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1.
Nutrients ; 11(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484459

RESUMO

Total plasma fatty acids or those in cholesteryl ester and phospholipids are often used to reflect fatty acid intake in epidemiological studies, but their relative performance as biomarkers of intake has not been clearly evaluated within a single population. The assessment of fatty acids in plasma fractions is more labor intensive. Thus, their use as biomarkers of dietary intake needs to be justified. Dietary intake was assessed in 200 population-based controls from a case-control study of diet and heart disease in Costa Rica by a validated food frequency questionnaire (FFQ). Fatty acids in fasting whole plasma and plasma fractions (cholesteryl ester, phospholipid, and triglyceride + free fatty acid) were measured in the 200 controls by the same laboratory using gas chromatography with flame ionization detection (GC-FID). We compared the plasma and plasma fractions data with the FFQ and adipose fatty acid profile using partial Spearman correlations to assess utility as biomarkers of intake and exposure. We found that whole plasma was equally or more strongly correlated with the FFQ and adipose fatty acid profile than either cholesteryl ester or phospholipid in most of the established markers of dietary intake, including dairy (15:0 and 17:0) and seafood (eicosapentaenoic acid and docosahexaenoic acid). Of the three plasma fractions, only fatty acids in the plasma triglyceride + free fatty acid fraction had stronger correlations with dietary intake than whole plasma. In our study population, fatty acids measured in fasting whole plasma perform as good as or better than those measured in plasma fractions as biomarkers for dietary fatty acid intake. Thus, the fractionation of plasma to evaluate long-term fatty acid intake may not be warranted.


Assuntos
Ésteres do Colesterol/sangue , Ácidos Graxos/administração & dosagem , Ácidos Graxos/sangue , Fosfolipídeos/sangue , Triglicerídeos/sangue , Biomarcadores/sangue , Dieta , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Cancer Sci ; 110(10): 3267-3274, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444836

RESUMO

Although the proteasome inhibitor bortezomib (BTZ) shows excellent efficacy in multiple myeloma (MM), a fraction of patients has a suboptimal or no response to this agent. In addition, BTZ-induced peripheral neuropathy (BiPN), a frequent side-effect of this therapy, limits its use in some patients. This study aimed to explore serum lipid biomarker candidates to predict the response to BTZ and the severity of BiPN. Fifty-nine serum samples were collected from patients with MM prior to receiving BTZ plus low-dose dexamethasone therapy. Serum levels of phospholipids, sphingolipids, neutral lipids, and polyunsaturated fatty acids and their oxidation products were measured by a comprehensive lipidomic study. Overall, 385 lipid metabolites were identified in patients' sera; lower levels of several glycerophospholipids, sphingolipids, and cholesteryl esters were associated with a poor treatment response. Metabolites related to platelet-activating factor biosynthesis and cholesterol metabolism appeared particularly relevant. Furthermore, several lysophosphatidylcholines, phosphatidylcholines, ceramides, neutral lipids, and oxidative fatty acids were significantly increased or decreased in patients with BiPN grades ranging from G0 to G3. Among these compounds, mediators reportedly inducing myelin breakdown and stimulating inflammatory responses were prominent. Although further study is necessary to validate these biomarker candidates, our results contribute to the development of predictive biomarkers for response to BTZ treatment, or ensuing severe BiPN, in patients with MM.


Assuntos
Bortezomib/administração & dosagem , Lipídeos/sangue , Metabolômica/métodos , Mieloma Múltiplo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Bortezomib/efeitos adversos , Ésteres do Colesterol/sangue , Feminino , Glicerofosfolipídeos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/química , Índice de Gravidade de Doença , Esfingolipídeos/sangue , Resultado do Tratamento
3.
J Am Soc Mass Spectrom ; 30(9): 1621-1630, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222675

