Plasma Ceramides and Sphingomyelins and Sudden Cardiac Death in the Cardiovascular Health Study.

Importance: Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities. Whether the length of the fatty acid acylated to plasma sphingolipid species is associated with SCD risk is not known. Objective: To determine whether the saturated fatty acid length of plasma ceramides and sphingomyelins influences the association with SCD risk. Design, Setting, and Participants: In this cohort study, multivariable Cox proportional hazards regression models were used to examine the association of sphingolipid species with SCD risk. The study population included 4612 participants in the Cardiovascular Health Study followed up prospectively for a median of 10.2 (IQR, 5.5-11.6) years. Baseline data were collected from January 1992 to December 1995 during annual examinations. Data were analyzed from February 11, 2020, to September 9, 2023. Exposures: Eight plasma sphingolipid species (4 ceramides and 4 sphingomyelins) with saturated fatty acids of 16, 20, 22, and 24 carbons. Main Outcome and Measure: Association of plasma ceramides and sphingomyelins with saturated fatty acids of different lengths with SCD risk. Results: Among the 4612 CHS participants included in the analysis (mean [SD] age, 77 [5] years; 2724 [59.1%] women; 6 [0.1%] American Indian; 4 [0.1%] Asian; 718 [15.6%] Black; 3869 [83.9%] White, and 15 [0.3%] Other), 215 SCD cases were identified. In adjusted Cox proportional hazards regression analyses, plasma ceramides and sphingomyelins with palmitic acid (Cer-16 and SM-16) were associated with higher SCD risk per higher SD of log sphingolipid levels (hazard ratio [HR] for Cer-16, 1.34 [95% CI, 1.12-1.59]; HR for SM-16, 1.37 [95% CI, 1.12-1.67]). Associations did not differ by baseline age, sex, race, or body mass index. No significant association of SCD with sphingolipids with very-long-chain saturated fatty acids was observed after correction for multiple testing (HR for ceramide with arachidic acid, 1.06 [95% CI, 0.90-1.24]; HR for ceramide with behenic acid, 0.92 [95% CI, 0.77-1.10]; HR for ceramide with lignoceric acid, 0.92 [95% CI, 0.77-1.09]; HR for sphingomyelin with arachidic acid, 0.83 [95% CI, 0.71-0.98]; HR for sphingomyelin with behenic acid, 0.84 [95% CI, 0.70-1.00]; HR for sphingomyelin with lignoceric acid, 0.86 [95% CI, 0.72-1.03]). Conclusions and Relevance: The findings of this large, population-based cohort study of SCD identified that higher plasma levels of Cer-16 and SM-16 were associated with higher risk of SCD. Future studies are needed to examine the underlying mechanism of these associations.

Mixing Behavior of the Binary Monolayers of Fatty Acids Based on Their Cohesive Energy Differences.

The morphology involving the height difference and the surface roughness of the binary monolayers of saturated fatty acids were evaluated using atomic force microscopy (AFM) to investigate the mixing behavior of their monolayers. AFM observations revealed that the mixed monolayers of (palmitic acid/arachidic acid) and (arachidic acid/lignoceric acid), which had four methylene group differences between fatty acids, were in a molecularly mixed state. Further, the mixed monolayer of (stearic acid/lignoceric acid), which had six methylene group differences, was in a phase-separated state. From the results of the present and previous studies, it became clear that the difference in the cohesive energy between fatty acids, which corresponds to the enthalpy difference, was an important factor in determining whether the molecular aggregation state of a fatty acid mixed monolayer was in a molecularly mixed or phase-separated state. Moreover, the boundary value of cohesive energy difference was approximately 2.5 kJ mol-1 at a subphase temperature of 293 K.

Tomato Cultivar Nyagous Fruit Surface Metabolite Changes during Ripening Affect Salmonella Newport.

