Activation of mTORC1 by Free Fatty Acids Suppresses LAMP2 and Autophagy Function via ER Stress in Alcohol-Related Liver Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mice
2.2. Human Liver Samples
2.3. Chronic Alcohol Feeding and Treatments
2.4. Western Blot
2.5. Cell Culture and Treatments
2.6. Plasmids Transfection
2.7. Histopathology and Immunohistochemistry
2.8. Immunofluorescence
2.9. Plasma ALT/AST Levels
2.10. RNA Isolation and Real-Time PCR
2.11. Quantification of FFAs and TG
2.12. Lactate Dehydrogenase (LDH) Assay
2.13. Statistical Analysis
3. Results
3.1. FFA-induced ER Stress, LAMP2 Reduction, and Impaired Autophagy Flux Is mTORC1-Dependent in Hepatocytes
3.2. mTORC1-Induced ER Stress Targets LAMP2 via ATF4-CHOP Pathway under FFA Treatment in Hepatocytes
3.3. Inhibition of mTORC1 Signaling by Dietary Rapamycin Supplementation Ameliorates Alcohol-Induced ER Stress and Improves Autophagy in Mice
3.4. Inhibition of mTORC1 Signaling by Dietary Rapamycin Supplementation Attenuates Alcohol-Induced Liver Injury in Mice
3.5. Activation of mTORC1 and Accumulation of CHOP in the Liver of Patients with SAH
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Guo, W.; Zhong, W.; Hao, L.; Sun, X.; Zhou, Z. Activation of mTORC1 by Free Fatty Acids Suppresses LAMP2 and Autophagy Function via ER Stress in Alcohol-Related Liver Disease. Cells 2021, 10, 2730. https://doi.org/10.3390/cells10102730
Guo W, Zhong W, Hao L, Sun X, Zhou Z. Activation of mTORC1 by Free Fatty Acids Suppresses LAMP2 and Autophagy Function via ER Stress in Alcohol-Related Liver Disease. Cells. 2021; 10(10):2730. https://doi.org/10.3390/cells10102730
Chicago/Turabian StyleGuo, Wei, Wei Zhong, Liuyi Hao, Xinguo Sun, and Zhanxiang Zhou. 2021. "Activation of mTORC1 by Free Fatty Acids Suppresses LAMP2 and Autophagy Function via ER Stress in Alcohol-Related Liver Disease" Cells 10, no. 10: 2730. https://doi.org/10.3390/cells10102730