title: Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance?
abstract: The polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is characterized by metabolic and cardiovascular aberrations similar to those seen in the so-called insulin resistance syndrome. The regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 10 nonobese women with PCOS and in 11 age- and body mass index-matched healthy women. Eight PCOS women were reinvestigated after 3 months of treatment with combined oral contraceptives containing ethinyl estradiol and norethisterone, which normalized hyperandrogenicity. The PCOS women showed a marked resistance to the lipolytic effect of noradrenaline due to defects at two different levels in the lipolytic cascade: first, a 7-fold reduction in sensitivity to the beta 2-selective agonist terbutaline (P < 0.005), which could be ascribed to a 50% lower beta 2-adrenoceptor density (P < 0.02) as determined with radioligand binding; there was no difference with regard to dobutamine (beta 1) or clonidine (alpha 2-sensitivity) or beta 1-adrenoceptor density; second, the maximum lipolytic response was also 35% lower (P < 0.02) in the PCOS women compared to that in the healthy women. This was seen with all beta-adrenergic agonists and the postreceptor-acting agents forskolin (activating adenylyl cyclase) and dibutyryl cAMP (activating protein kinase). Neither beta 2-adrenoceptor sensitivity or density nor the reduced lipolytic responsiveness was restored by 3 months of oral contraceptives treatment. The results indicate the existence of a marked impairment of catecholamine-induced lipolysis in nonobese PCOS women displaying early features of the insulin resistance syndrome due to multiple lipolysis defects as a lower beta 2-adrenoceptor density and reduced function of the protein kinase, hormone-sensitive lipase complex. These lipolysis defects are identical to those observed in the insulin resistance (metabolic) syndrome and could be a primary pathogenic mechanism for the development of these disorders.
authors.affiliation: Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Ek
authors.forename: P
authors.initials: P
authors.lastname: Arner
authors.forename: A
authors.initials: A
authors.lastname: Bergqvist
authors.forename: K
authors.initials: K
authors.lastname: Carlström
authors.forename: H
authors.initials: H
authors.lastname: Wahrenberg
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D003276:Contraceptives, Oral / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008066:Lipolysis / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012016:Reference Values
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D003276:Contraceptives, Oral; D011943:Receptors, Adrenergic, beta