Brown adipose tissue transplantation ameliorates polycystic ovary syndrome
Brown adipose tissue transplantation ameliorates polycystic ovary syndrome
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棕色脂肪组织移植改善多囊卵巢综合征
DOI：
10.1073/pnas.1523236113
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发表时间：
2016-03-08
影响因子：
11.1
通讯作者：
Chen, Zi-Jiang
中科院分区：
文献类型：
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作者：
Yuan, Xiaoxue;Hu, Tao;Chen, Zi-Jiang
多囊卵巢综合征（PCOS）以无排卵、高雄激素血症和多囊卵巢为特征，是一种复杂的内分泌疾病。由于在分子水平上PCOS的病因很大程度上未知，所以PCOS没有治愈方法或特效治疗手段。在此，我们表明，在脱氢表雄酮（DHEA）诱导的PCOS大鼠中，棕色脂肪组织（BAT）移植逆转了无排卵、高雄激素血症和多囊卵巢。将BAT移植到PCOS大鼠体内显著稳定了月经不规律情况，并将全身胰岛素敏感性提高到正常水平，而在假手术或肌肉移植的PCOS大鼠中未出现这种情况。此外，BAT移植（而非假手术或肌肉移植）令人惊讶地提高了PCOS大鼠的生育能力。有趣的是，BAT移植激活了内源性BAT，从而提高了脂联素的循环水平，脂联素在全身能量代谢和卵巢生理中起着重要作用。与BAT移植一致，给予脂联素蛋白显著挽救了DHEA诱导的PCOS表型。这些结果强调内源性BAT活性与PCOS表型的发展密切相关，并且BAT激活可能是治疗PCOS的一种有前景的治疗选择。
Significance In the current study, we show that brown adipose tissue (BAT) activity is dramatically reduced in a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) rat when compared with a normal control rat. Importantly, the key features of PCOS (such as insulin resistance and irregular estrous cycle) are alleviated after BAT transplantation. Mechanistically, transplanted BAT enhances endogenous BAT activity and thereby increases the circulating adiponectin level, which was lower in both the PCOS patient and PCOS rat model. Furthermore, exogenous adiponectin protein administration recapitulates beneficial effects from BAT transplantation in a PCOS rat. Taken together, these data highlight the important role of BAT in the development of PCOS and that BAT-induced adiponectin might open up a new way in the treatment of PCOS. Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS.