ArticleMetabolism: clinical and experimental2023
Loss of long-chain acyl-CoA synthetase 1 promotes hepatocyte death in alcohol-induced steatohepatitis.
Article in Metabolism: clinical and experimental, 2023. 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, 29 citations in OpenAlex.
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Carnitine dysregulation in diabetic kidney disease: from pathogenic mechanism to precision biomarker.Journal of translational medicine · 2026Review
- ACSL1-Dependent Microglial Lipoimmunometabolic Reprogramming Underlies Cognitive Deficits in Alcohol Use Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of mitochondria-associated hub genes related to alcohol-associated liver fibrosis progression in aldehyde dehydrogenase 2 deficiency.Frontiers in physiology · 2026Article
- Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Upregulation of ACSL1 in synovial macrophages promotes lipid peroxidation via the IκB/NF-κB pathway to accelerate osteoarthritis.Journal of orthopaedic translation · 2025Article
- Semaglutide Reprograms Macrophages via the GLP-1R/PPARG/ACSL1 Pathway to Suppress Papillary Thyroid Carcinoma Growth.The Journal of clinical endocrinology and metabolism · 2025Article
- Necroptosis in obesity: a complex cell death event.Apoptosis : an international journal on programmed cell death · 2025Review
- Acetylation of proximal cysteine-lysine pairs by alcohol metabolism.Redox biology · 2025Article
- Targeting the gut microbiota and lipid metabolism: potential mechanisms of natural products for the treatment of non-alcoholic fatty liver disease.Frontiers in pharmacology · 2025Review
- Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.International journal of molecular sciences · 2024Article
- Up-regulation of long non-coding RNA H19 ameliorates renal tubulointerstitial fibrosis by reducing lipid deposition and inflammatory response through regulation of the microRNA-130a-3p/long-chain acyl-CoA synthetase 1 axis.Non-coding RNA research · 2024Article
- Reversal of hepatic accumulation of nordeoxycholic acid underlines the beneficial effects of cholestyramine on alcohol-associated liver disease in mice.Hepatology communications · 2024Article
- Nicotinamide mitigates visceral leishmaniasis by regulating inflammatory response and enhancing lipid metabolism.Parasites & vectors · 2024Article
- BAX/MLKL signaling contributes to lipotoxicity-induced lysosomal membrane permeabilization in alcohol-associated liver disease.Autophagy · 2024Article
- Regulation of the Nur77-P2X7r Signaling Pathway by Nodakenin: A Potential Protective Function against Alcoholic Liver Disease.Molecules (Basel, Switzerland) · 2024Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAlcohol consumption has been shown to disrupt hepatic lipid homeostasis. Long-chain acyl-CoA synthetase 1 (ACSL1) critically regulates hepatic fatty acid metabolism and lipid homeostasis by channeling fatty acids to lipid metabolic pathways. However, it remains unclear how ACSL1 contributes to the development of alcohol-associated liver disease (ALD).
methodsWe performed chronic alcohol feeding animal studies with hepatocyte-specific ACSL1 knockout (ACSL1
resultsWe found that chronic alcohol consumption reduced hepatic ACSL1 expression in AH patients and ALD mice. Hepatocyte-specific ACSL1 deletion exacerbated alcohol-induced liver injury by increasing free fatty acids (FFA) accumulation and cell death. Cell studies revealed that FFA elicited the translocation of BAX and p-MLKL to the lysosomal membrane, resulting in lysosomal membrane permeabilization (LMP) and thereby initiating lysosomal-mediated cell death pathway. Furthermore, we identified that the signal transducer and activator of transcription 5 (STAT5) is a novel transcriptional regulator of ACSL1. Deletion of STAT5 exacerbated alcohol-induced liver injury in association with downregulation of ACSL1, and reactivation of ACSL1 by STAT5 overexpression effectively ameliorated alcohol-induced liver injury. In addition, ACSL1 expression was positively correlated with STAT5 and negatively correlated with cell death was also validated in the liver of AH patients.
conclusionsACSL1 deficiency due to STAT5 inactivation critically mediates alcohol-induced lipotoxicity and cell death in the development of ALD. These findings provide insights into alcohol-induced liver injury.
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