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1.
Nutr Metab Cardiovasc Dis ; 31(3): 894-901, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33549440

RESUMO

BACKGROUND AND AIMS: Omentin, as an adipokine, has been reported to improve insulin resistance and inflammation may be related to fatty acids (FAs). Plasma FAs can be used as biomarkers of dietary FAs and endogenous FA exposure. We aimed to evaluate the association between plasma FAs pattern and omentin gene expression in adipose tissue (AT). METHODS AND RESULTS: Visceral and subcutaneous AT and fasting blood were gathered from 97 adults aged >18 years. Participants were already admitted to hospitals for elective abdominal surgery. Dietary intakes were assessed using a food frequency questionnaire. The relative omentin gene expression in visceral and subcutaneous AT was measured by Real-Time PCR and plasma FAs was determined by gas chromatography. The principal component analysis was performed to derive the FAs pattern from plasma individual FAs. Three patterns were derived from plasma FAs, 1) high de-novo lipogenesis (DNL), 2) high trans saturated fatty acids (SFA), and docosahexaenoic acid (trans-SFA/DHA), and 3) high long-chain SFA (LC-SFA). After adjustment for age, sex, and insulin concentration, only the LC-SFA pattern was associated with omentin gene expression in visceral AT (ß = 2.25, P = 0.03). Other patterns were not associated with omentin gene expression in visceral and subcutaneous AT. CONCLUSION: A pattern characterized by high levels of myristic acid (14:0), heptadecanoic acid (17:0), pentadecanoic acid (15:0), and Cis_heptadecanoic acid (17:1), which named LC-SFA was related to omentin gene expression in visceral AT.


Assuntos
Citocinas/metabolismo , Ácidos Graxos/sangue , Gordura Intra-Abdominal/metabolismo , Lectinas/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Biomarcadores/sangue , Estudos Transversais , Citocinas/genética , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Regulação da Expressão Gênica , Humanos , Irã (Geográfico) , Lectinas/genética , Masculino , Pessoa de Meia-Idade
2.
Nutr Metab Cardiovasc Dis ; 31(3): 972-978, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33549451

RESUMO

BACKGROUND AND AIMS: Western dietary habits are partially characterized by increased uptake of fructose, which contributes to metabolic dysregulation and associated liver diseases. For example, a diet enriched with fructose drives insulin resistance and non-alcoholic fatty liver disease (NAFLD). The molecular hubs that control fructose-induced metabolic dysregulation are poorly understood. Apolipoprotein A5 (apoA5) controls triglyceride metabolism with a putative role in hepatic lipid deposition. We explored apoA5 as a rheostat for fructose-induced hepatic and metabolic disease in mammals. METHODS AND RESULTS: ApoA5 knock out (-/-) and wildtype (wt) mice were fed with high fructose diet or standard diet for 10 weeks. Afterwards, we conducted a metabolic characterization by insulin tolerance test as well as oral glucose tolerance test. Additionally, hepatic lipid content as well as transcription patterns of key enzymes and transcription factors in glucose and lipid metabolism were evaluated. Despite comparable body weight, insulin sensitivity was significantly improved in high fructose diet fed apoA5 (-/-) when compared to wildtype mice on the same diet. In parallel, hepatic triglyceride content was significantly lower in apoA5 (-/-) mice than in wt mice. No difference was seen between apoA5 (-/-) and wt mice on a standard diet. CONCLUSION: ApoA5 is involved in fructose-induced metabolic dysregulation and associated hepatic steatosis suggesting that apoA5 may be a novel target to treat metabolic diseases.


Assuntos
Apolipoproteína A-V/deficiência , Glicemia/metabolismo , Açúcares da Dieta , Frutose , Resistência à Insulina , Insulina/sangue , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Triglicerídeos/metabolismo , Animais , Apolipoproteína A-V/genética , Biomarcadores/sangue , Modelos Animais de Doenças , Ácidos Graxos/sangue , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/prevenção & controle
3.
Nutrients ; 13(1)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445698

RESUMO

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS-lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1 ± 0.0 to 9.7 ± 1.9, p < 0.001), docosahexaenoic acid, DHA (day 0 = 2.5 ± 0.7 to 13.6 ± 2.9, p < 0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1ß increased at the first hour of LPS infusion (296.6 ± 308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p < 0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit the initial LPS-induced inflammatory responses in preterm pigs.


