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

Abstract

To examine whether subcutaneous (SC) abdominal adipose stem cell differentiation into adipocytes invitro predicts insulin sensitivity (Si) invivo in normal-weight women with polycystic ovary syndrome (PCOS) and controls. Prospective cohort study. Academic medical center. Eight normal-weight women with PCOS and 8 age- and body mass index-matched controls. Women underwent circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. PPARγ and CEBPa gene expression and lipid content of adipocytes matured invitro were compared between women with PCOS and control women, and correlated with patient characteristics, systemic Si, and adipose insulin resistance (adipose-IR). 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. In normal-weight women with PCOS, accelerated SC abdominal adipose stem cell differentiation into adipocytes invitro favors Si invivo, suggesting a role for hyperandrogenism in the evolution of metabolic thrift to enhance fat storage through increased cellular glucose uptake.