ABSTRACT: Tomatoes are a valuable crop consumed year-round. Ripe fruit is picked for local sale, whereas tomatoes intended for transit may be harvested at late mature green or breaker stages when fruit firmness preserves quality. In this study, we evaluated Solanum lycopersicum cv. BHN602 association with three Salmonella serotypes and S. lycopersicum cv. Nyagous with Salmonella Newport using fruit at two ripeness stages. Counts of Salmonella Javiana and Typhimurium were higher from red ripe fruit surfaces of BHN602, and counts of Salmonella Newport were higher from ripe Nyagous fruit than from mature green fruit (P < 0.05). Aqueous fruit washes containing fruit surface compounds collected from ripe Nyagous fruit supported more Salmonella Newport growth than green fruit washes (P < 0.05). Growth curve analysis showed that between 2 and 6 h, Salmonella Newport grew at a rate of 0.25 log CFU/h in red fruit wash compared with 0.17 log CFU/h in green fruit wash (P < 0.05). The parallel trend in Salmonella interaction between fruit and wash suggested that surface metabolite differences between unripe and ripe fruit affect Salmonella dynamics. Untargeted phytochemical profiling of tomato fruit surface washes with gas chromatography time-of-flight mass spectrometry showed that ripe fruit had threefold-lower amino acid and fourfold-higher sugar (fructose, glucose, and xylose) levels than green fruit. Green fruit had higher levels of lauric, palmitic, margaric, and arachidic acids, whereas red fruit had more capric acid. The phenolics ferulic, chlorogenic, and vanillic acid, as well as tyrosol, also decreased with ripening. Although limitations of this study preclude conclusions on how specific compounds affect Salmonella, our study highlights the complexity of the plant niche for foodborne pathogens and the importance of understanding the metabolite landscape Salmonella encounters on fresh produce. Fruit surface phytochemical profiling generated testable hypotheses for future studies exploring the differential Salmonella interactions with tomato varieties and fruit at various ripeness stages.

Dietary omega-3 LCPUFA intake in the prevention of neovascular age-related macular degeneration: a systematic review and meta-analysis / La ingesta de AGPICL omega-3 en la prevención de la degeneración macular neovascular relacionada con la edad: revisión sistemática y metaanálisis

Purpose: to evaluate the protective effect of omega-3 long-chain unsaturated fatty acids on the progression of wet age-related macular degeneration (wAMD). Methods: this meta-analysis was designed, implemented, and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol and is reported following PRISMA guidelines. Results: in this study we included 5 observational trials, including 2 cross-sectional studies, 2 case-control studies, and 1 confrontation study. These tests are conducted in the U.S., Europe and Japan, and are of high quality. In general, people with high dietary long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) have a lower risk of progression to advanced age-related macular degeneration (AMD) (effect size, ES: 0.51, 95 % CI [0.34, 0.75], I2 = 70 %, p = 0.01). When assessing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake and wAMD risk a total of the three above studies were included, which also produced similar results. Conclusions: the highest DHA consumption reduced the risk of disease by 39 % (effect size: 0.61, 95 % CI [0.50, 0.74], I2 = 14 %, p = 0.31); compared with the lowest EPA consumption, the highest EPA consumption reduced the risk of wAMD by 32 % (ES: 0.68, 95 % CI [0.57, 0.82], I2 = 39 %, p = 0.20) (AU)

Propósito: evaluar el efecto protector de los AGPICL omega-3 sobre la degeneración macular húmeda asociada a la edad (DMAE). Métodos: este metaanálisis fue diseñado, implementado y analizado de acuerdo con el protocolo de Metaanálisis de Estudios Observacionales en Epidemiología (MOOSE) y se informa siguiendo las directrices de PRISMA. Resultados: en este estudio se incluyeron 5 ensayos observacionales, entre ellos 2 estudios transversales, 2 estudios de casos y controles y 1 estudio de confrontación. Estos ensayos se realizan en Estados Unidos, Europa y Japón y son de alta calidad. En general, las personas con una dieta alta en ácidos grasos poliinsaturados de cadena larga (AGPICL omega-3) tienen un menor riesgo de progresión hacia la degeneración macular avanzada relacionada con la edad (DMAE) (tamaño del efecto, ES: 0,51, IC 95 % [0,34, 0,75], I2 = 70 %, p = 0,01). Al evaluar la ingesta de ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA) y el riesgo de DMAE se incluyeron en total tres de los estudios anteriores, que también arrojaron resultados similares. Conclusiones: el mayor consumo de DHA redujo el riesgo de enfermedad en un 39 % (tamaño del efecto: 0,61, IC del 95 % [0,50, 0,74], I2 = 14 %, p = 0,31); en comparación con el menor consumo de EPA, el mayor consumo de EPA redujo el riesgo de wAMD en un 32 % (ES: 0,68, IC del 95 % [0,57, 0,82], I2 = 39 %, p = 0,20) (AU)

