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Métodos Terapéuticos y Terapias MTCI
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J Nutr ; 134(4): 861-7, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15051838


Decreased body fat mass and liver steatosis have been reported in mice fed diets containing the conjugated linoleic acid trans-10,cis-12-C18:2 (CLA2), but not in those fed diets containing cis-9,trans-11-C18:2 (CLA1). Because the decrease in fatty acid (FA) oxidation may cause fat accumulation, we questioned whether the effects of both CLAs on enzyme activities and mRNA expression were related to liver FA oxidation. To address this question, 7-wk-old male C57BL/6J mice were fed for 4 wk a diet supplemented with 1% CLA1, CLA2, or cis-9-C18:1 (control) esterified as triacylglycerols. In CLA2-fed mice, the proportions of CLA2 in the total FA of liver lipids were substantially lower than those of CLA1 in mice fed CLA1. The mitochondrial protein content per total liver was about 56% greater in CLA2-fed mice than in CLA1-fed mice and controls. Mitochondrial carnitine palmitoyltransferase I (CPT I) and carnitine-dependent palmitate oxidation activities were also significantly greater in CLA2-fed mice than in the two other groups. The amounts of malonyl-CoA per gram of liver and the sensitivity of CPT I to malonyl-CoA inhibition were greater in both groups of CLA-fed mice than in the controls. L-CPT I mRNA expression doubled in CLA2-fed mice and was 3 and 2 times greater for M-CPT I in the CLA1 and CLA2 groups, respectively, compared with controls. Peroxisomal FA oxidation-related activities and acyl-CoA oxidase mRNA expression were increased in CLA1-fed mice, and to a larger extent in CLA2-fed mice, relative to controls. These data indicate that FA oxidation capacities were increased in mice fed CLA2, but were likely depressed in vivo through malonyl-CoA inhibition.

Grasas Insaturadas en la Dieta/administración & dosificación , Ácidos Grasos/metabolismo , Hígado Graso/etiología , Ácidos Linoleicos Conjugados/administración & dosificación , Animales , Carnitina O-Palmitoiltransferasa/antagonistas & inhibidores , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Inhibidores Enzimáticos/farmacología , Esterificación , Hígado/química , Masculino , Malonil Coenzima A/análisis , Malonil Coenzima A/farmacología , Ratones , Ratones Endogámicos C57BL , Mitocondrias Hepáticas/enzimología , Oxidación-Reducción , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Triglicéridos/metabolismo
Biofactors ; 13(1-4): 5-8, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11237199


Some metabolic effects of dietary marine oils, or of dietary eicosapentaenoic or docosahexaenoic acid are reviewed. It is pointed out that docosahexaenoic acid appears more effective as regards induction of peroxisomal beta-oxidation. Similarly, docosahexaenoic appears more powerful in terms of suppression of hepatic delta9-desaturase activity and mRNA-levels. The potential inhibitory effect of polyunsaturated fatty acids, particularly docosahexaenoic acid, on mitochondrial beta-oxidation is discussed. Experiments with rats suggesting that the hypolipidaemic response of eicosapentaenoic acid is more marked when the fatty acid was given to fed rats, as compared to fasted rats, are discussed.

Grasas Insaturadas en la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Aceites de Pescado/farmacología , Mitocondrias/metabolismo , Estearoil-CoA Desaturasa/metabolismo , Animales , Humanos , Hígado/metabolismo , Mitocondrias/efectos de los fármacos , Peroxisomas/efectos de los fármacos , Peroxisomas/metabolismo
Biochem J ; 331 ( Pt 1): 153-60, 1998 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-9512474


