RESUMEN
The purpose of this presentation is to review the current state of knowledge regarding 5,8,11,14-eicosatetraynoic acid (ETYA, Ro 3-1428) and its effects on lipid metabolism. Accordingly, the topics discussed include hypocholesterolemic and dermatological studies involving ETYA in both animals and man, as well as the effects of ETYA on desaturase enzymes. Metabolic studies involving ETYA are also noted. Primary interest is focused on the effects of ETYA on selected processes of arachidonate metabolism, and the effect of ETYA on inflammation, platelet aggregation and tumor growth are discussed, keeping in mind the relevance of arachidonate metabolism to these processes.
Asunto(s)
Ácido 5,8,11,14-Eicosatetrainoico/farmacología , Ácidos Grasos Insaturados/farmacología , Metabolismo de los Lípidos , Ácido 5,8,11,14-Eicosatetrainoico/uso terapéutico , Animales , Ácidos Araquidónicos/metabolismo , Colesterol/metabolismo , Grasas de la Dieta/metabolismo , Epoprostenol/biosíntesis , Ácido Graso Desaturasas/metabolismo , Humanos , Indometacina/farmacología , Inflamación/tratamiento farmacológico , Ácidos Linoleicos/metabolismo , Lipooxigenasa/metabolismo , Hígado/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Masculino , Papiloma/metabolismo , Agregación Plaquetaria/efectos de los fármacos , Prostaglandina-Endoperóxido Sintasas/metabolismo , Prostaglandinas/biosíntesis , Glándulas Sebáceas/efectos de los fármacos , Sebo/metabolismo , Vesículas Seminales/metabolismo , Tromboxano-A Sintasa/metabolismoRESUMEN
The effects of saturated and unsaturated lipids on in vivo rates of hepatic lipogenesis and cholesterogenesis were compared. Lipogenic and cholesterogenic rates were determined in meal-fed rats either after feeding 1%, 5%, 10%, or 20% dietary corn oil or hydrogenated soybean oil for 14 days, or after intrgastric administration of fatty acyl ethyl esters (18:0, 18:1, or 18:2) for 1 and 3 days. Dietary hydrogenated soybean oil was not absorbed, whereas dietary corn oil and the intragastrically administered fatty acyl ethyl esters were well absorbed. Fatty acid synthesis measured from 3H2O and [14C] alanine was inversely correlated with unsaturated dietary fat content, but was unchanged by saturated dietary fat. A single daily administration of 18:0, 18:1, or 18:2 was ineffective in altering lipogenic rates. However, fatty acid synthesis was decreased by three consecutive daily doses of 18:1 or 18:2 (5 g/kg), but not by 18:0. Hepatic rates of cholesterogenesis from 3H2O and [14C] alanine were markedly enhanced by the administration of 10% or 20% saturated dietary fat. Feeding 1%, 5%, or 10% corn oil diets did not have an effect on cholesterogenesis. The 20% corn oil diet reduced the rate of conversion of [14C]anine into cholesterol while the rate of conversion of 3H2O remained unchanged. Neither the 1 day not 3 day oral administration of 18:0 or 18:1 had any effect on cholesterol synthesis; thereas the administration of 18:2 increased the conversion of [14C] alanine into cholesterol by 30% but did not after the rates of cholesterogenesis from 3H2O. These data suggest the following: a) fatty acid synthesis responds selectively to 18:0, 18:1, and 18:2; b) the inhibition of fatty acid synthesis by unsaturated fatty acids is time dependent; c) the rate of fatty acid synthesis is inversely proportional to the concentration of unsaturated dietary fat; d) prolonged feeding with a completely saturated diet will increase fecal fat excretion and hepatic cholesterol synthesis; and e) the regulation of fatty acid synthesis by dietary lipid is independent of the regulation of cholesterol synthesis.