Adrenergic regulation of human fat-cell lipolysis

The actual effects of adrenaline and noradrenaline on human fat cell lipolysis are the result of a balance of opposing signals which are mediated by alpha2- and beta-adrenergic receptors coupled to adenylate cyclase via stimulatory (beta-receptors) and inhibitory (alpha2-receptors) guanine nucleotide regulatory proteins. The signals transmitted by both hormones are therefore ambiguous. The physiological meaning of this ambiguity in signal transmission has not been satisfactorily explained. This report demonstrates that lipolysis first needs to be inhibited before it can be stimulated, indicating that current concepts on the role of lipolytic agents require re-evaluation. In the light of these findings it is concluded that a dual regulation of single metabolic pathways, i.e. lipolysis, by a single class of hormones, e.g. catecholamines, (1) prevents excessive activation of lipolysis and cyclic AMP accumulation which may lead to a depletion of cellular adenine nucleotides via an increased release of inosine and hypoxanthine which can not be re-utilized, and (2) adds a further degree of flexibility in regulation by restricting the stimulatory effects of both hormones to a narrow range of concentrations which is easily modified by inhibiting ligands.