(1) Effects of dietary treatment of male albino rats with eicosapentaenoic acid (EPA) or docosahexaenoic acid on hepatic mitochondrial lipid metabolism have been investigated. (2) Mitochondria isolated from rats given these treatments were shown to have increased ability to respire on acyl-CoA esters in the presence of malonate. This effect was expressed with most of the long-chain acyl-CoA esters used as substrates. When malonate in the incubations was replaced with malate, mitochondria from treated animals were found to exhibit diminished rates of respiration on polyunsaturated acyl-CoA esters, in particular linolenoyl-, eicosapentaenoyl- and docosahexaenoyl-CoA. This phenomenon could not be attributed to changes in activity of carnitine palmitoyltransferase I or in peroxisomal beta-oxidation. (3) Uncoupled respiration on glutamate, malate or succinate was also affected by treatment with EPA. With liver mitochondria isolated from rats that had been treated with a omega-3 fatty acid in the fasted state, the respiratory rates were lower than those observed with mitochondria isolated from control rats. Respiratory rates with mitochondria isolated from rats given the omega-3 fatty acid in the fed state was not significantly different from control rates. (4) In rats treated with EPA in the fed state, the amount of EPA incorporated into mitochondrial lipids was markedly more increased as compared to rats given omega-3 fatty acid in the fasted state. Incorporation of dietary EPA into tissue lipids was investigated, also following mildronate treatment of rats (an inhibitor of carnitine biosynthesis). (5) A hypolipidaemic effect of dietary EPA was only observed when the fatty acid was given to fed rats. Rats treated with EPA in the fasted state, in contrast, exhibited hypoglycaemia, the hypolipidaemic effects now being absent. (6) These results suggest that hypolipidaemia is most pronounced when the metabolic state favours incorporation of dietary EPA into body lipids rather than its beta-oxidation, as mediated by the fed/fasted transition or by treatment with mildronate.

Dieta , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Metabolismo de los Lípidos , Hígado/metabolismo , Mitocondrias Hepáticas/metabolismo , Animales , Aceites de Pescado , Peroxidación de Lípido , Hígado/ultraestructura , Masculino , Ratas , Ratas Wistar
Lipids ; 29(7): 481-9, 1994 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7968269


This study was designed to examine whether n-3 and n-6 polyunsaturated fatty acids at a very low dietary level (about 0.2%) would alter liver activities in respect to fatty acid oxidation. Obese Zucker rats were used because of their low level of fatty acid oxidation, which would make increases easier to detect. Zucker rats were fed diets containing different oil mixtures (5%, w/w) with the same ratio of n-6/n-3 fatty acids supplied either as fish oil or arachidonic acid concentrate. Decreased hepatic triacylglycerol levels were observed only with the diet containing fish oil. In mitochondrial outer membranes, which support carnitine palmitoyltransferase I activity, cholesterol content was similar for all diets, while the percentage of 22:6n-3 and 20:4n-6 in phospholipids was enhanced about by 6 and 3% with the diets containing fish oil and arachidonic acid, respectively. With the fish oil diet, the only difference found in activities related to fatty acid oxidation was the lower sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition. With the diet containing arachidonic acid, peroxisomal fatty acid oxidation and carnitine palmitoyltransferase I activity were markedly depressed. Compared with the control diet, the diets enriched in fish oil and in arachidonic acid gave rise to a higher specific activity of aryl-ester hydrolase in microsomal fractions. We suggest that slight changes in composition of n-3 or n-6 polyunsaturated fatty acids in mitochondrial outer membranes may alter carnitine palmitoyltransferase I activity.

Hidrolasas de Éster Carboxílico/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Insaturados/farmacología , Metabolismo de los Lípidos , Microsomas Hepáticos/enzimología , Mitocondrias Hepáticas/metabolismo , Monoaminooxidasa/metabolismo , Urato Oxidasa/metabolismo , Animales , Carnitina O-Palmitoiltransferasa/metabolismo , Ácidos Grasos Omega-6 , Masculino , Malonil Coenzima A/farmacología , Ratones , Microsomas Hepáticos/efectos de los fármacos , Obesidad/enzimología , Palmitoil Coenzima A/farmacología , Ratas , Ratas Zucker , Fracciones Subcelulares/metabolismo