PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Insulin action and lipotoxicity in the development of polycystic ovary syndrome: A review1

Abstract

Polycystic ovary syndrome (PCOS) is a common condition affecting women of reproductive age. This disorder is characterized by hyperandrogenism and anovulation and is frequently associated with comorbidities such as infertility, metabolic syndrome, type 2 diabetes, and cardiovascular risk factors. Although the causes of PCOS are unknown, this review focuses on the most accepted theory involving insulin action but will also elaborate on a novel concept: the role of lipotoxicity in the development of androgen overproduction, in addition to its known role in insulin resistance. This review will also shed a spotlight on 2 drugs that target lipotoxicity and are, therefore, known or promising for the treatment of PCOS manifestations: peroxisome proliferator-activated receptor γ and angiotensin II type 2 receptor agonists. This paper, therefore, emphasizes the need to further explore the pathophysiology of PCOS and particularly the role of lipotoxicity. Indeed, this new mechanism deserves attention to develop therapeutic approaches that will directly target the root of this condition and not only bandage its associated consequences.

Comparison of intra-ovarian metabolic environment between women with or without PCOS undergoing in vitro fertilization

“…It is therefore likely that the higher ovarian exposure to lipids found in women with PCOS may contribute to their increased androgen production (36). Several mechanisms have been proposed to explain lipotoxicity (37), including the accumulation of toxic lipid metabolites such as diacylglycerol and ceramides (38, 39), which are produced when the cell's ability to metabolize NEFA is exceeded and/or defective. Although our study was not designed to provide insight into the presence of these mediators in follicular uid, we found indicators of ine cient mitochondrial fatty acid oxidation in women with PCOS.…”

Lifestyle and Food Habits Impact on Chronic Diseases: Roles of PPARs

“…The pro-inflammatory state of obesity promotes IR and atherogenesis [231], thus in PCOS, the development of obesity induces a decline in insulin sensitivity [226]. Moreover, in PCOS women an imbalance between pro-inflammatory and anti-inflammatory mediators is associated with a systemic low-grade inflammation [232,233,234]; the lipotoxicity could be the key of PCOS pathogenesis [235]. The etiology of this chronic disease is still not fully understood [236]; it is probably due to a combination of genetic and environmental factors.…”