Alterations induced by a prolonged fasting: opposite effects on the beta-adrenergic receptor-coupled adenylate-cyclase system and on lipolysis in fat cells from rat.

1 The maximal number of β-adrenergic receptors in rat fat-cell membranes from 72-h-fasted rats is about two-times higher than in fed rats. However, the affinity of these receptors for β-agonists and antagonists and the ability of guanosine 5′-[β,γ-imido]triphosphate (100 μM) to reduce the receptor binding affinity for β-agonists are unaltered by fasting. 2 Basal and fluoride-stimulated activities of adenylate cyclase are similar in adipocyte membranes from 72-h- fasted and fed animals. However, relative to the basal activity, maximal stimulation by (—)-isoproterenol is 33 ±5 %higher in fasted than in fed adipocytes. The sensitivity of adenylate cyclase to (—)-isoproterenol is also increased in fat-cell membranes from fasted animals, as the concentration of (—)-isoproterenol required for half- maximal activation is three-times lower in fasted than in fed adipocytes. 3 Basal adenylate cyclase activity is also about three-times more sensitive to stimulation by guanosine 5′-[β,γ-imido]triphosphate in fasted than in fed adipocyte membranes. This increased sensitivity of adenylate cyclase to guanosine 5′-[β,γ-imido]triphosphate in fasting is much more pronounced when adenylate cyclase activity is stimulated by isoproterenol. 4 In contrast, although basal lipolysis is unaltered by fasting, lipolysis stimulated in vitro by isoproterenol, adrenocorticotropin or dibutyryladenosine 3′,5′-monophosphate is severely depressed in fat cells from 72-h-fasted rats. However, the concentration of (—)-isoproterenol and adrenocorticotropin required for half-maximal activation of lipolysis are similar in fasted and fed adipocytes. From this study, it is concluded that, contrary to the fasting-induced decreased lipolytic responsiveness which is paradoxically observed in adipocytes in vitro, the fasting-induced changes found in the adenylate cyclase- coupled-β-adrenergic receptor-system of rat adipocyte are most probably physiologically relevant as these changes contribute to promote cyclic AMP synthesis and, consequently, to stimulate lipolysis, as is observed in vivo during fasting.