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

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 (PPAR? 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 PPAR? 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.

SUBMITTER: Fisch SC

PROVIDER: S-EPMC6287278 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Fisch Samantha C SC Nikou Ariella Farzan AF Wright Elizabeth A EA Phan Julia D JD Leung Karen L KL Grogan Tristan R TR Abbott David H DH Chazenbalk Gregorio D GD Dumesic Daniel A DA

Fertility and sterility 20181201 7

<h4>Objective</h4>To examine whether abnormal subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes in polycystic ovary syndrome (PCOS) correlates with hyperandrogenism.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>Academic medical center.<h4>Patient(s)</h4>Eight normal-weight women with PCOS and eight normoandrogenic ovulatory (control) women matched for age and body mass index.<h4>Intervention(s)</h4>Circulating hormone and metabolic measurements, intravenous ...[more]

PMID: 30503136

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Project description:BackgroundPolycystic ovary syndrome (PCOS) has been recognized as a metabolic disorder, manifested by abdominal obesity, insulin resistance, dyslipidemia and hypertension. Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor family, is a pleiotropic protein known for its antiangiogenic, antioxidant, and neuroprotective properties and has been shown to induce insulin resistance and play a role in glucose metabolism. Recent studies investigating circulating PEDF levels show elevated serum PEDF in association with insulin resistance in normal-weight women with PCOS, but not in obese PCOS patients. The aims of this study were 1) to assess PEDF gene expression in subcutaneous adipose tissue (scAT) from women with PCOS and nonhirsute, ovulatory controls, and 2) to determine the circulating levels of PEDF in these groups.MethodsTotal RNA was extracted from adipose tissue biopsy samples and reverse-transcribed to cDNA. Real-time quantitative PCR was performed to determine relative gene expression levels.ResultsThe 22 women with PCOS and 14 non-PCOS controls included in the study had similar age, BMI, and fasting glucose, triglycerides, and HDL-cholesterol levels. Participants with PCOS exhibited higher 2 h oral glucose tolerance test levels (p?=?0.006), total (p?=?0.026) and LDL-cholesterol (p?=?0.036), Ferriman-Gallwey score (p?=?0.003) and total testosterone (p?=?0.001) as compared to controls. BMI-adjusted PEDF serum levels and scAT gene expression were similar in the PCOS and control groups (p?=?0.622 and p?=?0.509, respectively). Circulating PEDF levels were not associated with scAT PEDF gene expression. Multiple regression analysis revealed that, in women with PCOS, insulin contributed positively and significantly to serum PEDF (p = 0.027), independently of testosterone.ConclusionSerum PEDF levels and scAT gene expression were associated with metabolic risk factors, but did not differ between women with PCOS and age- and BMI-matched controls. Circulating levels and scAT gene expression of PEDF were not associated in the study subjects, suggesting additional sources for PEDF in addition to or instead of fat tissue.

Project description:Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation to be of uncertain cause: obesity, insulin resistance, or PCOS itself. The aim of the study was to investigate the WBC (white blood cell) count and CRP (C-reactive protein) concentration in women with PCOS and to determine the factors that affect their concentration. The study included 200 women aged 18-40 with PCOS and 105 healthy women as the control group, recruited in the Department of Gynaecological Endocrinology of Medical University in Warsaw from 2016 to 2018. Each patient underwent clinical, biochemical, and ultrasonographic assessments. WBC and CRP were significantly higher in the PCOS group (Z = -2,353, p = 0,019 and Z = -2,453, p = 0,014). WBC positively correlated with serum insulin at 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,221, p = 0,001; INS1: r = 0,194, p = 0,003; INS2: r = 0,022, p = 0,001), testosterone (r = 0,130, p = 0,046), androstenedione (r = 0,212, p = 0,001), and DHEAS (r = 0,178, p = 0,006) and negatively correlated with progesterone (r = -0,204, p = 0,002), estradiol (r = -0,140, p = 0,032), and SHBG (r = -0,308, p < 0,001). CRP positively correlated with insulin concentration in 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,343, p < 0,001; INS1: r = 0,276, p = 0,001; INS2: r = 0,320, p < 001) and negatively correlated with progesterone (r = -0,194, p = 0,030) and SHBG (-0,244, p = 0,005). We also estimated positive correlation between BMI and serum CRP and WBC concentration. Multiple linear regression analysis showed that CRP values are positively associated with BMI (beta = 0,374, p < 0,001) and insulin level (INS1) (beta = 0,282, p = 0,004); and WBC results are negatively associated with SHGB (beta = -0,284, p < 0,001) but positively associated with testosterone (beta = 0,163, p = 0,024) and BMI (beta = 0,157, p = 0,047). PCOS is associated with increased WBC and CRP concentrations. The main predicting factors of increased CRP are BMI and insulin resistance, but there is also a relationship between WBC count in PCOS and androgen concentration itself so that inflammation may be mediated not only through adiposity but also through increased androgen concentration.

Dataset Information

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

Publications

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

Similar Datasets

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