RESUMO

Over 1500 different lipids have been reported in human plasma at the sum composition level. Yet the number of unique lipids present is surely higher, once isomeric contributions from double bond location(s) and fatty acyl regiochemistry are considered. In order to resolve this ambiguity, herein, we describe the incorporation of ozone-induced dissociation (OzID) into data-independent shotgun lipidomics workflows on a high-resolution hybrid quadrupole-Orbitrap platform. In this configuration, [M + Na]+ ions generated by electrospray ionization of a plasma lipid extract were transmitted through the quadrupole in 1 Da segments. Reaction of mass-selected lipid ions with ozone in the octopole collision cell yielded diagnostic ions for each double bond position. The increased ozone concentration in this region significantly improved ozonolysis efficiency compared with prior implementations on linear ion-trap devices. This advancement translates into increased lipidome coverage and improvements in duty cycle for data-independent MS/MS analysis using shotgun workflows. Grouping all precursor ions with a common OzID neutral loss enables straightforward classification of the lipidome by unsaturation position (with respect to the methyl terminus). Two-dimensional maps obtained from this analysis provide a powerful visualization of structurally related lipids and lipid isomer families within plasma. Global profiling of lipid unsaturation in plasma extracts reveals that most unsaturated lipids are present as isomeric mixtures. These new insights provide a unique picture of underlying metabolism that could in the future provide novel indicators of health and disease.


Assuntos
Lipídeos/sangue , Lipídeos/química , Ozônio/química , Espectrometria de Massas em Tandem/métodos , Ésteres do Colesterol/sangue , Ésteres do Colesterol/química , Humanos , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/instrumentação , Fluxo de Trabalho
4.
Biomarkers ; 24(4): 360-372, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30773031

RESUMO

Background: C14:0, C15:0, C17:0 and trans-C16:1(n-7) are often used as biomarkers for dairy fat intake. Trans-C18:1(n-7) and CLA, two fatty acids which are also present in dairy, have hardly been explored. We investigated whether trans-C18:1(n-7) and CLA can enrich the existing biomarker portfolio. Methods: Data were obtained from Lifelines (n = 769). Dairy fat intake was determined by FFQ. Fatty acids were measured in fasting plasma triglycerides (TG), phospholipids (PL) and cholesterol esters (CE). Results: Median (25th-75th percentile) intakes of dairy and dairy fat were 322(209-447) and 12.3(8.4-17.4) g/d respectively. A pilot study showed that trans-C18:1(n-7) and CLA were only detectable in TG and PL. Of the established markers, TG C15:0 was most strongly associated with dairy fat intake (standardized ß (std.ß) = 0.286, R2 = 0.111). Of the less established markers, TG trans-C18:1(n-7) was most strongly associated with dairy fat intake (Std.ß = 0.292, R2 = 0.115), followed by PL CLA (Std.ß = 0.272, R2 = 0.103) and PL trans-C18:1(n-7) (Std.ß = 0.269, R2 = 0.099). In TG, a combination of C15:0 and trans-C18:1(n-7) performed best (R2 = 0.128). In PL, a combination of C14:0, C15:0, trans-C18:1(n-7) and CLA performed best (R2 = 0.143). Conclusion: Trans-C18:1(n-7) and CLA can be used as biomarkers of dairy fat intake. Additionally, combining established with less established markers allowed even stronger predictions for dairy fat intake.


Assuntos
Laticínios/análise , Gorduras na Dieta/sangue , Ácidos Linoleicos Conjugados/sangue , Ácidos Oleicos/sangue , Adulto , Idoso , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Ésteres do Colesterol/sangue , Ésteres do Colesterol/química , Estudos de Coortes , Dieta/métodos , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fosfolipídeos/sangue , Fosfolipídeos/química , Triglicerídeos/sangue , Triglicerídeos/química
5.
J Oleo Sci ; 68(3): 251-259, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30760672

RESUMO

The nutritional components in oat and tartary buckwheat had been assessed to have cholesterollowering effects. However, The effect of oat and tartary buckwheat based-food (OF) on cholesterol-lowering and gut microbiota in hypercholesterole hamsters was still limited studied because they are usually consumed in whole gran as well as after being processed. In this study, normal diets, high fat diet (HFD) with/without OF were fed to hamsters for 30 days respectively and growth parameters, metabolic parameters, and gut microbiota were investigated, respectively. It was found that OF significantly decreased plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol), lowered liver TC, cholesterol ester (CE), and triglycerides (TG) concentrations, and increased fecal weight and bile acids (BA) concentrations, compared with HFD (p < 0.05). Moreover, the concentrations of acetate, propionate, butyrate and total short-chain fatty acids (SCFAs) were significantly increased in hamsters fed with OF, compared with HFD (p < 0.05). OF changed the overall structure of gut microbiota. The relative abundances of Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae were decreased and the relative abundance of Eubacteriaceae was increased, compared with HFD. These results suggested that OF could reduce the concentrations of plasma lipid by inhibiting cholesterol absorption in liver and promoting excretions of fecal lipid and BA. And it also increased SCFAs and modulated the gut microbiota effectively to exert the hypocholesterolemic effects.


