disrupted leptin-fatty acid biosynthesis is an early manifestation of metabolic abnormalities in schizophrenia.

BACKGROUNDInsulin resistance (IR) and impaired energy expenditure (IEE) are irreparable metabolic comorbidities in schizophrenia. Although mechanism(s) underlying IR and IEE remains unclear, leptin and fatty acid signaling, which has profound influence on insulin secretion/sensitivity, glucose metabolism and energy expenditure, could be disrupted. However, no association of plasma leptin with erythrocyte membrane fatty acids, body mass index (BMI), and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis (FEP) or medicated patients with chronic schizophrenia (CSZ) is presented before. These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.AIMTo determine the association between plasma leptin, erythrocyte membrane fatty acids, particularly, saturated fatty acids (SFAs), BMI and psychotic symptoms in patients with FEP and CSZ.METHODSIn this study, twenty-two drug naive patients with FEP, twenty-one CSZ patients treated with atypical antipsychotic drugs, and fourteen healthy control (CNT) subjects were analyzed. Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay. Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography. BMI was calculated by using the formula: weight (kg)/height (m2). Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale (BPRS), and positive and negative syndrome scale (PANSS). The total BPRS scores, positive and negative symptom scores (PANSS-PSS and PANSS-NSS, respectively) were recorded. Pearson correlation coefficient (r) analyses were performed to find the nature and strength of association between plasma leptin, PANSS scores, BMI and SFAs, particularly, palmitic acid (PA). RESULTSIn patients with FEP, plasma leptin not BMI was significantly lower (P = 0.034), whereas, erythrocyte membrane SFAs were significantly higher (P < 0.005) compared to the CNT subjects. Further, plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA (r = −0.4972, P = 0.001), PANSS-PSS (r = −0.4034, P = 0.028), and PANSS-NSS (r = −0.3487, P = 0.048). However, erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS (r = 0.5844, P = 0.0034) and PANSS-NSS (r = 0.5380, P = 0.008). In CSZ patients, plasma leptin, BMI, and erythrocyte membrane SFAs, all were significantly higher (P < 0.05) compared to the CNT subjects. Plasma leptin showed positive correlation with BMI (r = 0.312, P = 0.032) but not with PANSS scores or erythrocyte membrane SFAs-PA. However, erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only (r = 0.4729, P = 0.031). Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultra-high risk of developing psychosis; therefore, the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.CONCLUSIONDisrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia. Large-scale studies are warranted to validate the above findings.

The Greenland population health survey 2018 – methods of a prospective study of risk factors for lifestyle related diseases and social determinants of health amongst Inuit

ABSTRACT Since 1993, regular population health surveys in Greenland have supported and monitored the public health strategy of Greenland and have monitored cardiometabolic and lung diseases. The most recent of these surveys included 2539 persons aged 15+ from 20 communities spread over the whole country. The survey instruments included personal interviews, self-administered questionnaires, blood sampling, anthropometric measurements, blood pressure, ECG, oral glucose test, pulmonary function, hand grip strength and chair stand test. Blood samples were analysed for glucose, glycated haemoglobin (HbA1c), insulin, incretin hormones, cholesterol, kidney function, fatty acids in erythrocyte membranes and mercury, urine for albumin-creatinine ratio, and aliquots were stored at −80°C for future use. Data were furthermore collected for studies of the gut microbiome and diabetes complications. Survey participants were followed up with register data. The potential of the study is to contribute to the continued monitoring of risk factors and health conditions as part of Greenland’s public health strategy and to study the epidemiology of cardiometabolic diseases and other chronic diseases and behavioural risk factors. The next population health survey is planned for 2024. The emphasis of the article is on the methods of the study and results will be presented in other publications.

Fatty acids of erythrocyte membranes and blood serum as biomarkers for early detection of colorectal cancer

