Cai Xiaqiang, Liu Zenghui, Dong Xu, Wang Ying, Zhu Luwei, Li Mengli, Xu Yan
State Key Laboratory of Tea Plant Biology and Utilization/Key Laboratory of Tea Biology and Tea Processing of Ministry of Agriculture/Anhui Provincial Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, China.
International Joint Laboratory on Tea Chemistry and Health Effects of Ministry of Education, Hefei, China.
Food Funct. 2021 Oct 19;12(20):9922-9931. doi: 10.1039/d1fo01966j.
Theaflavins (TFs) are the characteristic components of black tea and have been widely acknowledged for their health benefits. The current study aimed to investigate the effects and mechanism of TFs, TF1, TF2a and TF3 on glycolipid metabolism in obese mice induced by a high-fat diet (HFD). Mice were randomly divided into seven groups ( = 8 per group) as follows: low-fat diet (LFD), HFD, HFD + metformin (Met, 100 mg kg d), HFD + TFs (TFs, 200 mg kg d), HFD + TF1 (TF1, 100 mg kg d), HFD + TF2a (TF2a, 100 mg kg d), and HFD + TF3 (TF3, 100 mg kg d). All groups were studied for 9 weeks continuously. The levels of serum glucose, insulin, TC, TG, LDL and HLD in the plasma, lipid accumulation in the liver, and injury of the liver were investigated. In addition, the effects of TFs and their monomers on the SIRT6/AMPK/SREBP-1/FASN pathway were also evaluated. The results showed that oral administration of TFs, TF1, TF2a and TF3 not only dramatically suppressed weight gain, reduced blood glucose level, and ameliorated insulin resistance but also obviously lowered the levels of serum TC, TG and LDL, suppressed the activities of ALT and AST, and ameliorated hepatic damage in mice fed a HFD when compared to the HFD group. Western blot analysis showed that TFs, TF1, TF2a and TF3 treatments increased the expression of SIRT6 and suppressed the expression levels of SREBP-1 and FASN significantly in mice fed a HFD as compared to the HFD group. The phosphorylation of AMPK in mice fed a HFD was obviously elevated by TF2a and TF3 when compared to the HFD group. These results proved for the first time that TF1, TF2a and TF3 improved the glucolipid metabolism of mice fed a HFD, and activated the SIRT6/AMPK/SREBP-1/FASN signaling pathway to inhibit the synthesis and accumulation of lipids in the liver to ameliorate obesity in mice fed a HFD. These findings indicate that TFs, TF1, TF2a and TF3 as the main functional components of black tea might potentially be used as a food additive for improving glycolipid metabolism and ameliorating obesity, and TF3 may be the best choice.
茶黄素（TFs）是红茶的特征性成分，其对健康的益处已得到广泛认可。本研究旨在探讨TFs、TF1、TF2a和TF3对高脂饮食（HFD）诱导的肥胖小鼠糖脂代谢的影响及其机制。将小鼠随机分为七组（每组n = 8），如下：低脂饮食（LFD）组、HFD组、HFD +二甲双胍（Met，100 mg·kg⁻¹·d⁻¹）组、HFD + TFs（TFs，200 mg·kg⁻¹·d⁻¹）组、HFD + TF1（TF1，100 mg·kg⁻¹·d⁻¹）组、HFD + TF2a（TF2a，100 mg·kg⁻¹·d⁻¹）组和HFD + TF3（TF3，100 mg·kg⁻¹·d⁻¹）组。所有组连续研究9周。检测血浆中血清葡萄糖、胰岛素、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）水平、肝脏脂质蓄积情况以及肝脏损伤情况。此外，还评估了TFs及其单体对SIRT6/AMPK/SREBP-1/FASN通路的影响。结果表明，与HFD组相比，口服TFs、TF1、TF2a和TF3不仅显著抑制体重增加、降低血糖水平、改善胰岛素抵抗，还明显降低血清TC、TG和LDL水平，抑制谷丙转氨酶（ALT）和谷草转氨酶（AST）活性，改善HFD喂养小鼠的肝损伤。蛋白质免疫印迹分析表明，与HFD组相比，TFs、TF1、TF2a和TF3处理可增加HFD喂养小鼠中SIRT6的表达，并显著抑制SREBP-1和脂肪酸合酶（FASN）的表达水平。与HFD组相比，TF2a和TF3可明显提高HFD喂养小鼠中AMPK的磷酸化水平。这些结果首次证明TF1、TF2a和TF3可改善HFD喂养小鼠的糖脂代谢，激活SIRT6/AMPK/SREBP-1/FASN信号通路，抑制肝脏脂质合成和蓄积，从而改善HFD喂养小鼠的肥胖状况。这些发现表明，TFs、TF1、TF2a和TF3作为红茶的主要功能成分，可能有潜力用作改善糖脂代谢和缓解肥胖的食品添加剂，其中TF3可能是最佳选择。
