Association between plasma trans fatty acids and serum α-klotho levels in adults in the United States of America: an analysis of the NHANES 2009-2010 datasets.

BACKGROUND: This study aimed to explore the potential associations between trans fatty acid (TFA) and α-klotho levels. METHODS: Datasets from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) were analysed for this study. Multivariable linear regression and restricted cubic spline (RCS) analyses were performed to examine the relationships between plasma TFA and serum α-klotho levels. RESULTS: A total of 1,205 participants were included, with a geometric mean (GM) of 803.60 (95% CI: 787.45, 820.00) pg/mL for serum α-klotho levels. RCS analysis revealed L-shaped relationships between TFA and α-klotho levels. The inflection points for palmitelaidic acid (PA), vaccinic acid (VA), elaidic acid (EA), and total TFA levels were 4.55, 20.50, 18.70, and 46.40 µmol/L, respectively. Before reaching the inflection point, serum α-klotho levels were negatively correlated with plasma PA, VA, EA and total TFA levels, with ß values (95% CI) of -0.15 (-0.24, -0.06), -0.16 (-0.23, -0.09), -0.14 (-0.22, -0.05) and - 0.19 (-0.27, -0.11), respectively. Linolelaidic acid (LA) levels exhibited an inverse and linear association with α-klotho levels ( Pnonlinearity=0.167, Poverall<0.001). L-shaped relationships between TFA and α-klotho levels were also observed in the subgroups of participants who were aged < 65 years, were male, did not exercise, were ex-smokers, and were overweight/obese. CONCLUSIONS: L-shaped correlations between plasma PA, VA, EA, and total TFA levels and serum α-klotho levels were observed among adults in the United States.

Global Plasma Metabolomics to Identify Potential Biomarkers of Blood Pressure Progression.

OBJECTIVE: The pathophysiology of hypertension remains incompletely understood. We investigated associations of circulating metabolites with longitudinal blood pressure (BP) changes in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort and validated the findings in the Uppsala Longitudinal Study of Adult Men cohort. Approach and Results: Circulating metabolite levels were assessed with liquid- and gas-chromatography coupled to mass spectrometry among persons without BP-lowering medication at baseline. We studied associations of baseline levels of metabolites with changes in BP levels and the clinical BP stage between baseline and a follow-up examination 5 years later. In the discovery cohort, we investigated 504 individuals that contributed with 757 observations of paired BP measurements. The mean baseline systolic and diastolic BPs were 144 (19.7)/76 (9.7) mm Hg, and change in systolic and diastolic BPs were 3.7 (15.8)/-0.5 (8.6) mm Hg over 5 years. The metabolites associated with diastolic BP change were ceramide, triacylglycerol, total glycerolipids, oleic acid, and cholesterylester. No associations with longitudinal changes in systolic BP or BP stage were observed. Metabolites with similar structures to the 5 top findings in the discovery cohort were investigated in the validation cohort. Diacylglycerol (36:2) and monoacylglycerol (18:0), 2 glycerolipids, were associated with diastolic BP change in the validation cohort. CONCLUSIONS: Circulating baseline levels of ceramide, triacylglycerol, total glycerolipids, and oleic acid were positively associated with longitudinal diastolic BP change, whereas cholesterylester levels were inversely associated with longitudinal diastolic BP change. Two glycerolipids were validated in an independent cohort. These metabolites may point towards pathophysiological pathways of hypertension.

Comparison of the Postprandial Metabolic Fate of U-13C Stearic Acid and U-13C Oleic Acid in Postmenopausal Women.