Metabolic Alterations Differentiating Cardiovascular Maladaptation from Athletic Training in American-Style Football Athletes.

PURPOSE: Metabolomics identifies molecular products produced in response to numerous stimuli, including both adaptive (includes exercise training) and disease processes. We analyzed a longitudinal cohort of American-style football (ASF) athletes, who reliably acquire maladaptive cardiovascular (CV) phenotypes during competitive training, with high-resolution metabolomics to determine whether metabolomics can discriminate exercise-induced CV adaptations from early CV pathology. METHODS: Matched discovery ( n = 42) and validation ( n = 40) multicenter cohorts of collegiate freshman ASF athletes were studied with longitudinal echocardiography, applanation tonometry, and high-resolution metabolomics. Liquid chromatography-mass spectrometry identified metabolites that changed ( P < 0.05, false discovery rate <0.2) over the season. Metabolites demonstrating similar changes in both cohorts were further analyzed in linear and mixed-effects models to identify those associated with left ventricular mass, tissue-Doppler myocardial E ' velocity (diastolic function), and arterial function (pulse wave velocity). RESULTS: In both cohorts, 20 common metabolites changed similarly across the season. Metabolites reflective of favorable CV health included an increase in arginine and decreases in hypoxanthine and saturated fatty acids (heptadecanoate, arachidic acid, stearate, and hydroxydecanoate). In contrast, metabolic perturbations of increased lysine and pipecolate, reflective of adverse CV health, were also observed. Adjusting for player position, race, height, and changes in systolic blood pressure, weight, and pulse wave velocity, increased lysine ( ß = 0.018, P = 0.02) and pipecolate ( ß = 0.018, P = 0.02) were associated with increased left ventricular mass index. In addition, increased lysine ( ß = -0.049, P = 0.01) and pipecolate ( ß = -0.052, P = 0.008) were also associated with lower E ' (reduced diastolic function). CONCLUSIONS: ASF athletes seem to develop metabolomic changes reflective of both favorable CV health and early CV maladaptive phenotypes. Whether metabolomics can discriminate early pathologic CV transformations among athletes is a warranted future research direction.

15-hydroxy eicosadienoic acid is an exacerbating factor for nasal congestion in mice.

Allergic rhinitis (AR) is one of the most common allergic inflammatory diseases worldwide. In AR, increased blood flow and vascular permeability in nasal mucosa cause rhinorrhea and nasal congestion. We investigated the role of an 11Z,14Z-eicosadienoic acid-derived metabolite, 15-hydroxy-11Z,13Z-eicosadienoic acid (15-HEDE), in functional changes in vasculature and nasal congestion in AR. Repeated intranasal administration of Ovalbumin (OVA) caused AR symptoms, such as sneezing and nasal congestion, in mice. OVA administration increased the level of 15-HEDE in nasal lavage fluid, which reached approximately 0.6 ng/ml after ten OVA treatments. Upon measuring vascular contraction, treatment with 0.1-3 µM 15-HEDE did not cause contraction in mouse aortae, while it dilated aortae that were pre-contracted by thromboxane receptor stimulation. Pretreatment with the voltage-gated K+ (KV ) channel inhibitor 4-aminopyridine significantly inhibited the 15-HEDE-induced vascular relaxation. Intravital imaging showed that administration of 1 µg 15-HEDE dilated blood vessels, and Mile's assay demonstrated that this administration also caused dye leakage, indicating vascular hyperpermeability in mouse ears. Computed tomography scanning and morphological study revealed that administration of 3 µg 15-HEDE narrowed nasal passages and thickened nasal mucosa in mice. Finally, we confirmed that treating mice with 3 µg 15-HEDE caused rhinitis symptoms, such as abdominal breathing, and reduced respiratory frequency, suggesting nasal congestion. 15-HEDE caused vasodilation by activating KV channels and increased vascular permeability, which may lead to nasal congestion. Furthermore, 15-HEDE might be a new lipid mediator that exacerbates nasal congestion in AR.

