Mechanistic insights into EGCG's preventive effects on obesity-induced precocious puberty through multi-omics analyses

Abstract

Epigallocatechin gallate (EGCG) has demonstrated potential effects on obesity-induced precocious puberty, but the underlying mechanisms remain unclear. Female mice were randomly assigned into control (CON), EGCG-treated (EGCG), high-fat diet (HFD), and HFD with EGCG treatment (HFDEGCG) groups. Key measurements included body weight, vaginal opening time, and serum sex hormone levels. The gut microbiota was analyzed through 16S rRNA sequencing, fecal metabolites were assessed via metabolomics, and the hypothalamic transcriptome was examined using RNA sequencing. EGCG mitigated weight gain and delayed vaginal opening in mice with obesity-induced precocious puberty. Additionally, it reduced serum estradiol levels and decreased the number of mature ovarian follicles in the HFDEGCG group compared to the HFD group. EGCG treatment partially reversed HFD-induced dysbiosis by increasing the abundance of beneficial bacteria such as Akkermansia. Metabolomic analysis revealed significant alterations in tryptophan metabolism, while transcriptome analysis identified genes involved in metabolic pathways. Correlation analyses underscored the importance of the gut–brain axis in mediating EGCG's effects. Overall, EGCG prevents obesity-induced precocious puberty by modulating the gut microbiota, altering metabolic pathways, and regulating hypothalamic gene expression.