本研究旨在探索(-)-表没食子儿茶素没食子酸酯(EGCG)预防肥胖相关性早熟的潜在调控途径。对从人体随机对照试验中收集的血浆样本进行了EGCG对肥胖女孩青春期发作影响的回顾性分析。在审判中,参与者服用EGCG胶囊12周。在动物实验中,大鼠分为4组:正常饮食对照组(NC),高脂饮食(HFD)组,NC+EGCG组,HFD+EGCG组。在出生后第27、33和36天收集血液样本以检测性发育指标。通过RT-qPCR和Westernblot检测下丘脑kisspeptin/Kiss1R和神经激肽B(NKB)/NK3R信号的表达。通过免疫组织化学测定评估卵巢NKB蛋白表达。EGCG组的血清NKB水平比安慰剂组低0.599ng/mL[β=-0.599,95%CI:(-1.005,-0.193)],在干预结束时和校正混杂因素后(临床研究)。在动物实验中,EGCG干预能显著延缓HFD大鼠的阴道开放时间。第33天,EGCG干预可显著降低血清NKB,黄体生成素(LH)水平,卵巢NKB蛋白表达,和HFD喂养大鼠的子宫内膜厚度,EGCG干预能显著增加NKB/NK3R的mRNA和蛋白表达。EGCG通过NKB/NK3R信号通路预防肥胖相关性早熟,这可能为EGCG在预防肥胖女孩性早熟中的作用提供了新的见解。
This study aimed to explore the potential regulatory pathways of (-)-epigallocatechin-3-gallate (EGCG) in preventing obesity-related precocious puberty. A retrospective analysis on the impact of EGCG on puberty onset in obese girls was conducted on plasma samples collected from a human randomized controlled trial. In the trial, participants consumed EGCG capsules for 12 weeks. In the animal experiment, rats were divided into four groups: normal diet control (NC) group, high-fat diet (HFD) group, NC+EGCG group, and HFD+EGCG group. Blood samples were collected on postnatal days 27, 33, and 36 to detect sexual development indicators. The hypothalamic expressions of kisspeptin/Kiss1R and neurokinin B (NKB)/NK3R signaling were measured by RT-qPCR and Western blot assay. The ovary NKB protein expression was assessed by immunohistochemical assays. Serum NKB level in the EGCG group was lower than the placebo group by 0.599 ng/mL [β=-0.599, 95% CI: (-1.005, -0.193)], at the end of intervention and after adjusting for confounders (clinical study). In the animal experiment, EGCG intervention could significantly delay the vaginal opening (
VO) time of rats fed with HFD. On day 33, EGCG intervention could significantly reduce serum NKB, luteinizing hormone (LH) levels, ovarian NKB protein expression, and endometrial thickness of HFD-fed rats, while EGCG intervention could remarkably increase mRNA and protein expression of NKB/NK3R. EGCG could prevent obesity-related precocious puberty through NKB/NK3R signaling pathway, which may provide a novel insight into the role of EGCG in preventing precocious puberty in obese girls.