Theaflavins ameliorate obesity through enhanced antioxidant capacity, a suppressed hepatic BCAA degradation pathway, and gut microbiota modulation

Abstract

Obesity and its associated metabolic disorders pose a major global health challenge. Theaflavins (TFs), bioactive polyphenols derived from black tea, have demonstrated potential in alleviating metabolic diseases. This study aimed to investigate the ameliorative effects and underlying mechanisms of TFs on high-fat diet (HFD)-induced obesity from the perspectives of oxidative stress, the branched-chain amino acid (BCAA) degradation pathway, and the gut microbiota. In vitro, TFs exhibited potent free-radical scavenging capacity. In vivo, TFs dose-dependently attenuated HFD-induced weight gain, dyslipidemia and glucose intolerance. Concurrently, TF administration alleviated hepatic steatosis and ultrastructural damage and improved liver function. Importantly, TFs suppressed hepatic oxidative stress and downregulated the HFD-induced overexpression of the valine, leucine, and isoleucine degradation pathway at both mRNA and protein levels (HADH, HMGCL, ACSF3, ACADS, ALDH3A2, and ACAA2). Furthermore, gut microbiota analysis revealed that TFs improved HFD-induced gut dysbiosis, characterized by the enrichment of butyrate-producing genera (e.g., Akkermansia and Gastranaerophilales_norank) and a reduction in the relative abundance of harmful taxa (e.g., Enterococcus and Streptococcus). Correlation analysis integrated these findings, revealing significant associations between the TF-induced microbial shifts, the ameliorated metabolic phenotypes, and the suppressed hepatic BCAA catabolism. Our study demonstrated that the alleviation of obesity by TFs was associated with multifaceted improvements, including enhanced antioxidant capacity, amelioration of dysregulated hepatic BCAA catabolism, and modulation of gut microbial homeostasis, highlighting their potential as a dietary intervention for metabolic diseases.