The aim of the study was to identify fatty acids (FA) of erythrocyte membranes and blood serum, which can serve as potential biomarkers for early detection of colorectal cancer.Material and methods. the study involved 65 patients with stage I-II CRC (mean age 63,3 ± 9,6 years (30 men, 35 women) and 35 people in the comparison group, matched by age and sex. the composition of fatty acids of erythrocyte membranes and blood serum was studied using a gc/ms system based on three agilent 7000B quadrupoles (USA). methods of the MATLAB software (R2019a, MathWorks) and the R programming language were used for statistical processing: t-test, unsupervised principal component analysis (PCA), Fold change, Volcano plot, machine learning method (Random Forest), Roc analysis, Heatmaps.Results. patients with stage I-II CRC showed a decrease in the level of saturated, individual monounsaturated fatty acids and a highly significant increase in the most of the polyunsaturated fatty acids with a predominance of omega-3. For most of the fatty acid levels, significant differences in erythrocyte membranes and serum between the groups were found. the levels of erythrocyte myristic, pentadecanoic, 7-palmitoleic, saturated/polyunsaturated Fa ratios (the content of which was significantly lower at stages I-II CRC than those in the control) and the levels of α-linolenic, eicosapentaenoic, docosapentaenoic, docosahexaenoic, the amount of omega-3 Fa, EPA + DHA, docodienic, dihomo-γ-linolenic, docatetraenoic fatty acids (the content of which was significantly higher in colorectal cancer than those in healthy subjects) were the most discriminating parameters in distinguishing patients with I-II stage CRC and healthy individuals. in the blood serum, the level of biomarkers had the following fatty acids: arachidonic, myristic, docosahexaenoic, the amount of omega 3 puFa, the ratio of omega 6/omega 3 puFa, pentadecanoic, docosapentaenoic, and docodiene. a model that included a list of fatty acids, such as С14:0, С15:0, С16:1;7, С18:3 n-3, C20:2 n-6, C20:3 n-6, C20:5 n-3, C22:4 n-6, C22:5 n-3, C22:6 n-3, sum of omega-3, omega-3 (EPA + DHA), and saturated / polyunsaturated fatty acids ratio provided auc 0,916 with a specificity of 0,90 and sensitivity of 0,95 in distinguishing patients with stage I-II CRC from healthy individuals.Conclusion. the study of the levels and ratios of fatty acids in erythrocyte membranes and blood serum should be considered a promising trend in the search for biomarkers for the early diagnosis of colorectal cancer.

Investigation of the relationship between miR-33a, miR-122, erythrocyte membrane fatty acids profile, and serum lipids with components of metabolic syndrome in type 2 diabetic patients.

Background and purpose:MicroRNAs (miRNAs) are small non-coding RNA molecules acting as critical regulators of post-transcriptional gene expression. MiR-33a and miR-122 have a crucial role in cholesterol and lipid metabolism. Therefore, their dysregulation may contribute to metabolic abnormality and their inhibition may be a useful therapeutic strategy. The objective of the present study was to investigate the relationship between miR-33a, miR-122, erythrocyte membrane fatty acids profile, and serum lipids with components of metabolic syndrome in an Iranian population suffering from type 2 diabetes mellitus (T2DM).Experimental approach:Expression of miR-33a and miR-122 was measured by real-time polymerase chain reaction and erythrocyte membrane fatty acid profiles were analyzed by gas chromatography-mass spectrometry.Findings/Results:T2DM patients with and without metabolic syndrome had significantly higher miR-33a and miR-122 levels compared to controls. MiRNAs were significantly correlated with saturated fatty acid (SFAs), total SFAs/total polyunsaturated fatty acids (PUFAs) ratio, fasting plasma glucose, triacylglycerols, insulin and homeostatic model assessment of insulin resistance. In addition, there was a significant negative correlation between miR-33a and miR-122 levels and PUFAs, total PUFAs/total SFAs ratio and omega 6 fatty acids.Conclusion and implications:Considering the roles of miR-33a and miR-122 in cholesterol and lipids metabolism, it may be concluded that the measurement of their expression may be useful as a potential additional biomarker for cardiometabolic derangement in T2DM patients. In addition, these findings may suggest that the inhibition of these miRNAs by anti-miRNA therapies may be explored as a potential therapeutic strategy.

Machine learning based prediction and the influence of complement – Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial

BackgroundFunctional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR. Materials and methodsWe carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome. Results and conclusionA prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two proteins (coagulation factor IX and complement C5) positively associated with the PSS score. Our study does not provide support for the utility of cytokines, proteomic or fatty acid data for prediction of functional outcomes in individuals at high-risk for psychosis. However, the association of complement protein levels with clinical outcome suggests a role for the complement system and the activity of its related pathway in the functional impairment and positive symptom severity of CHR patients.

