Metabolic Syndrome and PCOS: Pathogenesis and the Role of Metabolites

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases among women of reproductive age and is associated with many metabolic manifestations, such as obesity, insulin resistance (IR) and hyperandrogenism. The underlying pathogenesis of these metabolic symptoms has not yet been fully elucidated. With the application of metabolomics techniques, a variety of metabolite changes have been observed in the serum and follicular fluid (FF) of PCOS patients and animal models. Changes in metabolites result from the daily diet and occur during uncommon physiological routines. However, some of these metabolite changes may provide evidence to explain possible mechanisms and new approaches for prevention and therapy. This article reviews the pathogenesis of PCOS metabolic symptoms and the relationship between metabolites and the pathophysiology of PCOS. Furthermore, the potential clinical application of some specific metabolites will be discussed.

Follicular Fluid: A Powerful Tool for the Understanding and Diagnosis of Polycystic Ovary Syndrome

“…Polycystic ovary syndrome (PCOS) is one of the prevailing gynecological and endocrine and metabolic disorders among women of reproductive age, representing one of the leading causes of anovulatory infertility. According to the criteria in practice, this disease affects 5% to 20% of women worldwide [ 1 , 2 , 3 , 4 ].…”

“…Within obese PCOS women, impaired glucose tolerance and type 2 diabetes are two common features, both being diagnosed by OGTT [ 8 , 21 ]. IR, common in PCOS patients, increases the risk of metabolic syndrome and cardiovascular morbidity, and it generates higher glucose concentrations [ 3 , 33 ]. PCOS women that present obesity, a family history of type 2 diabetes, IR, or beta-cell dysfunction have high probabilities of developing diabetes [ 20 , 21 , 22 , 34 , 35 ].…”

Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open

“…The key pathogenetic factors include hyperandrogenemia, subclinical inflammation, and defective insulin signaling [ 16 ]. It has been evidenced that up to 50–80% of women with PCOS are diagnosed with insulin resistance [ 10 , 12 , 17 ]. Hyperinsulinemia is responsible for metabolic and cardiovascular complications [ 18 ], as well as decreasing sex hormone binding globulin (SHBG) production in the liver (resulting in an increase of free and bioactive androgen levels in the circulation) and potentiating the luteinizing hormone (LH)-dependent effect on the ovarian cells, leading to the enhanced synthesis of androgens [ 5 ].…”

“…Recent studies have also focused on the dysregulation of intestinal microflora in PCOS individuals [ 21 , 22 , 23 ] and abnormalities in the level of metabolites generated by bacteria, such as bile acids (BAs), short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), ceramides, and trimethylamine N-oxide (TMAO) [ 17 ]. Interestingly, it has been shown that an imbalance in the gut microbiota in women with PCOS may be conducive to dysfunction of the immune system, development of chronic low-grade inflammation, and enhancement of the synthesis of proinflammatory cytokines, all of which may lead to defective signaling through insulin receptors [ 21 , 23 ].…”

“…Furthermore, there is also growing scientific interest in the study of microRNA (miRNA), which regulates gene expression at the post-transcriptional level and has been also shown to be altered in PCOS individuals [ 17 , 24 ].…”