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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.
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Proteínas Klotho , Encuestas Nutricionales , Ácidos Grasos trans , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Adulto , Ácidos Grasos trans/sangre , Glucuronidasa/sangre , Anciano , Ácidos Oléicos/sangre , Ácido Oléico/sangre , Modelos LinealesRESUMEN
Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.
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Adenoma , Biomarcadores de Tumor , Neoplasias Colorrectales , Progresión de la Enfermedad , Heces , Metabolómica , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Heces/química , Adenoma/metabolismo , Adenoma/diagnóstico , Adenoma/patología , Adenoma/sangre , Metabolómica/métodos , Animales , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/sangre , Ratones , Masculino , Femenino , Detección Precoz del Cáncer/métodos , Metaboloma , Persona de Mediana Edad , Ácido Oléico/metabolismo , Ácido Oléico/sangre , AncianoRESUMEN
OBJECTIVES: Trans-fatty acid (TFA) has been linked to an increased risk of a variety of diseases, such as cardiovascular disease (CVD), diabetes, and cancer. However, the relationship between plasma TFAs and migraine is little known. The current study aimed to determine the association between plasma TFAs and migraine in a large cross-sectional study among U.S. adults. METHODS: The participants from the US National Health and Nutrition Examination Survey (NHANES) were included during the period 1999-2000. The plasma concentrations of four major TFAs, including palmitelaidic acid (C16:1n-7t), elaidic acid (C18:1n-9t), vaccenic acid (C18:1n-7t), and linolelaidic acid (C18:2n-6t, 9t) were measured by gas chromatography/mass spectrometry (GC/MS). The presence of migraine headache was determined by self-report questionnaire. Weighted multivariable logistic regressions and restricted cubic spline (RCS) regressions were explored to assess the relationship between plasma TFAs and migraine. Furthermore, stratified analysis and testing of interaction terms were used to evaluate the effect modification by sex, age, race/ethnicity, family income, and BMI. RESULTS: A total of 1534 participants were included. The overall weighted prevalence of severe headache or migraine was 21.2 %. After adjusting for all potential covariates, plasma levels of elaidic acid and linolelaidic acid were positively associated with migraine. The adjusted OR values were 1.18 (95 %CI: 1.08-1.29, p=0.014, per 10 units increase) and 1.24 (95 %CI: 1.07-1.44, p=0.024). Then the included participants were divided into 2-quantiles by plasma TFA levels. Compared with participants with lower plasma levels of elaidic acid and linolelaidic acid (Q1 groups), those in the Q2 group had a higher prevalence of migraine when adjusted for all covariates in Model 2. The adjusted OR values were 2.43 (95 %CI: 1.14-5.18, p=0.037) for elaidic acid, and 2.18 (95 %CI: 1.14-4.20, p=0.036) for linolelaidic acid. Results were robust when analyses were stratified by sex, age, race/ethnicity, family income, and BMI, and no effect modification on the association was found. CONCLUSIONS: Our results demonstrated a positive association between migraine prevalence and plasma levels of elaidic acid and linolelaidic acid in US adults. These results highlight the connection between circulating TFAs and migraine.
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Trastornos Migrañosos , Encuestas Nutricionales , Ácidos Grasos trans , Humanos , Trastornos Migrañosos/sangre , Trastornos Migrañosos/epidemiología , Femenino , Masculino , Estudios Transversales , Adulto , Persona de Mediana Edad , Ácidos Grasos trans/sangre , Estados Unidos/epidemiología , Ácidos Oléicos/sangre , Ácido Oléico/sangre , AncianoRESUMEN
OBJECTIVES: Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. MATERIALS AND METHODS: Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. RESULTS: Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. CONCLUSIONS: Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.
