Erythrocyte Membrane Fatty Acid Composition Research Articles

Fatty acid composition of erythrocyte membranes in carries of rs174544 polymorphism of FADS1 gene and rs174583 polymorphism of FADS2 gene from central region of the Russian Federation before and after supplementation of their diet with ω-3 PUFAs

Numerous publications have demonstrated that polymorphisms in FADS1 and FADS2 gene cluster influence the levels of long chain polyunsaturated fatty acids (LC PUFAs) synthesized in the body from essential precursors. They can be consumed through the diet as well. These LC PUFAs perform important plastic and regulatory functions in the body. The associations between the polymorphisms of FADS genes and the fatty acid (FA) composition of the body with some inflammatory and chronic diseases were shown. To date, very few studies in the Russian Federation researched the distribution of polymorphic variants in FADS1 and FADS2 genes and no studies examined the effects of these polymorphisms on the level of FAs in tissues.So, the purpose of this paper was to study the frequency of genotypes and alleles of the rs174544 polymorphism of the FADS1 gene and the rs174583 polymorphism of the FADS2 gene and their influence on the FA composition of erythrocyte membranes in residents of the Central region of the Russian Federation (RF). Additionally, the effect of ω-3 PUFAs fortified food products on this composition was examined. MethodsThe study included 70 volunteers aged 23–69 years from Moscow region who provided informed consent. They were genotyped for rs174544 polymorphism of FADS1 gene and rs174583 polymorphism of FADS2 gene by real-time PCR. The participants of the study consumed fruit or vegetable smoothies enriched with either vegetable (chia seeds flour) or animal (fish oil flour) sources of ω-3 PUFAs for 1 month. The fatty acid composition of erythrocyte membranes in some of the volunteers was analysed using gas-chromatography before and after fortification of their diet with ω-3 PUFAs. Statistical analysis was performed using SPSS 23. ResultsThe frequency of genotypes and alleles of polymorphisms studied were similar to those published for the European region. For rs174544, the genotype frequencies were CC (61%), CA (29%), and AA (10%), frequency of allele A was 24%. For rs174583, the genotype frequencies were CC (51%), CT (39%), and TT (10%), frequency of allele T was 29%. Carriers of minor alleles of both polymorphisms studied had significantly higher levels of ω-6 and ω-3 LC PUFAs in erythrocyte membranes compared to those carrying other genotypes. This differs from the results of other studies where carriers of minor alleles as were shown to be slow converters of precursors to LC PUFAs. The reason of the discrepancy was most likely associated with the obesity and dietary preferences of our study participants who carry the minor alleles. Over the period of one-month consumption of food sources providing an additional intake of either 2 g/day ω-3 PUFAs from fish oil or 6.5 g/day of ω-3 PUFAs from chia seed flour markedly reduced the incorporation of ω-6 PUFAs into erythrocyte membranes in carriers of minor alleles. Additionally, there was an increase in the content of saturated palmitic acid in the membranes that noticeably changed the fatty acid composition of erythrocyte membranes. ConclusionOur results confirm the observation that blood fatty acid composition related to polymorphisms of FADS gene is highly influenced by BMI. The incorporation of ω-6 PUFAs into erythrocyte membranes decreases when the diet is fortified with ω-3 PUFAs. This decrease can help reduce the formation of pro-inflammatory eicosanoids and the risk of various inflammatory and chronic diseases, especially in carriers of minor alleles of the genetic polymorphisms studied.

Sex differences in erythrocyte fatty acid composition of first-diagnosed, drug-naïve patients with major depressive disorders.

Background: Since depression, sex hormones, and fatty acid status are interrelated, it is important to understand their relationships. In this study, we aimed to investigate sex differences in erythrocyte membrane fatty acid composition among first-diagnosed, drug-naïve patients with major depressive disorders. Methods: The study included 139 individuals with first-diagnosed, drug-naïve depression (male/female = 48/91) and 55 healthy controls (male/female = 24/31). The levels of erythrocyte membrane fatty acids were analyzed to compare the difference between males and females in both patients with depression and healthy controls, as well as to study their correlation with depressive symptoms. Results: In first-diagnosed, drug-naïve patients with major depressive disorders, sex disparities were observed in the levels of erythrocyte saturated fatty acids (SFAs) and n-6 PUFAs (such as C18:0, C20:4n6 and C22:4n6), where higher levels evident in females compared to in males. We found a noteworthy correlation between fatty acid levels and depressive symptoms, in which there is a significant association between female patients and depression but a weaker association between male patients and depression. Conclusion: Our findings demonstrate higher levels of n-6 PUFAs and SFAs in female patients with depression. The relationship between fatty acid composition and depressive symptoms was more prominent in females than males. These findings highlight the significance of considering sex as a crucial and interconnected factor in future investigations and potential adjunctive treatment for mood disorders by targeting fatty acid metabolism.

