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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1449178

The novel TFEB agonist desloratadine ameliorates hepatic steatosis by activating the autophagylysosome pathway

Provisionally accepted
Jieru Lin Jieru Lin 1Chunhuan Huang Chunhuan Huang 1Jingye Zhao Jingye Zhao 1Lu Li Lu Li 1Zhenwei Wu Zhenwei Wu 1Tingyu Zhang Tingyu Zhang 1Yuyin Li Yuyin Li 1Wei Li Wei Li 2Baoqiang Guo Baoqiang Guo 3Zhenxing Liu Zhenxing Liu 1Aipo Diao Aipo Diao 1*
  • 1 Tianjin University of Science and Technology, Tianjin, China
  • 2 Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
  • 3 Manchester Metropolitan University, Manchester, North West England, United Kingdom

The final, formatted version of the article will be published soon.

    The autophagy-lysosome pathway plays an essential role in promoting lipid catabolism and preventing hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). Transcription factor EB (TFEB) enhances the autophagy-lysosome pathway by regulating the expression of genes related to autophagy and lysosome biogenesis. Therefore, targeting TFEB provides a novel strategy for the treatment of lipid metabolic diseases. In this study, the antiallergic drug desloratadine was screened and identified as a novel TFEB agonist. Desloratadine effectively induced translocation of TFEB to the nucleus and promoted autophagy and lysosome biogenesis. Desloratadine-induced TFEB activation was dependent on AMPK rather than mTORC1. Moreover, desloratadine treatment enhanced clearance of lipid droplets in cells induced by fatty acids oleate and palmitate. Furthermore, high-fat diet (HFD) induced obesity mouse model experiments indicated treatment with desloratadine markedly reduced the body weight of HFD-fed mice, as well as the levels of hepatic triglycerides and total cholesterol, serum glutamic pyruvic transaminase and glutamic-oxaloacetic transaminase. Oil red O staining showed the liver fat was significantly reduced after desloratadine treatment, and H&E staining analysis demonstrated hepatocellular ballooning was improved. In addition, autophagy and lysosomal biogenesis was stimulated in the liver of desloratadine treated mice. Altogether, these findings demonstrate desloratadine ameliorates hepatic steatosis through activating the TFEB-mediated autophagy-lysosome pathway, thus desloratadine has an exciting potential to be used to treat fatty liver disease.

    Keywords: Desloratadine, TFEB agonist, Autophagy, Lysosome, Hepatic Steatosis, Obesity

    Received: 14 Jun 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 Lin, Huang, Zhao, Li, Wu, Zhang, Li, Li, Guo, Liu and Diao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Aipo Diao, Tianjin University of Science and Technology, Tianjin, 300222, China

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