Summary
Upper-body obesity is an important risk factor for developing non-insulin dependent diabetes. To investigate the possibility that a lipolysis defect is present in this form of obesity, we examined the adrenergic regulation of lipolysis in abdominal subcutaneous fat cells from 25 women with upper-body obesity and 24 non-obese women. Lipolytic noradrenaline sensitivity (but not the maximum rate of lipolysis) was reduced by 10-fold in obese women (p<0.01). The noradrenaline resistance could be ascribed to a 10-fold decrease in lipolytic beta2-adrenoceptor sensitivity (p<0.01). The lipolytic sensitivity of beta1- and alpha2-adrenergic receptors was normal in the obese women. A 70 % reduction in the cell surface density of beta2-adrenoceptors was observed compared to the control subjects (p<0.01). However, beta1-receptor density as well as steady-state mRNA levels for beta1- and beta2-receptors were normal in obese women. Lipolytic noradrenaline sensitivity correlated inversely with BMI (adjusted r 2=0.76 together with fat cell volume in stepwise regression analysis). The fasting plasma level of free cortisol was 30 % lower in obese compared to non-obese women (p<0.05) but obesity did not influence resting plasma catecholamine levels. Thus, 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 obesity remains to be established.
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Abbreviations
- ED50:
-
Hormone concentration giving half maximum effect
- pD2 :
-
negative logarithm of ED50
- amol:
-
10−18 mol
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Reynisdottir, S., Wahrenberg, H., Carlström, K. et al. Catecholamine resistance in fat cells of women with upper-body obesity due to decreased expression of beta2-adrenoceptors. Diabetologia 37, 428–435 (1994). https://doi.org/10.1007/BF00408482
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DOI: https://doi.org/10.1007/BF00408482