OBJECTIVE: Compare the postprandial fatty acid metabolism of isotopically labeled stearate (U-13C18:0) and oleate (U-13C18:1). Approach and Results: In conjunction with a randomized-controlled crossover trial, 6 hypercholesterolemic postmenopausal women (≥50 years; body mass index: 25.6±3.0 kg/m2; LDL [low-density lipoprotein]-cholesterol ≥110 mg/dL) consumed isocaloric diets enriched in 18:0 or 18:1 (10%-15% E) for 5 weeks each. On day 1 of week 5, following a 12-hour fast, participants receive their experimental diet divided into 13 hourly meals beginning at 8 am. U-13C18:0 or U-13C18:1 was incorporated into the 1:00 pm meal (1.0 mg/kg body weight). Serial blood and breath samples were collected over 12 hours and fasting samples at 24 and 48 hours. Plasma and lipid subfraction fatty acid profiles were assessed by gas chromatography-flame ionization detector, isotope-enrichment by liquid chromatography time-of-flight mass spectrometry, and fatty acid oxidation rate (expired 13CO2) by isotope ratio mass spectrometry. Both diets resulted in similar plasma LDL-cholesterol concentrations. Kinetic curves showed that U-13C18:0 had a higher plasma area under the curve (66%), lower plasma clearance rate (-46%), and a lower cumulative oxidation rate (-34%) than U-13C18:1. Three labeled plasma metabolites of U-13C18:0 were detected: 13C16:0, 13C16:1, and 13C18:1. No plasma metabolites of U-13C18:1 were detected within the study time-frame. Higher incorporation of 18:0 in cholesteryl ester and triglyceride fractions was observed on the 18:0 compared with the 18:1 diet. CONCLUSIONS: The neutrality of 18:0 on plasma LDL-cholesterol concentrations is not attributable to a single factor. Compared with 18:1, 18:0 had higher plasma area under the curve because of lower clearance and oxidation rates, underwent both a direct and a multistage conversion to 18:1, and was preferentially incorporated into cholesteryl esters and triglycerides.

Features of serum fatty acids in acute ischaemic stroke patients aged 50 years or older.

BACKGROUND: Serum fatty acid (s-FA) compositions and their correlation with serum lipids (s-LPs) such as total cholesterol (T-CHO) and triglycerides (TG) have been reported in healthy young subjects. However, little is known about such features in acute ischaemic stroke (AIS). The aim of our study was to investigate s-FA characteristics and their correlation with AIS in elderly patients. METHODS: We conducted a cross-sectional study of patients aged 50 years or older who were admitted between September 2015 and March 2017 within 24 h of the first AIS onset. We evaluated concentrations and compositions of s-FAs and their association with s-LPs, age, and ischaemic stroke subtypes, including large-artery atherosclerosis (LAA), small-vessel occlusion (SVO), and cardioembolism (CE) or others. RESULTS: One hundred ninety-one patients met our inclusion criteria. Their average age was 74.4 years, mean T-CHO and median TG were 203.4 and 94.5 mg/dl, respectively, and median or mean concentrations of palmitic acid (PA), oleic acid (OlA), linoleic acid (LiA), and docosahexaenoic acid (DHA) were 680.7, 602.5, 795.2, and 136.9 µg/ml, respectively, with mean compositions of 23.7, 21.3, 27.1, and 4.4%, respectively. PA, OlA, and LiA concentrations were weakly negatively associated with age and positively correlated with TG. In LAA or SVO (LAA_SVO) and CE or others (CE_O), mean age was 71.9 and 77.4 years (p < 0.001), mean T-CHO was 213.9 and 191.2 mg/dl (p < 0.0001), median TG was 106.5 and 88.5 mg/dl (p < 0.01), median PA was 717.2 and 648.4 µg/ml (p < 0.01), median OlA was 638.2 and 567.5 µg/ml (p < 0.01), and median LiA was 844.7 and 728.5 µg/ml (p < 0.01), respectively. DHA composition was weakly positively correlated with age. There were no differences in PA, OlA, LiA, and DHA compositions between LAA_SVO and CE_O. CONCLUSIONS: In AIS elderly patients, concentrations, rather than compositions of PA, OlA, and LiA, correlated with age, TG, and ischaemic stroke subtypes. Patients with LAA_SVO were younger and had higher concentrations of PA, OlA, and LiA than those with CE_O. There were no differences in such compositions between LAA_SVO and CE_O.

The C18:3n6/C22:4n6 ratio is a good lipid marker of chronic kidney disease (CKD) progression.

