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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:ContextOvarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production.ObjectivesTo compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition.DesignProspective, cross-sectional, cohort study.SettingAcademic medical center.PatientsTwenty normal-weight women with PCOS and 20 body mass index-/age-matched controls.InterventionsBlood sampling, IV glucose tolerance testing, and total-body dual-energy x-ray absorptiometry.Main outcome measuresClinical characteristics, hormonal concentrations, and body fat distribution.ResultsWomen with PCOS had higher serum total/free testosterone (T) and androstenedione (A4) levels and a greater android/gynoid fat mass than controls (androgens P < .001; android/gynoid fat mass ratio, P = .026). Serum total/free T and A4 levels correlated positively with android/gynoid fat mass ratio in all women combined (P < .025, all values). Serum 11ß-hydroxyA4, 11-ketoA4, 11ß-hydroxyT, 11-ketoT, cortisol, and cortisone levels were comparable between female types and unrelated to body fat distribution. Serum 11-oxyandrogens correlated negatively with % total body fat, but lost significance adjusting for cortisol. Serum cortisol levels, however, correlated inversely with android fat mass (P = .021), with a trend toward reduced serum cortisol to cortisone ratio in women with PCOS vs controls (P = .075), suggesting diminished 11β-hydroxysteroid dehydrogenase activity.ConclusionReduced cortisol may protect against preferential abdominal fat mass in normal-weight PCOS women with normal serum 11-oxyandrogens.

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.

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.

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