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Accelerated subcutaneous abdominal stem cell adipogenesis predicts insulin sensitivity in normal-weight women with polycystic ovary syndrome
Fertility and Sterility ( IF 6.6 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.fertnstert.2020.10.003
Daniel A Dumesic 1 , Ayli Tulberg 1 , Karen L Leung 1 , Samantha C Fisch 1 , Tristan R Grogan 2 , David H Abbott 3 , Rajanigandha Naik 1 , Gregorio D Chazenbalk 1
Affiliation  

OBJECTIVE To examine whether subcutaneous (SC) abdominal adipose stem cell differentiation into adipocytes in vitro predicts insulin sensitivity (Si) in vivo in normal-weight women with polycystic ovary syndrome (PCOS) and controls. DESIGN Prospective cohort study. SETTING Academic medical center. PATIENT(S) Eight normal-weight women with PCOS and 8 age- and body mass index-matched controls. INTERVENTION(S) Women underwent circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S) PPARγ and CEBPa gene expression and lipid content of adipocytes matured in vitro were compared between women with PCOS and control women, and correlated with patient characteristics, systemic Si, and adipose insulin resistance (adipose-IR). RESULT(S) Serum androgen levels, adipose-IR, and percentage of android fat were greater in women with PCOS than control women. Stem cell PPARγ and CEBPa gene expression increased maximally by day 12 without a female-type effect. In control cells, gene expression positively correlated with fasting serum insulin levels (both genes) and adipose-IR (CEBPa) and negatively correlated with Si (CEBPa). Conversely, CEBPa gene expression in PCOS cells negatively correlated with adipose-IR and serum free testosterone, whereas total lipid accumulation in these cells positively corelated with Si. CONCLUSION In normal-weight women with PCOS, accelerated SC abdominal adipose stem cell differentiation into adipocytes in vitro favors Si in vivo, suggesting a role for hyperandrogenism in the evolution of metabolic thrift to enhance fat storage through increased cellular glucose uptake.

中文翻译:

加速皮下腹部干细胞脂肪生成可预测体重正常的多囊卵巢综合征女性的胰岛素敏感性

目的 研究皮下 (SC) 腹部脂肪干细胞体外分化为脂肪细胞是否可以预测患有多囊卵巢综合征 (PCOS) 的正常体重女性和对照组的体内胰岛素敏感性 (Si)。设计前瞻性队列研究。设置 学术医疗中心。患者 8 名患有 PCOS 的正常体重女性和 8 名年龄和体重指数匹配的对照。干预措施 女性接受了循环激素/代谢测定、静脉葡萄糖耐量测试、全身双能 X 射线吸收测定和 SC 腹部脂肪活检。主要结果测量(S) PPARγ 和 CEBPa 基因表达和体外成熟脂肪细胞的脂质含量在 PCOS 女性和对照女性之间进行比较,并与患者特征、全身 Si 和脂肪胰岛素抵抗 (adipose-IR) 相关。结果(S) PCOS 女性的血清雄激素水平、脂肪-IR 和安卓脂肪百分比高于对照组女性。到第 12 天,干细胞 PPARγ 和 CEBPa 基因表达最大增加,而没有雌性效应。在对照细胞中,基因表达与空腹血清胰岛素水平(两个基因)和脂肪-IR (CEBPa) 呈正相关,与 Si (CEBPa) 呈负相关。相反,PCOS 细胞中的 CEBPa 基因表达与脂肪-IR 和血清游离睾酮呈负相关,而这些细胞中的总脂质积累与 Si 呈正相关。结论 在患有 PCOS 的正常体重女性中,体外加速 SC 腹部脂肪干细胞分化为脂肪细胞有利于体内 Si,
更新日期:2020-12-01
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