Assuntos
Ácidos Graxos/sangue , Óleos de Peixe/farmacologia , Interleucina-1beta/sangue , Lipopolissacarídeos/toxicidade , Oxilipinas/sangue , Animais , Animais Recém-Nascidos , Emulsões , Óleos de Peixe/farmacocinética , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Infusões Parenterais , Suínos
4.
Nutr Metab Cardiovasc Dis ; 31(1): 297-305, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33500106

RESUMO

BACKGROUND AND AIMS: Fatty acids (FAs) and their metabolizing enzymes have been associated with several cardiometabolic outcomes. Whether they correlate with cardiovascular risk in type 1 diabetes (T1D), it is unknown. We investigated whether erythrocyte FAs correlated with cardiovascular risk factors and dietary fats in youth with T1D. METHODS AND RESULTS: We recruited 154 adolescents with T1D (aged 17.3 ± 2 years, 82 boys) and assessed blood pressure, plasma lipids, HbA1c, estimated insulin sensitivity (eIS) and dietary fats based on a 3-days weighed dietary record. Erythrocyte FAs were measured by gas chromatography and desaturase and elongase activities were estimated as product/precursor ratios. Delta-6-desaturase (D6D) activity correlated inversely with eIS (r = -0.32,p = 6.6∗10-5) and directly with triglycerides (r = 0.24, p = 0.003), adjusted for z-BMI, age and gender. No single erythrocyte FA correlated with eIS. Erythrocyte membrane stearic acid (SA) correlated with HbA1c adjusted for confounders and eIS (r = -0.26, p = 0.002). We found some weak (r ≤ 0.20) correlations between erythrocyte membrane FAs and dietary fats, which were not retained by correction for multiple testing. CONCLUSION: In youth with T1D, D6D activity might exert unfavorable effects per se, beyond its role on FAs composition. This is in accordance with previous data associating D6D activity/D6D-enhancing polymorphisms with metabolic syndrome and incident type 2 diabetes, as well as D6D activity with the regulation of cellular red-ox balance. SA was a favorable marker of glycemic control. Future research is needed to clarify the biological pathways linking D6D and SA with the cardiometabolic health of youth with T1D.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/sangue , Membrana Eritrocítica/metabolismo , Ácidos Graxos/sangue , Adolescente , Fatores Etários , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Humanos , Linoleoil-CoA Desaturase/sangue , Masculino , Medição de Risco , Adulto Jovem
5.
ACS Appl Mater Interfaces ; 13(1): 1914-1920, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33378159

RESUMO

Graphdiyne (GD) is a new kind of carbon nanomaterial which has carbon-carbon triple bonds to form a layered structure. Here, we report the application of GD as the matrix for small molecule analysis in laser desorption ionization mass spectrometry (LDI MS). The GD matrix displayed two advantages: little background in the low mass range and good molecular ion signal in negative ion mode for many small molecules, e.g., fatty acids, amino acids, peptides, and drugs can be obtained in negative ion mode. By comparing the signal intensity of tetraphenylborate and juglone with and without GD existing, it was found that GD can enhance both of the desorption efficiency and ionization efficiency in LDI. Through analysis of the serum samples from liver cancer patients and healthy people, the GD-assisted LDI MS results showed that fatty acids could be used as potential biomarkers for the early diagnosis of liver cancer.


Assuntos
Aminoácidos/análise , Ácidos Graxos/sangue , Grafite/química , Compostos Orgânicos/análise , Preparações Farmacêuticas/análise , Biomarcadores Tumorais/sangue , Humanos , Limite de Detecção , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
6.
Artigo em Inglês | MEDLINE | ID: mdl-33010450

RESUMO

Toll-like receptors (TLR) are crucial for recognizing bacterial, viral or fungal pathogens and to orchestrate the appropriate immune response. The widely expressed TLR2 and TLR4 differentially recognize various pathogens to initiate partly overlapping immune cascades. To better understand the physiological consequences of both immune responses, we performed comparative lipidomic analyses of local paw inflammation in mice induced by the TLR2 and TLR4 agonists, zymosan and lipopolysaccharide (LPS), respectively, which are commonly used in models for inflammation and inflammatory pain. Doses for both agonists were chosen to cause mechanical hypersensitivity with identical strength and duration. Lipidomic analysis showed 5 h after LPS or zymosan injection in both models an increase of ether-phosphatidylcholines (PC O) and their corresponding lyso species with additional lipids being increased only in response to LPS. However, zymosan induced stronger immune cell recruitment and edema formation as compared to LPS. Importantly, only in LPS-induced inflammation the lipid profile in the contralateral paw was altered. Fittingly, the plasma level of various cytokines and chemokines, including IL-1ß and IL-6, were significantly increased only in LPS-treated mice. Accordingly LPS induced distinct changes in the lipid profiles of ipsilateral and contralateral paws. Here, oxydized fatty acids, phosphatidylcholines and phosphatidylethanolamines were uniquely upregulated on the contralateral side. Thus, both models cause increased levels of PC O and lyso-PC O lipids at the site of inflammation pointing at a common role in inflammation. Also, LPS initiates systemic changes, which can be detected by changes in the lipid profiles.