The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome: a randomized, placebo-controlled, double-blind study

The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing≈1.5g ALA/d (n=40) or an isocaloric placebo (n=41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n-3, n-6, and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed. Compared with placebo, camelina oil increased ALA (mean±SD: 0±0.04 compared with 0.08±0.06%, P<0.001), its elongation product EPA (0±0.5 compared with 0.16±0.65%, P<0.05), and the n-9 gondoic acid (GA; 0±0.04 compared with 0.08±0.04%, P<0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r=0.26, P=0.03). Compared with placebo, camelina oil increased fasting glycemia (-0.2±0.6 compared with 0.3±0.5mmol/L, P<0.001) and HOMA-IR index (-0.8±2.5 compared with 0.5±0.9, P<0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r=0.32, P<0.01). Nutritional intake remained similar between groups. ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated.

Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia

Antipsychotic effects seem to decrease in relapsed schizophrenia patients and the underlying mechanisms remain to be elucidated. Based on the essential role of polyunsaturated fatty acids in brain function and the treatment of schizophrenia, we hypothesize that disordered fatty acid metabolism may contribute to treatment resistance in multi-episode patients. We analyzed the erythrocyte membrane fatty acids in 327 schizophrenia patients under various episodes (numbers of patients: first-episode drug naïve 89; 2–3 episodes 110; 4–6 episodes 80; over 6 episodes 48) and 159 age- and gender-matched healthy controls. Membrane fatty acid levels and PANSS scales were assessed at baseline of antipsychotic-free period and one-month of follow-up after treatment. Totally, both saturated and unsaturated fatty acids were reduced at baseline when compared to healthy controls. Subgroup analyses among different episodes indicated that in response to atypical antipsychotic treatment, the membrane fatty acids were only increased in patients within 3 episodes, and this therapeutic effects on omega-3 index were merely present in the first episode. Results of fatty acid ratios suggested that dysregulations of enzymes such as D6 desaturase, D5 desaturase, and elongases for polyunsaturated fatty acids in patients with multi-episode schizophrenia could account for the differences. Additionally, certain fatty acid level/ratio changes were positively correlated with symptom improvement. The alterations of C22:5n3 and omega-3 index, gender, and the number of episodes were significant risk factors correlated with treatment responsiveness. Using targeted metabolomic approach, we revealed the potential mechanisms underlying abnormal fatty acid metabolism responsible for reduced treatment response in patients with multi-episode schizophrenia.

Association between the Erythrocyte Membrane Fatty Acid Profile and Cognitive Function in the Overweight and Obese Population Aged from 45 to 75 Years Old.

Dietary fatty acid intake is closely related to the cognitive function of the overweight and obese population. However, few studies have specified the correlation between exact fatty acids and cognitive functions in different body mass index (BMI) groups. We aimed to explain these relationships and reference guiding principles for the fatty acid intake of the overweight and obese population. Normal weight, overweight, and obese participants were recruited to receive a cognitive function assessment and dietary survey, dietary fatty acids intake was calculated, and the erythrocyte membrane fatty acid profile was tested by performing a gas chromatography analysis. The percentages of saturated fatty acids (SFAs) in the obese group were higher, while monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) were lower than in the normal weight and overweight groups. In the erythrocyte membrane, the increase of n-3 PUFAs was accompanied by cognitive decline in the overweight group, which could be a protective factor for cognitive function in the obese group. High n-6 PUFAs intake could exacerbate the cognitive decline in the obese population. Dietary fatty acid intake had different effects on the cognitive function of overweight and obese people, especially the protective effect of n-3 PUFAs; more precise dietary advice is needed to prevent cognitive impairment.

Influence of the SOD2 A16V gene polymorphism on alterations of redox markers and erythrocyte membrane fatty acid profiles in patients with multiple chemical sensitivity.

