Cacho Herrero, Judith

Se ha administrado una dieta semisintética conteniendo un 10% de aceite de oliva o de pescado como único componente graso no-vitamínico a ratas preñadas, que fueron estudiadas al día 20 de gestación. En plasma de las madres, los porcentajes de ácidos grasos saturados fueron similares en ambos grupos, el de ácido oleico y de ácido araquidónico fueron superiores en las de aceite de oliva, mientras que los de ácidos eicosapentaenoico y docosahexaenoico fueron superiores en las de aceite de pescado. En el plasma de los fetos, los cambios fueron similares a los de las madres, mostrando una insuficiencia de ácido araquidónico en los de madres alimentadas con aceite de pescado. Tanto en plasma como en hígado de los fetos, la concentración de vitamina E fué inferior en los de madres alimentadas con dieta de aceite de pescado que con la de aceite de oliva. A su vez, la respuesta lipolítica de los adipocitos a un agonista b3-adrenérgico fue inferior en ratas preñadas que en vírgenes, pero el efecto inhibidor que produce en éstas el anclaje euglucémico e hiperinsulinémico desaparece cuando son alimentadas con dieta de aceite de pescado. Estos resultados muestran que un exceso en ácidos grasos poliinsaturados en la dieta durante la gestación en la rata, como el producido cuando ésta contiene aceite de pescado en vez de aceite de oliva, da lugar a una deficiencia en ácido araquidónico y vitamina E en los fetos y altera la normal respuesta lipolítica del tejido adiposo de la madre, teniendo consecuencias que podrían ser indeseables para el desarrollo postnatal.

The effect of dietary olive oil and fish oil on the lipolytic dose-response of the lh-adrenergic agonists, epinephrine, isoproterenol, BRL-37344, and CGP-12177, in adipocytes was studied in pregnant and virgin rats either untreated or under hyperinsulinemic-euglycemic conditions. Rats were fed a semisynthetic diet containing 5% of either olive oil or fish oil and studied at day 20 of treatment and/or gestation. Plasma glucose was lower and plasma insulin, triglycerides, and free fatty acids (FFAs) were higher in pregnant versus virgin rats, and the insulin sensitivity index was lower in the former. Lumbar adipose tissue phospholipid fatty acids showed a significantly higher monounsaturated fatty acid and a lower (n - 3) fatty acid content in rats fed the olive oil diet versus the fish oil diet. The lipolytic dose-response curve of either adrenergic agent was always lower in adipocytes from untreated pregnant rats versus virgin rats, and whereas the hyperinsulinemic-euglycemic clamp decreased these responses in adipocytes from virgin rats fed the olive oil diet only, adipocytes from pregnant rats always showed a decreased dose-response lipolytic curve. Thus, the lipolytic responsiveness of lh-adrenoceptor (13rAR) agonists by adipocytes is impaired in cells from rats made hyperinsulinemic chronically by pregnancy or acutely by the hyperinsulinemic-euglycemic clamp, but such response to the acute condition disappears when the adipocyte phospholipid composition is modified by changes in dietary fatty acids.

Nitric oxide has been implicated in the inhibition of catecholamine-stimulated lipolysis in adipose tissue by as yet unknown mechanisms. In the present study, it is shown that the nitric oxide donor, 2,2-diethyl-1-nitroso-oxyhydrazine, antagonized isoproterenol (isoprenaline)-induced lipolysis in rat adipocytes, freshly isolated from white adipose tissue, by decreasing the potency of the b-agonist without affecting its efficacy. These data suggest that nitric oxide did not act downstream of the b-adrenoceptor but reduced the effective concentration of isoproterenol. In support of the latter hypothesis, we found that pre-treatment of isoproterenol with nitric oxide abolished the lipolytic activity of the catecholamine. Spectroscopic data and HPLC analysis con®rmed that the nitric oxide-mediated inactivation of isoproterenol was in fact because of the modi®cation of the catecholamine through a sequence of oxidation reactions, which apparently involved the generation of an aminochrome. Similarly, aminochrome was found to be the primary product of isoproterenol oxidation by 3-morpholinosydnonimine and peroxynitrite. Finally, it was shown that nitric oxide released from cytokine-stimulated adipocytes attenuated the lipolytic effect of isoproterenol by inactivating the catecholamine. In contrast with very recent ®ndings, which suggest that nitric oxide impairs the b-adrenergic action of isoproterenol through intracellular mechanisms and not through a chemical reaction between NO and the catecholamine, we showed that nitric oxide was able to attenuate the pharmacological activity of isoproterenol in itro as well as in a nitric oxide-generating cellular system through oxidation of the b-agonist. These ®ndings should be taken into account in both the design and interpretation of studies used to investigate the role of nitric oxide as a modulator of isoproterenol-stimulated signal transduction pathways.