BACKGROUND: Chronic kidney disease (CKD) is a major challenge for public health due to increased risk of cardiovascular diseases (CVD) and premature death. The aim of this study was to determine the clinical picture of FA and the course of the pathophysiological mechanisms of CKD. METHODS: The study involved 149 patients with CKD and a control group including 43 people. Fatty acid profiles were investigated using gas chromatography. A total of 30 fatty acids and their derivatives were identified and quantified. The omega3, omega6, SFA, MUFA, and PUFA fatty acid contents were calculated. The correlation matrix was obtained for parameters relating to patients with CKD vs. FA, taking patients' sex into consideration. The index C18:3n6/C22:4n6 was calculated according to the length of the treatment. Statistica 12.0 software (Tulsa, Oklahoma, USA) was used for the statistical analyses. RESULTS: The results showed decreased levels of total PUFA and increased concentrations of MUFA, including the activation of the palmitic and oleic acid pathway. An increase in the levels of n-6 9C22: 4n6 family fatty acids in all the patients and a reduction in the n-3 family (EPA, DHA) were observed. C18:3n6 was negatively correlated and C22:4n6 was positively correlated with the duration of the treatment. The index C18:3n6/C22:4n6 was defined as a new marker in the progression of the disease. Moreover, the index C18:3n6/ C22:4n6 was drastically decreased in later period. Nervonic acid was higher in the CKD group. In the group of men with CKD, there was a negative correlation between the excretion of K+, anthropometric measurements, and the levels of EPA and DHA. CONCLUSIONS: The course of inflammation in CKD occurs through the decrease in PUFA and the synthesis of MUFA. The dominating cascade of changes is the elongation of GLA-C18:3n6 into DGLA-C20:3n6 and AA-C20:4n6. As CKD progresses, along with worsening anthropometrical parameters and increased secretion of potassium, the activity of Ʌ6-desaturase decreases, reducing the synthesis of EPA and DHA. The synthesis of AdA-C22:4n6 increases and the ratio C18:3n6/C22:4n6 drastically decreases after 5 years. This parameter can be used to diagnose disease progression.

Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets.

Untargeted metabolomic analysis of coronary artery disease patients with diastolic dysfunction show disturbed oxidative pathway.

INTRODUCTION: Left ventricular diastolic dysfunction (LVDD) is common in patients with coronary artery disease (CAD) with prevalence estimates of 34% and constitutes a predictor of all-cause mortality. Although diastolic dysfunction is induced by myocardial ischemia and has been shown to alter the clinical course, the role of coronary artery disease in the diastolic dysfunction and its progression into heart failure has not been completely elucidated. OBJECTIVE: The present study was conducted to identify possible metabolites in coronary artery disease patients that are differentially regulated in patients with diastolic dysfunction. METHODS: The serum of CAD (n = 75) patients and young healthy volunteers (n = 43) were analysed by using gas chromatography mass spectrometry (GC-MS) technique. Pre-processing of data results in 1547 features; among them 1064 features were annotated using NIST library. RESULTS AND CONCLUSION: Fifteen metabolites were found to be statistically different between cases and control. Variation in metabolites were identified and correlated with several clinically important echocardiography parameters i.e. LVDD grades, ejection fraction (EF) and E/e' values. The results suggested that metabolic products of fatty acid oxidation and glucose oxidation pathways such as oleic acid, stearic acid, palmitic acid, linoleic acid, galactose, pyruvic and lactic acids are predominantly up regulated in patients with coronary artery disease and severity of diastolic dysfunction appears to be linked to increase in fatty acid oxidation and inflammation. The metabolic fingerprints of these patients give us an insight into the pathophysiological mechanism of diastolic dysfunction in coronary artery disease patients although it did not identify validated novel markers.

Decreased Oleic Acid and Marine n - 3 Polyunsaturated Fatty Acids in Tunisian Patients with Urothelial Bladder Cancer.

