Chen Peng, Ni Sha, Liu Qi-Fang, Ou-Yang Ling
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Front Nutr. 2024 Oct 23;11:1434648. doi: 10.3389/fnut.2024.1434648. eCollection 2024.
Polycystic Ovary Syndrome (PCOS) represents a complex endocrine disorder characterized by a significant interplay with metabolic dysfunction and obesity. This research endeavors to elucidate the causal dynamics among plasma metabolites, proteins, and PCOS, alongside Body Mass Index (BMI), to pinpoint prospective therapeutic interventions.
This investigation employed Mendelian randomization (MR) analyses combined with data derived from the National Health and Nutrition Examination Survey (NHANES) to explore the relationships between 1,400 plasma metabolites and PCOS, factoring in BMI adjustments. Additionally, the study examined the influence of plasma proteins and performed a retrospective cross-sectional analysis focusing on retinol consumption and testosterone levels.
MR analyses showed metabolite Glycosyl-N-(2-hydroxynervonoyl)-sphingosine (GNS) and protein Keratin 19 (KRT19) were identified as significant markers in the context of PCOS and BMI adjustments. A Phenome-Wide Association Study (PheWAS) underscored the linkage between KRT19 and BMI, while gene-drug interaction findings demonstrated a connection between KRT19 and retinol. Analysis for NHANES data disclosed a negative correlation between retinol intake and testosterone levels, particularly within normal weight and obese cohorts, suggesting the feasibility of dietary interventions for PCOS management.
The study sheds light on the intricate interactions between plasma metabolites, proteins, and PCOS, considering BMI variations, and highlights KRT19 protein as a promising therapeutic target. The outcomes support the integration of retinol consumption into dietary strategies to regulate testosterone levels and potentially alleviate PCOS symptoms, underscoring the necessity for personalized nutritional and therapeutic approaches in the effective management of PCOS.
多囊卵巢综合征(PCOS)是一种复杂的内分泌紊乱疾病,其特征是与代谢功能障碍和肥胖之间存在显著的相互作用。本研究旨在阐明血浆代谢物、蛋白质和PCOS之间的因果动态关系,以及与体重指数(BMI)的关系,以确定潜在的治疗干预措施。
本研究采用孟德尔随机化(MR)分析,并结合来自美国国家健康与营养检查调查(NHANES)的数据,探讨1400种血浆代谢物与PCOS之间的关系,并考虑BMI调整因素。此外,该研究还检测了血浆蛋白的影响,并对视黄醇摄入量和睾酮水平进行了回顾性横断面分析。
MR分析显示,在PCOS和BMI调整的背景下,代谢物糖基-N-(2-羟基神经酰胺)-鞘氨醇(GNS)和蛋白质角蛋白19(KRT19)被确定为显著标志物。全表型关联研究(PheWAS)强调了KRT19与BMI之间的联系,而基因-药物相互作用研究结果表明KRT19与视黄醇之间存在关联。对NHANES数据的分析揭示了视黄醇摄入量与睾酮水平之间的负相关,特别是在正常体重和肥胖人群中,这表明饮食干预对PCOS管理具有可行性。
该研究揭示了血浆代谢物、蛋白质和PCOS之间复杂的相互作用,并考虑了BMI的变化,突出了KRT19蛋白作为一个有前景的治疗靶点。研究结果支持将视黄醇摄入纳入饮食策略,以调节睾酮水平并可能缓解PCOS症状,强调了个性化营养和治疗方法在有效管理PCOS中的必要性。