Assuntos
Anticolesterolemiantes/uso terapêutico , Grão Comestível/química , Ácidos Graxos Voláteis/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercolesterolemia/dietoterapia , Animais , Avena , Ésteres do Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cricetinae , Dieta Hiperlipídica , Fagopyrum , Fezes/química , Hipercolesterolemia/sangue , Masculino , Mesocricetus , Triglicerídeos/sangue
6.
J Lipid Res ; 60(2): 436-445, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30563909

RESUMO

Atherosclerosis is associated with increased lipid peroxidation, leading to generation of multiple oxidation-specific epitopes (OSEs), contributing to the pathogenesis of atherosclerosis and its clinical manifestation. Oxidized cholesteryl esters (OxCEs) are a major class of OSEs found in human plasma and atherosclerotic tissue. To evaluate OxCEs as a candidate biomarker, we generated a novel mouse monoclonal Ab (mAb) specific to an OxCE modification of proteins. The mAb AG23 (IgG1) was raised in C57BL6 mice immunized with OxCE-modified keyhole limpet hemocyanin, and hybridomas were screened against OxCE-modified BSA. This method ensures mAb specificity to the OxCE modification, independent of a carrier protein. AG23 specifically stained human carotid artery atherosclerotic lesions. An ELISA method, with AG23 as a capture and either anti-apoAI or anti-apoB-100 as the detection Abs, was developed to assay apoAI and apoB-100 lipoproteins that have one or more OxCE epitopes. OxCE-apoA or OxCE-apoB did not correlate with the well-established oxidized phospholipid-apoB biomarker. In a cohort of subjects treated with atorvastatin, OxCE-apoA was significantly lower than in the placebo group, independent of the apoAI levels. These results suggest the potential diagnostic utility of a new biomarker assay to measure OxCE-modified lipoproteins in patients with CVD.


Assuntos
Anticorpos Monoclonais/imunologia , Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Ésteres do Colesterol/sangue , Ésteres do Colesterol/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Animais , Ésteres do Colesterol/imunologia , Humanos , Camundongos , Oxirredução
7.
J Perinat Med ; 47(2): 200-206, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30315737

RESUMO

Background The objective of the study was to compare the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary supplementation on their concentration in total lipids (TL) and lipid fractions of maternal and umbilical vein (UV) blood. The specific objective was to analyze the impact of EPA and DHA supplementation on pregnancy outcome and neonatal birth weight. Methods Women were randomly single-blinded (randomized controlled trial; ISRCTN36705743) allocated to the group receiving EPA and DHA supplementation (supplemented group) or the group receiving placebo-corn oil (control group) in the time period from January 1st, 2016 until March 1st, 2017. Women in the supplemented group (n=45) took 360 mg EPA and 240 mg DHA daily while controls (n=42) were given a placebo. Maternal and UV bloods were obtained at delivery. After lipid extraction, phospholipids (PL), cholesterol esters (CE), triacylglycerols (TG) and non-esterified fatty acids were separated by thin layer chromatography and analyzed by gas chromatography. Results Higher DHA concentrations in TL (37.24±21.87 mg/L), PL (13.14±8.07 mg/L) and triacylglycerols (2.24±2.21 mg/L) were recorded in mothers from the supplemented group when compared to the study group (TL 21.89±14.53 mg/L; P<0.001; PL 9.33±5.70 mg/L; P=0.013; TG 0.56±0.43 mg/L; P<0.001). Higher DHA concentrations in UV samples were found in TL (11.51±7.34 mg/L), PL (5.29±3.31 mg/L) and triacylglycerols (0.62±0.46 mg/L) from the supplemented groups compared with controls (TL 7.37±3.60 mg/L; P=0.002; PL 3.52±2.19 mg/L; P=0.005; TG 0.40±0.46 mg/L; P=0.035). The ratio of AA:DHA was lower in maternal (2.43) and UV serum (4.0) of the supplemented group than in the control group (maternal 3.85 P<0.001; UV 4.91 P<0.001). Conclusion The study demonstrated the higher ratio of AA/DHA in the control group indicating that pregnant women on the traditional Herzegovina diet need supplementation with DHA and EPA.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Ésteres do Colesterol/sangue , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Fosfolipídeos/sangue , Triglicerídeos/sangue , Adulto , Cromatografia/métodos , Suplementos Nutricionais , Monitoramento de Medicamentos/métodos , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Leite Humano/química , Gravidez , Resultado da Gravidez , Resultado do Tratamento
8.
Nutrients ; 10(12)2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513727

