{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:43:25Z","timestamp":1776087805071,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007708","name":"Fondo Nacional de Ciencia Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["3180656"],"award-info":[{"award-number":["3180656"]}],"id":[{"id":"10.13039\/501100007708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007708","name":"Fondo Nacional de Ciencia Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["1130053"],"award-info":[{"award-number":["1130053"]}],"id":[{"id":"10.13039\/501100007708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 TNF\u03b1 (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. TNF\u03b1-associated molecules were elevated in pathologic endometria, whereas MTF diminished these levels. The low levels of insulin\/adiponectin molecules in endometrial cells treated with TNF\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms23073922","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T21:22:39Z","timestamp":1648848159000},"page":"3922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["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"],"prefix":"10.3390","volume":"23","author":[{"given":"Maria Lorena","family":"Or\u00f3stica","sequence":"first","affiliation":[{"name":"Laboratorio de Fisiopatolog\u00eda Celular y C\u00e1ncer (FICEC), Centro de Investigaci\u00f3n Biom\u00e9dica (CIB), Facultad de Medicina, Universidad Diego Portales, Santiago 8370007, Chile"},{"name":"Laboratorio de Comunicaciones Celulares, Programa de Biolog\u00eda Celular y Molecular, Centro de Estudios en Ejercicio, Metabolismo y C\u00e1ncer (CEMC), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isis","family":"Astorga","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont #999, Santiago 8380456, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Plaza-Parrochia","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont #999, Santiago 8380456, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian","family":"Poblete","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont #999, Santiago 8380456, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Carvajal","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont #999, Santiago 8380456, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont #999, Santiago 8380456, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9818-8923","authenticated-orcid":false,"given":"Carmen","family":"Romero","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont #999, Santiago 8380456, Chile"},{"name":"Department of Obstetrics and Gynecology, School of Medicine, Clinical Hospital, University of Chile, Santiago 8380456, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Vega","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santos Dumont #999, Santiago 8380456, Chile"},{"name":"Department of Obstetrics and Gynecology, School of Medicine, Clinical Hospital, University of Chile, Santiago 8380456, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1017\/S1462399408000598","article-title":"Polycystic ovarian syndrome pathophysiology, molecular aspects and clinical implications","volume":"10","year":"2008","journal-title":"Expert Rev. 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