Abstract and Introduction
Abstract
Objective: Polycystic ovary syndrome (PCOS) is a pathophysiological disease affecting reproductive and metabolic indicators. Research has shown that kisspeptin might be involved in the regulation of pituitary hormone secretion and energy metabolism. The aim of this study was to investigate the relationship between serum kisspeptin levels and abnormal metabolism in PCOS.
Methods: Fifty patients with PCOS and 50 control patients were recruited for this study. Serum kisspeptin levels were measured via ELISA. High-performance liquid chromatography-tandem mass spectrometry metabolomics was used to study the changes in serum metabolism between the PCOS and control groups.
Results: Serum kisspeptin levels were significantly elevated in individuals with PCOS compared with those in healthy controls (p = 0.011) and positively correlated with LH, T, FFA, BA, and LEP levels (p < 0.05). Significantly dysregulated expression of several metabolites was observed in the intergroup comparisons of the high-kisspeptin PCOS, low-kisspeptin PCOS, and healthy control groups. These primarily consisted of lipid, amino acid, and carbohydrate metabolites, among which palmitic acid and N-formylkynurenine levels were lower in the high-kisspeptin group than in controls. Metabolite set enrichment analysis was also performed based on metabolites in the KEGG database. The results showed that owing to the differences in kisspeptin concentrations in individuals with PCOS, there was a significant difference in amino acid and pyruvate metabolism.
Conclusions: Kisspeptin could be a potential biomarker for the diagnosis of PCOS and plays an important role in metabolic regulation in individuals with PCOS. In addition, metabolomics provides a promising method for the study of metabolic abnormalities in individuals with PCOS, which might contribute to our understanding of its mechanisms.
Introduction
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects 4%–20% of women of reproductive age worldwide.[1] The condition is characterised by menstrual cycle irregularities, oligo-ovulation, polycystic ovarian morphology, insulin resistance-induced obesity, hyperandrogenism-induced hirsutism, and acne.[2] Many, but not all, women with PCOS exhibit metabolic disturbances, including obesity, insulin resistance, hypertension, dyslipidemia, and endocrine abnormalities.[3] Long-term PCOS increases the risk of gynaecological cancer, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease.[4,5]
Kisspeptin has been proven to be involved in regulating hypothalamic GnRH secretion and energy metabolism. Kisspeptin is encoded by the KISS1 gene, which was originally considered a tumour metastasis-suppressor protein that plays an irreplaceable role in the reproductive endocrine system.[6] Kisspeptin is also a key regulator of the hypothalamic–pituitary–gonadal axis and an important switch in the reproductive system.[7,8] Approximately 50%–70% of women with PCOS display insulin resistance,[9] which is widely considered an important risk factor for developing metabolic syndrome. In addition, circulating kisspeptin directly influences insulin secretion through GPR54.[10,11] Animal data has strongly indicated that kisspeptin plays a role in metabolism, and some in vivo studies have investigated the effect of kisspeptin on human β-cell function and appetite.[12] Some studies have also suggested that kisspeptin might play an important role in the development of ovulation disorders in individuals with PCOS.[13]
Metabolomics, the identification and analysis of metabolites in biological fluids, is an emerging field of research that provides an unbiased approach to identify novel pathways. Metabolomics involves the comprehensive characterisation of metabolites in biological systems and is widely applied for improving disease diagnosis and understanding potential mechanisms, identifying novel drug targets, customising drug treatments, and monitoring therapeutic outcomes.[14] Data in animals strongly suggest that kisspeptin plays a role in metabolism, but its effects on metabolic parameters in vivo in humans are currently unknown.
According to previous in vivo/in vitro study results, the kisspeptin level in women with PCOS was higher than that in a control group. However, there are limited data in the literature with regard to changes in kisspeptin levels and their relationship with metabolic parameters. In this study, based on a metabolomic approach utilising high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology, we explored the role of kisspeptin in serum metabolism in patients with PCOS in the hope of identifying potential metabolic markers for the prognosis and diagnosis of this disease.
Clin Endocrinol. 2023;99(3):315-325. © 2023 Blackwell Publishing