Antioxidant Assessment of Prenylated Stilbenoid-Rich Extracts from Elicited Hairy Root Cultures of Three Cultivars of Peanut (Arachis hypogaea).

Peanut produces prenylated stilbenoids upon biotic stress. However, the role of these compounds against oxidative stress have not been thoroughly elucidated. To this end, the antioxidant capacity of extracts enriched in prenylated stilbenoids and derivatives was studied. To produce these extracts, hairy root cultures of peanut cultivars Hull, Tifrunner, and Georgia Green were co-treated with methyl jasmonate, cyclodextrin, hydrogen peroxide, and magnesium chloride and then the stilbenoids were extracted from the culture medium. Among the three cultivars, higher levels of the stilbenoid derivatives arachidin-1 and arachidin-6 were detected in cultivar Tifrunner. Upon reaction with 2,2-diphenyl-1picrylhydrazyl, extracts from cultivar Tifrunner showed the highest antioxidant capacity with an IC50 of 6.004 µg/mL. Furthermore, these extracts had significantly higher antioxidant capacity at 6.25 µg/mL and 3.125 µg/mL when compared to extracts from cultivars Hull and Georgia Green. The stilbenoid-rich extracts from peanut hairy roots show high antioxidant capacity and merit further study as potential nutraceuticals to promote human health.

Rapid Detection of Fatty Acids in Edible Oils Using Vis-NIR Reflectance Spectroscopy with Multivariate Methods.

The composition and content of fatty acids are critical indicators to identify the quality of edible oils. This study was undertaken to establish a rapid determination method for quality detection of edible oils based on quantitative analysis of palmitic acid, stearic acid, arachidic acid, and behenic acid. Seven kinds of oils were measured to obtain Vis-NIR spectra. Multivariate methods combined with pretreatment methods were adopted to establish quantitative analysis models for the four fatty acids. The model of support vector machine (SVM) with standard normal variate (SNV) pretreatment showed the best predictive performance for the four fatty acids. For the palmitic acid, the determination coefficient of prediction (RP2) was 0.9504 and the root mean square error of prediction (RMSEP) was 0.8181. For the stearic acid, RP2 and RMSEP were 0.9636 and 0.2965. In the prediction of arachidic acid, RP2 and RMSEP were 0.9576 and 0.0577. In the prediction of behenic acid, the RP2 and RMSEP were 0.9521 and 0.1486. Furthermore, the effective wavelengths selected by successive projections algorithm (SPA) were useful for establishing simplified prediction models. The results demonstrate that Vis-NIR spectroscopy combined with multivariate methods can provide a rapid and accurate approach for fatty acids detection of edible oils.

Plasma lipid biomarkers in relation to BMI, lung function, and airway inflammation in pediatric asthma.

