Brown adipose tissue transplantation ameliorates polycystic ovary syndrome
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...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2016-03, Vol.113 (10), p.2708-2713 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1073/pnas.1523236113 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1523236113</identifier><identifier>PMID: 26903641</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adipocytes ; Adiponectin - blood ; Adiponectin - pharmacology ; Adipose Tissue, Brown - transplantation ; Adult ; Analysis of Variance ; Animals ; Biological Sciences ; Blood Glucose - metabolism ; Dehydroepiandrosterone ; Energy Metabolism - drug effects ; Estrous Cycle - drug effects ; Female ; Genotype & phenotype ; Humans ; Infertility, Female - surgery ; Insulin - blood ; Insulin Resistance ; Male ; Metabolism ; Physiology ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - chemically induced ; Polycystic Ovary Syndrome - metabolism ; Polycystic Ovary Syndrome - surgery ; Rats, Sprague-Dawley ; Rodents ; Transplants & implants ; Treatment Outcome</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2016-03, Vol.113 (10), p.2708-2713</ispartof><rights>Volumes 1–89 and 106–113, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Mar 8, 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-f96615ab2d774257747c0258c349dec473969038d851f59c9226a968f01f16ca3</citedby><cites>FETCH-LOGICAL-c533t-f96615ab2d774257747c0258c349dec473969038d851f59c9226a968f01f16ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/113/10.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26468613$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26468613$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26903641$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Xiaoxue</creatorcontrib><creatorcontrib>Hu, Tao</creatorcontrib><creatorcontrib>Zhao, Han</creatorcontrib><creatorcontrib>Huang, Yuanyuan</creatorcontrib><creatorcontrib>Ye, Rongcai</creatorcontrib><creatorcontrib>Lin, Jun</creatorcontrib><creatorcontrib>Zhang, Chuanhai</creatorcontrib><creatorcontrib>Zhang, Hanlin</creatorcontrib><creatorcontrib>Wei, Gang</creatorcontrib><creatorcontrib>Zhou, Huiqiao</creatorcontrib><creatorcontrib>Dong, Meng</creatorcontrib><creatorcontrib>Zhao, Jun</creatorcontrib><creatorcontrib>Wang, Haibin</creatorcontrib><creatorcontrib>Liu, Qingsong</creatorcontrib><creatorcontrib>Lee, Hyuek Jong</creatorcontrib><creatorcontrib>Jin, Wanzhu</creatorcontrib><creatorcontrib>Chen, Zi-Jiang</creatorcontrib><title>Brown adipose tissue transplantation ameliorates polycystic ovary syndrome</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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.</description><subject>Adipocytes</subject><subject>Adiponectin - blood</subject><subject>Adiponectin - pharmacology</subject><subject>Adipose Tissue, Brown - transplantation</subject><subject>Adult</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Dehydroepiandrosterone</subject><subject>Energy Metabolism - drug effects</subject><subject>Estrous Cycle - drug effects</subject><subject>Female</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Infertility, Female - surgery</subject><subject>Insulin - blood</subject><subject>Insulin Resistance</subject><subject>Male</subject><subject>Metabolism</subject><subject>Physiology</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - chemically induced</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Polycystic Ovary Syndrome - surgery</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Transplants & implants</subject><subject>Treatment Outcome</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtv1DAUhS0Eaoe2a1ZAJDZs0vr92CDRCkqrSt20a8t1HPAoiYNvUjT_vo5mGFo2vov73eNzdBB6R_ApwYqdjYODUyIoo0wSwl6hFcGG1JIb_BqtMKaq1pzyQ_QWYI0xNkLjA3RIpcFMcrJC1-c5_Rkq18QxQaimCDCXkd0AY-eGyU0xlXUfupiymwJUY-o2fgNT9FV6dHlTwWZocurDMXrTug7CyW4eofvv3-4uftQ3t5dXF19vai8Ym-rWSEmEe6CNUpyK8iiPqdCecdMEzxUzizvdaEFaYbyhVDojdYtJS6R37Ah92eqO80MfGh-GYrezY459sWOTi_blZoi_7M_0aLky2BhVBD7vBHL6PQeYbB_Bh67kDWkGS5SihAstZUE__Yeu05yHEm-hOGPU0EXwbEv5nAByaPdmCLZLT3bpyf7rqVx8eJ5hz_8tpgAfd8ByuZcjbJGkCutCvN8Sa5hSfqbApZbliyfzBKMJ</recordid><startdate>20160308</startdate><enddate>20160308</enddate><creator>Yuan, Xiaoxue</creator><creator>Hu, Tao</creator><creator>Zhao, Han</creator><creator>Huang, Yuanyuan</creator><creator>Ye, Rongcai</creator><creator>Lin, Jun</creator><creator>Zhang, Chuanhai</creator><creator>Zhang, Hanlin</creator><creator>Wei, Gang</creator><creator>Zhou, Huiqiao</creator><creator>Dong, Meng</creator><creator>Zhao, Jun</creator><creator>Wang, Haibin</creator><creator>Liu, Qingsong</creator><creator>Lee, Hyuek Jong</creator><creator>Jin, Wanzhu</creator><creator>Chen, Zi-Jiang</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160308</creationdate><title>Brown adipose tissue transplantation ameliorates polycystic ovary syndrome</title><author>Yuan, Xiaoxue ; 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>26903641</pmid><doi>10.1073/pnas.1523236113</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Adiponectin - blood Adiponectin - pharmacology Adipose Tissue, Brown - transplantation Adult Analysis of Variance Animals Biological Sciences Blood Glucose - metabolism Dehydroepiandrosterone Energy Metabolism - drug effects Estrous Cycle - drug effects Female Genotype & phenotype Humans Infertility, Female - surgery Insulin - blood Insulin Resistance Male Metabolism Physiology Polycystic ovary syndrome Polycystic Ovary Syndrome - chemically induced Polycystic Ovary Syndrome - metabolism Polycystic Ovary Syndrome - surgery Rats, Sprague-Dawley Rodents Transplants & implants Treatment Outcome |
| title | Brown adipose tissue transplantation ameliorates polycystic ovary syndrome |
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