RESUMO

Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry⁻mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p < 0.05 and q < 0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p < 0.05 and q > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.


Assuntos
Coffea , Café , Dieta , Metabolismo dos Lipídeos/efeitos dos fármacos , Preparações de Plantas/farmacologia , Adulto , Cafeína/farmacologia , Ésteres do Colesterol/sangue , Coffea/química , Café/química , Ingestão de Líquidos , Ácidos Graxos não Esterificados/sangue , Glicerofosfolipídeos/sangue , Humanos , Lisofosfatidilcolinas/sangue , Espectrometria de Massas , Fosfatidilcolinas/sangue , Triglicerídeos/sangue
9.
Nutrients ; 10(11)2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30453627

RESUMO

Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of δ-5-desaturase (D5D), δ-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters (n = 1453) and adipose tissue (n = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp (n = 554). Variants at the FADS1 were strongly associated with D5D in both cholesterol esters (p = 1.9 × 10-70) and adipose tissue (p = 1.1 × 10-27). Variants in three further loci were associated with D6D in cholesterol esters (FADS2, p = 3.0 × 10-67; PDXDCI, p = 4.8 × 10-8; and near MC4R, p = 3.7 × 10-8) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (PKDL1, p = 2.2 × 10-19). Genetic variants near MC4R were associated with IS (p = 3.8 × 10-3). The FADS cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS.


Assuntos
Tecido Adiposo/enzimologia , Ésteres do Colesterol/sangue , Ácidos Graxos Dessaturases/genética , Resistência à Insulina/genética , Análise por Conglomerados , Loci Gênicos/genética , Variação Genética/fisiologia , Estudo de Associação Genômica Ampla , Técnica Clamp de Glucose , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Receptor Tipo 4 de Melanocortina/genética , Suécia
10.
Sci Rep ; 8(1): 14764, 2018 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-30282999

RESUMO

Shotgun lipidomic analysis of 203 lipids in 13 lipid classes performed on blood plasma of donors who had just suffered an acute coronary syndrome (ACS, n = 74), or an ischemic stroke (IS, n = 21), or who suffer from stable angina pectoris (SAP, n = 78), and an age-matched control cohort (n = 52), showed some of the highest inter-lipid class correlations between cholesteryl esters (CE) and phosphatidylcholines (PC) sharing a common fatty acid. The concentration of lysophospatidylcholine (LPC) and ratios of concentrations of CE to free cholesterol (Chol) were also lower in the CVD cohorts than in the control cohort, indicating a deficient conversion of Chol to CE in the blood plasma in the CVD subjects. A non-equilibrium reaction quotient, Q', describing the global homeostasis of cholesterol as manifested in the blood plasma was shown to have a value in the CVD cohorts (Q'ACS = 0.217 ± 0.084; Q'IS = 0.201 ± 0.084; Q'SAP = 0.220 ± 0.071) that was about one third less than in the control cohort (Q'Control = 0.320 ± 0.095, p < 1 × 10-4), suggesting its potential use as a rapid predictive/diagnostic measure of CVD-related irregularities in cholesterol homeostasis.