Chronically increased oxidative stress has been reported in patients with multiple chemical sensitivity (MCS). Recently, a single nucleotide polymorphism of the gene coding for mitochondrial superoxide dismutase (SOD2), namely the missense substitution A16V (C47>T) resulting in alteration of SOD2 enzyme activity, has been reported to be associated with MCS. However, the influence of SOD2 A16V genetic background on redox status of patients with MCS has not yet been investigated. Here, the results of a retrospective analysis aimed to evaluate the role of the SOD2 A16V polymorphism in the alterations of antioxidant defense markers as well as fatty acid (FA) composition of erythrocyte membranes in 67 patients with MCS matched with 55 healthy controls is reported. The mutated SOD2 V16 variant was observed more frequently in the MCS group compared with the control group, and this difference was statistically significant. The most common genotype in both groups was the heterozygous SOD2 AV16 variant, whereas the mutated SOD2 VV16 variant was more frequently observed in the MCS group, although the difference was not significant. The MCS cohort showed significantly depleted levels of plasma total antioxidant activity, ubiquinol, erythrocyte reduced glutathione and membrane polyunsaturated FA levels, coupled with significant increases in glutathione peroxidase activity, likely accounting for sustained detoxification from lipoperoxides. Notably, the highest levels of oxidative stress were found in patients with MCS bearing the genotype SOD2 AA16, whereas intermediate levels were found in patients bearing the heterozygous AV16 genotype. Healthy subjects bearing the SOD2 AA16 genotype also showed increased oxidative stress compared with carriers of other SOD2 genotypes. Despite the need for further confirmations in larger cohorts, due to MCS population genetic heterogeneity, these preliminary findings suggest that SOD2 defective activity makes certain patients with MCS more susceptible to developing oxidative stress following a chronic daily exposure to pro-oxidant insults.

Serum and erythrocyte membrane fatty acid levels may be used as biomarkers to assess the severity of NAFLD

The aim of this work is to study the possibility of using blood serum (BS) fatty acids (FA) and erythrocytes (ER) as diagnostic markers of the severity of NAFLD. Materials and methods. We examined 52 patients with NAFLD (51.8 ± 3.9 years), confirmed by the NLFS index, and 20 apparently healthy men (49.2 ± 4.5 years). The degree of liver fibrosis was established by indirect elastometry (FibroScan® 502 Echosens, France). 27 patients had an initial degree of fibrosis (F0-1), 25 had severe fibrosis (F2-4). The study of the composition of fatty acids of Er and BS was carried out using a GC / MS system based on three Agilent 7000B quadrupoles (USA). Results. Significant differences in the levels of fatty acids in blood serum and erythrocyte membranes in patients with NAFLD were revealed, associated with the degree of fibrosis and necroinflammatory activity. To distinguish between mild and severe fibrosis in NAFLD, the levels of saturated fatty acids (myristic, pentadecane, margarine) and omega-3 PUFAs (eicosapentaenoic, docosapentaenoic, docosahexaenoic) were found to be significant (p = 0.002-0.0003). Saturated and monounsaturated FAs (palmitelaidic, palmitoleic, vaccenic) played a key role in differentiating the degree of necroinflammatory activity (minimal versus pronounced) (p = 0.03-0.005). The created diagnostic panels (FA of blood serum and erythrocyte membranes) made it possible to differentiate patients with NAFLD with varying degrees of fibrosis. Correlations of FA levels in erythrocyte membranes and blood serum with manifestations of metabolic syndrome, indicators of liver damage in patients with NAFLD were revealed. Conclusions. The established differences in fatty acid profiles of blood serum and erythrocyte membranes in patients with NAFLD, associated with the degree of fibrosis, necroinflammatory activity, manifestations of metabolic syndrome and indicators of liver damage, should be considered as promising biomarkers for assessing the severity of NAFLD.

Extended lipid profile in Romanian ischemic stroke patients in relation to stroke severity and outcome: a path analysis model.

IntroductionOur aim was to evaluate the extended lipid profile in ischemic stroke patients and the relationship with stroke type, severity and outcome.Material and methodsWe prospectively enrolled 124 ischemic stroke patients and 40 healthy controls; baseline plasma and erythrocyte membrane fatty acids concentrations and common lipid profile were analysed. Stroke severity was evaluated by NIHSS on admission, while the functional outcome was defined by mRS at discharge and after 3 months.ResultsTotal cholesterol, triglycerides, HDL-cholesterol, DHA, adrenic, stearic and lauric acid were all lower in patients, taking into account that 87.7% of patients did not receive statins before admission. There was a different pattern in plasma and erythrocyte membrane of fatty acids between patients and controls, also omega-3 index was significantly lower in patients. Patients with poor outcome without statins had significantly lower triglyceride (p = 0.028), while the total cholesterol levels were significantly lower in patients with poor outcome (p = 0.03) but with treatment initiated after admission. Bivariate analysis revealed that patients with poor outcome had significantly lower triglyceride levels regardless the statins use, while the total cholesterol and HDL-cholesterol levels were significantly lower in patients with poor outcome under statin treatment. The long-term outcome were positively influenced by age (β̂ = 0.22, p = 0.001), and NIHSS score at admission (β̂ = 0.55, p < 0.001), and negatively by cholesterol levels (β̂ = –0.17, p = 0.031).ConclusionsDHA, adrenic, stearic and lauric acid were lower in stroke patients; plasma adrenic acid was consumed during the acute phase. The most important predictors for long-term outcome was NIHSS at admission followed by age and total cholesterol.

