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SUN-107 Abdominal Adipose Stem Cell Dysfunction In Vitro May Reflect Adipose Insulin Resistance In Vivo in Normal Weight Polycystic Ovarian Syndrome Women

Abstract Subcutaneous (SC) abdominal adipose stem cells (ASCs) of normal-weight polycystic ovary syndrome (PCOS) women show exaggerated development to newly-formed adipocytes in vitro (1). To determine whether this phenomenon in PCOS was related to adipose insulin resistance (adipose-IR) in vivo, 8 normal-weight PCOS women and 8 age- and BMI-balanced controls underwent circulating androgen and fasting insulin/free fatty acid (FFA) measurements. SC abdominal ASCs were isolated by fat biopsy and cultured in adipogenic medium for 12 days. ASC commitment to preadipocytes and newly-formed adipocytes derived from preadipocytes were determined by ZFP423 protein expression on day 0 and cellular lipid content by Oil Red O staining on day 12, respectively (i.e. adipogenesis). Adipose-IR was calculated as the product of fasting circulating FFA and insulin levels (2). Student’s t-test compared serum androgen levels and adipose-IR by female type; partial correlation coefficients examined associations of ZFP423 protein expression and newly-formed adipocyte lipid content with adipose-IR, adjusting for androgen levels. PCOS women had greater serum total testosterone [T] and free [f] T (P<0.005, both androgens) levels and higher adipose-IR (P=0.01) than controls. Newly-formed adipocyte lipid content positively correlated with adipose-IR in all women combined (R=0.57, P=0.02), however, significance was lost when adjusted for serum androgen levels (R=0.44, P=0.10 and R=0.36, P=0.18, for total T and fT, respectively). ZFP423 protein expression was not significantly correlated with adipose-IR in all women combined (R=-0.28, P=0.29), but was negatively correlated with adipose-IR (R=-0.64, P=0.01) after adjusting for total T levels. Using exploratory subgroup analysis, the positive relationship of newly-formed adipocyte lipid content with adipose-IR was significant in PCOS women (R=0.67, P=0.05) but not in controls (R=0.10, P=0.80). Similarly, the negative relationship of ZFP423 protein expression with adipose-IR was characteristic of PCOS women (R=-0.88, P=0.002) but not controls (R=-0.26, P=0.50). Thus, given the limited number of subjects, we hypothesize that altered SC abdominal adipogenesis contributes to increased adipose-IR in normal-weight PCOS women and that this relationship is due in part to hyperandrogenism. References: (1) Fisch SC, et al. Fertil Steril 2018; in press. (2) Sondergaard E, et al. JCEM 2017;102:1193. Sources of Research Support: NIH Grants and Santa Monica Bay Woman’s Club.