Assuntos
Doenças Cardiovasculares/sangue , Ésteres do Colesterol/sangue , Colesterol/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Colesterol/genética , Ésteres do Colesterol/genética , Ácidos Graxos/sangue , Ácidos Graxos/genética , Feminino , Homeostase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Fosfatidilcolinas/genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-29735021

RESUMO

Glucocorticoid treatment decreases liver insulin sensitivity and may modify fatty acid metabolism. We investigated the influence of oral prednisolone on indices for de novo lipogenesis (DNLi), stearoyl-CoA desaturase (SCDi) and Δ6-desaturase (D6Di) activity in healthy males. In addition, we explored whether the changes may be associated with prednisolone-induced changes in glucose and lipid metabolism and insulin sensitivity. Thirty-two healthy young males (mean ±â€¯SD age 22 ±â€¯3 years, BMI 22.4 ±â€¯1.7 kg/m2) were allocated to receive prednisolone 7.5 mg/day (PRED7.5; n = 12), prednisolone 30 mg/day (PRED30; n = 12), or placebo (n = 8) in a randomized double-blind fashion for 2 weeks. Fatty acid compositions of plasma cholesteryl esters (CE), phospholipids (PL) and triglycerides (TG) were measured at baseline and on day 14. DNLi, SCDi and D6Di were estimated from product/precursor ratios in CE, with DNLi primary deriving from 16:1ω7/18:2ω6, SCDi from 16:1ω7/16:0 and D6Di from 22:6ω3/20:5ω3. Ratios were also assessed in PL and TG. In CE, PRED30 increased DNLi by 51.2 [95%CI 14.8; 87.6]%, increased SCDi by 48.6 [18.7; 78.5]%, and decreased D6Di by 57.7 [-91.8; -23.5]% (p ≤ 0.01 for all, compared to placebo). The prednisolone-induced increases in DNLi and SCDi were positively correlated with insulin sensitivity (r = 0.35 and 0.50, respectively). Similar results were found in PL and TG. Prednisolone dose-dependently increases DNLi and SCDi and decreases D6Di in plasma CE, PL and TG in healthy males after 2 weeks. The observed unfavorable effects on fatty acid metabolism were related to the induction of glucocorticoid-induced insulin resistance.


Assuntos
Anti-Inflamatórios/farmacologia , Linoleoil-CoA Desaturase/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Prednisolona/farmacologia , Estearoil-CoA Dessaturase/genética , Administração Oral , Adulto , Glicemia/efeitos dos fármacos , Ésteres do Colesterol/sangue , Método Duplo-Cego , Esquema de Medicação , Expressão Gênica , Voluntários Saudáveis , Humanos , Resistência à Insulina , Linoleoil-CoA Desaturase/sangue , Metabolismo dos Lipídeos/genética , Lipogênese/genética , Masculino , Fosfolipídeos/sangue , Estearoil-CoA Dessaturase/sangue , Triglicerídeos/sangue
12.
Br J Nutr ; 120(1): 23-32, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29729672

RESUMO

n-3 Fatty acids are associated with better cardiovascular and cognitive health. However, the concentration of EPA, DPA and DHA in different plasma lipid pools differs and factors influencing this heterogeneity are poorly understood. Our aim was to evaluate the association of oily fish intake, sex, age, BMI and APOE genotype with concentrations of EPA, DPA and DHA in plasma phosphatidylcholine (PC), NEFA, cholesteryl esters (CE) and TAG. Healthy adults (148 male, 158 female, age 20-71 years) were recruited according to APOE genotype, sex and age. The fatty acid composition was determined by GC. Oily fish intake was positively associated with EPA in PC, CE and TAG, DPA in TAG, and DHA in all fractions (P≤0·008). There was a positive association between age and EPA in PC, CE and TAG, DPA in NEFA and CE, and DHA in PC and CE (P≤0·034). DPA was higher in TAG in males than females (P<0·001). There was a positive association between BMI and DPA and DHA in TAG (P<0·006 and 0·02, respectively). APOE genotype×sex interactions were observed: the APOE4 allele associated with higher EPA in males (P=0·002), and there was also evidence for higher DPA and DHA (P≤0·032). In conclusion, EPA, DPA and DHA in plasma lipids are associated with oily fish intake, sex, age, BMI and APOE genotype. Such insights may be used to better understand the link between plasma fatty acid profiles and dietary exposure and may influence intake recommendations across population subgroups.


