Stabilization of hypoxia-inducible factor 1α and regulation of specific gut microbes by EGCG contribute to the alleviation of ileal barrier disorder and obesity

Abstract

Tea polyphenols have a regulatory effect on metabolic-related diseases, however, the underlying mechanism remains elusive. Our study aims to explore the dietary intervention effect of Epigallocatechin gallate (EGCG), the major polyphenol in green tea, on obesity and intestinal barrier disorders in mice fed a high-fat diet. By supplementing with 50 mg kg⁻¹ EGCG, we observed a significant amelioration in body weight gain, fat accumulation, and liver dysfunction. Furthermore, EGCG modulated the HFD-induced metabolomic alterations. In particular, EGCG intervention restored the ileal barrier by enhancing the expression of tight junction proteins and antimicrobial peptides. At the mechanistic level, EGCG treatment stabilized hypoxia-inducible factor 1α (HIF1α) both in vitro and in vivo. Meanwhile, EGCG significantly increased the abundance of Dubosiella and Akkermansia, along with the elevated SCFA contents. These findings suggest that the ability of EGCG to stabilize HIF1α and regulate specific gut microbes is pivotal in mitigating ileal barrier dysfunction and obesity. Moreover, serum metabolomics revealed potential biomarkers following EGCG intervention. This study supports the intake of EGCG or green tea in obesity management and offers a novel perspective for investigating the metabolic regulatory mechanism of other dietary polyphenols.