Fatty acids (FAs) are thought to impact carcinogenesis by affecting cell signaling. A case-control study including 250 patients with urothelial bladder cancer (UBC) and 250 controls was conducted. Plasma FAs composition was assessed using capillary gas chromatography. Associations of individual and classes of FAs with UBC were controlled for the main risk factors for UBC. Plasma FAs profile was different in patients compared to controls. Higher levels (third tertile vs. first tertile) in palmitic acid (PA) [multi-adjusted OR (95% CI), 1.83 (1.14-2.92)], and n - 6:n - 3 FA ratio [4.13 (2.38-7.16)] were associated with increased risk for UBC [multi-adjusted OR (95% CI), 1.83 (1.14-2.92)]. In contrast, higher levels (third tertile vs. first tertile) in oleic [0.54 (0.34-0.86)], dihomo-γ-linolenic (DGLA) [0.47 (0.29-0.74)], eicosapentaenoic (EPA) [0.32 (0.19-0.52)], and docosahexaenoic (DHA) acids [0.33 (0.20-0.53)] were associated with lower risk for UBC. Although the study design does not allow proving causality, the findings suggest a possible protective role of oleic acid and marine n - 3 polyunsaturated FAs (PUFAs) against bladder carcinogenesis.

Dorsal recruitment with flow-controlled expiration (FLEX): an experimental study in mechanically ventilated lung-healthy and lung-injured pigs.

BACKGROUND: Concepts for optimizing mechanical ventilation focus mainly on modifying the inspiratory phase. We propose flow-controlled expiration (FLEX) as an additional means for lung protective ventilation and hypothesize that it is capable of recruiting dependent areas of the lungs. This study investigates potential recruiting effects of FLEX using models of mechanically ventilated pigs before and after induction of lung injury with oleic acid. METHODS: Seven pigs in the supine position were ventilated with tidal volume 8 ml·kg- 1 and positive end-expiratory pressure (PEEP) set to maintain partial pressure of oxygen in arterial blood (paO2) at ≥ 60 mmHg and monitored with electrical impedance tomography (EIT). Two ventilation sequences were recorded - one before and one after induction of lung injury. Each sequence comprised 2 min of conventional volume-controlled ventilation (VCV), 2 min of VCV with FLEX and 1 min again of conventional VCV. Analysis of the EIT recordings comprised global and ventral and dorsal baseline levels of impedance curves, end-expiratory no-flow periods, tidal variation in ventral and dorsal areas, and regional ventilation delay index. RESULTS: With FLEX, the duration of the end-expiratory zero flow intervals was significantly shortened (VCV 1.4 ± 0.3 s; FLEX 0.7 ± 0.1 s, p < 0.001), functional residual capacity was significantly elevated in both conditions of the lungs (global: healthy, increase of 87 ± 12 ml, p < 0.001; injured, increase of 115 ± 44 ml, p < 0.001; ventral: healthy, increase of 64 ± 11 ml, p < 0.001; injured, increase of 83 ± 22 ml, p < 0.001; dorsal: healthy, increase of 23 ± 5 ml, p < 0.001; injured, increase of 32 ± 26 ml, p = 0.02), and ventilation was shifted from ventral to dorsal areas (dorsal increase: healthy, 1 ± 0.5%, p < 0.01; dorsal increase: injured, 6 ± 2%, p < 0.01), compared to conventional VCV. Recruiting effects of FLEX persisted during conventional VCV following FLEX ventilation mostly in the injured but also in the healthy lungs. CONCLUSIONS: FLEX shifts regional ventilation towards dependent lung areas in healthy and in injured pig lungs. The recruiting capabilities of FLEX may be mainly responsible for lung-protective effects observed in an earlier study.

Relation between plasma phospholipid oleic acid and risk of heart failure.

BACKGROUND AND AIMS: Although the association between monounsaturated fatty acids (MUFA) and risk factors for heart failure (HF) has been reported, it is unclear whether oleic acid, the predominant MUFA in olive oil, plays a role in the development of HF. Consequently, we sought to examine the relation of plasma phospholipid oleic acid with HF in a male cohort. In a secondary analysis, we examined the relation of the ratio of plasma monounsaturated-to-saturated fatty acids (MUFA: SFA) with HF. METHODS: This prospective nested case-control study was based on 788 incident HF cases and 788 controls from the Physicians' Health Study. Plasma phospholipid fatty acids were measured using gas chromatography and incident HF was self-reported via annual follow-up questionnaires and validated in a subsample using medical records. RESULTS: The mean age was 58.7 years at blood collection. In a conditional logistic regression, multivariable adjusted-odds ratios (95% confidence interval) for HF across consecutive quartiles of oleic acid were 1.0 (reference), 1.10 (0.79-1.54), 1.02 (0.72-1.44), and 1.05 (0.72-1.54). For MUFA:SFA ratio, corresponding odds ratios (95% CI) for HF were 1.0 (ref), 1.12 (0.80-1.58), 1.19 (0.84-1.68), and 0.97 (0.66-1.42). CONCLUSIONS: Our data do not lend support to an association between plasma phospholipid oleic acid or MUFA: SFA ratio and the risk of HF. These results warrant confirmation in the general population including women and other ethnic groups.

