Suppression of free fatty acids and triglycerides in normal and hypertriglyceridemic rats by the adenosine receptor agonist phenylisopropyladenosine.

Activation of adenosine receptors leads to the inhibition of lipolysis in the fat cells of several species including humans. We have examined the effects of the adenosine analog phenylisopropyladenosine (PIA) on lipolysis in vivo in intact rats. PIA suppresses markedly serum-free fatty acid (FFA) concentrations when injected s.c. (-)-PIA is more potent than (+)-PIA in suppressing FFA concentrations; also, this effect of (-)-PIA is blocked by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline. (-)-PIA also suppressed plasma triglyceride (TG) concentrations by approximately 50% in these rats. Utilizing Triton WR1339 injections, we found that the decrease in serum TG concentrations was associated with a marked fall in very low density lipoprotein secretion rate. We also examined the effects of (-)-PIA on FFA and TG concentrations in two models of hypertriglyceridemia in rats: stretozotocin-induced diabetes and sucrose feeding. Both groups had elevated FFA and TG concentrations compared with controls. An injection of (-)-PIA suppressed markedly FFA concentrations and essentially normalized the serum concentration of TG in these rats. We conclude that (-)-PIA suppresses markedly lipolysis and triglyceride secretion in control and hypertriglyceridemic rats suggesting that the activation of adenosine receptors may have major metabolic effects in vivo.