Yuan Xiaoxue, Hu Tao, Zhao Han, Huang Yuanyuan, Ye Rongcai, Lin Jun, Zhang Chuanhai, Zhang Hanlin, Wei Gang, Zhou Huiqiao, Dong Meng, Zhao Jun, Wang Haibin, Liu Qingsong, Lee Hyuek Jong, Jin Wanzhu, Chen Zi-Jiang
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; The University of the Chinese Academy of Sciences, Beijing 100049, China;
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China; The Key Laboratory for Reproductive Endocrinology of the Ministry of Education, Jinan, Shandong 250001, China;
Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):2708-13. doi: 10.1073/pnas.1523236113. Epub 2016 Feb 22.
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.
多囊卵巢综合征(PCOS)是一种复杂的内分泌疾病,其特征为无排卵、高雄激素血症和多囊卵巢。由于PCOS在分子水平上的病因很大程度上尚不清楚,因此目前尚无治愈方法或针对PCOS的特异性治疗方法。在此,我们表明,棕色脂肪组织(BAT)移植可逆转脱氢表雄酮(DHEA)诱导的PCOS大鼠的无排卵、高雄激素血症和多囊卵巢。将BAT移植到PCOS大鼠体内可显著稳定月经不规律,并将全身胰岛素敏感性提高到正常水平,而假手术或肌肉移植的PCOS大鼠则未出现这种情况。此外,令人惊讶的是,BAT移植而非假手术或肌肉移植可提高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,给予脂联素蛋白可显著挽救DHEA诱导的PCOS表型。这些结果表明,内源性BAT活性与PCOS表型的发展密切相关,BAT激活可能是治疗PCOS的一种有前景的治疗选择。