Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy–lysosomal pathway

• DOI: 10.1016/j.apsb.2021.12.012
• Publication Date: 2021-12-22T07:43:47Z
• Authors: Xiliang Du; Chiara Di Malta; Zhiyuan Fang; Taiyu Shen; Xiaodi Niu; Meng Chen; Bo Jin; Hao Yu; Lin Lei; Wenwen Gao; Yuxiang Song; Zhe Wang; Chuang Xu; Zhijun Cao; Guowen Liu; Xinwei Li
• Keywords: TFEB; Steatosis

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) subsequent impairment the transcription factor EB (TFEB)-mediated autophagy–lysosomal pathway (ALP) implicated in development NAFLD. Accordingly, agents that augment TFEB transcriptional activity may have therapeutic potential against The objective this study was to investigate effects nuciferine, a major active component from lotus leaf, on NAFLD underlying mechanism action. Here we show nuciferine activated ALP alleviated steatosis, livers mice palmitic acid-challenged hepatocytes TFEB-dependent manner. Mechanistic investigation revealed interacts with Ragulator subunit hepatitis B X-interacting protein impairs interaction Rag GTPases, thereby suppressing lysosomal localization mTORC1, which activates TFEB-mediated further ameliorates resistance. Our present results indicate be agent treating regulation mTORC1–TFEB–ALP axis could represent novel pharmacological strategy combat