Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

被引:140
作者
Yuan, Xiaoxue [1 ,2 ]
Hu, Tao [1 ,2 ]
Zhao, Han [3 ,4 ]
Huang, Yuanyuan [1 ]
Ye, Rongcai [1 ,2 ]
Lin, Jun [1 ,2 ]
Zhang, Chuanhai [1 ,5 ]
Zhang, Hanlin [1 ]
Wei, Gang [1 ,2 ]
Zhou, Huiqiao [1 ,2 ]
Dong, Meng [1 ,2 ]
Zhao, Jun [3 ,4 ]
Wang, Haibin [6 ]
Liu, Qingsong [7 ]
Lee, Hyuek Jong [1 ]
Jin, Wanzhu [1 ]
Chen, Zi-Jiang [3 ,4 ,8 ,9 ]
机构
[1] Chinese Acad Sci, Inst Zool, Key Lab Anim Ecol & Conservat Biol, Beijing 100101, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Shandong Univ, Shandong Prov Hosp, Ctr Reprod Med, Jinan 250021, Shandong, Peoples R China
[4] Minist Educ, Key Lab Reprod Endocrinol, Jinan 250001, Shandong, Peoples R China
[5] Nanjing Agr Univ, Nanjing 210095, Jiangsu, Peoples R China
[6] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China
[7] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China
[8] Shanghai Key Lab Assisted Reprod & Reprod Genet, Shanghai 200135, Peoples R China
[9] Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Ctr Reprod Med, Shanghai 200135, Peoples R China
基金
中国国家自然科学基金;
关键词
brown adipose tissue; transplantation; ameliorates; PCOS; adiponectin; PREVALENCE; INSULIN; MICE; THERMOGENESIS; DIAGNOSIS; FEATURES; WOMEN; MASS;
D O I
10.1073/pnas.1523236113
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2708 / 2713
页数:6
相关论文
共 39 条
[11]   Abdominal adiposity and the polycystic ovary syndrome [J].
Escobar-Morreale, Hector F. ;
Millan, Jose L. San .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2007, 18 (07) :266-272
[12]   PPARs and the complex journey to obesity [J].
Evans, RM ;
Barish, GD ;
Wang, YX .
NATURE MEDICINE, 2004, 10 (04) :355-361
[13]   Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS) [J].
Fauser, BCJM ;
Chang, J ;
Azziz, R ;
Legro, R ;
Dewailly, D ;
Franks, S ;
Tarlatzis, BC ;
Fauser, B ;
Balen, A ;
Bouchard, P ;
Dahlgren, E ;
Devoto, L ;
Diamanti, E ;
Dunaif, A ;
Filicori, M ;
Homburg, R ;
Ibanez, L ;
Laven, J ;
Magoffin, D ;
Nestler, J ;
Norman, RJ ;
Pasquali, R ;
Pugeat, M ;
Strauss, J ;
Tan, S ;
Taylor, A ;
Wild, R ;
Wild, S ;
Ehrmann, D ;
Lobo, R .
HUMAN REPRODUCTION, 2004, 19 (01) :41-47
[14]   Polycystic ovary syndrome: etiology, pathogenesis and diagnosis [J].
Goodarzi, Mark O. ;
Dumesic, Daniel A. ;
Chazenbalk, Gregorio ;
Azziz, Ricardo .
NATURE REVIEWS ENDOCRINOLOGY, 2011, 7 (04) :219-231
[15]   Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant [J].
Gunawardana, Subhadra C. ;
Piston, David W. .
DIABETES, 2012, 61 (03) :674-682
[16]   Genetic disruption of uncoupling protein 1 in mice renders brown adipose tissue a significant source of FGF21 secretion [J].
Keipert, Susanne ;
Kutschke, Maria ;
Lamp, Daniel ;
Brachthaeuser, Laura ;
Neff, Frauke ;
Meyer, Carola W. ;
Oelkrug, Rebecca ;
Kharitonenkov, Alexei ;
Jastroch, Martin .
MOLECULAR METABOLISM, 2015, 4 (07) :537-542
[17]   The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target? [J].
Lansdown, Andrew ;
Rees, D. Aled .
CLINICAL ENDOCRINOLOGY, 2012, 77 (06) :791-801
[18]   Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline [J].
Legro, Richard S. ;
Arslanian, Silva A. ;
Ehrmann, David A. ;
Hoeger, Kathleen M. ;
Murad, M. Hassan ;
Pasquali, Renato ;
Welt, Corrine K. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2013, 98 (12) :4565-4592
[19]   Polycystic ovary syndrome and cardiovascular disease: A premature association? [J].
Legro, RS .
ENDOCRINE REVIEWS, 2003, 24 (03) :302-312
[20]   Prevalence of symptoms associated with polycystic ovary syndrome [J].
Lindholm, Asa ;
Andersson, Liselott ;
Eliasson, Mats ;
Bixo, Marie ;
Sundstrom-Poromaa, Inger .
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, 2008, 102 (01) :39-43