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Ácidos Grasos , Ácido Linoleico , Pancreatitis Crónica , Humanos , Proyectos Piloto , Pancreatitis Crónica/sangre , Pancreatitis Crónica/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Ácidos Grasos/sangre , Ácido Linoleico/sangre , Estudios de Casos y Controles , Lipogénesis , Anciano , Ácido Palmítico/sangre , Ácido Oléico/sangre , Biomarcadores/sangreRESUMEN
BACKGROUND: The soluble form of receptor for advanced glycation end products (sRAGE) have been implicated in the prevention of numerous pathologic states, and highlights as an attractive therapeutic target. Because diets rich in monounsaturated fatty acids (MUFA) reduce postprandial oxidative stress and inflammation that is related to better health during aging, we investigated the association between red blood cell (RBC) fatty acids with circulatory AGE biomarkers and further stratified this correlation based on GG and GA + AA genotype. METHODS: A total of 172 healthy participants (median age = 53.74 ± 0.61 years) were recruited for the study. RBC fatty acid was analysed using gas chromatography and sRAGE was measured using a commercial ELISA kit. RESULTS: The result showed a non-significant correlation between total MUFA with sRAGE however oleic acid (C18:1) exhibited a positive correlation (r = 0.178, p = 0.01) that remained statistically significant (ß = 0.178, p = 0.02) after a stepwise multivariate regression analysis after adjusting for age, BMI and gender. In a univariate analysis, a positive significant correlation between C18:1 and sRAGE in GG genotype (r = 0.169, p = 0.02) and a non-significant correlation with GA + AA genotype (r = 0.192, p = 0.21) was evident. When C18:1 was stratified, a significant difference was observed for oleic acid and G82S polymorphism: low C18:1/GA + AA versus high C18:1/GG (p = 0.015) and high C18:1/GA + AA versus high C18:1/GG (p = 0.02). CONCLUSION: Our study suggests that increased levels of C18:1 may be a potential therapeutic approach in increasing sRAGE in those with GG genotype and play a role in modulating AGE metabolism.
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Eritrocitos , Reacción de Maillard , Ácido Oléico , Receptor para Productos Finales de Glicación Avanzada , Humanos , Persona de Mediana Edad , Alelos , Ácido Oléico/análisis , Ácido Oléico/sangre , Ácido Oléico/metabolismo , Polimorfismo Genético , Receptor para Productos Finales de Glicación Avanzada/genética , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Eritrocitos/químicaRESUMEN
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.
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Infecciones por Coronavirus/metabolismo , Metaboloma , Neumonía Viral/metabolismo , Anciano , Anciano de 80 o más Años , Aminoácidos/sangre , Ácido Araquidónico/sangre , Biomarcadores/sangre , COVID-19 , Ciclo del Ácido Cítrico , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/patología , Femenino , Gluconeogénesis , Humanos , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Pandemias , Fosfatidilcolinas/sangre , Fosfatidiletanolaminas/sangre , Fosfolipasas A2/sangre , Neumonía Viral/sangre , Neumonía Viral/patología , Triglicéridos/sangreRESUMEN
Intravenous administration of pure soybean oil emulsions high in linoleic acid may lead to inflammation and lipid peroxidation in preterm neonates. We aimed to investigate the effects of a medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched intravenous fat emulsion (IVFE) on plasma fatty acid (FA) profile and serum interleukin-6 (IL-6) in preterm neonates. In this double-blind randomized study, 92 preterm neonates (gestational age < 32 weeks, birth weight < 1500 g) were assigned to receive either MCT/ω-3 PUFA-enriched IVFE (Intervention Group) or soybean oil-based IVFE (Control Group). Levels of FAs were measured at baseline (day 0) and day 15 of parenteral nutrition with gas-chromatography mass-spectrometry. Serum IL-6 was measured with sandwich ELISA in 59 neonates. Plasma FAs changed significantly over time; the MCT/ω-3 PUFA-IVFE group showed higher ω-3 PUFAs (p = 0.031), eicosapentaenoic acid (p = 0.000), and oleic acid (p = 0.003), and lower ω-6/ω-3 PUFAs ratio (p = 0.001) and ω-6 PUFAs (p = 0.023) compared to control group. Linoleic acid was higher in the soybean oil (SO)-based IVFE arm compared to the MCT/ω-3 PUFAs-IVFE arm (p = 0.006). Both fat emulsion types decreased IL-6 compared to baseline, but changes were insignificant between groups. Administration of MCT/ω-3 PUFA-enriched IVFE in preterm neonates is beneficial in changing the FA profile consistent with attenuated inflammatory response.