INTRODUCTION: There is limited understanding of how plasma fatty acid levels affect pulmonary function in pediatric years. It has been speculated that polyunsaturated fatty acids influence asthma via anti or pro-inflammatory mechanisms. Metabolomics presents a new and promising resource for identifying molecular processes involved in asthma pathology. OBJECTIVES: We investigated the relationship of plasma fatty acid metabolites as biomarkers of the 'mild-asthma' phenotype and lung function including airway inflammation in children. METHODS: This cross-sectional study involved 64 children (5-12 years, 33 male) with mild-asthma phenotype attending an outpatient pediatric clinic in Athens, Greece. Clinical examination included spirometry (FVC, FEV1, FEV1/FVC, PEF, FEF25-75%) and Fractional exhaled Nitric Oxide (FeNO). Targeted metabolomic profiling was used to quantify plasma fatty acid composition. Associations between lipids and pulmonary function indices were investigated applying linear regression. RESULTS: Targeted GC-MS identified 25 unique plasma fatty acids in mild-asthmatic children. Linear regression revealed significant associations between linoleic, oleic, erucic, cis-11-eicosenoic, arachidic acids and FEV1, FVC, FEV1/FVC, PEF, FEF25-75% and FeNO in the overweight/obese group, adjusting for age and sex; and in the normo-weight between stearic and arachidic acids versus FEV1 and FEV1/FVC respectively. No associations were observed for arachidonic, α-linolenic, EPA and DHA. CONCLUSION: Metabolomics is a novel science that is useful to discover metabolic signatures specific to disease. Evaluation of fatty acid status could assist clinicians in decision-making about a dietary modification that can be used for personalized nutrition therapies to achieve better asthma control, optimum lung function, and therapeutic response in children.

Effect of Blanching Pomegranate Seeds on Physicochemical Attributes, Bioactive Compounds and Antioxidant Activity of Extracted Oil.

This study investigated the effect of blanching pomegranate seeds (PS) on oil yield, refractive index (RI), yellowness index (YI), conjugated dienes (K232), conjugated trienes (K270), total carotenoid content (TCC), total phenolic compounds (TPC) and DPPH radical scavenging of the extracted oil. Furthermore, phytosterol and fatty acid compositions of the oil extracted under optimum blanching conditions were compared with those from the oil extracted from unblanched PS. Three different blanching temperature levels (80, 90, and 100 °C) were studied at a constant blanching time of 3 min. The blanching time was then increased to 5 min at the established optimum blanching temperature (90 °C). Blanching PS increased oil yield, K232, K270, stigmasterol, punicic acid, TPC and DPPH radical scavenging, whereas YI, ß-sitosterol, palmitic acid and linoleic acid were decreased. The RI, TCC, brassicasterol, stearic acid, oleic acid and arachidic acid of the extracted oil were not significantly (p > 0.05) affected by blanching. Blanching PS at 90 °C for 3 to 5 min was associated with oil yield, TPC and DPPH. Blanching PS at 90 °C for 3 to 5 min will not only increase oil yield but could also improve functional properties such as antioxidant activity, which are desirable in the cosmetic, pharmaceutical, nutraceutical and food industries.

Anti-Inflammatory and Analgesic Effect of Arachic Acid Ethyl Ester Isolated from Propolis.

Inflammatory diseases are a real public health problem worldwide. Many synthetic drugs used in the treatment of inflammatory diseases such as steroidal anti-inflammatory drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressive drugs have harmful side effects. However, there are natural products like propolis, which is traditionally used in the treatment of pain. The objective of this work was to evaluate the anti-inflammatory and analgesic activities of the ethyl ester of arachic acid, a compound isolated from Cameroonian propolis. The ethyl ester of arachic acid was isolated by chromatography of the ethanolic extract of propolis harvested at Tala-Mokolo (Far North Region of Cameroon) and identified by nuclear magnetic resonance (NMR) spectra and the 1H-1H correlated spectroscopy. The anti-inflammatory and analgesic properties of oral administration of arachic acid ethyl ester (12.5, 25.0, and 50.0 mg/kg bw) were evaluated using carrageenan-induced paw edema, xylene-induced ear edema, cotton pellets-induced granuloma formation, and hot plate test in rat. Arachic acid ethyl ester produced maximum inhibition at 50.0 mg/kg for carrageenan-induced paw edema (62.5%), xylene-induced ear edema (54.5%), cotton pellet-induced granuloma (47.4%), and increased mean latency for hot plate test in rats. These results show clearly that the arachic acid ethyl ester has acute and chronic anti-inflammatory properties as well as central analgesic properties. This justifies the use of propolis in the treatment of pain in traditional medicine.

Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo/Yap signalling pathway.

Context: Emodin is a compound in Rheum undulatum Linne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects.Objective: Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism.Materials and methods: We used the hepatocyte stimulated by arachidonic acid (AA) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 ∼ 30 µM) for 1 h before AA + iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP.Results: In vitro, emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 µM (EC50 > 3 µM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 µM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway. In vivo, the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage.Conclusion: Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway.

Five serum fatty acids are associated with subclinical hypothyroidism in a Chinese pregnant population.

Subclinical hypothyroidism (SCH) is a common endocrine disorder affecting women of reproductive age. Although SCH and abnormal fatty acid composition are often associated with adverse pregnancy outcomes and metabolic syndrome later in maternal and fetal life, the longitudinal relationship between SCH and serum fatty acids during pregnancy has rarely been studied. Therefore, the aim of this study was to investigate the association between SCH and maternal serum fatty acids throughout gestation. A total of 240 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included in our study. Clinical information and maternal serum samples were collected at three time points during pregnancy: 11-14th, 22-28th, and 32-34th weeks of gestation. Twenty serum fatty acids were quantified using gas chromatography-mass spectrometry (GC-MS) analysis. A majority of the 20 serum fatty acids increased as gestation progressed in women with a normal pregnancy and women experiencing SCH. Levels of arachidic acid, docosahexaenoic acid, and eicosenoic acid were significantly higher in the serum of women with SCH when compared to women with a normal pregnancy, in the second trimester. On the other hand, the levels of eicosadienoic acid and octadecanoic acid were significantly higher in SCH in the third trimester. Our findings demonstrate that serum fatty acid composition during the second and third trimesters was significantly associated with SCH in pregnant Chinese women.

Plasma phospholipid very-long-chain SFAs in midlife and 20-year cognitive change in the Atherosclerosis Risk in Communities (ARIC): a cohort study.

BACKGROUND: Very-long-chain SFAs (VLSFAs) have recently gained considerable attention as having beneficial effects on health and aging. OBJECTIVES: The objective of this study was to assess the associations of plasma phospholipid VLSFAs [arachidic acid (20:0), behenic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0)] with 20-y cognitive decline in the Atherosclerosis Risk in Communities (ARIC) participants. Furthermore, this study compared the associations of plasma phospholipid VLSFAs with 5 common groups of fatty acids [i.e., total SFAs, total MUFAs, total ω-3 (n-3) PUFAs, total marine-derived ω-3 PUFAs, total ω-6 PUFAs]. METHODS: This study used a cohort study design of 3229 ARIC participants enrolled at the Minnesota field center. Fatty acids were measured at visit 1 (1987-1989); and cognition was assessed at visits 2 (1990-1992), 4 (1996-1998), and 5 (2011-2013) using 3 tests: the Delayed Word Recall Test (DWRT), the Digit-Symbol Substitution Test (DSST), and the Word Fluency Test (WFT). RESULTS: Higher proportions of plasma phospholipid total VLSFAs and each individual VLSFA were associated with less decline in WFT, a test of verbal fluency. For example, 1 SD higher in total VLSFAs at baseline was associated with 0.057 SD (95% CI: 0.018, 0.096, P = 0.004) less cognitive decline over 20 y as measured by WFT score. None of the 5 common fatty acid groups were associated with change in WFT, but a higher proportion of plasma phospholipid total MUFAs was associated with greater decline in DWRT; higher total ω-6 PUFAs with less decline in DWRT; and higher total ω-3 and total marine-derived ω-3 PUFAs with less decline in DSST. CONCLUSIONS: This study suggests that higher proportions of plasma phospholipid VLSFAs in midlife may be associated with less 20-y cognitive decline.

Identification and characterization of two fatty acid elongases in Lipomyces starkeyi.