Associations Between Erythrocyte Membrane Fatty Acid Compositions and Biomarkers of Vascular Health in Adults With Type 1 Diabetes With and Without Insulin Resistance: A Cross-Sectional Analysis

ObjectivesThe aim of this study was to assess the relationship between specific erythrocyte fatty acid levels and vascular health in type 1 diabetes (T1D) with and without insulin resistance (IR). MethodsWe analyzed baseline pretreatment data in a subset of 23 patients with T1D from a previously published randomized controlled trial consisting of comprehensive erythrocyte-derived fatty acid profiles and a panel of inflammation-associated endothelial markers. Estimated glucose disposal rate was used to identify and categorize patients with IR. We utilized principal component analysis (PCA) to cluster vascular biomarkers to compute a single “vascular signal” and utilized univariate linear regression models to investigate the association with IR and fatty acid profiles. ResultsSubjects with IR displayed significantly higher levels of linoleic acid (p=0.001), lower levels of eicosapentaenoic acid (EPA) (p<0.001), lower levels of omega-3 polyunsaturated fatty acid (n-3PUFA) (p<0.006) and an increased omega-6 (n-6)PUFA:n-3PUFA ratio (p=0.001). IR was associated with significantly higher linoleic acid levels, total n-6PUFA and an increased ratio of n-6PUFA:n-3PUFA, and negatively associated with arachidonic acid and EPA levels, total saturated fatty acid and total n-3PUFA. The PCA-derived vascular biomarker cluster was positively associated with linoleic acid and n-6PUFA:n-3PUFA ratio, and inversely associated with EPA. ConclusionsSpecific erythrocyte membrane fatty acid compositions are associated with impaired vascular health and IR in adults with T1D. These findings suggest that IR and risk of associated complications may be influenced by specific fatty acid profiles, and thus potentially modified by the selective targeting of dietary fatty acids.

Omega-3 Fatty Acids in Erythrocyte Membranes as Predictors of Lower Cardiovascular Risk in Adults without Previous Cardiovascular Events.

Background: This study investigated the association of omega-3 polyunsaturated fatty acids (n-3 PUFA) within erythrocyte membranes and cardiovascular risk assessed by three different estimates. Methods: Inclusion criteria were individuals of both sexes, 30 to 74 years, with at least one cardiovascular risk factor, and no previous cardiovascular events (n = 356). Exclusion criteria were individuals with acute or chronic severe diseases, infectious diseases, pregnant, and/or lactating women. Plasma biomarkers (lipids, glucose, and C-reactive protein) were analyzed, and nineteen erythrocyte membrane fatty acids (FA) were identified. The cardiovascular risk was estimated by Framingham (FRS), Reynolds (RRS), and ACC/AHA-2013 Risk Scores. Three patterns of FA were identified (Factor 1, poor in n-3 PUFA), (Factor 2, poor in PUFA), and (Factor 3, rich in n-3 PUFA). Results: Total cholesterol was inversely correlated with erythrocyte membranes C18:3 n-3 (r = −0.155; p = 0.004), C22:6 n-3 (r = −0.112; p = 0.041), and total n-3 (r = −0.211; p < 0.001). Total n-3 PUFA was associated with lower cardiovascular risk by FRS (OR = 0.811; 95% CI= 0.675–0.976). Regarding RRS, Factor 3 was associated with 25.3% lower odds to have moderate and high cardiovascular risk (OR = 0.747; 95% CI = 0.589–0.948). The ACC/AHA-2013 risk score was not associated with isolated and pooled FA. Conclusions: n-3 PUFA in erythrocyte membranes are independent predictors of low-risk classification estimated by FRS and RRS, which could be explained by cholesterol-lowering effects of n-3 PUFA.

Effect of pravastatin on erythrocyte membrane fatty acid contents in patients with chronic kidney disease.

