ArticleCells2021
Activation of mTORC1 by Free Fatty Acids Suppresses LAMP2 and Autophagy Function via ER Stress in Alcohol-Related Liver Disease.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Palmitate impairs autophagic degradation via oxidative stress/perilysosomal Ca2+ overload/mTORC1 activation pathway in pancreatic β cells.JCI insight · 2025Article
- A nutrigeroscience approach: Dietary macronutrients and cellular senescence.Cell metabolism · 2024Review
- Autophagy modulates physiologic and adaptive response in the liver.Liver research (Beijing, China) · 2023Review
- Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies.Biology · 2023Article
- Recent insights into the pathogenesis and therapeutic targets of chronic liver diseases.eGastroenterology · 2023Article
- Unfolded Protein Response Signaling in Liver Disorders: A 2023 Updated Review.International journal of molecular sciences · 2023Review
- Autophagy, Oxidative Stress, and Alcoholic Liver Disease: A Systematic Review and Potential Clinical Applications.Antioxidants (Basel, Switzerland) · 2023Review
- Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles.Cell communication and signaling : CCS · 2023Article
- Molecular mechanisms of autophagy and implications in liver diseases.Liver research (Beijing, China) · 2023Review
- Apoptosis mechanisms induced by 15d-PMJFrontiers in pharmacology · 2023Article
- Review
- Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease.Frontiers in endocrinology · 2023Article
- 4-O-Methylascochlorin-Mediated BNIP-3 Expression Controls the Balance of Apoptosis and Autophagy in Cervical Carcinoma Cells.International journal of molecular sciences · 2022Article
- Free fatty acid treatment of mouse preimplantation embryos demonstrates contrasting effects of palmitic acid and oleic acid on autophagy.American journal of physiology. Cell physiology · 2022Article
- Regulation of Autophagy by the Glycogen Synthase Kinase-3 (GSK-3) Signaling Pathway.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alcohol-related liver disease (ALD) is characterized by accumulation of hepatic free fatty acids (FFAs) and liver injury. The present study aimed to investigate if mechanistic target of rapamycin complex 1 (mTORC1) plays a role in FFA-induced organelle dysfunction, thereby contributing to the development of ALD. Cell studies were conducted to define the causal role and underlying mechanism of FFA-activated mTORC1 signaling in hepatocellular cell injury. C57BL/6J wild-type mice were subjected to chronic alcohol feeding with or without rapamycin to inhibit mTORC1 activation. We revealed that palmitic acid (PA)-induced ER stress and suppression of LAMP2 and autophagy flux were mTORC1-dependent as rapamycin reversed such deleterious effects. C/EBP homologous protein (CHOP) was downstream of ATF4 which partially modulated LAMP2. Supplementation with rapamycin to alcohol-fed mice attenuated mTORC1 activation and ER stress, restored LAMP2 protein, and improved autophagy, leading to amelioration of alcohol-induced liver injury. Induction of mTORC1 signaling and CHOP were also detected in the liver of patients with severe alcoholic hepatitis. This study demonstrates that hepatic FFAs play a crucial role in the pathogenesis of ALD by activating mTORC1 signaling, thereby inducing ER stress and suppressing LAMP2-autophagy flux pathway, which represents an important mechanism of FFA-induced hepatocellular injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.