Ek Ingvar, Arner Peter, Rydén Mikael, Holm Cecilia, Thörne Anders, Hoffstedt Johan, Wahrenberg Hans
Department of Gynecology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.
Diabetes. 2002 Feb;51(2):484-92. doi: 10.2337/diabetes.51.2.484.
The etiology of polycystic ovary syndrome (PCOS) is unknown. However, PCOS has a strong resemblance to the insulin resistance (metabolic) syndrome, where an increased rate of visceral fat cell lipolysis is believed to play a pathophysiological role. We hypothesized that primary defects in visceral lipolysis might also exist in PCOS. Ten young, nonobese, and otherwise healthy PCOS women were compared with 13 matched control women. In vitro lipolysis regulation and stoichiometric properties of the final step in lipolysis activation, namely the protein kinase A (PKA)-hormone sensitive lipase (HSL) complex, were investigated in isolated visceral (i.e., omental) fat cells. Body fat distribution and circulating levels of insulin, glucose, and lipids were normal in PCOS women. However, in vivo insulin sensitivity was slightly decreased (P = 0.03). Catecholamine-induced adipocyte lipolysis was markedly (i.e., about twofold) increased in PCOS women due to changes at the postreceptor level, although there was no change in the antilipolytic properties of visceral fat cells. Western blot analyses of visceral adipose tissue showed twofold increased levels of the catalytic and the regulatory Ialpha components of PKA. In contrast, the regulatory RIIbeta component of PKA was almost 50% decreased in visceral adipose tissue in PCOS women. Recent studies on genetically modified mice have shown that a similar transition in the regulatory PKA units induces an increased lipolytic response to catecholamines. Further analysis showed that the level of HSL-short, an enzymatically inactive splice form of HSL, was decreased in PCOS (P < 0.01). The altered lipolysis in PCOS is different from that observed in visceral fat cells in the insulin resistance syndrome that occurs at the level of adrenergic receptors. We concluded that increased catecholamine-induced lipolysis in visceral fat cells may be due to unique alterations in the stoichiometric properties of the adipose PKA-HSL holoenzymes. This could be an early and possibly primary lipolysis defect in PCOS.
多囊卵巢综合征（PCOS）的病因尚不清楚。然而，PCOS与胰岛素抵抗（代谢）综合征极为相似，据信内脏脂肪细胞脂解速率增加在其中发挥了病理生理作用。我们推测PCOS中可能也存在内脏脂解的原发性缺陷。将10名年轻、非肥胖且其他方面健康的PCOS女性与13名匹配的对照女性进行比较。在分离的内脏（即网膜）脂肪细胞中研究了体外脂解调节以及脂解激活最后一步的化学计量特性，即蛋白激酶A（PKA）-激素敏感脂肪酶（HSL）复合物。PCOS女性的体脂分布以及胰岛素、葡萄糖和脂质的循环水平均正常。然而，其体内胰岛素敏感性略有下降（P = 0.03）。由于受体后水平的变化，PCOS女性中儿茶酚胺诱导的脂肪细胞脂解显著增加（即约两倍），尽管内脏脂肪细胞的抗脂解特性没有变化。对内脏脂肪组织的蛋白质印迹分析显示，PKA的催化亚基和调节性Iα亚基水平增加了两倍。相比之下，PCOS女性内脏脂肪组织中PKA的调节性RIIβ亚基几乎减少了50%。最近对基因改造小鼠的研究表明，调节性PKA单位的类似转变会导致对儿茶酚胺的脂解反应增加。进一步分析表明，PCOS中HSL的一种无酶活性的剪接形式HSL-短的水平降低（P < 0.01）。PCOS中脂解的改变不同于在胰岛素抵抗综合征的内脏脂肪细胞中观察到的、发生在肾上腺素能受体水平的改变。我们得出结论，内脏脂肪细胞中儿茶酚胺诱导的脂解增加可能是由于脂肪组织PKA-HSL全酶化学计量特性的独特改变。这可能是PCOS早期且可能是原发性的脂解缺陷。