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Emulsiones Grasas Intravenosas/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Recien Nacido Prematuro/crecimiento & desarrollo , Nutrición Parenteral , Triglicéridos/administración & dosificación , Método Doble Ciego , Ácido Eicosapentaenoico/sangre , Emulsiones Grasas Intravenosas/química , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Femenino , Humanos , Recién Nacido , Interleucina-6/sangre , Ácido Linoleico/sangre , Masculino , Ácido Oléico/sangre , Aceite de Soja/administración & dosificaciónRESUMEN
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.
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Hipercolesterolemia/dietoterapia , Ácido Oléico/sangre , Posmenopausia/sangre , Periodo Posprandial , Ácidos Esteáricos/sangre , Anciano , Anciano de 80 o más Años , Isótopos de Carbono , Ésteres del Colesterol/sangre , LDL-Colesterol/sangre , Estudios Cruzados , Femenino , Absorción Gastrointestinal , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/diagnóstico , Persona de Mediana Edad , Ácido Oléico/administración & dosificación , Ácido Oléico/farmacocinética , Oxidación-Reducción , Ácidos Esteáricos/administración & dosificación , Ácidos Esteáricos/farmacocinética , Triglicéridos/sangreRESUMEN
Background: Colorectal cancer (CRC) progression and related mortality are highly associated with metabolic disorders. However, the molecular mechanism involved in the regulation of hyperlipidemia-associated CRC metastasis remains unclear. This study aimed to investigate the effects of angiopoietin-like 4 (ANGPTL4) on NADPH oxidase 4 (NOX4) expression and reactive oxygen species (ROS) production, which might provide new targets for improving outcomes in patients with hyperlipidemia-associated CRC metastasis. Methods: The clinical relevance of relationship between NOX4 expression and ANGPTL4 was examined in CRC patients by the Oncomine and TCGA data set. Expressions of NOX4, epithelial-mesenchymal transition (EMT) markers, and gene regulation of NOX4 in free fatty acids (FFAs)-treated CRC cells were determined. The FFAs-triggered metastatic ability of CRC cells under treatments of antioxidants or knockdown of NOX4, ANGPTL4, and MMPs was evaluated in vitro and in vivo. In addition, effects of antioxidants and depletion of metastasis-associated molecules on the correlation between ROS production and FFAs-promoted CRC metastasis were also clarified. Results: In this study, we found that the induction of NOX4, followed by the increased ROS was essential for oleic acid (OA)-promoted CRC cell metastasis. The depletion of ANGPTL4 significantly inhibited c-Jun-mediated transactivation of NOX4 expression, accompanied with reduced levels of ROS, MMP-1, and MMP-9, resulting in the disruption of OA-promoted CRC cell metastasis. Moreover, knockdown of ANGPTL4, NOX4, MMP-1, and MMP-9 or the treatment of antioxidants dramatically inhibited circulating OA-enhanced tumor cell extravasation and metastatic seeding of tumor cells in lungs, indicating that the ANGPTL4/NOX4 axis was critical for dyslipidemia-associated tumor metastasis. Conclusion: The coincident expression of NOX4 and ANGPTL4 in CRC tumor specimens provides the insight into the potential therapeutic targets for the treatment of dyslipidemia-associated CRC metastasis.
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Proteína 4 Similar a la Angiopoyetina/metabolismo , Neoplasias Colorrectales/patología , Hiperlipidemias/patología , Neoplasias Pulmonares/genética , NADPH Oxidasa 4/genética , Ácido Oléico/metabolismo , Proteína 4 Similar a la Angiopoyetina/sangre , Proteína 4 Similar a la Angiopoyetina/genética , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Línea Celular Tumoral , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Hiperlipidemias/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , NADPH Oxidasa 4/metabolismo , Ácido Oléico/sangre , Proteínas Proto-Oncogénicas c-jun/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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.