Assuntos
Reação de Fase Aguda/sangue , Edema/sangue , Lipopolissacarídeos/administração & dosagem , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Zimosan/administração & dosagem , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/genética , Reação de Fase Aguda/patologia , Animais , Edema/induzido quimicamente , Edema/genética , Edema/patologia , Ácidos Graxos/sangue , Ácidos Graxos/classificação , Regulação da Expressão Gênica , Membro Posterior/irrigação sanguínea , Membro Posterior/efeitos dos fármacos , Membro Posterior/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-6/sangue , Interleucina-6/genética , Lipidômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilcolinas/classificação , Fosfatidiletanolaminas/classificação , Transdução de Sinais , Receptor 2 Toll-Like/sangue , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/genética
7.
J Dairy Sci ; 104(2): 2008-2017, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33358169

RESUMO

Breeding objectives in the dairy industry have shifted from being solely focused on production to including fertility, animal health, and environmental impact. Increased serum concentrations of candidate biomarkers of health and fertility, such as ß-hydroxybutyric acid (BHB), fatty acids, and urea are difficult and costly to measure, and thus limit the number of records. Accurate genomic prediction requires a large reference population. The inclusion of milk mid-infrared (MIR) spectroscopic predictions of biomarkers may increase genomic prediction accuracy of these traits. Our objectives were to (1) estimate the heritability of, and genetic correlations between, selected serum biomarkers and their respective MIR predictions, and (2) evaluate genomic prediction accuracies of either only measured serum traits, or serum traits plus MIR-predicted traits. The MIR-predicted traits were either fitted in a single trait model, assuming the measured trait and predicted trait were the same trait, or in a multitrait model, where measured and predicted trait were assumed to be correlated traits. We performed all analyses using relationship matrices constructed from pedigree (A matrix), genotypes (G matrix), or both pedigree and genotypes (H matrix). Our data set comprised up to 2,198 and 9,657 Holstein cows with records for serum biomarkers and MIR-predicted traits, respectively. Heritabilities of measured serum traits ranged from 0.04 to 0.07 for BHB, from 0.13 to 0.21 for fatty acids, and from 0.10 to 0.12 for urea. Heritabilities for MIR-predicted traits were not significantly different from those for the measured traits. Genetic correlations between measured traits and MIR-predicted traits were close to 1 for urea. For BHB and fatty acids, genetic correlations were lower and had large standard errors. The inclusion of MIR predicted urea substantially increased prediction accuracy for urea. For BHB, including MIR-predicted BHB reduced the genomic prediction accuracy, whereas for fatty acids, prediction accuracies were similar with either measured fatty acids, MIR-predicted fatty acids, or both. The high genetic correlation between urea and MIR-predicted urea, in combination with the increased prediction accuracy, demonstrated the potential of using MIR-predicted urea for genomic prediction of urea. For BHB and fatty acids, further studies with larger data sets are required to obtain more accurate estimates of genetic correlations.


Assuntos
Biomarcadores/sangue , Bovinos/fisiologia , Fertilidade , Genômica , Leite/química , Espectrofotometria Infravermelho/veterinária , Ácido 3-Hidroxibutírico/sangue , Animais , Bovinos/sangue , Indústria de Laticínios , Ácidos Graxos/sangue , Feminino , Genótipo , Linhagem , Fenótipo , Ureia/sangue
8.
PLoS One ; 15(9): e0232069, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956351

RESUMO

Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SL versus the NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (-66%, p<0.001) and upon correction for liver weight (-44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype.