Alterations in plasma and erythrocyte membrane fatty acid composition following exposure to toxic copper level affect membrane deformability and fluidity in female wistar rats

BackgroundDeformability and fluidity function of the red blood cell membrane are properties defined by the lipid composition. Toxic copper level induces membrane lipid peroxidation which could cause membrane instability. This study therefore investigated the effect of exposure to toxic copper level for 30 days on red blood cell membrane deformability and fluidity in female Wistar rats. MethodsTwelve (12) female Wistar rats (160 ± 10 g) were randomly grouped (n = 6) into control (given 0.1 ml distilled water p.o.) and copper-toxic (100 mg/kg Copper Sulphate, p.o.), and treated for 30 days. Plasma obtained and RBC membrane prepared from blood collected over EDTA post-treatment were assayed for total cholesterol (TC), phospholipids and fatty acid profile using spectrophotometry and Gas chromatography while heparinized blood was subjected to fragility test. Data were analyzed using student T-test for statistical significance at p < 0.05. Results and conclusionPlasma TC increased by 4.33% while RBC membrane TC decreased by 20.32% in copper-toxic group compared to control. Compared to control, excess copper significantly increased membrane phospholipids level (0.72 ± 0.01 vs 0.59 ± 0.04 mg/dL) but reduced membrane cholesterol/phospholipid ratio (46.61 ± 4.72 vs 72.66 ± 6.47) and stability (by 23.53%). Number of cis- and saturated fatty acids increased in copper-treated plasma and RBC membrane compared to control. Exposure to toxic copper level alters erythrocyte membrane fluidity and deformability by disrupting membrane lipid composition, saturation, bond configuration in phospholipids and permeability.

Erythrocyte Membrane Fatty Acid Composition as a Potential Biomarker for Depression.

Major depressive disorders is a chronic and severe psychiatric disorder with poor prognosis and quality of life. Abnormal erythrocyte fatty acid (FA) composition in depressed patients were found in our previous study, but the relationship between erythrocyte membrane FA levels and different severity of depressive and anxiety symptoms remains to be explored. This cross-sectional study included 139 patients with first-diagnosed, drug-naïve depression and 55 healthy controls whose erythrocyte FA composition was analyzed. Patients with depression were divided into severe depression and mild to moderate depression or depression with severe anxiety and mild to moderate anxiety. Then the differences of FA levels among different groups were analyzed. Finally, the receiver operating characteristic curve analysis was applied to identify potential biomarkers in distinguishing the severity of depressive symptoms. Levels of erythrocyte membrane FAs were elevated among patients with severe depression compared with healthy controls or patients with mild to moderate depression of almost all kinds. While C18:1n9t (elaidic acid), C20:3n6 (eicosatrienoic acid), C20:4n6 (arachidonic acid), C22:5n3 (docosapentaenoic acid), total fatty acids (FAs), and total monounsaturated FAs were elevated in patients with severe anxiety compared with patients with mild to moderate anxiety. Furthermore, the level of arachidonic acid, C22:4n6 (docosatetraenoic acid), elaidic acid, and the combination of all 3 were associated with the severity of depressive symptoms. The results suggested that erythrocyte membrane FA levels have the potential to be the biological indicator of clinical characteristics for depression, such as depressive symptoms and anxiety. In the future, more research is needed to explore the causal association between FA metabolism and depression.

High levels of eicosapentaenoic acid are associated with lower pericoronary adipose tissue attenuation as measured by coronary CTA

