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1.
Clin Sci (Lond) ; 133(3): 409-423, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29122967

RESUMO

Progression of non-alcoholic fatty liver disease (NAFLD) in the context of metabolic syndrome (MetS) is only partially explored due to the lack of preclinical models. In order to study the alterations in hepatic metabolism that accompany this condition, we developed a model of MetS accompanied by the onset of steatohepatitis (NASH) by challenging golden hamsters with a high-fat diet low in vitamin E and selenium (HFD), since combined deficiency results in hepatic necroinflammation in rodents. Metabolomics and transcriptomics integrated analyses of livers revealed an unexpected accumulation of hepatic S-Adenosylmethionine (SAM) when compared with healthy livers likely due to diminished methylation reactions and repression of GNMT. SAM plays a key role in the maintenance of cellular homeostasis and cell cycle control. In agreement, analysis of over-represented transcription factors revealed a central role of c-myc and c-Jun pathways accompanied by negative correlations between SAM concentration, MYC expression and AMPK phosphorylation. These findings point to a drift of cell cycle control toward senescence in livers of HFD animals, which could explain the onset of NASH in this model. In contrast, hamsters with NAFLD induced by a conventional high-fat diet did not show SAM accumulation, suggesting a key role of selenium and vitamin E in SAM homeostasis. In conclusion, our results suggest that progression of NAFLD in the context of MetS can take place even in a situation of hepatic SAM excess and that selenium and vitamin E status might be considered in current therapies against NASH based on SAM supplementation.


Assuntos
Fígado/metabolismo , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , S-Adenosilmetionina/metabolismo , Selênio/deficiência , Vitamina E/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Animais , Cricetinae , Dieta Hiperlipídica/efeitos adversos , Progressão da Doença , Humanos , Masculino , Mesocricetus , Síndrome Metabólica/genética , Hepatopatia Gordurosa não Alcoólica/genética , Proteína Oncogênica p55(v-myc)/genética , Proteína Oncogênica p55(v-myc)/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Selênio/análise , Vitamina E/análise
2.
Food Funct ; 7(9): 3981-3988, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27722538

RESUMO

A high intake of fat and sucrose can dramatically increase bioactive lipids such as ceramides in tissues. Ceramides regulate several steps in the insulin signal pathway. The effects of n-3 PUFA on insulin resistance are inconsistent, especially in liver. We investigated the effect of n-3 PUFA (EPA/DHA 1 : 1) from fish oil on hepatic ceramides in a pre-diabetic animal model. Three groups of rats were fed standard feed, high fat high sucrose feed (HFHS) or HFHS enriched with n-3 PUFA. We investigated by lipidomic analysis how supplementation of a HFHS diet with n-3 PUFA modifies the hepatic ceramide profile triggered by a HFHS diet. Our results show that n-3 PUFA modified the ceramide profile of the liver and reduced their total content in pre-diabetic rats. Significant linear correlations were observed between ceramides and biochemical insulin parameters. Long chain ceramide 18:1/18:0 showed a positive correlation with the HOMA index. Very long chain ceramide 18:1/24:0 showed a negative correlation with insulin and the HOMA index. Finally, very long chain ceramide 18:1/20:0 correlated negatively with glucose levels, plasmatic insulin levels and the HOMA index. In conclusion, the modulation of the ceramide profile in pre-diabetic rats may explain the protective action of n-3 PUFA against liver insulin resistance (IR) caused by an HFHS diet. We confirm the protective role of very long chain ceramide 18:1/24:0 and the harmful role of long chain ceramide 18:1/18:0 in the pre-diabetic state and propose ceramide 18:1/20:0 as a biomarker of early liver IR in rats.


Assuntos
Ceramidas/metabolismo , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/uso terapêutico , Resistência à Insulina , Fígado/metabolismo , Estado Pré-Diabético/prevenção & controle , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Ceramidas/química , Dieta Ocidental/efeitos adversos , Feminino , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Mobilização Lipídica , Metabolômica/métodos , Peso Molecular , Estado Pré-Diabético/sangue , Estado Pré-Diabético/etiologia , Estado Pré-Diabético/metabolismo , Distribuição Aleatória , Ratos Endogâmicos WKY
3.
J Chromatogr A ; 1428: 16-38, 2016 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-26275862

RESUMO

In recent years, sphingolipidomics has emerged as an interesting omic science that encompasses the study of the full sphingolipidome characterization, content, structure and activity in cells, tissues or organisms. Like other omics, it has the potential to impact biomarker discovery, drug development and systems biology knowledge. Concretely, dietary food sphingolipids have gained considerable importance due to their extensively reported bioactivity. Because of the complexity of this lipid family and their diversity among foods, powerful analytical methodologies are needed for their study. The analytical tools developed in the past have been improved with the enormous advances made in recent years in mass spectrometry (MS) and chromatography, which allow the convenient and sensitive identification and quantitation of sphingolipid classes and form the basis of current sphingolipidomics methodologies. In addition, novel hyphenated nuclear magnetic resonance (NMR) strategies, new ionization strategies, and MS imaging are outlined as promising technologies to shape the future of sphingolipid analyses. This review traces the analytical methods of sphingolipidomics in food analysis concerning sample extraction, chromatographic separation, the identification and quantification of sphingolipids by MS and their structural elucidation by NMR.


Assuntos
Análise de Alimentos/métodos , Esfingolipídeos/análise , Humanos , Lipídeos/análise , Espectrometria de Massas
4.
Talanta ; 100: 145-52, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23141322

RESUMO

Different sampling methods involving the collection of biogas by Tedlar bags or adsorption tubes, and different GC-MS injection systems, loop injection or cold trap injection (with bags or by tube desorption), were compared to establish the best method to determine the minority compounds in biogas from sewage treatment plants (STPs). A study of parameters is included, such as the stability of compounds in Tedlar bags or cartridges and the adsorption effect of some less volatile compounds in the thermal desorption system (TD). The optimized methods allowed to determine most compounds at low mgm(-3) levels. Among them, maximum values of D5 (4.84 mg m(-3)), decane (95-118 mg m(-3)) and H(2)S (2223 mg m(-3)) were found in biogas samples.


Assuntos
Biocombustíveis/análise , Poluentes Ambientais/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Adsorção , Poluentes Ambientais/química , Reprodutibilidade dos Testes , Esgotos/química , Temperatura , Eliminação de Resíduos Líquidos
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