Assuntos
Ração Animal/efeitos adversos , Fígado Gorduroso/metabolismo , Fígado/patologia , Animais , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Modelos Animais de Doenças , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Feminino , Humanos , Metabolismo dos Lipídeos , Lipoproteínas VLDL/sangue , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores Sexuais , Triglicerídeos/sangue , Triglicerídeos/metabolismo
9.
PLoS One ; 15(9): e0238304, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915819

RESUMO

Epistasis analysis elucidates the effects of gene-gene interactions (G×G) between multiple loci for complex traits. However, the large computational demands and the high multiple testing burden impede their discoveries. Here, we illustrate the utilization of two methods, main effect filtering based on individual GWAS results and biological knowledge-based modeling through Biofilter software, to reduce the number of interactions tested among single nucleotide polymorphisms (SNPs) for 15 cardiac-related traits and 14 fatty acids. We performed interaction analyses using the two filtering methods, adjusting for age, sex, body mass index (BMI), waist-hip ratio, and the first three principal components from genetic data, among 2,824 samples from the Ludwigshafen Risk and Cardiovascular (LURIC) Health Study. Using Biofilter, one interaction nearly met Bonferroni significance: an interaction between rs7735781 in XRCC4 and rs10804247 in XRCC5 was identified for venous thrombosis with a Bonferroni-adjusted likelihood ratio test (LRT) p: 0.0627. A total of 57 interactions were identified from main effect filtering for the cardiac traits G×G (10) and fatty acids G×G (47) at Bonferroni-adjusted LRT p < 0.05. For cardiac traits, the top interaction involved SNPs rs1383819 in SNTG1 and rs1493939 (138kb from 5' of SAMD12) with Bonferroni-adjusted LRT p: 0.0228 which was significantly associated with history of arterial hypertension. For fatty acids, the top interaction between rs4839193 in KCND3 and rs10829717 in LOC107984002 with Bonferroni-adjusted LRT p: 2.28×10-5 was associated with 9-trans 12-trans octadecanoic acid, an omega-6 trans fatty acid. The model inflation factor for the interactions under different filtering methods was evaluated from the standard median and the linear regression approach. Here, we applied filtering approaches to identify numerous genetic interactions related to cardiac-related outcomes as potential targets for therapy. The approaches described offer ways to detect epistasis in the complex traits and to improve precision medicine capability.


Assuntos
Doenças Cardiovasculares/epidemiologia , Biologia Computacional/métodos , Epistasia Genética , Ácidos Graxos/sangue , Marcadores Genéticos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Prospectivos , Adulto Jovem
11.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(6): 374-382, jun.-jul. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-193362

RESUMO

BACKGROUND: The role of ADIPOQ gene rs266729 variants on weight loss after a dietary intervention are still unclear. OBJECTIVE: To analyze the effects of the ADIPOQ gene rs266729 variant n weight loss, cardiovascular risk factors, and adiponectin levels after two hypocaloric diets with different dietary fatty profiles. DESIGN: A population of 362 obese patients was enrolled in a randomized clinical trial with two diets (Diet M, monounsaturated fat-enriched diet, and Diet P, polyunsaturated-fat enriched diet). Anthropometric measurements, an assessment of nutritional intake, and biochemical tests were performed at baseline and after 12 weeks. RESULTS: Weight loss was similar with both diets. After Diet M, only subjects with CC genotype showed significant improvements in total cholesterol (CC vs. CG ± GG) -9.0 ±1.1 mU/L vs. -4.5 ± 2.4 mg/dL, p = 0.01), LDL cholesterol (-6.0 ± 1.1 mg/dL vs. -3.0 ± 0.9 mg/dL, p = 0.03), glucose (-4.7 ± 1.1 mg/dL vs. -0.6 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.6 ±1.0 mU/L vs. -0.7 ± 0.3 mU/L, p = 0.02) and in HOMA-IR (-0.5 ± 0.2 units vs. -0.2 ± 0.4 units, p = 0.03). The same improvement was reported after Diet P in all parameters, including total cholesterol (CC vs. CG±GG) (-8.0 ± 1.2mU/L vs. -2.1 ± 1.4 mg/dL, p = 0.02), LDL cholesterol (-7.3 ± 1.2 mg/dL vs. -2.1 ± 0.8 mg/dL, p = 0.02), glucose (-3.2 ± 0.1mg/dL vs. -0.2 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.5 ± 1.0 mU/L vs. -1 ± 0.6 mU/L, p = 0.02) and HOMA-IR (-0.5 ± 0.1 units vs. −0.3 ± 0.4 units, p = 0.02). Only subjects with CC genotype showed significant increases in adiponectin levels after both diets: (Diet M: 10.3 ± 2.0 ng/dL vs. Diet P: 9.3 ± 2.9 ng/dL, p = 0.43). CONCLUSION: The CC genotype of ADIPOQ gene rs266729 variant is associated to increased adiponectin levels and decreases in LDL cholesterol, glucose, insulin, and HOMA-IR levels after weight loss