Correlation of trans fatty acids with the severity of coronary artery disease lesions.

BACKGROUND: Nutritional choices, which include the source of dietary fatty acids (FA), have an important significant impact on coronary artery disease (CAD). We aimed to determine on patients with CAD the relationships between Trans fatty acids (Trans FA) and different CAD associated parameters such as inflammatory and oxidative stress parameters in addition to Gensini score as a vascular severity index. METHODS: Fatty acid profiles were established by gas chromatography from 111 CAD patients compared to 120 age-matched control group. Lipid peroxidation biomarkers, oxidative stress, inflammatory parameters and Gensini score were studied. RESULTS: Our study showed a significant decrease of the antioxidant parameters levels such as erythrocyte glutathione peroxydase (GPx) and superoxide dismutase (SOD) activities, plasma antioxidant status (FRAP) and thiol (SH) groups in CAD patients. On the other hand, catalase activity, conjugated dienes and malondialdehyde were increased. Plasmatic and erythrocyte Trans FA were also increased in CAD patients compared to controls. Furthermore, divergent associations of these Trans FA accumulations were observed with low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio, Apolipoprotein B (ApoB), lipid peroxidation parameters, high-sensitivity C Reactive Protein (hs-CRP), Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and Gensini score. Especially, elaidic acid (C18:1 trans 9), trans C18:2 isomers and trans 11 eicosanoic acid are correlated with these parameters. Trans FA are also associated with oxidative stress, confirmed by a positive correlation between C20:1 trans 11 and GPx in erythrocytes. CONCLUSIONS: High level of Trans FA was highly associated with the induction of inflammation, oxidative stress and lipoperoxidation which appear to be based on the vascular severity and might be of interest to assess the stage and progression of atherosclerosis. The measurement of these Trans FA would be of great value for the screening of lipid metabolism disorders in CAD patients.

Relationship between plasma trans-fatty acid isomer concentrations and self-reported cardiovascular disease risk in US adults.

The effect of different individual TFA isomers on cardiovascular disease (CVD) has been a limited study, especially for stroke. We aimed to investigate the relationships between four major plasma TFA isomer (elaidic, vaccenic, palmitelaidic and linolelaidic acid) concentrations and the risk of CVD, stroke and non-stroke CVD. A cross-sectional study was conducted, utilising a nationally representative sample of US adults in the National Health and Nutrition Examination Survey. Among the 3504 participants, 304 participants self-reported CVD history. The highest quintile of elaidic acid intake was associated with a 233% higher CVD risk (p = .010). Adjusted for age, gender and race, palmitelaidic acid was associated with a decreased CVD risk, but the effect size was diminished in a subsequent analysis model. For stroke risk, we failed to identify any associations. In addition to elaidic acid, the health effect of palmitelaidic acid should be paid more attention in the future studies.

Polymorphisms of the TNF-α gene interact with plasma fatty acids on inflammatory biomarker profile: a population-based, cross-sectional study in São Paulo, Brazil.

The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1ß (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population.

α1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression.

