Adrenoceptor Interplay in the Regulation of Adipocyte Metabolism

Abstract

Catecholamines affect fat metabolism in a variety of ways through the mobilisation of five adrenoceptor subtypes (β₁, β₂, β₃, α₁ & α₂). Selective and non-selective β adrenoceptor agonists stimulate lipolysis while α₂ adrenoceptor agonists inhibit lipolysis. Since β and α₂ adrenoceptors produce antagonistic effects, the balance between activation and inactivation of these adrenoceptors defines the net outcome of catecholamine-induced adipocyte metabolism in humans. The coexistence of these receptors on the same cell is puzzling and raises a question about its functional significance. Since α₂ adrenoceptors can be activated at low catecholamine concentrations, a plausible theory regarding this question is that a permanent inhibition of lipolysis exists during basal conditions. Analysis of factors like the count of adrenoceptors on a cell, their differential affinities, and their susceptibility to desensitisation backs up this theory. Another possibility is that these adrenoceptors may have distinct roles in different adipose tissue depots and under different pathophysiological conditions. The existence of catecholamine resistance in the adipocytes of obese subjects is well documented. It can be attributed, in part, to a major decrease in the cell-surface density of β₂ adrenoceptors. Similar differences in adipose tissue metabolism have been observed in conditions which include different body states (resting and exercise), locations of fat (subcutaneous and omental fat) and sexes etc. Many of these anomalies can be traced back to discrepancies in adrenoceptor activity. In this review, two hypotheses explaining the coexistence of five adrenoceptor subtypes on adipose tissue are discussed. Furthermore, the interplay of adrenoceptors that generates variations in lipolysis between subcutaneous and omental fat, peripheral and abdominal fat, men and women, and non-obese and obese people is analysed in the context of the physiology of these conditions.