RESUMEN
OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.
Asunto(s)
Arritmias Cardíacas/inducido químicamente , Ácidos Grasos Omega-3/administración & dosificación , Animales , Arritmias Cardíacas/fisiopatología , Suplementos Dietéticos , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/análisis , Ácido Eicosapentaenoico/sangre , Electrocardiografía , Corazón/fisiopatología , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , Perfusión , Aceites de Plantas/administración & dosificación , Aceite de Girasol , PorcinosRESUMEN
BACKGROUND: Conjugated linoleic acids (CLAs) exert numerous effects in animal models as well as in humans. Among other things, CLAs decrease plasma lipid levels and bring about hepatic steatosis. The latter effects are attributed to an agonistic action of CLAs on the peroxisome-proliferator-activated receptor family primarily responsible for activating genes involved in lipid metabolism and are related to changes in mRNA levels. Such changes are not necessarily reflected in changes in activity of controlling enzymes. AIM OF THE STUDY: To investigate the effects of CLAs treatment on lipid metabolism, we determined lipid concentrations in plasma, lipoproteins and liver and measured the activity of a number of key enzymes in hepatic lipid metabolism as differences in lipid concentrations should be related to changes in enzyme activities. These variables were determined with the rat as a model. METHODS: Rats were fed a control diet or a diet containing 1.15% trans-10, cis-12 isomer and 1.11% cis-9, trans-11 isomer as part of a commercial mixture of CLAs. After 2 w the animals were killed, and plasma and liver fractions isolated. Subsequently, lipid concentrations of cholesterol, triacylglycerols and phospholipids were determined in the isolated lipoproteins. In livers homogenates, the concentrations of glycogen, cholesterol, triacylglycerol and phospholipids and the activities of enzymes catalyzing pacesetting steps of metabolism were determined, i. e. acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, 3-hydroxy- acyl-CoA dehydrogenase, citrate synthase and phosphofructokinase. RESULTS: CLAs induced a lowering of the cholesterol levels in total plasma and in LDL and HDL lipoproteins and of phospholipid concentrations in LDL and HDL. CLAs treatment decreased the hepatic activity of diacylglycerol acyltransferase and had no effect on any of the other enzyme activities. CONCLUSIONS: In other studies enhanced specific activities of ACC and FAS were found in livers of mice using the same or similar methods and experimental protocol as in the present study. The lack of effect of CLAs treatment on hepatic key enzymes of fatty acid synthesis and oxidation in Wistar rats questions the use of this strain for studying the mechanism(s) underlying CLA's effects on these parameters. However, in the rat model we observed reduced levels of cholesterol in total plasma and in LDL and HDL. Therefore, some aspects like loss of body fat are better studied in mice; for other aspects like reduction in serum cholesterol level the rat may be the model of choice.
Asunto(s)
Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Ácidos Linoleicos Conjugados/administración & dosificación , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Acetil-CoA Carboxilasa/efectos de los fármacos , Acetil-CoA Carboxilasa/metabolismo , Animales , Biomarcadores/sangre , Peso Corporal/efectos de los fármacos , Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/metabolismo , Diacilglicerol O-Acetiltransferasa/efectos de los fármacos , Diacilglicerol O-Acetiltransferasa/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Ácido Graso Sintasas/efectos de los fármacos , Ácido Graso Sintasas/metabolismo , Glucógeno/metabolismo , Lípidos/sangre , Hígado/anatomía & histología , Masculino , Modelos Animales , Tamaño de los Órganos/efectos de los fármacos , Fosfofructoquinasas/efectos de los fármacos , Fosfofructoquinasas/metabolismo , Ratas , Ratas WistarRESUMEN
The concept of refinement is an important issue in the field of laboratory animal science. Refinement-based research aims to improve animal welfare, to increase the reliability of experimental outcome, and to diminish variation. In search of refinement of experimental techniques, this study investigated whether urinary corticosterone can be used as a noninvasive measure of acute stress in mice.
