Catecholamine resistance in fat cells of women with upper-body obesity due to decreased expression of beta 2-adrenoceptors.
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 beta 2-adrenoceptor sensitivity (p < 0.01). The lipolytic sensitivity of beta 1- and alpha 2-adrenergic receptors was normal in the obese women. A 70% reduction in the cell surface density of beta 2-adrenoceptors was observed compared to the control subjects (p < 0.01). However, beta 1-receptor density as well as steady-state mRNA levels for beta 1- and beta 2-receptors were normal in obese women. Lipolytic noradrenaline sensitivity correlated inversely with BMI (adjusted r2 = 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 beta 2-adrenoceptors, which in its turn may be caused by a post-transcriptional defect in beta 2-receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Reynisdottir
S
S
Department of Medicine, Huddinge Hospital, Karolinska Institute, Sweden.
Wahrenberg
H
H
Carlström
K
K
Rössner
S
S
Arner
P
P
D000005:Abdomen; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015992:Body Mass Index; D002395:Catecholamines / Q000494:pharmacology*; D002452:Cell Count; D005260:Female; D006801:Humans; D008066:Lipolysis / Q000187:drug effects; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
D002395:Catecholamines; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2