ANTECEDENTES: El papel de las variantes del gen ADIPOQ en la pérdida de peso después de una intervención dietética sigue sin estar claro. OBJETIVO: Nuestro objetivo fue analizar los efectos de la variante rs266729 del gen ADIPOQ sobre la pérdida de peso, los factores de riesgo cardiovascular y los niveles de adiponectina después de 2 dietas hipocalóricas con diferentes perfiles de grasas en la dieta. DISEÑO: Una población de 362 pacientes obesos se incluyeron en un ensayo clínico aleatorizado con 2 dietas (dieta M: dieta enriquecida con grasas monoinsaturadas y dieta P: dieta enriquecida con grasas poliinsaturadas). Antes y tras 12 semanas, se realizó una evaluación antropométrica, evaluación de la ingesta nutricional y un análisis bioquímico. RESULTADOS: La pérdida de peso fue similar con ambas dietas. Después de la dieta M, solo los sujetos con genotipo CC mostraron una mejoría significativa en el colesterol total (CC vs. CG±GG) (-9,0 ± 1,1 mU/l vs. - 4,5 ± 2,4 mg/dl; p = 0,01), colesterol LDL (-6,0 ± 1,1 mg/dl vs. - 3,0 ± 0,9 mg/dl; p = 0,03), glucosa (-4,7 ± 1,1 mg/dl vs. -0,6 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,6 ± 1,0 mU/l vs. -0,7± 0,3 mU/l; p = 0,02) y HOMA-IR (- 0,5 ± 0,2 unidades vs. -0,2 ± 0,4 unidades; p = 0,03). La misma mejora en todos los parámetros se informó después de la dieta P; niveles de colesterol total (CC vs. CG ± GG) (-8,0 ± 1,2 mU/l vs. -2,1 ± 1,4 mg/dl; p = 0,02), colesterol LDL (-7,3 ± 1,2 mg/dl vs. -2,1 ±0,8 mg/dl; p = 0,02), glucosa (-3,2 ± 0,1 mg/dl vs. -0,2 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,5 ±1,0 mU/l vs. -1 ±0,6 mU/l; p = 0,02) y HOMA-IR (-0,5 ± 0,1 unidades vs. -0,3 ± 0,4 unidades; p = 0,02). Solo los sujetos con genotipo CC mostraron un aumento significativo de los niveles de adiponectina después de ambas dietas: (dieta M: 10,3 ± 2,0 ng/dl vs. dieta P: 9,3 ± 2,9 ng/dl; p = 0,43). CONCLUSIÓN: El genotipo CC de la variante rs266729 del gen ADIPOQ se asocia con aumentos en los niveles de adiponectina y disminución del colesterol LDL, glucosa, insulina y HOMA-IR tras la pérdida de peso


Assuntos
Humanos , Ácidos Graxos/sangue , Adiponectina/genética , Dieta Redutora/métodos , Perda de Peso , Gorduras na Dieta/uso terapêutico , Adiponectina/sangue , Obesidade/dietoterapia , Antropometria , LDL-Colesterol , Genótipo , Estudos Prospectivos , Adiponectina/metabolismo , Receptores de Adipocina/sangue , Análise de Variância
12.
PLoS One ; 15(6): e0234404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555688