α1-Antitrypsin (A1AT) purified from human plasma upregulates expression and release of angiopoietin-like protein 4 (Angptl4) in adherent human blood monocytes and in human lung microvascular endothelial cells, providing a mechanism for the broad immune-regulatory properties of A1AT independent of its antiprotease activity. In this study, we demonstrate that A1AT (Prolastin), a potent inducer of Angptl4, contains significant quantities of the fatty acids (FA) linoleic acid (C18:2) and oleic acid (C18:1). However, only trace amounts of FAs were present in preparations that failed to increase Angplt4 expression, for example, A1AT (Zemaira) or M-type A1AT purified by affinity chromatography. FA pull-down assays with Western blot analysis revealed a FA-binding ability of A1AT. In human blood-adherent monocytes, A1AT-FA conjugates upregulated expression of Angptl4 (54.9-fold, p < 0.001), FA-binding protein 4 (FABP4) (11.4-fold, p < 0.001), and, to a lesser degree, FA translocase (CD36) (3.1-fold, p < 0.001) relative to A1AT devoid of FA (A1AT-0). These latter effects of A1AT-FA were blocked by inhibitors of peroxisome proliferator-activated receptor (PPAR) ß/δ (ST247) and PPARγ (GW9662). When compared with controls, cell pretreatment with ST247 diminished the effect of A1AT-LA on Angptl4 mRNA (11.6- versus 4.1-fold, p < 0.001) and FABP4 mRNA (5.4- versus 2.8-fold, p < 0.001). Similarly, preincubation of cells with GW9662 inhibited inducing effect of A1AT-LA on Angptl4 mRNA (by 2-fold, p < 0.001) and FABP4 mRNA (by 3-fold, p < 0.001). Thus, A1AT binds to FA, and it is this form of A1AT that induces Angptl4 and FABP4 expression via a PPAR-dependent pathway. These findings provide a mechanism for the unexplored area of A1AT biology independent of its antiprotease properties.

The role of fatty acids on ICSI outcomes: a prospective cohort study.

BACKGROUND: Our objective was to determine the effect of fatty acids (FAs) in serum and follicular fluid (FF) on fertilization and intracytoplasmic sperm injection (ICSI) outcomes. METHODS: One hundred five women aged 18-38 years undergoing ICSI were recruited in this prospective cohort study. oocyte and emberyo quality was morphologically assessed. FAs in serum and FF were analyzed, using gas chromatography-mass spectrometry (GC-MS). RESULTS: The mean number of mature oocytes was associated with serum levels of oleic acid (r = 0.58; P = 0.002). There were negative correlations between metaphase II oocytes and FF levels of stearic acid (r = -0.19; P = 0.04) and linolenic acid (r = -0.37; P = 0.004). According to the obtained Spearman's correlation coefficients, serum levels of stearic, palmitoleic and tricosanoic acids were positively correlated with the percent of germinal vesicle (GV) stage oocyte. The mean serum level of eicosapentaenoic acid was significantly higher in pregnant women than in non-pregnant patients (P = 0.006). Good quality embryos' percentages were negatively correlated with the concentrations of palmitic acid (r = -0.22; P = 0.02). After adjusting the effects of body mass index and age, total FAs were found to have a significant effect on the odds of having high-quality oocytes (percentage of oocytes > 80%; odds ratio =2.55; P = 0.054). CONCLUSION: Particular FAs affect oocyte maturation and implantation. Apparently, while higher FF levels of saturated FAs, especially palmitic and stearic acids, observed in some metabolic contexts have harmful effects on oocyte maturation and implantation, such effects can be counteracted and developmental competence can be enhanced (at least in vitro) by the presence of unsaturated FAs, e.g. oleic and eicosapentaenoic acids.

Plasma trans-fatty acids levels and mortality: a cohort study based on 1999-2000 National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Trans-fatty acids (TFAs) occur in small amounts in nature but became widely produced by the food industry. The hazardous effects of different TFA subtypes to human health are controversial. We aimed to evaluate the association of plasma TFAs levels (elaidic acid, vaccenic acid, palmitelaidic acid, and linoelaidic acid) with mortality. METHODS: Utilizing 1999-2000 Nutrition Examination Survey (NHANES) and linked mortality data, we performed a cohort study with 1456 participants and used Cox proportional hazards models and penalized smoothing spline plots to elucidate the relationships between TFAs and all-cause, cardiovascular diseases (CVD) and cancer mortality. RESULTS: During 16,034 person-years of follow-up, a total of 221 deaths occurred. In the multivariate model, including mutual adjustment for the 4 TFA subtypes, elaidic acid associated with higher all-cause mortality (hazard ratio (HR) = 2.00, 95% confidence interval (CI) = 1.18 to 3.40, fourth quartiles versus second quartiles) and CVD mortality (HR = 1.64, 95% CI = 1.07 to 2.50, per 10 units increase). Higher palmitelaidic acid levels were associated with increased cancer mortality (HR = 2.91, 95% CI = 1.09 to 7.81, fourth quartiles versus second quartiles). A J-shaped pattern was observed in the regression curve of elaidic acid and all-cause mortality, as well palmitelaidic acid and cancer mortality. CONCLUSIONS: Plasma elaidic acid levels are associated with higher risk of all-cause and CVD mortality, and palmitelaidic acid levels are associated with higher cancer mortality in later life. Further studies are needed to investigate current inconsistent results in this field and the possible underlying mechanisms.

