ArticleThe Journal of biological chemistry2016
Liver-specific Gene Inactivation of the Transcription Factor ATF4 Alleviates Alcoholic Liver Steatosis in Mice.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
- ATF4 Is Dispensable for Spermatogenesis but Protective Against ER Stress Under Normal Conditions.Biology · 2026Article
- Transcriptional readthrough at Atf4 locus suppresses Rps19bp1 and impairs heart development.Cardiovascular research · 2026Article
- B-Cell Receptor-Associated Protein 31 Deficiency Aggravates Ethanol-Induced Liver Steatosis and Liver Injury via Attenuating Fatty Acid Oxidation and Glycogen Synthesis.International journal of molecular sciences · 2025Article
- AP-1 elements in the promoter and second intron mediate endoplasmic reticulum stress-induced expression of the GPAT3 gene.Scientific reports · 2025Article
- Transcriptional Readthrough atbioRxiv : the preprint server for biology · 2025Article
- Key Transcription Factors: Avenue for Treating Alcoholic Liver Disease.Current medical science · 2025Review
- ATF4 in proximal tubules modulates kidney function and modifies the metabolome.Journal of molecular medicine (Berlin, Germany) · 2025Article
- MIST1 regulates endoplasmic reticulum stress-induced hepatic apoptosis as a candidate marker of fatty liver disease progression.Cell death & disease · 2024Article
- Medaka liver developed Human NAFLD-NASH transcriptional signatures in response to ancestral bisphenol A exposure.Research square · 2024Article
- Sex-specific expression of the human NAFLD-NASH transcriptional signatures in the liver of medaka with a history of ancestral bisphenol A exposure.bioRxiv : the preprint server for biology · 2024Article
- Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway.Cardiovascular diabetology · 2024Article
- ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.Journal of hepatology · 2023Article
- Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.International journal of molecular sciences · 2023Article
- Mitochondrial stress induces hepatic stellate cell activation in response to the ATF4/TRIB3 pathway stimulation.Journal of gastroenterology · 2023Article
- ATF4-mediated CD36 upregulation contributes to palmitate-induced lipotoxicity in hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression.Cellular and molecular gastroenterology and hepatology · 2023Article
- Aberrant iron distribution via hepatocyte-stellate cell axis drives liver lipogenesis and fibrosis.Cell metabolism · 2022Article
- Ethanol attenuates presentation of cytotoxic T-lymphocyte epitopes on hepatocytes of HBV-infected humanized mice.Alcoholism, clinical and experimental research · 2022Article
- Global Microbiota-Dependent Histone Acetylation Patterns Are Irreversible and Independent of Short Chain Fatty Acids.Hepatology (Baltimore, Md.) · 2021Article
- Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium.Stem cell research & therapy · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although numerous biological functions of the activating transcription factor 4 (ATF4) have been identified, a direct effect of ATF4 on alcoholic liver steatosis has not been described previously. The aim of our current study is to investigate the role of ATF4 in alcoholic liver steatosis and elucidate the underlying mechanisms. Here, we showed that the expression of ATF4 is induced by ethanol in hepatocytes in vitro and in vivo, and liver-specific ATF4 knock-out mice are resistant to ethanol-induced liver steatosis, associated with stimulated hepatic AMP-activated protein kinase (AMPK) activity. Furthermore, adenovirus-mediated AMPK knockdown significantly reversed the suppressive effects of ATF4 deficiency on ethanol-induced liver steatosis in mice. In addition, ethanol-fed ATF4 knock-out mice exhibit AMPK-dependent inhibition of fatty acid synthase and stimulation of carnitine palmitoyltransferase 1 (CPT1) in the liver. Moreover, hepatic Tribbles homolog 3 (TRB3) expression was stimulated by ethanol in an ATF4-dependent manner, and adenovirus-mediated TRB3 knockdown blocked ATF4-dependent ethanol-induced AMPK inhibition and triglyceride accumulation in AML-12 cells. Finally, TRB3 directly interacted with AMPK to suppress its phosphorylation. Taken together, these results identify the ATF4-TRB3-AMPK axis as a novel pathway responsible for ethanol-induced liver steatosis.
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