The oleaginous yeast Lipomyces starkeyi is a potential cost-effective source for the production of microbial lipids. Fatty acid elongases have vital roles in the syntheses of long-chain fatty acids. In this study, two genes encoding fatty acid elongases of L. starkeyi, LsELO1, and LsELO2 were identified and characterized. Heterologous expression of these genes in Saccharomyces cerevisiae revealed that LsElo1 is involved in the production of saturated long-chain fatty acids with 24 carbon atoms (C24:0) and that LsElo2 is involved in the conversion of C16 fatty acids to C18 fatty acids. In addition, both LsElo1 and LsElo2 were able to elongate polyunsaturated fatty acids. LsElo1 elongated linoleic acid (C18:2) to eicosadienoic acid (C20:2), and LsElo2 elongated α-linolenic acid (C18:3) to eicosatrienoic acid (C20:3). Overexpression of LsElo2 in L. starkeyi caused a reduction in C16 fatty acids, such as palmitic and palmitoleic acids, and an accumulation of C18 fatty acids such as oleic and linoleic acids. Our findings have the potential to contribute to the remodeling of fatty acid composition and the production of polyunsaturated long-chain fatty acids in oleaginous yeasts.

Fatty acid desaturase 2 is up-regulated by the treatment with statin through geranylgeranyl pyrophosphate-dependent Rho kinase pathway in HepG2 cells.

Statins have been reported to increase the plasma concentration of arachidonic acid (AA), an omega-6 long chain polyunsaturated fatty acid (LCPUFA) in several clinical studies indicating that statins affect the endogenous synthesis of LCUFAs. In the present study, we investigated the roles of the intrinsic mevalonate cascade and Rho-dependent pathway in LCPUFA synthesis, especially focusing on fatty acid desaturases (Fads) 2, using the human hepatocellular carcinoma cell line HepG2. Cell number and the activity of caspase-3 and 7 (caspase-3/7) was measured using a commercial kit. Gene expression was analyzed by quantitative real-time PCR. Protein expression was detected by Western blot analysis. Atorvastatin decreased cell viability and increased caspase-3/7 activity in a dose-dependent manner. At lower concentrations, atorvastatin stimulated both mRNA and protein expression of Fads2, and increased mRNA expression of FADS1 and ELVOL5. Both mevalonate and geranylgeranyl-pyrophosphate (GGPP), but not cholesterol, fully reversed atorvastatin-induced upregulation of Fads2, and mevalonate-effected reversal was inhibited by treatment with the Rho-associated protein kinase inhibitor Y-27632. These data clearly demonstrated that in human HepG2 cells, statins affect the endogenous synthesis of LCPUFAs by regulation of not only Fads2, but also Fads1 and Elovl5, through the GGPP-dependent Rho kinase pathway.

Plasma Ceramides and Sphingomyelins in Relation to Heart Failure Risk.

BACKGROUND: Ceramides exhibit multiple biological activities that may influence the pathophysiology of heart failure. These activities may be influenced by the saturated fatty acid carried by the ceramide (Cer). However, the associations of different circulating Cer species, and their sphingomyelin (SM) precursors, with heart failure have received limited attention. METHODS AND RESULTS: We studied the associations of plasma Cer and SM species with incident heart failure in the Cardiovascular Health Study. We examined 8 species: Cer and SM with palmitic acid (Cer-16 and SM-16), species with arachidic acid (Cer-20 and SM-20), species with behenic acid (Cer-22 and SM-22), and species with lignoceric acid (Cer-24 and SM-24). During a median follow-up of 9.4 years, we identified 1179 cases of incident heart failure among 4249 study participants. In Cox regression analyses adjusted for risk factors, higher levels of Cer-16 and SM-16 were associated with higher risk of incident heart failure (hazard ratio for one SD increase:1.25 [95% CI, 1.16-1.36] and 1.28 [1.18-1.40], respectively). In contrast, higher levels of Cer-22 were associated with lower risk of heart failure in multivariable analyses further adjusted for Cer-16 (hazard ratio, 0.85 [0.78-0.92]); and higher levels of SM-20, SM-22 and SM-24 were associated with lower risk of heart failure in analyses further adjusted for SM-16 (hazard ratios, 0.83 [0.77-0.90], 0.81 [0.75-0.88], and 0.83 [0.77-0.90], respectively). No statistically significant interactions with age, sex, black race, body mass index, or baseline coronary heart disease were detected. Similar associations were observed for heart failure with preserved (n=529) or reduced (n=348) ejection fraction. CONCLUSIONS: This study shows associations of higher plasma levels of Cer-16 and SM-16 with increased risk of heart failure and higher levels of Cer-22, SM-20, SM-22, and SM-24 with decreased risk of heart failure. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005133.

