Gan Jingwen, Chen Jie, Ma Rui-Lin, Deng Yan, Ding Xue-Song, Zhu Shi-Yang, Sun Ai-Jun
National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China.
Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
Int J Endocrinol. 2023 Dec 14;2023:4288004. doi: 10.1155/2023/4288004. eCollection 2023.
Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age, whose clinical characteristics are hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovary, often accompanied by insulin resistance (IR) and metabolic abnormalities. Glucagon-like peptide (GLP)-1 receptor agonists (GLP-1Ra), such as exenatide, can bind to specific receptors on tissues such as the ovaries to improve the clinical phenotype of PCOS, while insulin-sensitizing agents, such as metformin, can also benefit to metabolic abnormalities in PCOS. Liquid chromatography-mass spectrometry (LC/MS) metabolomics revealed differences between the mechanisms of exenatide and metformin treatment of PCOS to some extent.
In this study, 50 obese subjects with PCOS were randomly divided into the exenatide combined with metformin group (COM group, = 28) and the metformin group (MF group, = 22) for 12-week treatment. Before and after, serum samples were subjected to LC/MS analysis.
After treatment, there were 153 named differential metabolites in the COM group and 99 in the MF group. Most phosphatidylcholines (PC) and deoxycholic acid 3-glucuronide (DA3G) were significantly upregulated, while most glycerophosphoethanolamine (PE-NMe2), glycerophosphocholine (GPC), and threonine were downregulated in both groups. Only the decrease of neuromedin B, glutamate, and glutamyl groups and the increase of chenodeoxycholic acid sulfate docosadienoate (22: 2n6), and prostaglandin E2 have been observed in the COM group. In addition, salicylic acid and spisulosine increased and decanoylcarnitine decreased in the MF group. Both groups were enriched in glycerophospholipid, choline, and sphingolipid metabolism, while the COM group was especially superior in the glutamine and glutamate, bile secretion, and amino acid metabolism.
Compared with metformin alone in the treatment of PCOS, the differential metabolites of the exenatide combined with metformin group are more extensive. The COM group may act on the hypothalamic-pituitary-gonadal axis (HPO) and its bypass, regulate multiple metabolism pathways such as phospholipids, amino acids, fatty acids, carnitine, bile acids, and glucose directly or indirectly in obese PCOS patients.
多囊卵巢综合征（PCOS）是育龄期女性最常见的内分泌疾病，其临床特征为高雄激素血症（HA）、排卵功能障碍和多囊卵巢，常伴有胰岛素抵抗（IR）和代谢异常。胰高血糖素样肽（GLP）-1受体激动剂（GLP-1Ra），如艾塞那肽，可与卵巢等组织上的特定受体结合，改善PCOS的临床表型，而胰岛素增敏剂，如二甲双胍，也可改善PCOS的代谢异常。液相色谱-质谱联用（LC/MS）代谢组学在一定程度上揭示了艾塞那肽和二甲双胍治疗PCOS机制的差异。
本研究将50例肥胖PCOS患者随机分为艾塞那肽联合二甲双胍组（COM组，n = 28）和二甲双胍组（MF组，n = 22），进行为期12周的治疗。治疗前后，对血清样本进行LC/MS分析。
治疗后，COM组有153种命名的差异代谢物，MF组有99种。两组中大多数磷脂酰胆碱（PC）和脱氧胆酸3-葡萄糖醛酸苷（DA3G）显著上调，而大多数甘油磷酰乙醇胺（PE-NMe2）、甘油磷酰胆碱（GPC）和苏氨酸下调。COM组仅观察到神经介素B、谷氨酸和谷氨酰基减少，鹅去氧胆酸硫酸二十二碳二烯酸酯（22:2n6）和前列腺素E2增加。此外，MF组中水杨酸和螺旋霉素增加，癸酰肉碱减少。两组均在甘油磷脂、胆碱和鞘脂代谢中富集，而COM组在谷氨酰胺和谷氨酸、胆汁分泌及氨基酸代谢方面尤其突出。
与单用二甲双胍治疗PCOS相比，艾塞那肽联合二甲双胍组的差异代谢物更广泛。COM组可能作用于下丘脑-垂体-性腺轴（HPO）及其旁路，直接或间接调节肥胖PCOS患者的磷脂、氨基酸、脂肪酸、肉碱、胆汁酸和葡萄糖等多种代谢途径。
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