Serum metabolomics of Indian women with polycystic ovary syndrome using ¹H NMR coupled with a pattern recognition approach

Abstract

Polycystic ovary syndrome (PCOS) is one of the most commonly occurring metabolic and endocrinological disorders affecting women of reproductive age. Metabolomics is an emerging field that holds promise in understanding disease pathophysiology. Recently, a few metabolomics based studies have been attempted in PCOS patients; however, none of them have included patients from the Indian population. The main objective of this study was to investigate the serum metabolomic profile of Indian women with PCOS and compare them with controls. Proton nuclear magnetic resonance (H NMR) was used to first identify the differentially expressed metabolites among women with PCOS from the Eastern region of India during the discovery phase and further validated in a separate cohort of PCOS and control subjects. Multivariate analysis of the binned spectra indicated 16 dysregulated bins in the sera of these women with PCOS. Out of these 16 bins, 13 identified bins corresponded to 12 metabolites including 8 amino acids and 4 energy metabolites. Amongst the amino acids, alanine, valine, leucine and threonine and amongst the energy metabolites, lactate and acetate were observed to be significantly up-regulated in women with PCOS when compared with controls. The remaining 4 amino acids, l-glutamine, proline, glutamate and histidine were down-regulated along with 2 energy metabolites: glucose and 3-hydroxybutyric acid. Our findings showed dysregulations in the expression of different metabolites in the serum of women with PCOS suggesting the involvement of multiple pathways including amino acid metabolism, carbohydrate/lipid metabolism, purine and pyrimidine metabolism and protein synthesis.

Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome

“…Comparisons to previous studies of plasma metabolomics profiles in PCOS are limited by small sample sizes, further diluted by subgroups of BMI and insulin resistance status (14, 15, 21), as well as by different analytic techniques, including less-sensitive nuclear magnetic resonance or nontargeted metabolomics and lack of BMI matching in control groups (13, 14, 16, 18). Most prior studies used the Rotterdam criteria for PCOS and did not restrict study participants to those with the more severe phenotype of oligomenorrhea and anovulation.…”

“…Genomic (9–11), proteomic (11, 12), and metabolomic (13–20) approaches to study the pathogenesis of PCOS have implicated various pathways, including oxidative stress, immune function, and lipid metabolism. However, the activation of these pathways might reflect the high prevalence of obesity in women with PCOS, rather than the underlying pathogenesis of insulin resistance associated with PCOS.…”

Changes in human hepatic metabolism in steatosis and cirrhosis

“…This is important as we would wish to develop diagnostic markers that could ultimately be measured in blood samples rather than tissue specimens. Recent evidence from patients with metabolic disturbance associated with polycystic ovary syndrome confirms that it is indeed possible to detect changes in circulating amino acids and carbohydrates in serum using an NMR approach[50]. In addition, give the important contribution of exercise to management of NAFLD[51] and links between skeletal muscle activity and hepatic metabolism[52,53] it would be important to assess the contribution of sarcopenia in advanced cirrhosis to the hepatic metabolome.…”

Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry

“…PCOS has been reported to be associated with impaired lipid metabolism, and a dramatic increase in fatty acids leads to significant lipid profile changes in PCOS patients. [ 6 15 16 17 ] Fatty acids are an important energy source in the body and provide energy through β-oxidation. Studies have shown that PCOS is related to a decreased fatty acid oxidation capacity, and as a result, excessive fatty acids accumulate in the body causing lipotoxicity.…”

“…Metabolomics is a powerful tool for identifying useful biomarkers in the diagnosis of PCOS and for studying its pathogenesis. Metabolomic studies of PCOS plasma samples have been performed using hydrogen-1 nuclear magnetic resonance,[ 5 6 ] gas chromatography-mass spectrometry (GC-MS),[ 7 ] and liquid chromatography-mass spectrometry (LC-MS). [ 8 ] Multiple metabolic disorders have been observed in PCOS, including the metabolism of steroid hormones, carbohydrates, amino acid, and lipids.…”