PMID- 28323956
OWN - NLM
STAT- MEDLINE
DCOM- 20171010
LR  - 20180203
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 158
IP  - 5
DP  - 2017 May 1
TI  - Hyperhomocysteinemia Promotes Insulin Resistance and Adipose Tissue Inflammation 
      in PCOS Mice Through Modulating M2 Macrophage Polarization via Estrogen 
      Suppression.
PG  - 1181-1193
LID - 10.1210/en.2017-00039 [doi]
AB  - It has been shown that serum homocysteine (Hcy) levels are higher in women with 
      polycystic ovary syndrome (PCOS). However, the specific role of 
      hyperhomocysteinemia (HHcy) in the development of PCOS has never been reported. 
      Adipose tissue inflammation is featured by the infiltration of macrophages, which 
      plays a critical role in the pathogenesis of glucose and insulin intolerance. In 
      this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) and/or a 
      high methionine diet to induce PCOS and HHcy mice models. We showed that DHEA 
      induced a PCOS-like phenotypes, irregular estrous cycles, weight gain, abnormal 
      sex hormone production, glucose and insulin resistance, and polycystic ovaries. 
      HHcy further intensified the effects DHEA on the metabolic, endocrinal, hormonal, 
      and morphological changes in PCOS-like mice. In addition, HHcy attenuated the 
      DHEA-induced increase in serum estrogen levels in mice. Furthermore, HHcy may 
      exacerbate the insulin resistance in PCOS-like mice, most likely through 
      modulating the macrophage M1/M2 polarization pathways via the suppression of 
      estrogen. Most important, our clinical data showed that there were increases in 
      serum Hcy levels in patients with PCOS. These findings deepen our understanding 
      of the pathological roles of HHcy in the development of PCOS and provide a 
      promising target for PCOS therapy in clinical application.
CI  - Copyright (c) 2017 Endocrine Society.
FAU - Qi, Xinyu
AU  - Qi X
AD  - Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking 
      University Third Hospital, Beijing 100191, China.
AD  - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive 
      Technology, Beijing 100191, China.
AD  - Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, 
      China.
FAU - Zhang, Bochun
AU  - Zhang B
AD  - Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking 
      University Third Hospital, Beijing 100191, China.
AD  - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive 
      Technology, Beijing 100191, China.
AD  - Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, 
      China.
FAU - Zhao, Yue
AU  - Zhao Y
AD  - Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking 
      University Third Hospital, Beijing 100191, China.
AD  - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive 
      Technology, Beijing 100191, China.
AD  - Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, 
      China.
FAU - Li, Rong
AU  - Li R
AD  - Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking 
      University Third Hospital, Beijing 100191, China.
AD  - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive 
      Technology, Beijing 100191, China.
AD  - Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, 
      China.
FAU - Chang, Hsun-Ming
AU  - Chang HM
AD  - Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking 
      University Third Hospital, Beijing 100191, China.
AD  - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive 
      Technology, Beijing 100191, China.
FAU - Pang, Yanli
AU  - Pang Y
AD  - Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking 
      University Third Hospital, Beijing 100191, China.
AD  - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive 
      Technology, Beijing 100191, China.
AD  - Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, 
      China.
FAU - Qiao, Jie
AU  - Qiao J
AD  - Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking 
      University Third Hospital, Beijing 100191, China.
AD  - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive 
      Technology, Beijing 100191, China.
AD  - Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Estrogens)
SB  - IM
MH  - Adipose Tissue/metabolism/pathology
MH  - Animals
MH  - Cell Polarity/immunology
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Estrogens/blood/*metabolism
MH  - Female
MH  - Hyperhomocysteinemia/*complications/metabolism
MH  - Inflammation/metabolism/pathology
MH  - *Insulin Resistance
MH  - Macrophage Activation
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Panniculitis/*etiology/metabolism
MH  - Polycystic Ovary Syndrome/*complications/immunology/metabolism
EDAT- 2017/03/23 06:00
MHDA- 2017/10/11 06:00
CRDT- 2017/03/22 06:00
PHST- 2017/01/08 00:00 [received]
PHST- 2017/03/10 00:00 [accepted]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2017/03/22 06:00 [entrez]
AID - 3070535 [pii]
AID - 10.1210/en.2017-00039 [doi]
PST - ppublish
SO  - Endocrinology. 2017 May 1;158(5):1181-1193. doi: 10.1210/en.2017-00039.