Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is a common and significant condition associated with hyperandrogenism, infertility, low quality of life, and metabolic comorbidities. One possible explanation of PCOS development is cellular dysfunction induced by nonesterified fatty acids (NEFAs), that is, lipotoxi...
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Wiley
2018-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2018/4315413 |
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| author | Alexandre Connolly Samuel Leblanc Jean-Patrice Baillargeon |
| author_facet | Alexandre Connolly Samuel Leblanc Jean-Patrice Baillargeon |
| author_sort | Alexandre Connolly |
| collection | DOAJ |
| description | Polycystic ovary syndrome (PCOS) is a common and significant condition associated with hyperandrogenism, infertility, low quality of life, and metabolic comorbidities. One possible explanation of PCOS development is cellular dysfunction induced by nonesterified fatty acids (NEFAs), that is, lipotoxicity, which could explain both the hyperandrogenemia and insulin resistance that characterize women with PCOS. The literature suggests that androgen biosynthesis may be induced by overexposure of androgen-secreting tissues to NEFA and/or defective NEFA metabolism, leading to lipotoxic effects. Indeed, lipotoxicity could trigger androgenic hyperresponsiveness to insulin, LH, and ACTH. In most PCOS women, lipotoxicity also causes insulin resistance, inducing compensatory hyperinsulinemia, and may thus further increase hyperandrogenemia. Many approaches aimed at insulin sensitization also reduce lipotoxicity and have been shown to treat PCOS hyperandrogenemia. Furthermore, our group and others found that angiotensin II type 2 receptor (AT2R) activation is able to improve lipotoxicity. We provided evidence, using C21/M24, that AT2R activation improves adipocytes’ size and insulin sensitivity in an insulin-resistant rat model, as well as androgen levels in a PCOS obese rat model. Taken together, these findings point toward the important role of lipotoxicity in PCOS development and of the RAS system as a new target for the treatment of PCOS. |
| format | Article |
| id | doaj-art-b11a8f9fef6142bfb533136a9217fde9 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | International Journal of Endocrinology |
| spelling | doaj-art-b11a8f9fef6142bfb533136a9217fde92025-02-03T06:44:15ZengWileyInternational Journal of Endocrinology1687-83371687-83452018-01-01201810.1155/2018/43154134315413Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary SyndromeAlexandre Connolly0Samuel Leblanc1Jean-Patrice Baillargeon2Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, 3001 12e Avenue Nord, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, CanadaDivision of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, 3001 12e Avenue Nord, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, CanadaDivision of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, 3001 12e Avenue Nord, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, CanadaPolycystic ovary syndrome (PCOS) is a common and significant condition associated with hyperandrogenism, infertility, low quality of life, and metabolic comorbidities. One possible explanation of PCOS development is cellular dysfunction induced by nonesterified fatty acids (NEFAs), that is, lipotoxicity, which could explain both the hyperandrogenemia and insulin resistance that characterize women with PCOS. The literature suggests that androgen biosynthesis may be induced by overexposure of androgen-secreting tissues to NEFA and/or defective NEFA metabolism, leading to lipotoxic effects. Indeed, lipotoxicity could trigger androgenic hyperresponsiveness to insulin, LH, and ACTH. In most PCOS women, lipotoxicity also causes insulin resistance, inducing compensatory hyperinsulinemia, and may thus further increase hyperandrogenemia. Many approaches aimed at insulin sensitization also reduce lipotoxicity and have been shown to treat PCOS hyperandrogenemia. Furthermore, our group and others found that angiotensin II type 2 receptor (AT2R) activation is able to improve lipotoxicity. We provided evidence, using C21/M24, that AT2R activation improves adipocytes’ size and insulin sensitivity in an insulin-resistant rat model, as well as androgen levels in a PCOS obese rat model. Taken together, these findings point toward the important role of lipotoxicity in PCOS development and of the RAS system as a new target for the treatment of PCOS.http://dx.doi.org/10.1155/2018/4315413 |
| spellingShingle | Alexandre Connolly Samuel Leblanc Jean-Patrice Baillargeon Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome International Journal of Endocrinology |
| title | Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome |
| title_full | Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome |
| title_fullStr | Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome |
| title_full_unstemmed | Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome |
| title_short | Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome |
| title_sort | role of lipotoxicity and contribution of the renin angiotensin system in the development of polycystic ovary syndrome |
| url | http://dx.doi.org/10.1155/2018/4315413 |
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