BackgroundStatin treatment has decreased the risk of cardiovascular events in patients with chronic kidney disease (CKD). Erythrocyte membrane oleic acid level is higher in patients with acute coronary syndrome. This study aimed to evaluate the effect of pravastatin on the erythrocyte membrane fatty acid (FA) contents in patients with CKD.MethodsSixty-two patients were enrolled from January 2017 to March 2019 (NCT02992548). Pravastatin was initially administered at a dose of 20 mg for 24 weeks. The pravastatin dose was increased to 40 mg after 12 weeks if it was necessary to control dyslipidemia. The primary outcome was change in erythrocyte membrane FA, including oleic acid, after pravastatin treatment for 24 weeks.ResultsForty-five patients finished this study, and there was no adverse effect related to pravastatin. Compared with baseline, total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased after pravastatin treatment. Compared with baseline, saturated FA, oleic acid, and arachidonic acid levels were significantly increased and polyunsaturated FA and linoleic acid (LA) levels were significantly decreased after pravastatin treatment. There was also a decrease in eicosapentaenoic acid after pravastatin treatment in CKD patients with estimated glomerular filtration rate < 60 mL/min/1.73 m2.ConclusionAdministration of pravastatin in patients with CKD leads to a decrease in FA known to be protective against the risk of CVD. Omega-3 FA or LA supplementation might be necessary to recover changes in erythrocyte membrane FA contents when pravastatin is used for treating dyslipidemia in patients with CKD.

DeltaF508 CFTR Hetero- and Homozygous Paediatric Patients with Cystic Fibrosis Do Not Differ with Regard to Nutritional Status.

The purpose of this study was to compare the nutritional status between deltaF508 CFTR hetero- and homozygous paediatric patients with cystic fibrosis. We assessed the percentage profiles of fatty acids measured in erythrocyte membranes and the serum levels of vitamins A, D3, E and K1 in the studied groups. We also measured the weights and heights and calculated the body mass indexes (BMIs). The studied groups consisted of 34 heterozygous and 30 homozygous patients. No statistically significant differences were found in the serum vitamins or erythrocyte membrane fatty acid profiles between the hetero- and homozygous patient groups, except for heptadecanoic acid (p = 0.038). The mean percentiles of height, weight and BMI did not differ significantly between the two groups. The homozygous and heterozygous paediatric patients with cystic fibrosis were similar in terms of their nutritional statuses.

Proportions of long-chain ω-3 fatty acids in erythrocyte membranes of Canadian adults: Results from the Canadian Health Measures Survey 2012–2015

The Omega-3 Index (OI) is a proposed marker of coronary artery disease (CAD) risk. Another index, the EPA/arachidonic acid (AA) ratio has also been proposed as a possible risk marker for CAD. Our primary objective was to characterize the Canadian population subgroups that have an undesirable OI (<4%, associated with high CAD risk) and to identify the participants' characteristics most strongly associated with the OI. Our secondary objective was to identify the characteristics most strongly associated with the EPA/AA ratio. Data from 4025 adult participants of cycles 3 and 4 (2012-2015) of the cross-sectional Canadian Health Measures Survey were pooled. Adjusted mean proportions of erythrocyte membrane ω-3 (n-3) fatty acids, total ω-6 fatty acids, and ratios were analyzed by sociodemographic, health, and lifestyle characteristics using covariate-adjusted models. The mean OI was 4.5%. Almost 40% of Canadians had an undesirable (<4%) OI. ω-3 supplement use, fish intake, and race were the variables most strongly associated with OI scores. The prevalence of undesirable OI was significantly higher among participants consuming fish less than twice a week (43.8%; 95% CI: 39.0%, 48.6%) than among those consuming more fish (12.7%; 95% CI: 7.8%, 19.9%), among smokers (62.7%; 95% CI: 52.9%, 71.7%) than nonsmokers (33.4%; 95% CI: 29.4%, 37.7%), in whites (42.7%; 95% CI: 38.2%, 47.4%) than in Asians (23.0%; 95% CI: 15.4%, 33.0%), and in adults aged 20-39 y (49.6%; 95% CI: 42.3%, 56.9%) than in those aged 60-79 y (24.4%; 95% CI: 21.0%, 28.1%). ω-3 supplement intake and fish intake were the characteristics most strongly associated with EPA/AA. All P≤0.05. An important proportion of Canadian adults has an undesirable (<4%) OI, with higher prevalence in some subgroups. Further assessment is required to determine the value and feasibility of an increase in the population's OI to the currently proposed target of≥8% as a potential public health objective.

