A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance
A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance
复制标题
DOI：
10.2337/diabetes.51.2.484
复制
发表时间：
2002-02-01
期刊：
影响因子：
7.7
通讯作者：
Wahrenberg, H
中科院分区：
文献类型：
--
作者：
Ek, I;Arner, P;Wahrenberg, H
多囊卵巢综合征（PCOS）的病因是什么？然而，多囊卵巢综合征与胰岛素抵抗（代谢）综合征有很强的相似性，其中内脏脂肪细胞脂解速率增加被认为起着病理生理作用。我们推测原发性内脏脂肪分解缺陷也可能存在于PCOS中。10名年轻、非肥胖、其他方面健康的PCOS妇女与13名匹配的对照妇女进行比较。在分离的内脏（即，网膜）脂肪细胞。PCOS妇女的体脂分布和循环胰岛素、葡萄糖和脂质水平均正常。然而，体内胰岛素敏感性略有下降（P = 0.03）。儿茶酚胺诱导的脂肪细胞脂解作用显著（即，在PCOS妇女中，由于受体后水平的变化，增加了约两倍），尽管内脏脂肪细胞的抗脂肪分解特性没有变化。内脏脂肪组织的蛋白质印迹分析显示PKA的催化和调节la组分的水平增加了两倍。相比之下，PCOS女性内脏脂肪组织中PKA的调节RII β组分几乎减少了50%。最近对转基因小鼠的研究表明，PKA调节单位的类似转变诱导了对儿茶酚胺的脂解反应增加。进一步分析表明，PCOS患者HSL的一种无酶活性剪接形式HSL-short的水平降低（P < 0.01）。PCOS患者脂肪分解的改变与胰岛素抵抗综合征患者内脏脂肪细胞中观察到的不同，后者发生在肾上腺素受体水平。我们的结论是，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PKA-HSL全酶化学计量特性的独特改变。这可能是PCOS的早期和可能的原发性脂解缺陷。
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 la 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.