Adenosine, thyroid status and regulation of lipolysis

Abstract

Adipocytes from hypothyroid rats do not respond to adrenaline with increased glycerol release. Adenosine deaminase largely restores lipolytic sensitivity. This effect is reversed by 2-deoxycoformycin, an inhibitor of the enzyme, and by N6-(phenylisopropyl)adenosine, which is not deaminated. Lipolytic response of normal cells to adrenaline is only 50% inhibited by phenylisopropyladenosine, whereas in cells from hypothyroid rats blockage is total. Inhibition of 50% was seen at 100 and 1 nM concentrations respectively. Insensitivity to adrenaline of hypothyroid-rat adipocytes can, at least partly, be explained by increased sensitivity to adenosine.

Adenosine deaminase normalizes cyclic AMP responses of hypothyroid rat fat cells to forskolin, but not β‐adrenergic agonists

“…These investigators however, compared the lipolytic response of hypothyroid rat fat cells incubated in the presence of adenosine deaminase to that of euthyroid rat fat cells incubated in the absence of adenosine deaminase [8]. Here, we show that adenosine deaminase enhances the lipolytic responses of both hypothyroid and euthyroid rat fat cells to ,&-adrenergic agonist stimulation and fails to normalize the blunted lipolytic and cyclic AMP responses observed in hypothyroidism.…”

“…It has been reported [8] that adenosine deaminase normalized the lipolytic response of hypothyroid rat fat cells challenged with fladrenergic agonists. These investigators however, compared the lipolytic response of hypothyroid rat fat cells incubated in the presence of adenosine deaminase to that of euthyroid rat fat cells incubated in the absence of adenosine deaminase [8].…”

Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms.

“…The role of adenosine and of E-type prostaglandins as physiologic regulators of adipose tissue is unknown at present. However, there is mounting evidence from in vitro experiments suggesting that local regulators are important in long-term regulation of lipolysis of different species including humans (1)(2)(3)(25)(26)(27)(28)(29). Previous studies with adipocytes of starved subjects led us to conclude that the increase in basal lipolytic rate seen in starvation is mainly due to reliefof endogenous inhibition (19).…”

Sensitivity of adipocyte lipolysis to stimulatory and inhibitory agonists in hypothyroidism and starvation

“…In hypothyroidism adenylate cyclase, the increase in cyclic AMP, and lipolysis all show diminished responsiveness to the stimulatory agonists (Goodman & Bray, 1966;Armstrong et al, 1974;Correze et al, 1974;Malbon et al, 1978;Ohisalo & Stouffer, 1979;Goswami & Rosenberg, 1980). Conversely, the inhibitory effect of adenosine mediated by the A1 (Van Calker et al, 1979) or Ri (Londos et al, 1980) adenosine receptor is increased in hypothyroidism (Ohisalo & Stouffer, 1979;Malbon & Graziano, 1983;Chohan et al, 1984;Malbon et al, 1985). This enhanced responsiveness is most easily measured in the presence of adenosine deaminase by using the non-metabolized analogue PIA and appears to reflect an increase in the abundance of Ni in the adipocyte plasma membrane (Malbon et al, 1985) without any increase in receptor number (Chohan et al, 1984;Malbon et al, 1985).…”

“…Receptors for the inhibitory agonists are coupled to adenylate cyclase by a guanine nucleotide-binding protein (N1) distinct from that (N.) which couples receptors for stimulatory agonists to the enzyme (Rodbell, 1980;Murayama & Ui, 1983;Olansky et al, 1983;Moreno et al, 1983;Bokoch et al, 1984;Codina et al, 1984). In hypothyroidism adenylate cyclase, the increase in cyclic AMP, and lipolysis all show diminished responsiveness to the stimulatory agonists (Goodman & Bray, 1966;Armstrong et al, 1974;Correze et al, 1974;Malbon et al, 1978;Ohisalo & Stouffer, 1979;Goswami & Rosenberg, 1980). Conversely, the inhibitory effect of adenosine mediated by the A1 (Van Calker et al, 1979) or Ri (Londos et al, 1980) adenosine receptor is increased in hypothyroidism (Ohisalo & Stouffer, 1979;Malbon & Graziano, 1983;Chohan et al, 1984;Malbon et al, 1985).…”