Quercetin ameliorates autophagy in alcohol liver disease associated with lysosome through mTOR-TFEB pathway

Abstract

This study aimed to investigate the effects of quercetin that is natural functional component in food on lysosome damage-mediated autophagy dysfunction in ALD and its possible underlying mechanisms. The C57BL/6J mice were divided into four groups and pair-fed with either regular or ethanol-containing Lieber De Carli liquids diets for 15 weeks. Quercetin was received by gavage. According to the purpose of experiments, primary hepatocytes were pretreated with various pharmacological reagents. Results showed that quercetin alleviated chronic ethanol consumption induced liver injury and autophagic flux suppression. Quercetin decreased the abnormal LC3-II and p62 accumulation and increased the expression of LAMP1, LAMP2 and Rab7. Besides, quercetin reversed the inhibition of TFEB nuclear translocation incited by ethanol and exhibited similar effect to Torin 1 (mTOR activity inhibitor) which could promote TFEB nuclear translocation. Thus, regulating mTOR-TFEB pathway may be a major mechanism of quercetin for ameliorating lysosomal autophagy dysfunction induced by ethanol.

Keywords

• Quercetin
• Ethanol
• Lysosome
• Autophagy flux
• TFEB
• mTOR