Assuntos
Fatores Etários , Apolipoproteínas E/genética , Índice de Massa Corporal , Dieta , Ácidos Graxos Ômega-3/sangue , Óleos de Peixe , Fatores Sexuais , Adulto , Idoso , Alelos , Animais , Ésteres do Colesterol/sangue , Estudos Cross-Over , Método Duplo-Cego , Ácidos Graxos Insaturados/sangue , Feminino , Peixes , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Reino Unido , Adulto Jovem
13.
Lipids ; 53(1): 27-40, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29488637

RESUMO

Hepatic endocannabinoids (EC) and their major binding/"chaperone" protein (i.e., liver fatty acid binding protein-1 [FABP1]) are associated with development of nonalcoholic fatty liver (NAFLD) in animal models and humans. Since expression of the highly prevalent human FABP1 T94A variant induces serum lipid accumulation, it is important to determine its impact on hepatic lipid accumulation and the EC system. This issue was addressed in livers from human subjects expressing only wild-type (WT) FABP1 T94T (TT genotype) or T94A variant (TC or CC genotype). WT FABP1 males had lower total lipids (both neutral cholesteryl esters, triacylglycerols) and phospholipids than females. WT FABP1 males' lower lipids correlated with lower levels of the N-acylethanolamide DHEA and 2-monoacylglycerols (2-MAG) (2-OG, 2-PG). T94A expression in males increased the hepatic total lipids (triacylglycerol, cholesteryl ester), which is consistent with their higher level of CB1-potentiating 2-OG and lower antagonistic EPEA. In contrast, in females, T94A expression did not alter the total lipids, neutral lipids, or phospholipids, which is attributable to the higher cannabinoid receptor-1 (CB1) agonist arachidonoylethanolamide (AEA) and its CB1-potentiator OEA being largely offset by reduced potentiating 2-OG and increased antagonistic EPEA. Taken together, these findings indicate that T94A-induced alterations in the hepatic EC system contribute at least in part to the hepatic accumulation of lipids associated with NAFLD, especially in males.


Assuntos
Endocanabinoides/genética , Proteínas de Ligação a Ácido Graxo/genética , Estudos de Associação Genética , Hepatopatia Gordurosa não Alcoólica/genética , Ésteres do Colesterol/sangue , Endocanabinoides/metabolismo , Feminino , Regulação da Expressão Gênica , Genótipo , Humanos , Lipídeos/sangue , Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Polimorfismo de Nucleotídeo Único/genética , Receptores de Canabinoides/genética , Caracteres Sexuais , Triglicerídeos/sangue
14.
Int J Cardiol ; 253: 126-132, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29306452

RESUMO

BACKGROUND: The study of the plasma lipidome may help to better characterize molecular mechanisms underlying cardiovascular disease. The identification of new lipid biomarkers could provide future targets for prevention and innovative therapeutic approaches. In the frame of the PREDIMED trial, our aim was to examine the associations of baseline lipidome patterns or their changes with the risk of clinical CVD events. METHODS: We included 983 participants in our case-cohort study. The end-point was the incidence of major CVD during 4.8years of median follow-up. We repeatedly measured 202 plasma known lipid metabolites at baseline and after 1-year of intervention. Principal component analysis was used to identify lipidome factors. Among the 15 identified factors, 7 were significantly associated with CVD. Considering common patterns among factors, lipids were grouped (summed) into scores. RESULTS: After adjustment for traditional CVD risk factors, scores of baseline polyunsaturated phosphatidylcholines (PC)/lysoPC/PC-plasmalogens and polyunsaturated cholesterol esters (CE) showed inverse associations with CVD (p=0.036 and 0.012, respectively); whereas scores of monoacylglycerols (MAGs)/diacylglycerols (DAGs) and short triacylglycerols (TAGs) showed a direct association with CVD (p=0.026 and 0.037, respectively). Baseline phosphatidylethanolamines (PEs) and their 1-y changes tended to be associated with higher CVD risk (p=0.066 and 0.081, respectively). We did not find a significant effect of the intervention with the Mediterranean Diet on these scores. CONCLUSIONS: Our study suggests that polyunsaturated PCs and CEs may confer protection against CVD. In contrast, MAGs, DAGs, TAGs and PEs appeared to be associated with higher CVD risk.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/dietoterapia , Ésteres do Colesterol/sangue , Dieta Mediterrânea , Fosfatidilcolinas/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Nozes , Azeite de Oliva/administração & dosagem , Fatores de Risco
15.
Mol Nutr Food Res ; 62(2)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28981995