Dietary patterns, plasma vitamins and Trans fatty acids are associated with peripheral artery disease.

BACKGROUND: To investigate the association between dietary patterns (DP), plasma vitamins and trans fatty acids (TFAs) with the likelihood of peripheral artery disease (PAD). METHODS: National Health and Nutrition Examination Survey (NHANES) data for the years 1999-2002 were used. PAD was diagnosed by ankle brachial index assessment. Plasma concentrations of vitamins were measured using high performance liquid chromatography. Vitamin D levels were measured by radioimmunoassay. Analysis of covariance, principal components analysis (PCA) and adjusted logistic regression were applied, accounting for the survey design and sample weights. RESULTS: Of the 4864 eligible participants, 2482 (51.0%) were men and 269 (5.5%) had prevalent PAD. PCA uncovered three DPs which accounted for 56.8% of the variance in dietary nutrients consumption including DP1 (fatty acids and cholesterol), DP2 (minerals, vitamins and fiber), and DP3 (polyunsaturated fatty acids [PUFA]). PAD patients had a significantly higher serum concentrations of trans 9-octadecenoic acid and trans 9, trans 12-octadienoic acid as well as lower plasma levels of vitamin D, retinol, retinyl stearate and retinyl palmitate (p < 0.001 for all comparisons). In models adjusted for age, race, diabetes, cholesterol, hypertension, smoking and energy intake, individuals in the highest quartile of the DP1 had higher odds for PAD compared with those in the lowest quartile [(odds ratio (OR): 6.43, 95% confidence interval (CI): 2.00-20.63 p < 0.001], while those in the highest quartile of DP2 and DP3 had lower odds of PAD relative to those in the lowest quartile (OR:0.28, OR:0.44, respectively; p < 0.001 for both comparisons). CONCLUSION: We found that quality of diet, plasma vitamins and TFAs are associated with the likelihood of PAD. If confirmed in prospective studies, the possibility that dietary factors, plasma vitamins and TFAs might be valuable for preventing or delaying the clinical progression of PAD, should be investigated in intervention trials.

Metabolic signatures and risk of type 2 diabetes in a Chinese population: an untargeted metabolomics study using both LC-MS and GC-MS.

AIMS/HYPOTHESIS: Metabolomics has provided new insight into diabetes risk assessment. In this study we characterised the human serum metabolic profiles of participants in the Singapore Chinese Health Study cohort to identify metabolic signatures associated with an increased risk of type 2 diabetes. METHODS: In this nested case-control study, baseline serum metabolite profiles were measured using LC-MS and GC-MS during a 6-year follow-up of 197 individuals with type 2 diabetes but without a history of cardiovascular disease or cancer before diabetes diagnosis, and 197 healthy controls matched by age, sex and date of blood collection. RESULTS: A total of 51 differential metabolites were identified between cases and controls. Of these, 35 were significantly associated with diabetes risk in the multivariate analysis after false discovery rate adjustment, such as increased branched-chain amino acids (leucine, isoleucine and valine), non-esterified fatty acids (palmitic acid, stearic acid, oleic acid and linoleic acid) and lysophosphatidylinositol (LPI) species (16:1, 18:1, 18:2, 20:3, 20:4 and 22:6). A combination of six metabolites including proline, glycerol, aminomalonic acid, LPI (16:1), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and urea showed the potential to predict type 2 diabetes in at-risk individuals with high baseline HbA1c levels (≥6.5% [47.5 mmol/mol]) with an AUC of 0.935. Combined lysophosphatidylglycerol (LPG) (12:0) and LPI (16:1) also showed the potential to predict type 2 diabetes in individuals with normal baseline HbA1c levels (<6.5% [47.5 mmol/mol]; AUC = 0.781). CONCLUSIONS/INTERPRETATION: Our findings show that branched-chain amino acids and NEFA are potent predictors of diabetes development in Chinese adults. Our results also indicate the potential of lysophospholipids for predicting diabetes.

