DIFFERENTIAL ACTIVATION OF BETA(1)-ADRENOCEPTOR, BETA(2)-ADRENOCEPTOR AND BETA(3)-ADRENOCEPTOR BY CATECHOLAMINES IN WHITE AND BROWN ADIPOCYTES

This review summarizes the experiments performed by various groups to determine how the activation of the different beta-adrenoceptors (beta-ARs) is ordinated when they are present in the same fat cell and involved in the same biological event. When expressed after the transfection of their genes in Chinese hamster ovary cell (CHO cells), beta(1) and beta(2)-ARs present a higher affinity for catecholamines than beta(3)-ARs. In vitro, the lipolytic effect induced by low concentrations of catecholamines in dog and rat white fat cells is due to the selective activation of beta(1)- and/or beta(2)-ARs. Higher concentrations only are able to activate beta(3)-ARs. Similar results have been obtained in rat brown adipocytes. On the other hand, the lipolytic effect of catecholamines in human and primate adipocytes does not involve a beta(3)-AR component whatever the concentration used. In vivo experiments in the dog have also shown that lipomobilization induced by low doses of isoprenaline only involved beta(1)- and beta(2)-AR activation, this effect being blocked by beta(1)-/beta(2)-antagonist pretreatment. However, in the same blockade conditions, perfusion of a 10-fold higher dose of isoprenaline revealed a beta(3)-AR contribution in the lipomobilizing effect. These data showed that brown and white adipocyte beta(3)-ARs possess a lower affinity for catecholamines than beta(1)- and beta(2)-ARs and are only recruited by high concentrations of the amines. Thus, even if the beta(3)-AR plays an indisputable role in the white and brown adipose tissue of some species, its physiological status and its expression are still subject to debate in human white fat cells.