Mechanism of Dark Tea Water Extract in Regulating Autophagy in Non-Alcoholic Fatty Liver via the AMPK/mTOR Signaling Pathway
This study aimed to investigate the intricate mechanisms underlying the modulatory effects of Anhua dark tea on autophagy to ameliorate steatosis induced by a high-fat and high-sucrose diet (HFHS) in mice with non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were divided into different groups, including a normal group, a model group, a Western medicine group (10 mg·kg-1), and various doses of dark tea groups (0.75, 1.5, 3.0 g·kg-1). The therapeutic regimen was administered concurrently with the modeling process for a duration of 10 weeks using the HFHS-induced NAFLD model. At the end of the experiment, liver indices, blood lipids, liver function, liver pathology indicators, autophagy markers, and expression levels of key genes in the autophagy-related signaling pathway were assessed. Comparative analyses with the normal group revealed significant increases in liver index and levels of serum cholesterol (CHO), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as a substantial reduction in high-density lipoprotein cholesterol (HDL-C) levels in the model group. The liver of the mice exhibits signs of steatosis, characterized by an abundance of lipid droplets of different sizes. Protein expression analysis reveals a marked decrease in the levels of microtubule-associated protein light-chain-3B (LC3B), Bcl-2-interacting coiled-coil protein 1 (Beclin1), and phosphorylated adenosine monophosphate-activated protein kinase/adenosine monophosphate-activated protein kinase (p-AMPK/AMPK). Conversely, there was a significant increase in the levels of sequestosome-1 (p62) and phosphorylated mammalian target of rapamycin/mammalian target of rapamycin (p-mTOR/mTOR). Compared to the model group, gavage with dark tea decreased the liver index, serum levels of CHO, TG, LDL-C, AST, ALT, p62, and p-mTOR/mTOR in NAFLD mice, and increased serum HDL-C, along with LC3B, Beclin1, and p-AMPK/AMPK protein levels. The improvements were confirmed by tissue staining results and observations using transmission electron microscopy. In summary, our findings suggest that dark tea, by activating the AMPK/mTOR signaling pathway, may regulate autophagy, thereby alleviating hepatic steatosis and improving non-alcoholic fatty liver disease (NAFLD).
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