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多囊卵巢综合征正常体重女性中早发皮下腹部干细胞向脂肪细胞的发育。

Precocious subcutaneous abdominal stem cell development to adipocytes in normal-weight women with polycystic ovary syndrome.

机构信息

Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California.

Department of Medicine Statistics Core, University of California-Los Angeles, Los Angeles, California.

出版信息

Fertil Steril. 2018 Dec;110(7):1367-1376. doi: 10.1016/j.fertnstert.2018.08.042.

Abstract

OBJECTIVE

To examine whether abnormal subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes in polycystic ovary syndrome (PCOS) correlates with hyperandrogenism.

DESIGN

Prospective cohort study.

SETTING

Academic medical center.

PATIENT(S): Eight normal-weight women with PCOS and eight normoandrogenic ovulatory (control) women matched for age and body mass index.

INTERVENTION(S): Circulating hormone and metabolic measurements, intravenous glucose tolerance testing, total body dual-energy X-ray absorptiometry, and SC abdominal fat biopsy.

MAIN OUTCOME MEASURE(S): In vitro ASC commitment to preadipocytes (ZFP423 protein expression, day 0.5), preadipocyte differentiation to adipocytes (PPARγ gene expression, day 3) and adipocyte lipid content (Oil-Red-O fluorescence, day 12) comparisons correlated with clinical outcomes.

RESULT(S): In women with PCOS, SC abdominal ASCs compared with those of control women showed exaggerated commitment to preadipocytes and had greater lipid content in newly formed adipocytes after in vitro maturation. In all women combined, ZFP423 protein expression negatively correlated with fasting plasma glucose levels whereas the lipid content of newly formed adipocytes positively correlated with both PPARγ gene expression and serum free testosterone levels.

CONCLUSION(S): In normal-weight women with PCOS compared with the control group, exaggerated SC abdominal ASC commitment to preadipocytes and enhanced adipocyte lipid content during maturation in vitro negatively and positively correlate with circulating fasting glucose and androgen levels, respectively, as a possible mechanism to maintain glucose-insulin homeostasis when fat accretion is accelerated.

摘要

目的

研究多囊卵巢综合征(PCOS)患者皮下(SC)腹部脂肪干细胞(ASC)向脂肪细胞的异常发育是否与高雄激素血症有关。

设计

前瞻性队列研究。

地点

学术医疗中心。

患者

8 名体质量正常的 PCOS 患者和 8 名年龄和体质量指数匹配的正常排卵(对照)患者。

干预

循环激素和代谢测量、静脉葡萄糖耐量试验、全身双能 X 射线吸收仪和 SC 腹部脂肪活检。

主要观察指标

体外 ASC 向前体脂肪细胞的定向(ZFP423 蛋白表达,第 0.5 天)、前体脂肪细胞向脂肪细胞的分化(PPARγ 基因表达,第 3 天)和脂肪细胞脂质含量(油红 O 荧光,第 12 天)的比较与临床结果相关。

结果

与对照组相比,PCOS 患者的 SC 腹部 ASC 表现出向前体脂肪细胞的定向过度,并且在体外成熟后新形成的脂肪细胞中的脂质含量更高。在所有女性中,ZFP423 蛋白表达与空腹血糖水平呈负相关,而新形成的脂肪细胞的脂质含量与 PPARγ 基因表达和血清游离睾酮水平均呈正相关。

结论

与对照组相比,体质量正常的 PCOS 患者的 SC 腹部 ASC 向前体脂肪细胞的定向过度和体外成熟过程中脂肪细胞脂质含量增加,可能是加速脂肪堆积时维持血糖-胰岛素稳态的一种机制,分别与循环空腹血糖和雄激素水平呈负相关和正相关。

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