Dark tea has great potential in regulating glycolipid metabolism, and theabrownin (TB) is considered to be the characteristic and bioactive constituent of dark tea. This study evaluated the ability of TB1 (fermented for 7 days) and TB2 (fermented for 14 days) isolated from dark tea to reverse insulin resistance (IR) in HepG2 cells. The results indicated that TB significantly ameliorated oxidative stress by improving mitochondrial function. In addition, TB improved glycogen synthesis and glucose consumption, and inhibited gluconeogenesis and fatty acid synthesis, by regulating GSK3β (Glycogen synthase kinase 3β), G6Pase (Glucose-6-phosphatase), GCK (Glucokinase), PEPCK1 (Phosphoenolpyruvate carboxy kinase 1), SREBP-1C (sterol regulatory element-binding protein 1C), FASN (fatty acid synthase), and ACC (Acetyl-CoA carboxylase). Additionally, the results of Western blot and real-time PCR experiments demonstrated that TB modulated glucolipid metabolism through the IRS-1 (Insulin receptor substrate 1)/PI3K (phosphatidylinositol-3 kinase)/Akt (protein kinase B) signaling pathway. Treatment with the PI3K inhibitor demonstrated a favorable correlation between PI3K activation and TB action on glycolipid metabolism. Notably, we observed that TB2 had a greater effect on improving insulin resistance compared with TB1, which, due to its prolonged fermentation time, increased the degree of oxidative polymerization of TB.

Pyranoanthocyanins exhibit greater bioactivity compared to monomeric anthocyanins, yet the lipid-lowering effects of pyranoanthocyanin Vitisin A, a primary derivative found in aged red wines, have not been extensively studied in vivo. This study evaluated the triglyceride-lowering effects of Vitisin A and its anthocyanin counterpart Cyanidin-3-O-glucoside (C3G) in both free fatty acid -induced HepG2 cells and high-fat diet-fed ApoE^-/- mice, with a focus on their roles in lipid metabolism. In vitro, Vitisin A significantly reduced triglyceride levels and lipid accumulation in HepG2 cells compared to C3G at equivalent concentrate. In vivo, dietary supplementation with 100 mg/kg of Vitisin A reduced body weight gain and plasma triglyceride levels by 19.6% and 29.5%, respectively, whereas no significant effects were observed with C3G. Mechanistically, Vitisin A markedly inhibited hepatic de novo lipogenesis (DNL) by activating the AMPK/ACC signaling pathway and downregulating FASN expression. Concurrently, Vitisin A enhanced fatty acid β-oxidation more robustly than C3G by upregulating CPT-1A via AMPK/SIRT1/PGC-1α and PPAR-α/PGC-1α pathways. Both Vitisin A and C3G driving peroxisomal β-oxidation of very-long-chain fatty acids. In summary, Vitisin A demonstrated superior triglyceride-lowering effects compared to C3G, primarily through dual mechanisms of inhibiting hepatic DNL and enhancing fatty acid β-oxidation.