Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS

International Journal of Molecular Sciences

Maria Lorena Oróstica¹  Cristian Poblete²  Rodrigo Carvajal²  Isis Astorga²  Víctor García²  Carmen Romero²  Francisca Plaza-Parrochia²  Margarita Vega² 

[1] Laboratorio de Fisiopatología Celular y Cáncer (FICEC), Centro de Investigación Biomédica (CIB), Facultad de Medicina, Universidad Diego Portales, Santiago 8370007, Chile;Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont 999, Santiago 8380456, Chile;

关键词: metformin;    adiponectin;    insulin resistance;    obesity;    PCOS;    endometrium;   

DOI  :  10.3390/ijms23073922

来源: DOAJ

【 摘 要 】

Polycystic ovary syndrome (PCOS) is an endocrine/metabolic disorder associated with insulin resistance (IR) and obesity. Endometria from women with PCOS present failures in insulin action, glucose uptake and signaling of insulin-sensitizing molecules, such as adiponectin, with consequences for reproduction. Metformin (MTF) treatment improves insulin signaling in endometrial tissues, but its mechanism is not fully understood. This study addresses the MTF effect, as well as adiponectin agonist action, on levels of molecules associated with insulin and adiponectin signaling pathways in endometrial tissue and cells, as assessed by immunohistochemistry and immunocytochemistry, respectively. Endometrial tissues were obtained from women and divided into five groups: Normal Weight (control); Obesity + IR; Obesity + IR + PCOS; Obesity + IR + MTF; Obesity + IR + PCOS + MTF. Endometrial cells stimulated with TNFα (as obesity-marker) were also used to partially emulate an obesity environment. The results showed low levels of insulin/adiponectin signaling in the endometria from women with obesity, IR and PCOS compared with the control group. MTF re-established these levels, independently of PCOS. TNFα-associated molecules were elevated in pathologic endometria, whereas MTF diminished these levels. The low levels of insulin/adiponectin molecules in endometrial cells treated with TNFα were reverted by MTF, similar to what was observed in the case of the adiponectin agonist. Therefore, independently of PCOS, MTF can re-establish levels of molecules involved in insulin/adiponectin signaling in endometrial cells, suggesting an improvement in insulin action and reproductive failures observed in endometria from women with obesity/PCOS.

【 授权许可】

Unknown