CATECHOLAMINE RESISTANCE IN FAT-CELLS OF WOMEN WITH UPPER-BODY OBESITY DUE TO DECREASED EXPRESSION OF BETA2-ADRENOCEPTORS

Upper-body obesity is an important risk factor for developing non-insu lin dependent diabetes. To investigate the possibility that a lipolysi s defect is present in this form of obesity, we examined the adrenergi c regulation of lipolysis in abdominal subcutaneous fat cells from 25 women with upper-body obesity and 24 non-obese women. Lipolytic noradr enaline sensitivity (but not the maximum rate of lipolysis) was reduce d by 10-fold in obese women (p < 0.01). The noradrenaline resistance c ould be ascribed to a 10-fold decrease in lipolytic beta2-adrenoceptor sensitivity (p < 0.01). The lipolytic sensitivity of beta1- and alpha 2-adrenergic receptors was normal in the obese women. A 70 % reduction in the cell surface density of beta2-adrenoceptors was observed compa red to the control subjects (p < 0.01). However, beta1-receptor densit y as well as steady-state mRNA levels for beta1-and beta2-receptors we re normal in obese women. Lipolytic noradrenaline sensitivity correlat ed inversely with BMI (adjusted r2 = 0.76 together with fat cell volum e in stepwise regression analysis). The fasting plasma level of free c ortisol was 30 % lower in obese compared to non-obese women (p < 0.05) but obesity did not influence resting plasma catecholamine levels. Th us, lipolytic catecholamine resistance is present in abdominal obesity , due to low density of beta2-adrenoceptors, which in its turn may be caused by a post-transcriptional defect in beta2-receptor expression. Whether abnormalities in circulating free cortisol levels have caused the impaired lipolytic function of these receptors in upper-body obesi ty remains to be established.