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Hipertensión/etiología , Metabolómica/métodos , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Presión Sanguínea/fisiología , Ceramidas/sangre , Humanos , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Triglicéridos/sangreRESUMEN
Several associations between non-genetic biomarkers and colorectal cancer (CRC) risk have been detected, but the strength of evidence and the direction of associations are not confirmed. We aimed to evaluate the evidence of these associations and integrate results from different approaches to assess causal inference. We searched Medline and Embase for meta-analyses of observational studies, meta-analyses of randomized clinical trials (RCTs), and Mendelian randomization (MR) studies measuring the associations between non-genetic biomarkers and CRC risk and meta-analyses of RCTs on supplementary micronutrients. We repeated the meta-analyses using random-effects models and categorized the evidence based on predefined criteria. We described each MR study and evaluated their credibility. Seventy-two meta-analyses of observational studies and 18 MR studies on non-genetic biomarkers and six meta-analyses of RCTs on micronutrient intake and CRC risk considering 65, 42, and five unique associations, respectively, were identified. No meta-analyses of RCTs on blood level biomarkers have been found. None of the associations were classified as convincing or highly suggestive, three were classified as suggestive, and 26 were classified as weak. For three biomarkers explored in MR studies, there was evidence of causality and seven were classified as likely noncausal. For the first time, results from both observational and MR studies were integrated by triangulating the evidence for a wide variety of non-genetic biomarkers and CRC risk. At blood level, lower vitamin D, higher homeostatic model assessment-insulin resistance, and human papillomavirus infection were associated with higher CRC risk while increased linoleic acid and oleic acid and decreased arachidonic acid were likely causally associated with lower CRC risk. No association was found convincing in both study types.
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Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/etiología , Ácido Araquidónico/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/virología , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Resistencia a la Insulina , Ácido Linoleico/sangre , Análisis de la Aleatorización Mendeliana , Metaanálisis como Asunto , Micronutrientes/administración & dosificación , Estudios Observacionales como Asunto , Ácido Oléico/sangre , Infecciones por Papillomavirus/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Riesgo , Vitamina D/sangreRESUMEN
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 É 6-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.
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Ácidos Grasos/sangre , Insuficiencia Renal Crónica/sangre , Anciano , Biomarcadores/sangre , Cromatografía de Gases , Progresión de la Enfermedad , Ácidos Grasos/metabolismo , Ácidos Grasos Monoinsaturados/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Polonia , Estudios Prospectivos , Insuficiencia Renal Crónica/metabolismoRESUMEN
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.
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Isquemia Encefálica/sangre , Ácidos Grasos/sangre , Accidente Cerebrovascular/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/diagnóstico , Estudios Transversales , Femenino , Humanos , Ácido Linoleico/sangre , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Ácido Palmítico/sangre , Estudios Retrospectivos , Accidente Cerebrovascular/diagnósticoRESUMEN
Plasma metabolic profiles were compared between patients with hypertension with and without left ventricular hypertrophy and significantly decreased oleic acid (OA) levels were observed in the peripheral blood of patients with hypertension with left ventricular hypertrophy. We sought to determine the effect and underlying mechanisms of OA on cardiac remodeling. In vitro studies with isolated neonatal mouse cardiomyocytes and cardiac fibroblasts revealed that OA significantly attenuated Ang II (angiotensin II)-induced cardiomyocyte growth and cardiac fibroblast collagen expression. In vivo, cardiac function, hypertrophic growth of cardiomyocytes, and fibrosis were analyzed after an Ang II (1000 ng/kg/minute) pump was implanted for 14 days. We found that OA could significantly prevent Ang II-induced cardiac remodeling in mice. RNA sequencing served as a gene expression roadmap highlighting gene expression changes in the hearts of Ang II-induced mice and OA-treated mice. The results revealed that FGF23 (fibroblast growth factor 23) expression was significantly upregulated in mouse hearts in response to Ang II infusion, which was significantly suppressed in the hearts of OA-treated mice. Furthermore, overexpression of FGF23 in the heart by injection of an AAV-9 vector aggravated Ang II-induced cardiac remodeling and impaired the protective effect of OA on cardiac remodeling. Further study found that OA could suppress Ang II-induced FGF23 expression by inhibiting the translocation of Nurr1 (nuclear receptor-related 1 protein) from the cytoplasm to the nucleus. Our findings suggest a novel role of OA in preventing Ang II-induced cardiac remodeling via suppression of FGF23 expression.