RESUMO

SCOPE: Ethnic minority groups have a higher risk of type 2 diabetes (T2D) than the host population. Our aim is to identify whether plasma cholesteryl ester fatty acids (CEFA) mediate the ethnic differences in type 2 diabetes. METHODS AND RESULTS: We included 202 Dutch, 206 South-Asian Surinamese, 205 African Surinamese, 215 Turkish, and 213 Moroccan origin participants of the HELIUS study (Amsterdam, the Netherlands). Logistic regression is used to determine the associations between plasma CEFA and T2D. Mediation analysis is used to identify whether CEFA contributed to the association between ethnicity and T2D. We adjusted for ethnicity, age, sex, smoking, physical activity, and BMI. Associations between plasma CEFA and T2D were similar across all ethnic groups. Although differences in plasma CEFA across ethnic groups were observed, CEFA did not mediate the differences in T2D prevalence between ethnic groups. CONCLUSION: Although ethnic differences in plasma CEFA are found and CEFA are associated with T2D, CEFA does not contribute to the difference in T2D prevalence between ethnic groups. If confirmed, this implies that maintenance of the more beneficial CEFA profiles in the non-Dutch ethnic groups may be encouraged to prevent an even higher prevalence of T2D in these groups.


Assuntos
Ésteres do Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Adulto , Ingestão de Energia , Grupos Étnicos , Ácidos Graxos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/etnologia , Prevalência
16.
J Steroid Biochem Mol Biol ; 179: 45-54, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28743544

RESUMO

The sodium-dependent organic anion transporter SOAT (gene name SLC10A6 in man and Slc10a6 in mice) is a plasma membrane transporter for sulfated steroids, which is highly expressed in germ cells of the testis. SOAT can transport biologically inactive sulfated steroids into specific target cells, where they can be reactivated by the steroid sulfatase (STS) to biologically active, unconjugated steroids known to regulate spermatogenesis. Significantly reduced SOAT mRNA expression was previously found in different forms of impaired spermatogenesis in man. It was supposed that SOAT plays a role for the local supply of steroids in the testis and consequently for spermatogenesis and fertility. Thus, an Slc10a6-/- Soat knockout mouse model was established by recombination-based target deletion of the Slc10a6 gene to elucidate the role of Soat in reproduction. However, the Slc10a6-/- knockout mice were fertile, produced normal litter sizes, and had normal spermatogenesis and sperm vitality. This phenotype suggests that the loss of Soat can be compensated in the knockout mice or that Soat function is not essential for reproduction. In addition to reproductive phenotyping, a comprehensive targeted steroid analysis including a set of 9 un-conjugated and 12 sulfo-conjugated steroids was performed in serum of Slc10a6-/- knockout and Slc10a6+/+ wildtype mice. Only cholesterol sulfate, corticosterone, and testosterone (only in the males) could be detected in considerable amounts. Interestingly, male Slc10a6-/- knockout mice showed significantly higher serum levels for cholesterol sulfate compared to their wildtype controls. As cholesterol sulfate has a broader impact apart from the testis, further analysis of this phenotype will include other organs such as skin and lung, which also show high Soat expression in the mouse.


Assuntos
Ésteres do Colesterol/sangue , Fertilidade/fisiologia , Transportadores de Ânions Orgânicos/genética , Espermatogênese/genética , Animais , Ésteres do Colesterol/genética , Feminino , Fertilidade/genética , Tamanho da Ninhada de Vivíparos , Masculino , Camundongos Knockout , Transportadores de Ânions Orgânicos/metabolismo , Espermatogênese/fisiologia , Esteroides/sangue , Esteroides/metabolismo , Testículo/fisiologia
17.
Clin Nutr ; 37(2): 618-623, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28249700

RESUMO

The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food.


