RESUMEN
Fat may affect progression of liver damage in patients with non-alcoholic fatty liver disease (NAFLD). In this study we characterize the state of lipid metabolism in 22 patients with NAFLD and different Apo-E variants. Total concentration of plasma total fatty acids was quantified by gas chromatography, while their derivatives by liquid chromatography/tandem mass spectrometry (LC ESI MS/MS). The ratio of plasma saturated fatty acid to monounsaturated fatty acid increased, whereas the ratio of polyunsaturated fatty acids to saturated fatty acids was reduced in Apo-E4 carriers. Simultaneously, the levels of individual plasma linoleic, arachidonic, and alpha linolenic acids significantly increased in subjects with the Apo-E4 allele. The 15-lipoxygenase metabolite, 13-hydroxyoctadecadienoic acid, was significantly higher in Apo-E3 carriers (p<0.006). 5-oxo-6,8,11,14-eicosatetraenoic acid was significantly elevated in Apo-E4 carriers (p<0.009). A significant difference in hyaluronic acid concentration (p<0.0016) as well as predicted advanced fibrosis (using the BARD scoring system) was found in Apo-E4 carriers (p<0.01). We suggest that a distinct mechanism of fibrosis between Apo E alleles. In Apo-E4 carriers, an elevation in 5-oxo-6,8,11,14-eicosatetraenoic acid synthesis and fatty acid dysfunction may induce fibrosis, while an inflammatory process may be the main cause of fibrosis in Apo-E3 carriers.
Asunto(s)
Apolipoproteína E4/genética , Ácidos Grasos/sangre , Hígado Graso/sangre , Hígado Graso/genética , Ácido Hialurónico/sangre , Adulto , Anciano , Alelos , Ácidos Araquidónicos/sangre , Femenino , Genotipo , Humanos , Ácidos Linoleicos/sangre , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no AlcohólicoRESUMEN
The elicitor activity and structural characteristics of chemically synthesized hepta- and octa-beta-D-glucopyranosides were compared with the same properties of an elicitor-active mycelial-wall-derived hexa(beta-D-glucopyranosyl)-D-glucitol. The specific elicitor activities, retention times on reversed-phase liquid chromatography columns, glycosyl-linkage compositions, 1H NMR analyses, and glycosyl-sequence analyses of the synthetic and mycelial-wall-derived hexa(beta-D-glucopyranosyl)-D-glucitols were indistinguishable. This work provided conclusive proof that elicitor activity was associated with the structure proposed (Sharp, J. K., McNeil, M., and Albersheim, P. (1984) J. Biol. Chem. 259, 11321-11336) for the elicitor-active mycelial-wall-derived hexa(beta-D-glucopyranosyl)-D-glucitol.
Asunto(s)
Glucanos/síntesis química , Conformación de Carbohidratos , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Glucanos/farmacología , Espectroscopía de Resonancia Magnética , Phytophthora/análisis , Plantas/metabolismoRESUMEN
The glucoheptaose 1 and the glucooctaose 2 have been synthesized using unambiguous methods. The former is identical with an elicitor-active heptasaccharide obtained from partially hydrolyzed mycelium of Phytophthora megasperma f. sp. glycinea. The octasaccharide is also elicitor active, although to a lesser extent than the heptasaccharide. 1:R = H; 2:R = beta-D-Glcp. (Formula: see text)