Abstract
Hyperhomocysteinemia (HHcy) is characterized by disrupted methionine and one-carbon metabolism. Although epigallocatechin gallate (EGCG) can lower homocysteine levels, how it regulates methionine metabolism in vivo, especially at the intestinal level, remains unclear. This study aimed to determine whether EGCG alleviates HHcy by modulating methionine availability. An HHcy model was established in Drosophila melanogaster using a high-methionine diet. The effects of tea extracts and catechins were first evaluated using metabolic and physiological indicators. Methionine metabolism and N-EGCG formation were then characterized using targeted metabolomics and LC-MS/MS. Finally, transcriptomic and epigenetic analyses were performed to examine downstream regulatory changes. Green tea, which contains the highest EGCG level, showed the strongest protection against HHcy. EGCG significantly improved HHcy phenotypes in a dose-dependent manner. It reduced homocysteine levels by approximately 55%. This indicates a strong effect on methionine metabolism. It also significantly extended lifespan. Importantly, EGCG reduced intestinal methionine levels by approximately 58% and promoted the formation of N-EGCG in vivo. These changes were accompanied by recovery of metabolic pathways. Transcriptional and epigenetic patterns were also normalized. EGCG alleviates HHcy by limiting intestinal methionine availability and restoring one-carbon metabolism. This study reveals a gut associated metabolic mechanism. It links dietary polyphenols to systemic metabolic regulation. It also highlights a potential target for dietary intervention of HHcy.