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Angiotensina II/farmacología , Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Hipertrofia Ventricular Izquierda/sangre , Ácido Oléico/fisiología , Remodelación Ventricular/fisiología , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Colágeno/biosíntesis , Dependovirus/genética , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/biosíntesis , Factores de Crecimiento de Fibroblastos/genética , Fibroblastos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Ontología de Genes , Vectores Genéticos , Humanos , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Ácido Oléico/sangre , Ácido Oléico/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Organismos Libres de Patógenos Específicos , Remodelación Ventricular/efectos de los fármacosRESUMEN
Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes ?5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma α-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma α-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.
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Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/genética , Ácido Graso Desaturasas/genética , Ácidos Grasos/sangre , Fosfolípidos/sangre , Alelos , Ácido Araquidónico/sangre , Enfermedades Cardiovasculares/clasificación , Análisis de Datos , delta-5 Desaturasa de Ácido Graso , Predisposición Genética a la Enfermedad , Humanos , Ácido Linoleico/sangre , Análisis de la Aleatorización Mendeliana , Oportunidad Relativa , Ácido Oléico/sangre , Polimorfismo de Nucleótido Simple , Factores Protectores , Factores de Riesgo , Ácidos Esteáricos/sangre , Ácido alfa-Linolénico/sangreRESUMEN
Background Synthesized fatty acids (FAs) from de novo lipogenesis may affect cardiometabolic health, but longitudinal associations between serially measured de novo lipogenesis-related fatty acid biomarkers and mortality or cardiovascular disease (CVD) are not well established. Methods and Results We investigated longitudinal associations between de novo lipogenesis-related fatty acids with all-cause mortality, cause-specific mortality, and incident CVD among 3869 older US adults, mean (SD) age 75 (5) years and free of prevalent CVD at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), oleic acid (18:1n-9), and other risk factors were serially measured at baseline, 6 years, and 13 years. All-cause mortality, cause-specific mortality, and incident fatal and nonfatal CVD were centrally adjudicated. Risk was assessed in multivariable-adjusted Cox models with time-varying FAs and covariates. During 13 years, median follow-up (maximum 22.4 years), participants experienced 3227 deaths (1131 CVD, 2096 non-CVD) and 1753 incident CVD events. After multivariable adjustment, higher cumulative levels of 16:0, 16:1n-7, and 18:1n-9 were associated with higher all-cause mortality, with extreme-quintile hazard ratios (95% CIs) of 1.35 (1.17-1.56), 1.40 (1.21-1.62), and 1.56 (1.35-1.80), respectively, whereas higher levels of 18:0 were associated with lower mortality (hazard ratio=0.76; 95% CI=0.66-0.88). Associations were generally similar for CVD mortality versus non-CVD mortality, as well as total incident CVD. Changes in levels of 16:0 were positively, and 18:0 inversely, associated with all-cause mortality (hazard ratio=1.23, 95% CI=1.08-1.41; and hazard ratio=0.78, 95% CI=0.68-0.90). Conclusions Higher long-term levels of 16:0, 16:1n-7, and 18:1n-9 and changes in 16:0 were positively, whereas long-term levels and changes in 18:0 were inversely, associated with all-cause mortality in older adults.
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Enfermedades Cardiovasculares/mortalidad , Ácidos Grasos/sangre , Lipogénesis , Fosfolípidos/sangre , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte , Estudios de Cohortes , Ácidos Grasos Monoinsaturados/sangre , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Mortalidad , Análisis Multivariante , Ácido Oléico/sangre , Ácido Palmítico/sangre , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Ácidos Esteáricos/sangreRESUMEN
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.
