Determination of β3‐Adrenoceptor Mediated Lipolysis in Human Fat Cells

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Abstract
The existence and relative importance of β3-adrenoceptors in man is still controversial. The aim of the present study was 1) to find further evidence for the existence of functional β3-adrenoceptors in human fat, and 2) to investigate factors that may influence this β3-adrenoceptor function. Fifty individuals were examined. Lipolysis mediated by the selective β3-adrenoceptor agonist CGP 12177 in omental fat cells correlated with the response in subcutaneous fat cells. However, lipolysis was more pronounced in omental as compared to subcutaneous adipocytes, the intrinsic activity for CGP 12177 was 41% and 33%, respectively, while dobutamine, terbutaline and norepinephrine were full agonists. Both the lipolytic response and the sensitivity to CGP 12177 correlated with the effects of norepinephrine in the omental fat cells (r2= 0. 68 and 0. 50, respectively, p=0. 0001). The β2-adrenoceptor mediated lipolytic response did also correlate with the responses induced by β1- and β2-agonists and by postreceptor acting agents. The antagonistic properties (pA2) of the β-adrenoceptor subtypes were also investigated. The pA2 for the selective β1- and β2-adrenoceptor antagonists versus CGP 12177-induced lipolysis were 2 to 3 log units lower than those for the β1-antagonist versus dobutamine or for the β2-antagonist versus terbutaline. Furthermore, bupranolol had a significantly better antagonistic effect (pA2 7. 17, p1- and β2-adrenoceptor antagonists (pA2 6. 26 and 6. 05, respectively). These data clearly support the existence of a third human β-adrenoceptor. Several factors may contribute to the contradictory β3-adrenoceptor results in man. The sensitivity of the different lipolytic systems vary considerably. Omental fat cells are preferable to subcutaneous cells for β3-adrenoceptor studies in man. The β3-responses are more attenuated in isolated fat cell preparations than in tissue fragments. Furthermore, as the β3-adrenoceptor activity correlates to the norepinephrine activity, more pronounced effects will be expected in catecholamine sensitive subjects. At present, the number of tools available for β3-adrenoceptor studies are limited, and the receptor is hard to study, why it is essential to perform β3-adrenoceptor studies under optimal conditions in order to obtain conclusive effects.