Daniel A Dumesic1, Julia D Phan1, Karen L Leung1, Tristan R Grogan2, Xiangmiang Ding3, Xinmin Li3, Luis R Hoyos1, David H Abbott4, Gregorio D Chazenbalk1. 1. Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles, California. 2. Department of Medicine Statistics Core, David Geffen School of Medicine at University of California, Los Angeles, California. 3. Technology Center for Genomics and Bioinformatics, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California. 4. Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin.
Abstract
CONTEXT: Normal-weight women with polycystic ovary syndrome (PCOS) may have adipose tissue insulin resistance (adipose-IR). OBJECTIVE: To examine whether adipose-IR and subcutaneous (SC) abdominal adipose stem cell (ASC) gene expression are altered in normal-weight women with PCOS and correlated with hyperandrogenemia and/or whole-body IR. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: Ten normal-weight women with PCOS and 18 control subjects matched for age and body mass index. INTERVENTION(S): Women underwent circulating hormone and metabolic measurements, IV glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S): Adipose-IR (fasting insulin × total fatty acid levels) and SC abdominal ASC gene expression were compared between groups and correlated with clinical outcomes. RESULTS: Adipose-IR was greater in women with PCOS than in control subjects (P < 0.01), with 29 pmol/L × mmol/L providing 94% specificity and 80% sensitivity in discriminating the two groups (P < 0.001). Adipose-IR positively correlated with serum androgen and log of fasting triglyceride (TG) levels, percentage of small adipocytes (P < 0.01, all correlations), and acute insulin response to glucose (P < 0.05); and negatively correlated with insulin sensitivity (Si; P < 0.025) and serum adiponectin levels (P < 0.05). Adjusting for serum androgens, adipose-IR correlations with Si and log TG levels remained significant. ASC genes were differentially expressed by the two groups. Expression of functionally critical genes was associated with serum testosterone and/or fasting insulin levels. CONCLUSION: Normal-weight women with PCOS have increased adipose-IR and altered ASC gene expression related to hyperandrogenism and IR.
CONTEXT: Normal-weight women with polycystic ovary syndrome (PCOS) may have adipose tissue insulin resistance (adipose-IR). OBJECTIVE: To examine whether adipose-IR and subcutaneous (SC) abdominal adipose stem cell (ASC) gene expression are altered in normal-weight women with PCOS and correlated with hyperandrogenemia and/or whole-body IR. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: Ten normal-weight women with PCOS and 18 control subjects matched for age and body mass index. INTERVENTION(S): Women underwent circulating hormone and metabolic measurements, IV glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S): Adipose-IR (fasting insulin × total fatty acid levels) and SC abdominal ASC gene expression were compared between groups and correlated with clinical outcomes. RESULTS: Adipose-IR was greater in women with PCOS than in control subjects (P < 0.01), with 29 pmol/L × mmol/L providing 94% specificity and 80% sensitivity in discriminating the two groups (P < 0.001). Adipose-IR positively correlated with serum androgen and log of fasting triglyceride (TG) levels, percentage of small adipocytes (P < 0.01, all correlations), and acute insulin response to glucose (P < 0.05); and negatively correlated with insulin sensitivity (Si; P < 0.025) and serum adiponectin levels (P < 0.05). Adjusting for serum androgens, adipose-IR correlations with Si and log TG levels remained significant. ASC genes were differentially expressed by the two groups. Expression of functionally critical genes was associated with serum testosterone and/or fasting insulin levels. CONCLUSION: Normal-weight women with PCOS have increased adipose-IR and altered ASC gene expression related to hyperandrogenism and IR.
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