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Insulin Resistance and Lipotoxicity in PCOS: Causes and Consequences

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Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome is a common endocrinopathy of unclear etiology. The cardinal feature of the syndrome is hyperandrogenism. However, it is also highly associated with metabolic disorders that have in common the development of insulin resistance. Despite the evidences in literature, the exact roles of insulin resistance and associated compensatory hyperinsulinemia for hyperandrogenism of PCOS are still debated. The existence of non-insulin-resistant PCOS phenotype in a subset of women with typical hyperandrogenism suggests that insulin resistance is not a requisite for the development of this syndrome. Nevertheless, several evidences suggest that impairment in insulin signaling may be implicated in androgen overproduction at the level of androgen producing organs. After a short historical reminder, this chapter will first address in vivo studies assessing insulin action in PCOS women. We will focus on the main results describing the effects of insulin resistance on hyperandrogenism in PCOS. We will then discuss the different insulin signaling anomalies occurring in both metabolic and mitogenic insulin signaling pathways. In addition, we will describe how these signaling dysfunctions may hypothetically influence androgen synthesis in these women. Finally, we will discuss the lipotoxicity theory. We will describe how tissue fatty acid overflow could lead to the development of insulin resistance in PCOS, as it does in other conditions such as type 2 diabetes. More importantly, we will present recent literature suggesting potential direct effects of lipotoxicity on androgen production and address potential underlying mechanisms. Through this chapter, we will discuss whether insulin resistance may be the main cause of hyperandrogenism in PCOS or whether it could be the consequence of an upstream dysfunction, namely lipotoxicity.

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Authors and Affiliations

  1. Program of Physiology (Endocrinologie), Université de Sherbrooke, 3001, 12th Ave North, Sherbrooke, QC, Canada, J1H 5N4

    Sylvain Bellanger M.Sc.

  2. Division of Endocrinology, Department of Medicine, Université de Sherbrooke, 3001, 12th North Avenue, Sherbrooke, QC, Canada, J1H 5N4

    Marie-Claude Battista Ph.D. & Jean-Patrice Baillargeon M.D., M.Sc.

Authors
  1. Sylvain Bellanger M.Sc.
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  2. Marie-Claude Battista Ph.D.
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  3. Jean-Patrice Baillargeon M.D., M.Sc.
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Corresponding author

Correspondence to Jean-Patrice Baillargeon M.D., M.Sc. .

Editor information

Editors and Affiliations

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine Program for Polycystic Ovary Syndrome Yale Reproductive Endocrinology, New Haven, Connecticut, USA

    Lubna Pal

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Bellanger, S., Battista, MC., Baillargeon, JP. (2014). Insulin Resistance and Lipotoxicity in PCOS: Causes and Consequences. In: Pal, L. (eds) Polycystic Ovary Syndrome. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8394-6_7

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  • DOI: https://doi.org/10.1007/978-1-4614-8394-6_7

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