Background and aimsHigher pericoronary adipose tissue (PCAT) attenuation, a novel marker of inflammation in coronary CT angiography (CTA), has been shown to indicate increased cardiac mortality. Supplementation of eicosapentaenoic acid (EPA) has been shown to decrease cardiovascular death. Whether blood levels of n-3 fatty acids are associated with differences in PCAT attenuation is unknown. MethodsThis is a cross-sectional analysis including 64 symptomatic patients who underwent coronary CTA. PCAT attenuation was measured in Hounsfield Units (HU) around the proximal 40 mm of the right coronary artery using semi-automated software. Erythrocyte membrane fatty acid composition was analyzed using gas chromatography. Individual fatty acids were expressed as a percentage of total identified fatty acids. ResultsThe patient cohort was divided into two groups using the median PCAT attenuation of −78.1 HU (each n = 32). No differences were seen in age, sex, BMI or traditional cardiovascular risk factors (CVRF) between groups (all p > 0.05). In univariable analysis, significantly higher values of EPA (1.00% [0.78; 1.26] vs. 0.78% [0.63; 0.99]; p = 0.02) were seen in patients with lower PCAT attenuation. All other fatty acids showed no differences (all p > 0.05). Moreover, a significant negative correlation was seen between PCAT attenuation and EPA (CC: 0.38; p = 0.002). In multivariable analysis, an inverse association of EPA with PCAT attenuation existed (ß = −0.31, p = 0.017), independent of age, gender, BMI and number of CVRF (all p > 0.1). ConclusionsHigh levels of EPA are associated with lower PCAT attenuation on coronary CTA. This may indicate a different composition of pericoronary adipose tissue, potentially caused by a lower degree of coronary inflammation.

Fatty acid composition of the erythrocyte membrane and risk of hepatocellular carcinoma in cirrhotic patients.

Disturbances in fatty acid (FA) metabolism have been reported in cirrhosis, but the role of FAs in the development of hepatocellular carcinoma (HCC) is still unclear. Biomarkers are a promising means to explore the associations between exogenous intake or endogenous production of FAs and cancer risk. To estimate the relationship between fatty acid content in erythrocyte membranes and HCC risk in cirrhotic patients METHODS: The "CiRCE" case-control study recruited cirrhotic patients from six French hospitals between 2008 and 2012. Cases were cirrhotic patients with HCC (n = 349); controls were cirrhotic patients without HCC at inclusion (n = 550). FA composition of phospholipids in erythrocyte membranes was determined by high performance gas chromatography. Odds ratios for HCC risk according to FA concentrations were estimated with multivariable logistic regression. HCC patients were older and more often men (P < 0.001). In both groups, saturated FAs represented more than 39% of all FAs in erythrocyte membranes, mono-unsaturated FAs around 14%, and polyunsaturated FAs around 46%. High levels of C15:0 + C17:0, C20:1 n-9, C18:2 n-6 and C20:2 n-6 were associated with higher risk of HCC. The levels of C18:0 and C20:4 n-6 were lower in HCC cases than in controls. The FA composition of erythrocyte membranes differed according to the presence of HCC with higher levels of saturated FAs, linoleic and eicosadienoic acids, and lower levels of stearic and arachidonic acids. These alterations may reflect particular dietary patterns and/or altered FA metabolism. Further investigations are warranted.

Effect of flaxseed oil supplementation on the erythrocyte membrane fatty acid composition and endocannabinoid system modulation in patients with coronary artery disease: a double-blind randomized controlled trial

BackgroundThe endocannabinoid system (ECS) overactivation, associated with increased inflammatory process, may act as a risk factor for coronary artery disease (CAD). Dietary fat may influence the ECS tone. The aim of the present study was to investigate the effect of flaxseed oil on the erythrocyte membrane fatty acid profile and ECS activity by the measurement of serum N-arachydonoil ethanolamine (AEA) and cannabinoid receptor type-1 (CB1), cannabinoid receptor type-2 (CB2), and fatty acid amide hydrolase (FAAH) mRNA expression.MethodsThis clinical trial was performed on 44 patients with CAD. The intervention group received 1.5% fat milk supplemented with flaxseed oil (containing 2.5 g α-linolenic acid or ALA), while the placebo group received 1.5% fat milk for 10 weeks. The fatty acid profile of erythrocyte membrane phospholipids was measured by gas chromatography. The AEA level was determined using an ELISA kit, and real-time PCR was performed to measure CB1, CB2, and FAAH mRNA expression pre- and post-intervention.ResultsFlaxseed oil supplementation resulted in a significant increase in the ALA content and a significant reduction in linoleic acid (LA) content of membrane phospholipids, compared to the placebo group (MD = − 0.35 and 2.89, respectively; P < 0.05). The within group analysis showed that flaxseed oil supplementation caused a significant reduction in both LA and arachidonic acid (MD = − 4.84 and − 4.03, respectively; P < 0.05) and an elevation in the ALA (MD = 0.37, P < 0.001) content of membrane phospholipids compared with the baseline. In the intervention group, a marked reduction was observed in the serum AEA level after 10 weeks of intervention, compared with the placebo group (MD = 0.64, P = 0.016). Changes in CB2 mRNA expression in the flaxseed oil group were significant (fold change = 1.30, P = 0.003), compared with the placebo group.ConclusionFlaxseed oil supplementation could attenuate the ECS tone by decreasing the AEA level and increasing CB2 mRNA expression. Therefore, flaxseed oil may be considered a promising agent with cardioprotective properties.