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Enfermedad de la Arteria Coronaria/patología , Metaboloma , Metabolómica/métodos , Estrés Oxidativo , Disfunción Ventricular Izquierda/complicaciones , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/metabolismo , Análisis Discriminante , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Femenino , Cromatografía de Gases y Espectrometría de Masas , Glucosa/química , Glucosa/metabolismo , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Ácido Pirúvico/sangre , Disfunción Ventricular Izquierda/metabolismoRESUMEN
OBJECTIVE: The aim of the study was to investigate the endogenous metabolites of patients with psoriasis vulgaris which will be helpful for the diagnosis of the disease and to provide the evidence of pathogenesis and the formulation for the individualized dosage regimen. PATIENTS AND METHODS: This study investigated the plasma metabolomic profiling between the psoriasis vulgaris patients (N=12) and the healthy volunteers (N=12) using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) metabolomic techniques. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to identify and visualize the metabolic data clusters. RESULTS: A total of 22 differential metabolites contributing to the clusters were identified, among which the levels of threonine (p<0.001), leucine (p<0.001), phenylalanine (p<0.001), tryptophan (p=0.018), palmitamide (p<0.001), Linoleic amide (p<0.001), oleamide (p<0.001), stearamide (p<0.001), cis-11- eicosenamide (p< 0.001), trans-13-Docosenamide (p<0.001), uric acid (p=0.034), LysoPC (16:0) (p<0.001), LysoPC (18:3) (p<0.001), LysoPC (18:2) (p=0.024), LysoPC (18:1) (P=0.012) and LysoPC (18:0) (p=0.002) were significantly higher in the plasma of psoriasis vulgaris patients compared with the healthy controls, whereas oleic acid (p<0.001), arachidonic acid (p<0.001) and N-linoleoyl taurine (p<0.001) were significantly lower. These biomarkers are related to glucose metabolism, lipid metabolism, amino acid metabolism, nucleic acid metabolism and so on. CONCLUSIONS: The data suggest that psoriasis vulgaris patients may have disrupted lipid and amino acid metabolism, as well as inflammation and functional lesions in the liver and kidney. This study deepens the understanding of psoriasis vulgaris pathogenesis and proposes novel ideas and methods for auxiliary diagnosis and treatment of the disease.
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Biomarcadores/sangre , Metabolómica/métodos , Psoriasis/diagnóstico , Adulto , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Análisis Discriminante , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Leucina/sangre , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Ácido Oléico/sangre , Análisis de Componente Principal , Psoriasis/metabolismo , Treonina/sangreRESUMEN
Changes in lipid metabolism occur during the development and progression non-alcoholic fatty liver disease (NAFLD). However, the fatty acid (FA) profile in red blood cells (RBC) from patients with liver fibrosis remains unexplored. Thus, the goal of this study was to evaluate the fatty acid profile in RBC, dietary lipid intake and insulin resistance indicators in patients with NAFLD, according to the degree of hepatic fibrosis. Using elastography, patients were classified with (n = 52) and without (n = 37) advanced liver fibrosis. The fatty acid profile in RBC was analyzed using gas chromatography and the lipid intake was evaluated through a 24-h dietary recall. Subjects with advanced liver fibrosis had higher levels of palmitic, stearic and oleic acid and total monounsaturated fatty acid (MUFA) and insulin (p < 0.05), and lower levels of elongase very long chain fatty acids protein-6 and the delta-5-desaturase enzymatic activity (p < 0.05). These results suggest a lack of regulation of enzymes related to FA metabolism in patients with advanced fibrosis.
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Eritrocitos/química , Insulina/sangre , Cirrosis Hepática/etiología , Enfermedad del Hígado Graso no Alcohólico/sangre , Ácido Palmítico/sangre , Acetiltransferasas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , delta-5 Desaturasa de Ácido Graso , Registros de Dieta , Grasas de la Dieta/análisis , Diagnóstico por Imagen de Elasticidad , Ácido Graso Desaturasas/sangre , Elongasas de Ácidos Grasos , Ácidos Grasos Monoinsaturados/sangre , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/metabolismo , Cirrosis Hepática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Ácido Oléico/sangre , Ácidos Esteáricos/sangreRESUMEN
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.