Circulating Saturated Fatty Acids and Incident Type 2 Diabetes: A Systematic Review and Meta-Analysis.

The effect of saturated fatty acids (SFAs) on incident type 2 diabetes (T2D) is controversial and few have systematically appraised the evidence. We conducted a comprehensive search of prospective studies examining these relationships that were published in PubMed, Web of Science, or EMBASE from 21 February 1989 to 21 February 2019. A total of 19 studies were included for systematic review and 10 for meta-analysis. We estimated the summarized relative risk (RR) and 95% confidence interval (95% CI) using a random (if I2 > 50%) or a fixed effects model (if I2 ≤ 50%). Although the included studies reported inconclusive results, the majority supported a protective effect of odd-chain and an adverse impact of even-chain SFAs. Meta-analysis showed that the per standard deviation (SD) increase in odd-chain SFAs was associated with a reduced risk of incident T2D (C15:0: 0.86, 0.76-0.98; C17:0: 0.76, 0.59-0.97), while a per SD increase in one even-chain SFA was associated with an increased risk of incident T2D (C14:0: 1.13, 1.09-1.18). No associations were found between other SFAs and incident T2D. In conclusion, our findings suggest an overall protective effect of odd-chain SFAs and the inconclusive impact of even- and very-long-chain SFAs on incident T2D.

Associations of circulating very-long-chain saturated fatty acids and incident type 2 diabetes: a pooled analysis of prospective cohort studies.

BACKGROUND: Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed. OBJECTIVE: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies. METHODS: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants. RESULTS: There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides. CONCLUSIONS: Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.

Effects of saturated and polyunsaturated fatty acids on interactions with cholesterol versus 7-ketocholesterol in Langmuir monolayers and their potential biological implications.

In this work the Langmuir monolayer technique was used to study interactions between cholesterol (chol) and 7-ketocholesterol (7-KC) with saturated (arachidic acid, AA) and polyunsaturated fatty acids (PUFAs) (ω-3 α-linolenic acid, α-LA,and ω-6 γ- linolenic, γ-LA) in order to get insight into their potential role in atherosclerosis. For this study, surface pressure (π)-area (A) isotherms, compressibility modulus (Cs-1) versus π plots, Brewster angle microscopy (BAM) images and excess functions (Aexc and ΔGexc) were analysed. Different behaviour has been observed. For cholesterol/AA mixed monolayers, components immiscibility occurs, whatever the surface pressure or the mixtures composition is, whereas for the 7-KC/AA mixed system, ideal behaviour was observed at low and high surface pressures for all the investigated compositions. However, the remaining mixed studied systems (sterol/PUFA) exhibit negative deviations from the ideality, although some differences do occurr. The magnitude of these deviations depend on the kind of a PUFA (for ω-3 PUFA greater than for ω-6) - attributed to the different geometry of their acyl chains- and the type of a sterol (for 7-KC greater than for cholesterol).The strength of attractive interactions followed the order: chol/ γ-LA <7-KC/γ-LA < chol/α-LA < 7-KC/ α-LA, postulating the formation of stable complexes of 1:2 stoichiometry for 7-KC/α-LA mixed monolayers and 1:1 stoichiometry for chol/α-LA mixed films. For 7-KC/γ-LA system, the formation of a low stability complex of 2:1 stoichiometry was suggested. The existence of these complexes can play an important role in diminishing the circulating sterols in the blood stream, thus decreasing the probability of atherosclerotic plaques formation.