Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have a high prevalence of obesity, insulin resistance (IR), increased blood pressure (BP), and activation of the reni...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2576 |
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| author | Jacob E. Pruett Edgar D. Torres Fernandez Steven J. Everman Ruth M. Vinson Kacey Davenport Madelyn K. Logan Stephanie A. Ye Damian G. Romero Licy L. Yanes Cardozo |
| author_facet | Jacob E. Pruett Edgar D. Torres Fernandez Steven J. Everman Ruth M. Vinson Kacey Davenport Madelyn K. Logan Stephanie A. Ye Damian G. Romero Licy L. Yanes Cardozo |
| author_sort | Jacob E. Pruett |
| collection | DOAJ |
| description | Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have a high prevalence of obesity, insulin resistance (IR), increased blood pressure (BP), and activation of the renin angiotensin system (RAS). Effective evidence-based therapeutics to ameliorate the cardiometabolic complications in PCOS are lacking. The sodium-glucose cotransporter-2 (SGLT2) inhibitor Empagliflozin (EMPA) reduces BP and hyperglycemia in type 2 diabetes mellitus. We hypothesized that hyperandrogenemia upregulates renal SGLT2 expression and that EMPA ameliorates cardiometabolic complications in a hyperandrogenemic PCOS model. Four-week-old female Sprague Dawley rats were treated with dihydrotestosterone (DHT) for 90 days, and EMPA was co-administered for the last three weeks. DHT upregulated renal SGLT2, SGLT4, and GLUT2, but downregulated SGLT3 mRNA expression. EMPA decreased DHT-mediated increases in fat mass, plasma leptin, and BP, but failed to decrease plasma insulin, HbA1c, or albuminuria. EMPA decreased DHT-mediated increase in renal angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), and angiotensin II type 1 receptor (AGT1R) mRNA and protein expression. In summary, SGLT2 inhibition proved beneficial in adiposity and BP reduction in a hyperandrogenemic PCOS model; however, additional therapies may be needed to improve IR and renal injury. |
| first_indexed | 2024-03-09T05:32:31Z |
| format | Article |
| id | doaj.art-a3aafdc791b048f99119bfa1baf6ac9e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:32:31Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a3aafdc791b048f99119bfa1baf6ac9e2023-12-03T12:31:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225257610.3390/ijms22052576Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary SyndromeJacob E. Pruett0Edgar D. Torres Fernandez1Steven J. Everman2Ruth M. Vinson3Kacey Davenport4Madelyn K. Logan5Stephanie A. Ye6Damian G. Romero7Licy L. Yanes Cardozo8Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USAPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have a high prevalence of obesity, insulin resistance (IR), increased blood pressure (BP), and activation of the renin angiotensin system (RAS). Effective evidence-based therapeutics to ameliorate the cardiometabolic complications in PCOS are lacking. The sodium-glucose cotransporter-2 (SGLT2) inhibitor Empagliflozin (EMPA) reduces BP and hyperglycemia in type 2 diabetes mellitus. We hypothesized that hyperandrogenemia upregulates renal SGLT2 expression and that EMPA ameliorates cardiometabolic complications in a hyperandrogenemic PCOS model. Four-week-old female Sprague Dawley rats were treated with dihydrotestosterone (DHT) for 90 days, and EMPA was co-administered for the last three weeks. DHT upregulated renal SGLT2, SGLT4, and GLUT2, but downregulated SGLT3 mRNA expression. EMPA decreased DHT-mediated increases in fat mass, plasma leptin, and BP, but failed to decrease plasma insulin, HbA1c, or albuminuria. EMPA decreased DHT-mediated increase in renal angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), and angiotensin II type 1 receptor (AGT1R) mRNA and protein expression. In summary, SGLT2 inhibition proved beneficial in adiposity and BP reduction in a hyperandrogenemic PCOS model; however, additional therapies may be needed to improve IR and renal injury.https://www.mdpi.com/1422-0067/22/5/2576polycystic ovary syndromeandrogensobesityrenin-angiotensin systemblood pressuresodium glucose cotransporter-2 |
| spellingShingle | Jacob E. Pruett Edgar D. Torres Fernandez Steven J. Everman Ruth M. Vinson Kacey Davenport Madelyn K. Logan Stephanie A. Ye Damian G. Romero Licy L. Yanes Cardozo Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome International Journal of Molecular Sciences polycystic ovary syndrome androgens obesity renin-angiotensin system blood pressure sodium glucose cotransporter-2 |
| title | Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome |
| title_full | Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome |
| title_fullStr | Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome |
| title_full_unstemmed | Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome |
| title_short | Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome |
| title_sort | impact of sglt 2 inhibition on cardiometabolic abnormalities in a rat model of polycystic ovary syndrome |
| topic | polycystic ovary syndrome androgens obesity renin-angiotensin system blood pressure sodium glucose cotransporter-2 |
| url | https://www.mdpi.com/1422-0067/22/5/2576 |
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