RESUMO

Myocardial energy deprivation plays a causal role in the development of heart failure. A cardiac protection blend (CPB) of nutrients including medium chain triglycerides, fish oil and other key nutrients was developed to slow the progression of canine myxomatous mitral valve disease (MMVD). A six-month dietary intervention demonstrated efficacy of CPB in slowing MMVD progression. Untargeted metabolomic analysis of serum from these dogs identified 102 differential metabolites (adjusted P < 0.05). The ratios of omega-6 to omega-3 fatty acid (FA) changed from 2.41 and 1.46 in control and CPB groups at baseline to 4.30 and 0.46 at 6 months respectively. A 2.7-fold increase of α-aminobutyrate, a myocardial modulator of glutathione homeostasis, was found in CPB dogs compared to 1.3-fold increase in control dogs. Arginine and citrulline, precursors of nitric oxide biosynthesis, were both increased 2-fold; caprate, a medium chain FA, was increased 3-fold; and deoxycarnitine, precursor of carnitine biosynthesis, was increased 2.5-fold in CPB dogs. Margarate and methylpalmitate decreased in response to CPB, a potential benefit in MMVD dogs as positive correlations were found between changes in both these FAs and left atrial diameter (r = 0.69, r = 0.87 respectively, adjusted P < 0.05). Sphingomyelins with very long chain saturated FAs associated with decreased risk of heart failure in humans were increased in MMVD dogs fed the CPB diet. Our data supports the hypothesis that CPB improves FA utilization and energetics, reduces oxidative stress and inflammation in MMVD dogs. More studies are needed to understand the roles of specific metabolites in MMVD.


Assuntos
Doenças do Cão/sangue , Doenças do Cão/dietoterapia , Metaboloma , Insuficiência da Valva Mitral/veterinária , Aminoácidos/sangue , Ração Animal/análise , Animais , Dietoterapia/veterinária , Doenças do Cão/patologia , Cães , Ácidos Graxos/sangue , Feminino , Átrios do Coração/patologia , Masculino , Metabolômica , Insuficiência da Valva Mitral/sangue , Insuficiência da Valva Mitral/dietoterapia , Fosfolipídeos/sangue
13.
PLoS Med ; 17(6): e1003102, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32530938

RESUMO

BACKGROUND: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). METHODS AND FINDINGS: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. CONCLUSIONS: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos/metabolismo , Lipogênese , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Ácidos Graxos/sangue , Feminino , Humanos , Incidência , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Arch Environ Contam Toxicol ; 79(2): 184-194, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32494886

RESUMO

The widespread human exposure to perfluoroalkyl acids (PFAAs) has led to increasing public concern. In this study, we present a comprehensive measurement of total fluorine (TF), extractable organic fluorine (EOF), identified organic fluorine (IOF, total concentration of identified PFAAs quantified as fluorine) and 11 target PFAAs in human serum (n = 60), hair (n = 49) and nails (n = 39) collected from non-occupation exposed volunteers in 10 cities of Guangdong Province, China. The results indicated that EOF was the major form of fluorine in serum, accounting for 70-80% of TF. The levels of IOF contributed less than 10% of EOF. Perfluorooctane sulfonic acid (PFOS) was found to be the dominant PFAA with mean concentration of 23 ng·mL-1 in serum, 35 ng·g-1 in hair and 33 ng·g-1 in nail, respectively. Short-chain PFAAs (C ≤ 10) were the predominant PFAAs in three matrices. Levels of PFOS, perfluorohexane sulfonic acid (PFHxS), perfluoroundecanoic acid (PFUdA) and perfluorotridecanoic acid (PFTrDA) in males are significantly higher than those in females (p < 0.01). Significant positive correlations were observed between nail and serum for PFOS (p < 0.01), perfluorooctanoic acid (PFOA) (p < 0.05) and PFHxS (p < 0.01), suggesting that human nails, a noninvasive sample, are a promising bio-indicator for PFAA risk assessment.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Adulto , Ácidos Alcanossulfônicos/sangue , Ácidos Alcanossulfônicos/química , Ácidos Alcanossulfônicos/metabolismo , Caprilatos/sangue , Caprilatos/química , Caprilatos/metabolismo , China , Cidades , Ácidos Graxos/sangue , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Feminino , Fluorcarbonetos/sangue , Fluorcarbonetos/química , Fluorcarbonetos/metabolismo , Cabelo , Humanos , Masculino , Unhas , Adulto Jovem
15.
Thorax ; 75(8): 679-688, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32467337