Older adults have an altered chylomicron response to a high-fat meal.

Ageing is associated with a prolonged and exaggerated postprandial lipaemia. This study aimed to examine the contribution of alterations in chylomicron synthesis, size and lipid composition to increased lipaemia. Healthy older (60-75 years; n 15) and younger (20-25 years; n 15) subjects consumed a high-fat breakfast. Chylomicron dynamics and fatty acid composition were analysed for 5 h in the postprandial state. Plasma TAG levels were elevated following the meal in the older subjects, relative to younger subjects (P<0·01). For older subjects compared with younger subjects, circulating chylomicron particle size was smaller (P<0·05), with greater apoB content (P<0·05) at all postprandial time points. However, total chylomicron TAG concentration between the groups was unaltered post-meal. Compared with younger subjects, the older subjects exhibited a greater proportion of oleic acid in the TAG and phospholipid (PL) fraction (P<0·05), plus lower proportions of linoleic acid in the TAG fraction of the chylomicrons (P<0·01). Thus, following the ingestion of a high-fat meal, older individuals demonstrate both smaller, more numerous chylomicrons, with a greater total MUFA and lower PUFA contents. These data suggest that the increased postprandial lipaemia of ageing cannot be attributed to increased chylomicron TAG. Rather, ageing is associated with changes in chylomicron particle size, apoB content and fatty acid composition of the chylomicron TAG and PL fractions.

Serum Trans Fatty Acids Are Not Associated with Weight Gain or Linear Growth in School-Age Children.

BACKGROUND: Animal and human adult studies indicate that long-term intake of trans fatty acids (TFAs) may be associated with weight gain. High intake of fast foods and snacks, which are rich in TFAs, is linked to overweight status among school-age children. However, the specific effects of TFAs in this population are unknown. OBJECTIVE: We examined whether serum TFAs, used as biomarkers of intake, are associated with faster weight gain and linear growth during school years. METHODS: We quantified TFAs by GLC in serum samples of 668 children aged 5-12 y at the time of recruitment into an ongoing cohort study performed in Bogota (Colombia) since 2006. Serum proportions of trans palmitoleic acid (16:1t), trans oleic acid (18:1t), trans linoleic acid (18:2t), and total TFAs were used as biomarkers of intake. Anthropometric characteristics were measured periodically for a median of 30 mo. Body mass index-for-age z scores (BAZs) and height-for-age z scores (HAZs) were calculated with the use of the WHO reference. We estimated mean changes in BAZs and HAZs over follow-up according to quartiles of each TFA at baseline by using mixed-effects regression models with restricted cubic splines. RESULTS: Proportions of trans palmitoleic acid, trans oleic acid, trans linoleic acid, and total TFAs (mean ± SD, % of total serum FAs), were 0.22 ± 0.06, 0.91 ± 0.37, 0.96 ± 0.27, and 2.10 ± 0.59, respectively. Serum TFAs were not associated with changes in BAZs and HAZs after adjusting for sex, baseline age, and socioeconomic status. In a subgroup analysis by sex, serum trans palmitoleic acid was positively associated with the estimated change in HAZs from ages 6 to 14 y in boys (with use of the first quartile as the reference, differences in HAZs for trans palmitoleic acid quartiles were 0.73, 0.53, and 0.70, P-trend = 0.03). CONCLUSIONS: Proportions of serum TFAs, used as biomarkers of TFA intake, were not associated with weight gain in children aged 6-14 y in low- and middle-income populations in Bogota. The proportion of trans palmitoleic acid was positively associated with linear growth in boys. Longer follow-up and studies in diverse cohorts with wider ranges of TFA intake are warranted.