Erythrocyte Membrane and Plasma Fatty Acids Composition in Patients with Coronary Heart Disease Requiring Percutaneous Angioplasty

Aims: Atherosclerosis is associated with oxidative stress and fatty acid composition plays a critical role in vascular endothelial dysfunction and injury leading to the coronary atherosclerotic progression. However, the correlation between the fatty acid profile and coronary atherosclerosis is debatable. The goal of this study is to assess the erythrocyte membrane and plasma fatty acid composition in patients with coronary heart disease.&#x0D; Methods: The erythrocyte membrane and plasma distributions of fatty acids were quantified in patients with coronary heart disease (n = 30, group A) which needs both intensive medication and elective percutaneous coronary intervention and age-matched controls (n = 38, group B) using high-performance liquid chromatography combined with evaporative light scattering detection method. Baseline data were extracted from medical records.&#x0D; Results: Logistic regression analysis demonstrated that hypoalbuminemia (p = 0.010) and HbA1c (p = 0.005) are associated with required percutaneous coronary intervention. Although appropriate logistic regression model for percutaneous coronary intervention could not be obtained by incorporating fatty acid components, percutaneous coronary intervention was correlated mostly to the increased oleic acid and decreased stearic acid in both erythrocyte membrane and plasma in receiver-operating characteristic analysis.&#x0D; Conclusion: This single-center, cross-sectional study indicated that erythrocyte membrane and plasma fatty acids have a potential impact on the coronary atherosclerotic progression which requires coronary intervention. Longitudinal studies are necessary to clarify the clinical role of fatty acids distribution as a novel atherogenic marker.

P6164High level of EPA is associated with lower perivascular coronary attenuation as measured by coronary CTA

Abstract Introduction Pericoronary adipose tissue (PCAT) composition has been recently shown to be a potential novel marker of coronary inflammation with higher PCAT attenuation shown to indicate increased cardiac mortality. Polyunsaturated fatty acids (PUFAs), especially Omega-3 fatty acids (n3), are thought to alter inflammatory response and intake of high dose Eicosapentaenoic acid (EPA, C20_5 n3) was shown to decrease mortality, however exact pathophysiological mechanisms are unclear. Therefore, we sought to determine whether blood levels of PUFAs are associated with differences in pericoronary fat attenuation. Methods In 64 symptomatic patients with intermediate pretest-likelihood for coronary artery disease presenting with atypical angina, coronary CTA was performed. PCAT attenuation was measured in Hounsfield Units (HU) around the proximal 40mm of the right coronary artery (RCA) using semi-automated software. Erythrocyte membrane fatty acid composition (in percentage) was analyzed with a standardized analytical methodology, displaying a variety of fatty acids including n-3 fatty acids using gas chromatography. Results Patients were divided into two groups (each n=32) using the median PCAT attenuation of −78.1 Hounsfield units (HU), resulting in one group with low (−95.58 to −78.17 HU) and one with high (−78.06 to −62.92 HU) PCAT attenuation. Among both groups, no differences were seen in age, sex, BMI, traditional cardiovascular risk factors or the number of cardiovascular risk factors (all p&gt;0.05). In univariate analysis, significantly higher values of EPA (1.00% [0.78; 1.26] vs. 0.78% [0.63; 0.99]; p=0.02) were seen in patients with lower PCAT attenuation. All other fatty acids showed no significant differences (all p&gt;0.05). Moreover, a significant negative correlation was seen between PCAT attenuation and EPA (Pearson correlation coefficient −0.38; p=0.002), but not for age, sex, BMI or number of cardiovascular risk factors (all p&gt;0.1). Multivariable linear regression analysis confirmed this association and showed a significant inverse association of EPA to PCAT attenuation (β=−0.31, p=0.017), independent of age, gender, BMI and number of CV risk factors (all p&gt;0.1). Conclusion High levels of EPA are associated with lower PCAT attenuation on coronary CTA indicating different composition of pericoronary adipose tissue potentially caused by a lesser degree of coronary inflammation.

Association between Erythrocyte Membrane Phospholipid Fatty Acids and Sleep Disturbance in Chinese Children and Adolescents.