RESUMO

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare multisystem disease almost exclusively affecting women which causes loss of lung function, lymphatic abnormalities and angiomyolipomas. LAM occurs sporadically and in people with tuberous sclerosis complex (TSC). Loss of TSC gene function leads to dysregulated mechanistic target of rapamycin (mTOR) signalling. As mTOR is a regulator of lipid and nucleotide synthesis, we hypothesised that the serum metabolome would be altered in LAM and related to disease severity and activity. METHODS: Ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to examine the serum metabolome of 79 closely phenotyped women with LAM, including 29 receiving treatment with an mTOR inhibitor and 43 healthy control women. RESULTS: Sphingolipid, fatty acid and phospholipid metabolites were associated with FEV1 in women with LAM (eg, behenoyl sphingomyelin adjusted (adj.) p=8.10 × 10-3). Those with higher disease-burden scores had abnormalities in fatty acid, phospholipid and lysolipids. Rate of loss of FEV1 was associated with differences in acyl-carnitine, acyl-glycines, acyl-glutamine, fatty acids, endocanbinoids and sphingolipids (eg, myristoleoylcarnitine adj. p=0.07). In TSC-LAM, rapamycin affected modules of interrelated metabolites which comprised linoleic acid, the tricarboxylic acid cycle, aminoacyl-tRNA biosynthesis, cysteine, methionine, arginine and proline metabolism. Metabolomic pathway analysis within modules reiterated the importance of glycerophospholipid metabolites (adj. p=0.047). CONCLUSIONS: Women with LAM have altered lipid metabolism. The associations between these metabolites, multiple markers of disease activity and their potential biological roles in cell survival and signalling, suggest that lipid species may be both disease-relevant biomarkers and potential therapeutic targets for LAM.


Assuntos
Ácidos Graxos/sangue , Linfangioleiomiomatose/sangue , Linfangioleiomiomatose/tratamento farmacológico , Fosfolipídeos/sangue , Esfingolipídeos/sangue , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico
16.
Am J Clin Nutr ; 111(6): 1252-1258, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320012

RESUMO

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


Assuntos
Aterosclerose/sangue , Transtornos Cognitivos/sangue , Cognição , Ácidos Graxos/sangue , Fosfolipídeos/sangue , Idoso , Aterosclerose/diagnóstico , Aterosclerose/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Estudos de Coortes , Ácidos Eicosanoicos/sangue , Ácidos Graxos/química , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Food Chem ; 322: 126736, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32325363

RESUMO

Fundamental nutritional studies on bioactive molecules require minimizing exposure to confounding foreign elements, like solvents. Herein, aqueous formulations of lecithin nanovesicles are proposed to study three individual trans fatty acids relevant to human nutrition: elaidic acid, trans-vaccenic acid and trans-palmitoleic acid. This proof-of-concept study describes the encapsulation of fatty acids, in vivo bioavailability, and the use of nanovesicles in behavioral experiments. The oral bioavailability of the encapsulated molecules and the selective exposure of animals to each trans-fatty acid of interest were confirmed in healthy rats. Behavioral studies also evidenced that nanovesicles can be used to evaluate the palatability of the lipids and investigate food preferences in mice. Altogether this study shows that lecithin nanovesicles offer an elegant tool to efficiently deliver hydrophobic molecules to animal models. This approach paves the way for future studies deconvoluting the nutritional effects of trans-fatty acids.


Assuntos
Lecitinas/química , Nanoestruturas/química , Nutrientes/química , Administração Oral , Animais , Disponibilidade Biológica , Dieta/veterinária , Ácidos Graxos/sangue , Ácidos Graxos/química , Feminino , Preferências Alimentares/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lecitinas/farmacocinética , Lecitinas/farmacologia , Lipídeos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Oleicos/química , Ácidos Oleicos/farmacologia , Ratos , Ácidos Graxos Trans/análise , Ácidos Graxos Trans/química , Ácidos Graxos Trans/farmacologia
18.
Int J Gynaecol Obstet ; 149(3): 309-317, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32246773

RESUMO

OBJECTIVE: To evaluate the concentration and profile of fatty acids (FAs) among macrosomic neonates delivered by healthy pregnant women and pregnant women with type 1 diabetes mellitus (T1DM). METHODS: A prospective study of women who delivered macrosomic neonates at a University Hospital Center, Zagreb, Croatia, 2016-2018. Maternal, umbilical vein, and arterial blood samples were collected immediately on delivery. After lipid extraction, total FAs in maternal, umbilical vein, and arterial serum samples were assessed by gas chromatography. Data were compared between women with T1DM and healthy control women. RESULTS: In total, 50 women were enrolled: 22 with T1DM and 28 control women. Neonates in the T1DM group had a higher ponderal index as compared with the control group (P=0.006). Umbilical vein insulin, insulin resistance, and leptin concentration were higher in the T1DM group than in the control group (all P<0.001). Umbilical vein serum concentrations of total saturated, monounsaturated, n-3 polyunsaturated, and n-6 polyunsaturated FAs were higher in the T1DM group (P=0.004, P<0.001, P=0.015, and P=0.014, respectively). CONCLUSION: Macrosomic neonates delivered by women with T1DM had a higher Ponderal index, and higher concentrations of insulin, leptin, and FAs in the umbilical vein and artery as compared with control group newborns.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Macrossomia Fetal/sangue , Gravidez em Diabéticas/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Croácia , Ácidos Graxos/sangue , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos
19.
Int J Sports Med ; 41(9): 603-609, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32252101

