Increased Expression of Insulin Signaling Intermediates after Six Months of Metformin Medical Intervention in Women with Obesity and Polycystic Ovary Syndrome

Objective: We hypothesize that in women experiencing obesity and PCOS, the women with higher levels of free androgen index will display more dysregulation in the insulin signaling pathway in adipose tissue. More specifically, we believe that visceral more than subcutaneous adipose tissue in the women in the study will display more dysregulation; and lastly that bariatric surgery will alleviate insulin signaling dysregulation. Methods: Here, we performed molecular analyses (Western blots and qPRC) exploring the insulin signaling pathway in visceral and subcutaneous (SubQ) adipose tissue from women with obesity and PCOS undergoing RYGB bariatric surgery; and SubQ WAT from women with obesity and PCOS at baseline and six-months after medical intervention with metformin (MTF) . Results: Subcutaneous (SubQ) white adipose tissue (WAT) displayed a trending (p=0.2) but non-significant increase in p-ACC compared to visceral WAT from women with PCOS and obesity pre-bariatric surgery. Six months of MTF increased p-ACC in SubQ WAT by 5-fold compared to zero months (baseline) in women with PCOS and obesity. IR displayed similar expression in the visceral compared to SubQ WAT in women with PCOS and obesity pre-bariatric surgery. IR expression increased by 20-fold at 6-months of MTF compared to baseline in SubQ WAT of women with PCOS and obesity. Phosphorylated forkhead box 01 (p-FOXO1) displayed similar expression in the visceral compared to SubQ WAT in women with PCOS and obesity. However, p-FOXO1 was decreased at 6-months of MTF compared to baseline in women with PCOS and obesity. p-AKT levels were similar in visceral compared to SubQ WAT in women with PCOS and obesity pre-bariatric surgery. However, p-AKT levels were significantly increased by 4-fold at 6-months of MTF compared to 0-months in women with PCOS and obesity. Conclusion: None of the insulin signaling intermediates measured were altered in visceral compared to SubQ in women with obesity and PCOS. Disclosure S. Andrisse: None.