Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome.
Lipolytic catecholamine resistance in sc fat cells is observed in polycystic ovarian syndrome (PCOS). The mechanisms behind this lipolysis defect were explored in vitro; sc fat cells were obtained from 10 young, nonobese PCOS women and from 14 matched, healthy control women. Fasting plasma glycerol levels were reduced by one third in PCOS (P < 0.05). Adipocytes of PCOS women were about 25% larger than in the controls (P < 0.05) and had 40% reduced noradrenaline-induced lipolysis (P < 0.05), which could be attributed to a 10-fold decreased beta(2)-adrenoceptor sensitivity (P < 0.05) and low ability of cAMP to activate the protein kinase A (PKA)/hormone-sensitive lipase (HSL) complex (P < 0.05). In PCOS, the adipocyte protein content of beta(2)-adrenoceptors, HSL, and the regulatory II beta-component of PKA were 70%, 55%, and 25% decreased, respectively (P < 0.001); but there was no change in the amount of the catalytic subunit of PKA or of beta(1)-adrenoceptors. Thus, lipolytic catecholamine resistance of sc adipocytes in PCOS is probably attributable to a combination of decreased amounts of beta(2)-adrenergic receptors, the regulatory II beta-component of PKA, and HSL. This may cause low in vivo lipolytic activity and enlarged sc fat cell size and promote later development of obesity in PCOS.
Department of Medicine, Huddinge University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden.
Gary
G
Faulds
Mikael
M
Rydén
Ingvar
I
Ek
Hans
H
Wahrenberg
Peter
P
Arner
D017667:Adipocytes / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D002395:Catecholamines / Q000494:pharmacology*; D048429:Cell Size; D000242:Cyclic AMP / Q000494:pharmacology; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D005215:Fasting; D005260:Female; D005990:Glycerol / Q000097:blood; D006801:Humans; D008066:Lipolysis / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000187:drug effects; D002787:Sterol Esterase / Q000032:analysis / Q000378:metabolism
D002395:Catecholamines; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; C517837:PRKAR2B protein, human; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase; D005990:Glycerol; D009638:Norepinephrine