Accelerated subcutaneous abdominal stem cell adipogenesis predicts insulin sensitivity in normal-weight women with polycystic ovary syndrome

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): PPAR' 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 PPAR' 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. (Fertil Steril (R) 2021;116:232-42. (c) 2020 by American Society for Reproductive Medicine.)

Automated summary

In vitro differentiation of adipose stem cells into adipocytes in SC abdominal fat may predict insulin sensitivity in vivo in normal-weight women with PCOS, suggesting a potential role for hyperandrogenism in metabolic thrift. PCOS patients exhibited higher androgen levels, adipose-IR, and android fat percentage, while their adipocyte differentiation and gene expression in vitro were negatively correlated with adipose-IR and serum free testosterone but positively correlated with insulin sensitivity.