Assuntos
Apolipoproteínas/sangue , Ésteres do Colesterol/sangue , Euterpe/metabolismo , Lipoproteínas HDL/sangue , Extratos Vegetais/farmacologia , Adulto , Apolipoproteínas/efeitos dos fármacos , Biomarcadores/sangue , Dieta/métodos , Feminino , Frutas/metabolismo , Humanos , Lipídeos/sangue , Lipoproteínas HDL/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/metabolismo , Estudos Prospectivos , Valores de Referência , Adulto Jovem
18.
Metabolomics ; 14(4): 38, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30830369

RESUMO

INTRODUCTION: Atherosclerotic diseases are the leading cause of death worldwide. Biomarkers of atherosclerosis are required to monitor and prevent disease progression. While mass spectrometry is a promising technique to search for such biomarkers, its clinical application is hampered by the laborious processes for sample preparation and analysis. METHODS: We developed a rapid method to detect plasma metabolites by probe electrospray ionization mass spectrometry (PESI-MS), which employs an ambient ionization technique enabling atmospheric pressure rapid mass spectrometry. To create an automatic diagnosis system of atherosclerotic disorders, we applied machine learning techniques to the obtained spectra. RESULTS: Using our system, we successfully discriminated between rabbits with and without dyslipidemia. The causes of dyslipidemia (genetic lipoprotein receptor deficiency or dietary cholesterol overload) were also distinguishable by this method. Furthermore, after induction of atherosclerosis in rabbits with a cholesterol-rich diet, we were able to detect dynamic changes in plasma metabolites. The major metabolites detected by PESI-MS included cholesterol sulfate and a phospholipid (PE18:0/20:4), which are promising new biomarkers of atherosclerosis. CONCLUSION: We developed a remarkably fast and easy method to detect potential new biomarkers of atherosclerosis in plasma using PESI-MS.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Ésteres do Colesterol/sangue , Metabolômica , Fosfolipídeos/sangue , Animais , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Biomarcadores/metabolismo , Ésteres do Colesterol/metabolismo , Cromatografia Líquida , Aprendizado de Máquina , Fosfolipídeos/metabolismo , Coelhos , Espectrometria de Massas por Ionização por Electrospray
19.
J Nutr Biochem ; 54: 57-65, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29257986

RESUMO

Plasma levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) are associated with a reduction in risk of cardiovascular disease and other chronic, age-related diseases like Alzheimer's disease. In this work, we tested the hypothesis that n-3 LCPUFA fatty acids in human plasma are incorporated into selective lipid species following intake of n-3 LCPUFA rich marine fish. To test this hypothesis, we performed lipidomic analysis on plasma samples from a clinical trial in which participants consumed increasing amounts of farmed Atlantic salmon (Salmo salar). Under basal conditions, n-3 and n-6 LCPUFA were selectively incorporated into plasma phosphatidylcholine (PC) species containing saturated fatty acids (SFA) versus unsaturated fatty acids as the complementary fatty acids. LCPUFA were incorporated into selective triacylglycerol (TAG) species with complementary diacylglyceryl environments of 34:1 or 34:2 (for 20:5 and 22:5) and 36:2>36:3>36:4 and 36:1 (for 20:4 and 22:6). High n-3 LCPUFA marine fish intake resulted in selective increases of PC SFA_n-3 LCPUFA species and LCPUFA-containing TAG species. Changes in cholesteryl esters and phosphatidylethanolamines also occurred following fish intake. Our results highlight the importance of discriminating phospholipid and TAG species and dietary background when evaluating lipidomic outcomes and disease associations.


Assuntos
Ácidos Graxos Ômega-3/sangue , Produtos Pesqueiros , Lipídeos/sangue , Salmo salar , Adulto , Idoso , Animais , Ésteres do Colesterol/sangue , Dieta , Ácidos Graxos Ômega-6/sangue , Feminino , Humanos , Lipídeos/química , Masculino , Fosfatidilcolinas/sangue , Fosfatidilcolinas/química , Triglicerídeos/sangue
20.
J Biol Regul Homeost Agents ; 31(4): 1087-1093, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29254319

RESUMO

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.


Assuntos
Suplementos Nutricionais , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Óleos Vegetais/farmacologia , Esterol Esterase/antagonistas & inibidores , Animais , Colesterol/administração & dosagem , Colesterol/sangue , Ésteres do Colesterol/sangue , Ácido Cólico/administração & dosagem , Ácido Cólico/sangue , Absorção Gastrointestinal/fisiologia , Humanos , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipolipemiantes/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Óleos Vegetais/metabolismo , Ratos , Ratos Sprague-Dawley , Esterol Esterase/metabolismo , Triglicerídeos/sangue
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