Alterations Induced by a Prolonged Fasting: Opposite Effects on the β‐Adrenergic Receptor‐Coupled Adenylate‐Cyclase System and on Lipolysis in Fat Cells from Rat

Abstract

1. The maximal number of j-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 j-agonists and antagonists and the ability of guanosine 5'-[P,y-imido]triphosphate (100 pM) to reduce the receptor binding affinity for P-agonists are unaltered by fasting.2. Basal and fluoride-stimulated activities of adenylate cyclase are similar in adipocyte membranes from 72-hfasted and fed animals. However, relative to the basal activity, maximal stimulation by (-)-isoproterenol is 33 f 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 halfmaximal 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'-[P,y-imido]triphosphate in fasted than in fed adipocyte membranes. This increased sensitivity of adenylate cyclase to guanosine 5'-[P,y-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-hfasted 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 cyclasecoupled-0-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.

Effects of diet on lipolysis and its regulation

“…Fasting did not increase maximum response to catecholamines in isolated fat cells from humans (Andrews et al 1984), in perfused canine adipose tissue (Fredholm et al 1973) and in some studies with rat (Zapf et al 1977;Dax et al 1981;Saggerson, 1986) fat cells. Another study with rats suggests that fasting results in a reduced response to noradrenaline (Giudicelli et al 1982). This apparent discrepancy is probably due to a change which develops as fasting proceeds, with a decrease in response occurring around 72 h of fasting.…”

“…The molecular mechanism responsible for the diminished response to catecholamines has not been elucidated, but does not appear to involve a loss of p-adrenergic receptors or adenylate cyclase activity, at least in rats (Giudicelli et al 1982) indicating a defect in the distal portion of the signal transduction system.…”

Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine.

“…f3-adrenergic mechanisms appear to predominate both in vitro (8) and in vivo; infusions of mixed a-and fl-adrenergic agonists such as epinephrine result in increased lipolysis as evidenced by increments in the circulating levels of FFA and glycerol and increments in FFA appearance rates (6). Fasting has been reported to increase adipocyte fl-adrenergic receptor numbers in rats (10) but to decrease fl-adrenergic receptor number in some human adipose tissue sites (1 1). Adipocytes from calorically restricted or fasting humans exhibit increased basal lipolytic rates but decreased lipolytic (indeed even antilipolytic) responses to epinephrine and norepinephrine (10 -16).…”

Influences of variation in total energy intake and dietary composition on regulation of fat cell lipolysis in ideal-weight subjects.

“…Recognizing the prominent role of adipose tissue in the formation, storage and supply of energy reserves, considerable attention has been paid to metabolism of this tissue (2)(3)(4)(5)(6)(7).…”