SATURATED FATTY ACIDS IN ERYTHROCYTE MEMBRANES IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

Objective: Type 1 diabetes mellitus (T1DM) is associated with early development of atherosclerosis. The aim of this study was to assess the association between saturated fatty acids (SFAs) contained in erythrocyte membranes and some indices of vascular damage in a sample of adolescents with T1DM. Design and method: Participants in regular follow-up at the Paediatric Diabetology Unit of Verona were sent for evaluation at the Vascular Laboratory of the General Medicine &amp; Hypertension Unit Central blood pressure (BP), Pulse Wave Velocity (PWV) and Pulse Wave Analysis (PWA) were measured by the SphygmoCor Xcel, carotid Intima Media Thickness (cIMT) and carotid distensibility (DC) by ultrasound and elaborated with a dedicated hardware. Blood samples were evaluated for erythrocyte membrane SFA, expressed as a percentage of total Fatty Acids (FAs). Results: Hundred and forty-seven adolescents (78 males and 69 females, mean age 17,25 ± 1,93 years) were studied. Fifteen patients were classified as hypertensive (10,2%) according to current European Guidelines. Thirteen patients had central systolic BP (cSBP) (8,8%), 60 cIMT (40,8%), 49 (33,3%) DC and 1 PWV (0,7%) above the 95th percentile for sex and age/height. We observed a correlation between total SFAs and cSB and z-cSBP (r = 0,260 and 0,269 respectively, p &lt; 0,05), not confirmed when each SFA was analysed separately. Furthermore, a positive correlation between total SFAs and either PWV or z-PWV was detectable (r = 0,241 and 0,251 respectively, p &lt; 0,05). The latter association remained significant even after adjustment for age, sex, Body Mass Index (BMI), duration of diabetes, HbA1c, total cholesterol, triglycerides-HDL ratio. Total SFAs were also associated with BMI (r = 0,191, p &lt; 0,05). Conclusions: Erythrocyte membrane FAs are associated with vascular (cSBP and PWV) and anthropometric parameters in patients with T1DM. The amount of SFAs in membranes does not depend only on diet, as they are also neo-synthetized from glucidic precursors. Thus, it can be speculated that a bad glycemic control could translate into a higher substrate amount to produce the different SFAs. Further studies are needed to better understand the mechanisms and the regulations of these pathways

Type 2 diabetes preventive effects with a 12-months sardine-enriched diet in elderly population with prediabetes: An interventional, randomized and controlled trial

Fish could play a role in preventing type 2 diabetes (T2D) but there has been little specification about the type of fish and the preventive mechanism involved in its health claim. The sardine is a source of omega-3 and taurine that, in isolation or in synergy, would produce T2D-delaying through different molecular mechanism. The consumption of twice a week of sardine, during one year would reduce T2D-developing risk in a population with prediabetes (preDM) and old age. 152 subjects with fasting glucose between 100-124 mg/dL aged ≥65 yo were recruited from three primary care centers in Barcelona and were randomly distributed among two interventional groups: control group (CG) and sardine group (SG). Both groups received same T2D-prevention nutritional during a year but only SG had to add 200 g of sardine per week. All variables were collected before to start and at the end of the diet. (ClinicalTrials.gov: NCT03557541). 152 people were randomized into CG (n=77) and SG (n=75) with 18 and 12 drop outs respectively. Subjects in SG, significantly compared to CG, decreased percentage classified-individuals in a very high risk group to develop T2D according to FINDRISC (p=0.035). In addition to increasing HDL-cholesterol and adiponectin and decreasing triglycerides (p<0.05) and blood pressure (<0.05), SG showed a lower HOMA-IR (p=0.032). The consumption of sardine characteristics nutrients as omega-3, EPA and DHA, vitamin D, fluorine and taurine were higher for SG (p<0.05). These results agreed with the increased of taurine, fatty acid (FA) omega-3 and bile acids circulating metabolites (p<0.05). Changes erythrocyte membrane FA were detected only in SG with a decrease of 5 omega-6 FA (p<0.001) and an increase of 3 omega-3 FA types (p<0.001). We conclude that a year T2D-prevention diet with sardine supplementation has a greater protective effect against developing T2D and CV events.