TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation
AbstractAutophagy flux deficiency is closely related to the development of hepatic steatosis. Transcription factor E3 (TFE3) is reported to be a crucial gene that regulates autophagy flux and lysosome function. Therefore, we investigated the role of TFE3 in a cell model of hepatic steatosis. We constructed L02 hepatocyte lines that stably over-expressed or knocked down the expression of TFE3. Subsequently, the effects of TFE3 on hepatocellular lipid metabolism were determined by autophagy flux assay, lipid oil red O (ORO) staining, immunofluorescence staining, and mitochondrial β-oxidation assessment. Finally, we analyzed whether peroxisome proliferative activated receptor gamma coactivator 1α (PGC1α) was the potential target gene of TFE3 in the regulation of hepatic steatosis using a chromatin immunoprecipitation (CHIP) assay and a luciferase reporter system. We found that overexpression of TFE3 markedly alleviated hepatocellular steatosis. On the contrary, downregulation of TFE3 resulted in an aggravated steatosis. The mechanistic studies revealed that the TFE3-manipulated regulatory effects on hepatocellular steatosis are dependent on autophagy-induced lipophagy and PGC1α-mediated fatty acid β-oxidation because blocking these pathways with an Atg5 small interfering RNA (siRNA) or PGC1α siRNA dramatically blunted the TFE3-mediated regulation of steatosis. In conclusion, TFE3 gene provides a novel insight into the treatment of hepatic steatosis and other metabolic disease. View Full-Text
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Xiong, J.; Wang, K.; He, J.; Zhang, G.; Zhang, D.; Chen, F. TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation. Int. J. Mol. Sci. 2016, 17, 387.
Xiong J, Wang K, He J, Zhang G, Zhang D, Chen F. TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation. International Journal of Molecular Sciences. 2016; 17(3):387.Chicago/Turabian Style
Xiong, Jie; Wang, Kezhou; He, Jiangping; Zhang, Guangya; Zhang, Dandan; Chen, Fengling. 2016. "TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation." Int. J. Mol. Sci. 17, no. 3: 387.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.