The relationship between circulating fatty acid (FA) composition and childhood sleep disturbance remains largely unclear. We aimed to investigate the association of erythrocyte membrane FA composition with prevalence of sleep disturbance in Chinese children and adolescents. A cross-sectional survey was conducted among 2337 school-aged children and adolescents who completed a clinical assessment in Beijing, China. Presence of sleep disturbance was self-reported or parent-reported by questionnaires. Erythrocyte FAs were measured by gas chromatography, and desaturase activities were estimated by FA ratios. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for sleep disturbance across FA quartiles were calculated by a logistical regression model. We found higher proportions of erythrocyte phospholipid 24:0, 24:1n-9, and lower proportions of total n-3 polyunsaturated FA (PUFA), 22:5n-3 and 22:6n-3 in participants with sleep disturbance compared with those without. In the logistical regression models, significant inverse associations were found for total n-3 PUFA, 22:5n-3 and 22:6n-3, the highest versus lowest quartile ORs and 95% CIs were 0.57 (0.40, 0.82), 0.67 (0.47, 0.97) and 0.69 (0.49, 0.96), respectively. For per 1 SD difference of proportion, OR and 95% CI of prevalence of sleep disturbance was 0.91 (0.86, 0.97) for total n-3 PUFA, 0.90 (0.82, 0.98) for 22:5n-3, and 0.92 (0.86, 0.99) for 22:6n-3, respectively. No significant association was found for saturated fatty acids, monounsaturated fatty acids, n-6 polyunsaturated fatty acids or FA ratios. The present study suggested that erythrocyte n-3 PUFAs, especially 22:5n-3 and 22:6n-3, are inversely associated with prevalence of sleep disturbance in Chinese children and adolescents.

Randomized trial of omega-3 for autism spectrum disorders: Effect on cell membrane composition and behavior

A high ω6/ω3 ratio [fatty acid (FA) index] in the cell membrane has been associated with inadequate brain development. It has started to be used as a biomarker of treatment efficacy in human diseases. The aim of this study was to investigate if omega-3 supplementation improves erythrocyte membrane ω6/ω3, plasma antioxidant status (TAS) and autistic behaviors. A randomized, crossover, placebo-controlled study was designed to investigate the effect of 8 weeks of supplementation with ω3 (962mg/d and 1155mg/d for children and adolescents, respectively). Sixty-eight children and adolescents with Autism Spectrum Disorders (ASD) completed the full protocol. Primary outcome measures were erythrocyte membrane FA composition and TAS. Secondary outcome measures were Social Responsiveness Scale and Clinical Global Impression-Severity. Treatment with ω3 improved the erythrocyte membrane ω6/ω3 ratio (treatment effect p<0.008, d=0.66; within subjects effect p<0.007, d=0.5) without changing TAS. There was a within subjects significant improvement in Social Motivation and Social Communication subscales scores, with a moderate to large effect size (p=0.004, d=0.73 and p=0.025, d=0.79 respectively), but no treatment effect (treatment-placebo order). Carryover effects cannot be discarded as responsible for the results in behavioral measures. In conclusion, supplementation with ω3 FA might be studied as an add-on to behavioral therapies in ASD. Optimal duration of treatment requires further investigation. With regard to side effects, the effect of this supplementation on the lipid profile needs monitoring.

Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders.

Fatty acids (FAs) are involved in cellular processes important for normal body function, and perturbation of FA balance has been linked to metabolic disturbances, including type 2 diabetes. An individual’s level of FAs is affected by diet, lifestyle, and genetic variation. We aimed to improve the understanding of the mechanisms and pathways involved in regulation of FA tissue levels, by identifying genetic loci associated with inter-individual differences in erythrocyte membrane FA levels. We assessed the levels of 22 FAs in the phospholipid fraction of erythrocyte membranes from 2,626 Greenlanders in relation to single nucleotide polymorphisms genotyped on the MetaboChip or imputed. We identified six independent association signals. Novel loci were identified on chromosomes 5 and 11 showing strongest association with oleic acid (rs76430747 in ACSL6, beta (SE): -0.386% (0.034), p = 1.8x10-28) and docosahexaenoic acid (rs6035106 in DTD1, 0.137% (0.025), p = 6.4x10-8), respectively. For a missense variant (rs80356779) in CPT1A, we identified a number of novel FA associations, the strongest with 11-eicosenoic acid (0.473% (0.035), p = 2.6x10-38), and for variants in FADS2 (rs174570), LPCAT3 (rs2110073), and CERS4 (rs11881630) we replicated known FA associations. Moreover, we observed metabolic implications of the ACSL6 (rs76430747) and CPT1A (rs80356779) variants, which both were associated with altered HbA1c (0.051% (0.013), p = 5.6x10-6 and -0.034% (0.016), p = 3.1x10-4, respectively). The latter variant was also associated with reduced insulin resistance (HOMA-IR, -0.193 (0.050), p = 3.8x10-6), as well as measures of smaller body size, including weight (-2.676 kg (0.523), p = 2.4x10-7), lean mass (-1.200 kg (0.271), p = 1.7x10-6), height (-0.966 cm (0.230), p = 2.0x10-5), and BMI (-0.638 kg/m2 (0.181), p = 2.8x10-4). In conclusion, we have identified novel genetic determinants of FA composition in phospholipids in erythrocyte membranes, and have shown examples of links between genetic variants associated with altered FA membrane levels and changes in metabolic traits.

Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial.

BackgroundNutrition therapy is the cornerstone of treating diabetes mellitus. The inclusion of fish (particularly oily fish) at least two times per week is recommended by current international dietary guidelines for type 2 diabetes. In contrast to a large number of human studies examining the effects of oily fish on different cardiovascular risk factors, little research on this topic is available in patients with type 2 diabetes. The aims of this pilot study were to investigate the effects of a sardine-enriched diet on metabolic control, adiponectin, inflammatory markers, erythrocyte membrane fatty acid (EMFA) composition, and gut microbiota in drug-naïve patients with type 2 diabetes.Methods35 drug-naïve patients with type 2 diabetes were randomized to follow either a type 2 diabetes standard diet (control group: CG), or a standard diet enriched with 100 g of sardines 5 days a week (sardine group: SG) for 6 months. Anthropometric, dietary information, fasting glycated hemoglobin, glucose, insulin, adiponectin, inflammatory markers, EMFA and specific bacterial strains were determined before and after intervention.ResultsThere were no significant differences in glycemic control between groups at the end of the study. Both groups decreased plasma insulin (SG: −35.3 %, P = 0.01, CG: −22.6 %, P = 0.02) and homeostasis model of assessment - insulin resistance (HOMA-IR) (SG: −39.2 %, P = 0.007, CG: −21.8 %, P = 0.04) at 6-months from baseline. However only SG increased adiponectin in plasma compared to baseline level (+40.7 %, P = 0.04). The omega-3 index increased 2.6 % in the SG compared to 0.6 % in the CG (P = 0.001). Both dietary interventions decreased phylum Firmicutes (SG and CG: P = 0.04) and increased E. coli concentrations (SG: P = 0.01, CG: P = 0.03) at the end of the study from baseline, whereas SG decreased Firmicutes/Bacteroidetes ratio (P = 0.04) and increased Bacteroides-Prevotella (P = 0.004) compared to baseline.ConclusionsAlthough enriching diet with 100 g of sardines 5 days a week during 6 months to a type 2 diabetes standard diet seems to have neutral effects on glycemic control in drug-naïve patients with type 2 diabetes, this nutritional intervention could have beneficial effects on cardiovascular risk. Furthermore, both dietary interventions decreased HOMA-IR and altered gut microbiota composition of drug-naïve patients with type 2 diabetes.Trial registrationTrial number and name of the registry: NCT02294526, ClinicalTrials.govElectronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0245-0) contains supplementary material, which is available to authorized users.

Automodification of PARP and fatty acid-based membrane lipidome as a promising integrated biomarker panel in molecular medicine.

Establishing by statistical analyses whether the analyses of auto-modified poly(ADP-ribose)polymerase and erythrocyte membrane fatty acid composition (Fat Profile(®)), separately or in tandem, help monitoring the physio-pathology of the cell, and correlate with diseases, if present. Ninety five subjects were interviewed and analyzed blindly. Blood lymphocytes and erythrocytes were prepared to assay poly(ADP-ribose)polymerase automodification and fatty acid based membrane lipidome, respectively. Poly(ADP-ribose)polymerase automodification levels confirmed their correlation with DNA damage extent, and allowed monitoring disease activity, upon surgical/therapeutic treatment. Membrane lipidome profiles showed lipid unbalance mainly linked to inflammatory states. Statistically both tests were separately significant, and correlated each other within some pathologies. In the laboratory routine, both tests, separately or in tandem, might be a preliminary and helpful step to investigate the occurrence of a given disease. Their combination represents a promising integrated panel for sensible, noninvasive and routine health monitoring.

