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1.
Br J Nutr ; 107(9): 1254-73, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21914239

RESUMEN

Long-chain (LC) n-3 PUFA have a broad range of biological properties that can be achieved at the gene expression level. This has been well described in liver, where LC n-3 PUFA modulate the expression of genes related to lipid metabolism. However, the complexity of biological pathway modulations and the nature of bioactive molecules are still under investigation. The present study aimed to investigate the dose-response effects of LC n-3 PUFA on the production of peroxidised metabolites, as potential bioactive molecules, and on global gene expression in liver. Hypercholesterolaemic rabbits received by daily oral administration (7 weeks) either oleic acid-rich oil or a mixture of oils providing 0.1, 0.5 or 1 % (groups 1, 2 and 3 respectively) of energy as DHA. Levels of specific peroxidised metabolites, namely 4-hydroxyhexenal (4-HHE)-protein adducts, issued from LC n-3 PUFA were measured by GC/MS/MS in liver in parallel to transcription profiling. The intake of LC n-3 PUFA increased, in a dose-dependent manner, the hepatic production of 4-HHE. At the highest dose, LC n-3 PUFA provoked an accumulation of TAG in liver, which can be directly linked to increased mRNA levels of lipoprotein hepatic receptors (LDL-receptor and VLDL-receptor). In groups 1 and 2, the mRNA levels of microsomal TAG transfer protein decreased, suggesting a possible new mechanism to reduce VLDL secretion. These modulations of genes related to lipoprotein metabolism were independent of PPARα signalling but were probably linked to the activation of the farnesol X receptor pathway by LC n-3 PUFA and/or their metabolites such as HHE.


Asunto(s)
Ácidos Grasos Omega-3/metabolismo , Regulación de la Expresión Génica , Peroxidación de Lípido , Hígado/metabolismo , Administración Oral , Aldehídos/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas , Perfilación de la Expresión Génica , Hipercolesterolemia/tratamiento farmacológico , Metabolismo de los Lípidos , Microsomas Hepáticos/metabolismo , Conejos , Receptores Citoplasmáticos y Nucleares/metabolismo , Espectrometría de Masas en Tándem
2.
Sante Publique ; 1 Suppl: 9-11, 2015.
Artículo en Francés | MEDLINE | ID: mdl-26414251
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