Schisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway
| Autor: | Li-Shan, Yan, Shuo-Feng, Zhang, Gan, Luo, Brian Chi-Yan, Cheng, Chao, Zhang, Yi-Wei, Wang, Xin-Yu, Qiu, Xiao-Hong, Zhou, Qing-Gao, Wang, Xue-Lan, Song, Si-Yuan, Pan, Yi, Zhang |
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| Rok vydání: | 2022 |
| Předmět: |
TOR Serine-Threonine Kinases
Endocrinology Diabetes and Metabolism Ketone Bodies AMP-Activated Protein Kinases Fatty Acids Nonesterified Diet High-Fat Lipid Metabolism Lignans Cyclooctanes Mice Endocrinology Liver Non-alcoholic Fatty Liver Disease Autophagy Hepatocytes Animals Polycyclic Compounds Signal Transduction |
| Zdroj: | Metabolism. 131:155200 |
| ISSN: | 0026-0495 |
| DOI: | 10.1016/j.metabol.2022.155200 |
| Popis: | Schisandrin B (Sch B), which inhibits hepatic steatosis caused by non-alcoholic fatty liver disease (NAFLD), is one of the most active dibenzocyclooctadienes isolated from Schisandra chinensis (Turcz.) Baill with various pharmacological activities. In this study, the role of Sch B-induced autophagy in lipid-lowering activities of Sch B was examined and the underlying mechanisms were elucidated.Free fatty acid (FFA)-stimulated HepG2 cells and mouse primary hepatocytes (MPHs) and high-fat diet (HFD)-fed mice were used as NAFLD models. The role of Sch B-induced autophagy in lipid-lowering effects of Sch B was assessed using ATG5/TFEB-deficient cells and 3-methyladenine (3-MA)-treated hepatocytes and mice.Sch B simultaneously active autophagy through AMPK/mTOR pathway and decreased the number of lipid droplets in FFA-treated HepG2 cells and MPHs. Additionally, siATG5/siTFEB transfection or 3-MA treatment mitigated Sch B-induced autophagy and activation of fatty acid oxidation (FAO) and ketogenesis in FFA-treated HepG2 cells and MPHs. Sch B markedly decreased hepatic lipid content and activated the autophagy through AMPK/mTOR pathway in HFD-fed mice. However, the activities of Sch B were suppressed upon 3-MA treatment. Sch B upregulated the expression of key enzymes involved in FAO and ketogenesis, which was mitigated upon 3-MA treatment. Moreover, changes in hepatic lipid components and amino acids may be related to the Sch B-induced autophagy pathway.These results suggested that Sch B inhibited hepatic steatosis and promoted FAO by activation of autophagy through AMPK/mTOR pathway. Our study provides novel insights into the hepatic lipophagic activity of Sch B and its potential application in the management of NAFLD. |
| Databáze: | OpenAIRE |
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