Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice
Coumestrol, a phytoestrogen compound found in various plants, has been shown to act as a potent estrogen receptor (ER) agonist, with a higher binding affinity for ERβ than for ERα. However, there is currently limited information regarding its beneficial effects in postmenopausal disorders and its ER...
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MDPI AG
2023-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/4/954 |
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| author | Song Park Kyu-Sang Sim Wan Heo Jun-Ho Kim |
| author_facet | Song Park Kyu-Sang Sim Wan Heo Jun-Ho Kim |
| author_sort | Song Park |
| collection | DOAJ |
| description | Coumestrol, a phytoestrogen compound found in various plants, has been shown to act as a potent estrogen receptor (ER) agonist, with a higher binding affinity for ERβ than for ERα. However, there is currently limited information regarding its beneficial effects in postmenopausal disorders and its ER-mediated mechanisms. Herein, we investigated the effects of coumestrol (subcutaneous or oral treatment) on metabolic dysfunction in ovariectomized (OVX) mice fed a high-fat diet, in comparison with the effects of 17β-estradiol (E2) replacement. Coumestrol was administered daily at a dose of 5 mg/kg for 10 weeks. Coumestrol treatment through the subcutaneous route stimulated uterine growth in OVX mice at a level lower than that of E2. E2 and coumestrol prevented body fat accumulation, adipocyte hypertrophy, and hepatic steatosis, and enhanced voluntary physical activity. Coumestrol showed estrogen-mimetic effects in the regulation of the protein expressions involved in browning of white fat and insulin signaling, including increased hepatic expression of fibroblast growth factor 21. Importantly, the metabolic effects of coumestrol (oral administration at 10 mg/kg for 7 weeks) were mostly abolished following co-treatment with an ERβ-selective antagonist but not with an ERα-selective antagonist, indicating that the metabolic actions of coumestrol in OVX mice are primarily mediated by ERβ. These findings provide important insights into the beneficial effects of coumestrol as a phytoestrogen supplement for the prevention and treatment of postmenopausal symptoms. |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T08:19:10Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-b665d2e77e0b4130a615ed7a1ba5abb32023-11-16T22:31:12ZengMDPI AGNutrients2072-66432023-02-0115495410.3390/nu15040954Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized MiceSong Park0Kyu-Sang Sim1Wan Heo2Jun-Ho Kim3Department of Food Science and Biotechnology, Andong National University, Andong 36729, Republic of KoreaBiomaterials Research Institute, Kyochon F&B, Andong 36618, Republic of KoreaDepartment of Food Science and Engineering, Seowon University, Cheongju 28674, Republic of KoreaDepartment of Food Science and Biotechnology, Andong National University, Andong 36729, Republic of KoreaCoumestrol, a phytoestrogen compound found in various plants, has been shown to act as a potent estrogen receptor (ER) agonist, with a higher binding affinity for ERβ than for ERα. However, there is currently limited information regarding its beneficial effects in postmenopausal disorders and its ER-mediated mechanisms. Herein, we investigated the effects of coumestrol (subcutaneous or oral treatment) on metabolic dysfunction in ovariectomized (OVX) mice fed a high-fat diet, in comparison with the effects of 17β-estradiol (E2) replacement. Coumestrol was administered daily at a dose of 5 mg/kg for 10 weeks. Coumestrol treatment through the subcutaneous route stimulated uterine growth in OVX mice at a level lower than that of E2. E2 and coumestrol prevented body fat accumulation, adipocyte hypertrophy, and hepatic steatosis, and enhanced voluntary physical activity. Coumestrol showed estrogen-mimetic effects in the regulation of the protein expressions involved in browning of white fat and insulin signaling, including increased hepatic expression of fibroblast growth factor 21. Importantly, the metabolic effects of coumestrol (oral administration at 10 mg/kg for 7 weeks) were mostly abolished following co-treatment with an ERβ-selective antagonist but not with an ERα-selective antagonist, indicating that the metabolic actions of coumestrol in OVX mice are primarily mediated by ERβ. These findings provide important insights into the beneficial effects of coumestrol as a phytoestrogen supplement for the prevention and treatment of postmenopausal symptoms.https://www.mdpi.com/2072-6643/15/4/954coumestrolestrogen receptormetabolic dysfunctionpostmenopausal disordersovariectomized mouse |
| spellingShingle | Song Park Kyu-Sang Sim Wan Heo Jun-Ho Kim Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice Nutrients coumestrol estrogen receptor metabolic dysfunction postmenopausal disorders ovariectomized mouse |
| title | Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice |
| title_full | Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice |
| title_fullStr | Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice |
| title_full_unstemmed | Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice |
| title_short | Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice |
| title_sort | protective effects of coumestrol on metabolic dysfunction and its estrogen receptor mediated action in ovariectomized mice |
| topic | coumestrol estrogen receptor metabolic dysfunction postmenopausal disorders ovariectomized mouse |
| url | https://www.mdpi.com/2072-6643/15/4/954 |
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