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Volume 17
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10.3390/ijms17030387
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Open AccessArticle

TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation

by
Jie Xiong
1,2,†,
Kezhou Wang
3,†,
Jiangping He
1,
Guangya Zhang
1,
Dandan Zhang
1 and
Fengling Chen
1,*
1
Department of Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China
2
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
3
Department of Pathology and Pathophysiology, Dalian Medical University, Dalian 116044, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Ge Zhang
Int. J. Mol. Sci. 2016, 17(3), 387; https://doi.org/10.3390/ijms17030387
Received: 13 February 2016 / Revised: 6 March 2016 / Accepted: 7 March 2016 / Published: 18 March 2016
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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Abstract

Autophagy 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
Keywords: TFE3; hepatic steatosis; autophagy; PGC1α; β-oxidation TFE3; hepatic steatosis; autophagy; PGC1α; β-oxidation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style

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. https://doi.org/10.3390/ijms17030387

AMA Style

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. https://doi.org/10.3390/ijms17030387

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. https://doi.org/10.3390/ijms17030387

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