Evaluation of adenosine or related nucleosides as physiological regulators of lipolysis in adipose tissue.

The removal of extracellular, endogenously produced adenosine in isolated rat adipocytes by treatment with adenosine deaminase enhanced their responsiveness to various lipolytic agents, i.e. the response to catecholamines, glucagon, LH, TSH, and cholera toxin was elicited at concentrations that were 10-500 times lower than those required for the stimulation of lipolysis in untreated cells in vitro. The removal of adenosine from intact fat cells largely potentiated the isoproterenol-stimulated increase in cAmP level. However, a similar treatment of undissociated segments of adipose tissue failed to influence further the response to isoproterenol. These results strongly suggest that in the intact adipose tissue, adenosine and related nucleosides are absent and do not function as modulators of adenylate cyclase or lipolysis. Under these circumstances the estimated "low" physiological concentrations of the neurotransmitters in the adipose tissue are able to modulate lipid mobilization. Previous studies have shown that insulin failed to inhibit lipolysis, induced by micromolar norepinephrine concentrations, in adenosine-free adipocytes. The present study demonstrates that at physiological catecholamine concentrations, insulin is a potent antilipolytic agent.