{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T19:57:40Z","timestamp":1769111860421,"version":"3.49.0"},"reference-count":46,"publisher":"Canadian Science Publishing","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p> Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but the reverse is the case after menopause, indicating a possible protective effect of estrogen on cardiometabolic function. Although various hormonal therapies have been formulated to combat the CVD risks in postmenopausal state, the beneficial effects have not been consistent. Obesity with insulin resistance (IR) is closely linked to CVD risks while ovariectomized rodents have been shown to mimic a state of obesity and IR. We therefore hypothesized that low-dose spironolactone would ameliorate obesity and IR in estrogen-deprived rats by replenishing estrogen and suppressing elevated glycogen synthase kinase-3 (GSK-3). Ten-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM), spironolactone (SPL; 0.25 mg\/kg), and ovariectomized (OVX) rats treated with or without spironolactone daily for 8 weeks. Results showed that estrogen deprivation through ovariectomy caused increased body mass gain and visceral adiposity that are accompanied by increased HOMA-IR, HOMA-\u03b2, 1-hour postload glucose, glucose intolerance, platelet\/lymphocyte ratio, plasma insulin, atherogenic dyslipidemia, uric acid, GSK-3, corticosterone, and aldosterone and depressed 17\u03b2-estradiol. However, treatment of OVX rats with spironolactone ameliorated all these effects. Taken together, the results demonstrate that treatment with low-dose spironolactone improves obesity and IR, which appears to involve replenishment of estrogen and suppression of GSK-3 along with circulating mineralocorticoid and glucocorticoid. The findings imply a positive cardiometabolic effect of low-dose spironolactone usage in estrogen-deprived conditions. <\/jats:p>","DOI":"10.1139\/cjpp-2018-0416","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T21:36:53Z","timestamp":1542145013000},"page":"65-74","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Ameliorative effect of low-dose spironolactone on obesity and insulin resistance is through replenishment of estrogen in ovariectomized rats"],"prefix":"10.1139","volume":"97","author":[{"given":"Lawrence A.","family":"Olatunji","sequence":"first","affiliation":[{"name":"HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oluwaseun A.","family":"Adeyanju","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."},{"name":"Cardiometabolic Research Unit, Department of Physiology, Afe Babalola University, Ado-Ekiti, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olugbenga S.","family":"Michael","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."},{"name":"Cardiometabolic Research Unit, Department of Physiology, College of Health Sciences, Bowen University, Iwo, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taofeek O.","family":"Usman","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."},{"name":"Cardiometabolic Research Unit, Department of Physiology, College of Health Sciences, Osun State University, Osogbo, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita C.","family":"Tostes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of S\u00e3o Paulo, Ribeirao Preto Medical School, Ribeirao Preto, S\u00e3o Paulo, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayodele O.","family":"Soladoye","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."},{"name":"Cardiometabolic Research Unit, Department of Physiology, College of Health Sciences, Bowen University, Iwo, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2017-0630"},{"key":"refg47\/ref47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2004.05.009"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-245415"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.005"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3971"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.8.2087"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2012.10.002"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1363685"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1684-1"},{"issue":"2","key":"refg8\/ref8","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/S0022-3565(25)22580-0","volume":"240","author":"De Gasparo M.","year":"1987","journal-title":"J. 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