Erythrocyte Membrane Fatty Acid Composition in Premenopausal Patients with Iron Deficiency Anemia

Iron deficiency anemia (IDA) is one of the most common nutritional disorders in the world. In the present study, we evaluated erythrocyte membrane fatty acid composition in premenopausal patients with IDA. Blood samples of 102 premenopausal women and 88 healthy control subjects were collected. After the erythrocytes were separated from the blood samples, the membrane lipids were carefully extracted, and the various membrane fatty acids were measured by gas chromatography (GC). Statistical analyses were performed with the SPSS software program. We used blood ferritin concentration <15 ng/mL as cut-off for the diagnosis of IDA. The five most abundant individual fatty acids obtained were palmitic acid (16:0), oleic acid (18:1, n-9c), linoleic acid (18:2, n-6c), stearic acid (18:0), and erucic acid (C22:1, n-9c). These compounds constituted about 87% of the total membrane fatty acids in patients with IDA, and 79% of the total membrane fatty acids in the control group. Compared with control subjects, case patients had higher percentages of palmitic acid (29.9% case versus 25.3% control), oleic acid (16.8% case versus 15.1% control), and stearic acid (13.5% case versus 10.5% control), and lower percentages of erucic acid (11.5% case versus 13.6% control) and linoleic acid (15.2% case versus 15.4% control) in their erythrocyte membranes. In conclusion, the total-erythrocyte-membrane saturated fatty acid (SFA) composition in premenopausal women with IDA was found to be higher than that in the control group; however, the total-erythrocyte-membrane unsaturated fatty acid (UFA) composition in premenopausal women with IDA was found to be lower than that in the control group. The differences in these values were statistically significant.

Associations between a fatty acid desaturase gene polymorphism and blood arachidonic acid compositions in Japanese elderly

We investigated whether the single nucleotide polymorphism rs174547 (T/C) of the fatty acid desaturase-1 gene, FADS1, is associated with changes in erythrocyte membrane and plasma phospholipid (PL) long-chain polyunsaturated fatty acid (LCPUFA) composition in elderly Japanese participants (n=124; 65 years or older; self-feeding and oral intake). The rs174547 C-allele carriers had significantly lower arachidonic acid (ARA; n-6 PUFA) and higher linoleic acid (LA, n-6 PUFA precursor) levels in erythrocyte membrane and plasma PL (15% and 6% ARA reduction, respectively, per C-allele), suggesting a low LA to ARA conversion rate in erythrocyte membrane and plasma PL of C-allele carriers. α-linolenic acid (n-3 PUFA precursor) levels were higher in the plasma PL of C-allele carriers, whereas levels of the n-3 LCPUFAs eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) were unchanged in erythrocyte membrane and plasma PL. Thus, rs174547 genotypes were significantly associated with different ARA compositions of the blood of elderly Japanese.

First-episode bipolar disorder is associated with erythrocyte membrane docosahexaenoic acid deficits: Dissociation from clinical response to lithium or quetiapine

Deficits in long-chain omega-3 (LCn−3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with the pathophysiology of bipolar disorder. However, LCn−3 fatty acid status at the initial onset of mania and its association with treatment response are not known. Erythrocyte membrane fatty acid composition was determined in first-episode bipolar manic or mixed (n=40) and healthy (n=40) subjects. Mood symptom ratings were obtained with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Erythrocyte fatty acid composition and clinical ratings were also determined within a sub-group of bipolar subjects following 8-week (n=19) or 52-week (n=11) open-label treatment with lithium or quetiapine. At baseline bipolar subjects exhibited significantly lower erythrocyte docosahexaenoic acid (DHA, 22:6n−3) composition compared with healthy subjects (−23%, p<0.0001). EPA (20:5n−3) and docosapentanoic acid (22:5n−3), and LCn−6 fatty acids including arachidonic acid were not different. Following 8- or 52-week treatment with lithium or quetiapine, YMRS and HDRS total scores decreased significantly whereas erythrocyte fatty acids including DHA did not change. These data indicate that selective erythrocyte DHA deficits coincide with the initial onset of manic symptoms, and reductions in mood symptoms following treatment are not mediated by changes in fatty acid status.

Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): A randomized placebo-controlled intervention trial

ObjectiveTo determine whether supplementation with the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) affects behavioral symptoms and cognitive impairments in children 6–12 years of age diagnosed with attention-deficit/hyperactivity disorder (ADHD). Study designThe randomized, double-blind placebo-controlled 16 weeks trial was conducted with 95 children diagnosed with ADHD according to DSM-IV criteria. Behavior was assessed by parents, teachers and investigators using standardized rating scales and questionnaires. Further outcome variables were working memory, speed of information processing and various measures of attention. For a subgroup of 81 participants, erythrocyte membrane fatty acid composition was analyzed before and after the intervention. ResultsSupplementation with the omega-3 fatty acid mix increased EPA and DHA concentrations in erythrocyte membranes and improved working memory function, but had no effect on other cognitive measures and parent- and teacher-rated behavior in the study population. Improved working memory correlated significantly with increased EPA, DHA and decreased AA (arachidonic acid).

Dietary fish oil improves endothelial function and lowers blood pressure via suppression of sphingolipid-mediated contractions in spontaneously hypertensive rats

Long-chain n-3 polyunsaturated fatty acids from oily fish reduce blood pressure (BP) in hypertension. Previously, we demonstrated that hypertension is associated with marked alterations in sphingolipid biology and elevated ceramide-induced vasoconstriction. Here we investigated in spontaneously hypertensive rats (SHRs) whether fish oil improves endothelial function including reduced vascular contraction induced via the sphingolipid cascade, resulting in reduced BP. Twelve-week-old SHRs were fed a control or fish oil-enriched diet during 12 weeks, and BP was recorded. Plasma sphingolipid levels were quantified by mass spectrometry and the response of isolated carotid arteries towards different stimuli was measured. Furthermore, erythrocyte membrane fatty acid composition, thromboxane A2 formation and cytokine secretion in ex-vivo lipopolysaccharide-stimulated thoracic aorta segments were determined. The fish oil diet reduced the mean arterial BP (P < 0.001) and improved endothelial function, as indicated by a substantially increased relaxation potential towards ex-vivo methacholine exposure of the carotid arteries (P < 0.001). The long-chain n-3 polyunsaturated fatty acid diet resulted in altered levels of specific (glucosyl)ceramide subspecies (P < 0.05), reduced membrane arachidonic acid content (P < 0.001) and decreased thromboxane concentrations in plasma (P < 0.01). Concomitantly, the fish oil diet largely reduced ceramide-induced contractions (P < 0.01), which are predominantly mediated by thromboxane. Furthermore, thromboxane A2 and interleukin-10 were reduced in supernatants of lipopolysaccharide-stimulated thoracic aorta of SHRs fed the fish oil diet while RANTES (regulated on activation, normal T-cell expressed and secreted) was enhanced. This may contribute to reduced vasoconstriction in vivo. Dietary fish oil lowers BP in SHRs and improves endothelial function in association with suppression of sphingolipid-dependent vascular contraction.

Auto-Modification of Poly (ADP-Ribose) Polymerase and Membrane Lipid Composition as Diagnostic Tools to Measure the Physio-Pathological State of the Cell

Poly(ADPribosyl)ation, catalysed by poly(ADP-ribose)polymerases, affects many cellular events and has a recognized epigenetic role. Nuclear poly(ADP-ribose)polymerases 1 and 2 are hyper activated by DNA strandbreaks. They auto-modify with large polymers of ADP-ribose and recruit DNA repair proteins. The more the DNA strand-breaks, the more poly(ADP-ribose) polymerase modifies itself. On the other hand, dietary lipids can be signaling molecules, lead to pro-(ω6)/ anti-(ω3) inflammatory compounds, and be included in biomembranes, good biomarkers of their unbalance. Here, we report the results obtained from an epidemiological study to establish whether the combination of two different analyses, i.e. detecting auto-modified poly (ADP-ribose) polymerase levels and analyzing erythrocyte membrane fatty acid composition, might help to monitor the physio-pathological state of the cell, and to correlate with lifestyle, diet or diseases. The two analyses were carried blindly on 70 subjects undergoing endoscopy. They were first interviewed, to collect anamnesis and clinical data, if present. Lymphocytes and erythrocytes were prepared from venous blood to assay poly (ADP-ribose) polymerase auto modification and membrane fatty acid content, respectively. The results were statistically evaluated. The measure of poly (ADP-ribose) polymerase automodification confirmed that its levels correlate with DNA damage extent, within the same pathology, and allowed to monitor the clinical activity of the disease, depending on ongoing therapeutic/surgical treatment. Membrane fat profile was able to evidence unbalance of lipids linked to both diet/lifestyle and inflammatory states leading to diseases. Both analyses provide possible biomarkers for sensible, non-invasive and routine monitoring.