RESUMO

The ergogenic effect of caffeine is well established, although no investigations providing a high carbohydrate feeding strategy (pre-exercise meal=2 g/kg BM) co-ingested with caffeine exist for soccer. This investigation examines the effect of caffeine in addition to a pre-exercise carbohydrate meal and drink mid-way through a soccer simulation. Eight recreational soccer players completed an 85-minute soccer simulation followed by an exercise capacity test (Yo-yo Intermittent Endurance test level 2) on two occasions. Prior to exercise participants consumed a high carbohydrate meal, with placebo or 5 mg/kg BM-1 caffeine. No significant performance effect was identified (p=0.099) despite a 12.8% (109 m) improvement in exercise capacity following caffeine. Rates of carbohydrate and fat oxidation did not differ between conditions and nor were differences apparent for plasma glucose, fatty acids, glycerol, ß-hydroxybutyrate (p>0.05). However, an increase in lactate was observed for caffeine (p=0.039). A significant condition effect on rating of perceived exertion was identified (p<0.001), with the overall mean for the protocol lowered to 11.7±0.9 au for caffeine compared to 12.8±1.3 au. Caffeine supplementation with a carbohydrate feeding strategy failed to affect metabolic and metabolite responses, although reductions in perception of exercise were observed. While a 12.8% increase in exercise capacity was noted the findings were not significant, possibly due to the small sample size.


Assuntos
Desempenho Atlético/fisiologia , Cafeína/administração & dosagem , Dieta da Carga de Carboidratos , Exercício Físico/fisiologia , Substâncias para Melhoria do Desempenho/administração & dosagem , Futebol/fisiologia , Ácido 3-Hidroxibutírico/sangue , Glicemia/metabolismo , Carboidratos da Dieta/sangue , Método Duplo-Cego , Metabolismo Energético , Ácidos Graxos/sangue , Glicerol/sangue , Humanos , Ácido Láctico/sangue , Masculino , Percepção/fisiologia , Esforço Físico/fisiologia , Adulto Jovem
20.
Anal Chim Acta ; 1105: 105-111, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32138907

RESUMO

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are an important family of endogenous lipids, possessing antidiabetic and anti-inflammatory functions. Therefore, analysis of FAHFAs in biological samples obtained under healthy and disease states can uncover underlying mechanisms of various relevant disorders (e.g., diabetes and autoimmune diseases). Up to now, due to their extremely low abundance, the determination of the changed levels of these species is still a huge challenge, even though great efforts have been made by utilizing liquid chromatography-tandem mass spectrometry with or without derivatization. Herein, we described a novel method for analysis of FAHFAs present in lipid extracts of biological examples after solid-phase extraction and chemical derivatization with one authentic FAHFA specie as an internal standard based on the principles of multi-dimensional mass spectrometry-based shotgun lipidomics. The approach possessed marked sensitivity, high specificity, and broad linear dynamic range of over 3 orders without obvious matrix effects. Moreover, after chemical derivatization, the molecular masses of FAHFAs shift from an overlapped region with ceramide species to a new region without overlaps, removing these contaminating signals from ceramides, and thereby reducing the false results of FAHFAs. Finally, this novel method was successfully applied for determining FAHFAs levels in varieties of representative biological samples, including plasma from lean and overweight/obese individuals of normoglycemia, and tissue samples (such as liver and white adipose tissue from diabetic (db/db) mice). We revealed significant alterations of FAHFAs in samples under patho(physio)logical conditions compared to their respective controls. Taken together, the developed method could greatly contribute to studying altered FAHFA levels under a variety of biological/biomedical conditions, and facilitate the understanding of these lipid species in the patho(physio)logical process.


Assuntos
Ésteres/sangue , Ácidos Graxos/sangue , Lipidômica , Lipídeos/química , Adulto , Animais , Feminino , Voluntários Saudáveis , Humanos , Lipídeos/isolamento & purificação , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Estrutura Molecular , Extração em Fase Sólida , Adulto Jovem
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