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.

Abstract

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. 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. 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. 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.