Theaflavins in black tea ameliorate high-fat diet-induced obesity and inflammation via gut microbiota, AMPK-mediated metabolism, and NF-κB pathway.

Background: Obesity is typically identified by a high body mass index. Chronic inflammation is a central characteristic of obesity, contributing to many complications. The unrelenting rise in obesity and inflammation has been a global crisis. Due to the weight loss effects of black tea and anti-inflammatory effect of polyphenols, Theaflavins (TFs), the major bioactive polyphenols of black tea, may provide new strategies against obesity and inflammation.

Purpose: This study aimed to investigate the potential regulatory roles and the underlying molecular mechanism of TFs on obesity and obesity-related inflammation.

Study design: Animal experiments were performed using high-fat diet induced obese SD rats. TFs were orally administered at doses of 25, 50, and 100 mg·kg⁻¹ for 8 consecutive weeks. The rats' weight and length were recorded. The blood, liver, epididymal fat pads, colon, interscapular adipose tissue, and feces were collected and stored.

Methods: TFs' effects on obesity and inflammation were evaluated by body weight (daily observation) and inflammatory cytokines (ELISA). The lipid deposition and hepatic function was examined using biochemical assessment and histopathological analysis. AMPK-mediated metabolism assessed by Western blotting (WB), immunohistochemistry, and qRT-PCR. The intestinal barrier integrity was evaluated by biochemical assessment, histopathological analysis, WB, qRT-PCR, and immunofluorescence staining. Gut microbiota and fecal metabolites were using 16S rRNA sequencing and LC-MS/MS analysis, respectively.

Results: TFs exerted protective effects by mitigating body weight, lipid deposition, and immune response in the whole body, adipose tissues, and colon. The underlying mechanism was associated with the gut microbiota, AMPK-mediated metabolism, and NF-κB pathway. Specifically, TFs promoted the potential probiotics (Alistipes, Akkermansia, Coprococcus, NK4A214_group, Collinsella, and Rikenellaceae_RC9_gut_group) and regulated metabolic pathway (starch and sucrose metabolism, α-linolenic acid metabolism, and glycine‑serine-threonine metabolism), thereby inhibiting TRL4/MyD88/NF-κB pathway and protecting the intestinal barrier. Moreover, TFs activated the AMPK/SREBP-1 pathway and AMPK/SIRT1/PGC-1α/UCP1 pathway to mitigate the lipid metabolism and energy metabolism, respectively.

Conclusion: We have innovatively demonstrated for the first time that TFs could alleviate the obesity and systemic inflammation via the modulation of gut microbiota and AMPK-mediated metabolism in HFD-fed rats. The impacts on white adipose tissue browning and thermogenic activity of brown adipose tissue of theaflavins firstly proposed a potential mechanism underlying the protection of theaflavins through the gut microbiota-liver/adipose tissue axis. These findings provide new sights on the bioactive ingredients through which black tea modulates obesity and the underlying mechanism.