Asunto(s)
Corticosterona/orina , Ratones , Enfermedades de los Roedores/orina , Cloruro de Sodio/administración & dosificación , Estrés Fisiológico/veterinaria , Animales , Animales de Laboratorio , Área Bajo la Curva , Biomarcadores/orina , Creatinina/orina , Femenino , Inyecciones Intraperitoneales/veterinaria , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Radioinmunoensayo/veterinaria , Enfermedades de los Roedores/diagnóstico , Cloruro de Sodio/farmacología , Estrés Fisiológico/diagnóstico , Estrés Fisiológico/orinaRESUMEN
Feeding mice conjugated linoleic acid (9 cis,11 trans/9 trans,11 cis-and 10 trans,12 cis-CLA in equal amounts) resulted in triacylglycerol accumulation in the liver. The objective of this study was to examine whether this steatosis is associated with changes in hepatic fatty acid synthesis and oxidation. Therefore, we measured the activities of key enzymes of fatty acid synthesis, i.e., acetyl-CoA carboxylase and fatty acid synthase and of fatty acid oxidation, i.e., 3-hydroxy-acyl-CoA dehydrogenase and citrate synthase in livers of mice fed a diet with 0.5% (w/w) CLA. CLA (a 1:1 mixture of the 10 trans, 12 cis and 9 cis, 11 trans isomers of octadecadenoic acid) was administered for 3 and 12 weeks with high-oleic sunflower oil fed as control. The proportion of body fat was significantly lower on the CLA than on the control diet and this effect was already significant after 3 weeks. The specific activites of 3-hydroxy-acyl-CoA dehydrogenase and citrate synthase were unaffected by CLA both after 3 and 12 weeks. The specific activity of fatty acid synthase was nonsignificantly raised (by 12%) after 3 weeks on the CLA diet but had increased significantly (by 34%) after 12 weeks of feeding. The specific activity of acetyl-CoA carboxylase had also increased both after 3 weeks (by 53%) and 12 weeks (by 23%) on the CLA diet, but this effect did not reach statistical significance. Due to CLA-induced hepatomegaly, the overall capacity for both fatty acid oxidation and synthesis-as evidenced by the total hepatic activities of 3-hydroxy-acyl-CoA dehydrogenase, citrate synthase, acetyl-CoA carboxylase, and fatty acid synthase-was significantly greater in the CLA-fed group after 12 weeks, although the overall capacity for fatty acid synthesis had increased more than that for fatty acid oxidation. Thus, this study indicates that prolonged, but not short-term, feeding mice with CLA increased hepatic fatty acid synthesis relative to oxidation, despite the decrease in body fat and the increase in liver weight seen earlier. It is concluded that the observed CLA-induced changes in hepatic fatty acid synthesis and oxidation are the result, rather than the cause, of the lowering of body fat.
Asunto(s)
Ácidos Grasos/biosíntesis , Ácido Linoleico/farmacología , Hígado/metabolismo , Animales , Composición Corporal , Peso Corporal , Citrato (si)-Sintasa/metabolismo , Ácido Graso Sintasas/metabolismo , Conducta Alimentaria , Hepatomegalia/inducido químicamente , Ácido Linoleico/administración & dosificación , Lípidos/análisis , Hígado/efectos de los fármacos , Hígado/enzimología , Ratones , Ratones Endogámicos BALB C , Tamaño de los Órganos , Oxidación-Reducción , Regulación hacia ArribaRESUMEN
In the present study the effects of some C18 fatty acids on hepatic fatty acid metabolism have been compared. Male rats were fed cholesterol-free diets containing either C18:0, C18:1 cis or C18:1 trans isomers as the variables. In accordance with previous work, oleic acid in the diet caused an increase in cholesterol concentration in the liver and in the lipoprotein fraction of density (d; kg/l) < 1.006. Oleic acid also reduced the triacylglycerol:cholesterol value in this fraction. Surprisingly, the C18:1 trans isomers diet induced a decrease in the amount of cholesterol in total plasma as well as in the 1.019 < d < 1.063 lipoprotein fraction. Both oleic acid and C18:1 trans isomers increased the concentration of triacylglycerols in the liver. The two C18:1 fatty acids differently influenced the hepatic activities of carnitine palmitoyltransferase-I and 3-hydroxy-acyl-CoA dehydrogenase; both enzymes were inhibited by C18:1 trans isomers, while no change was induced by oleic acid. The activity of the citrate carrier was lower in the oleic acid- and C18:1 trans isomers-fed rats, when compared with the rats fed stearic acid. No diet effects were seen for the activities of acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, citrate synthase and phosphofructokinase. The results are interpreted in that oleic acid raised liver triacylglycerol by reducing the secretion of it with the d < 1.006 lipoprotein fraction whereas the C18:1 trans isomers enhanced liver triacylglycerol by lowering the hepatic oxidation of fatty acids.