ArticleMolecular metabolism2018
A role for long-chain acyl-CoA synthetase-4 (ACSL4) in diet-induced phospholipid remodeling and obesity-associated adipocyte dysfunction.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 128 citations in OpenAlex.
- Cordycepin Alleviates Non Alcoholic Fatty Liver Disease Progression by Stabilizing GCH1 to Inhibit Ferroptosis.Phytotherapy research : PTR · 2026Article
- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- Targeting Hippocampal PTEN Suppresses Ferroptosis and Rescues Cognitive Decline in Alzheimer's Disease via Dual AKT/GSK3β/Nrf2 and AKT/STAT3 Axes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Reprogramming in delipidated adipocytes: metabolism, regulation and progress.Cell death discovery · 2026Review
- GOT2-mediated suppression of CoQCommunications biology · 2026Article
- Article
- Acsl4-mediated Lipid Homeostasis Orchestrates Synaptic and Cognitive Plasticity.Research square · 2026Article
- Nuclear Myosin 1 links genomic architecture to adipose tissue remodeling, metabolic inflammation and obesity in mice.Cell death & disease · 2026Article
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy.Virulence · 2025Review
- Gut Microbiota and Ferroptosis in Colorectal Cancer: A Comprehensive Review of Mechanisms and Therapeutic Strategies to Overcome Immune Checkpoint Resistance.Biomolecules · 2025Review
- Fibroblast lipid metabolism through ACSL4 regulates epithelial sensitivity to ferroptosis in IBD.Nature metabolism · 2025Article
- Targeting Acyl-CoA synthetase long-chain family member 4: a potential approach for the treatment of cerebral ischemia/reperfusion injury.Metabolic brain disease · 2025Review
- The role of ACSL4 in stroke: mechanisms and potential therapeutic target.Molecular and cellular biochemistry · 2025Review
- Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism.Acta pharmaceutica Sinica. B · 2025Article
- Comprehensive analysis of histophysiology, transcriptomics and metabolomics in goslings exposed to gossypol acetate: unraveling hepatotoxic mechanisms.Frontiers in veterinary science · 2025Article
- ACSL4 accelerates osteosarcoma progression via modulating TGF-β/Smad2 signaling pathway.Molecular and cellular biochemistry · 2025Article
- ASPP2 deficiency promotes the progression of metabolic dysfunction-associated steatohepatitis via ACSL4 upregulation.Scientific reports · 2024Article
- Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
objectiveRegulation of fatty acid (FA) metabolism is central to adipocyte dysfunction during diet-induced obesity (DIO). Long-chain acyl-CoA synthetase-4 (ACSL4) has been hypothesized to modulate the metabolic fates of polyunsaturated FA (PUFA), including arachidonic acid (AA), but the in vivo actions of ACSL4 are unknown. The purpose of our studies was to determine the in vivo role of adipocyte ACSL4 in regulating obesity-associated adipocyte dysfunction.
methodsWe developed a novel mouse model with adipocyte-specific ablation of ACSL4 (Ad-KO) using loxP Cre recombinase technology. Metabolic phenotyping of Ad-KO mice relative to their floxed littermates (ACSL4
resultsAd-KO mice were protected against DIO, adipocyte death, and metabolic dysfunction. Adipocytes from Ad-KO mice fed high-fat diet (HFD) had reduced incorporation of AA into phospholipids (PL), free AA, and levels of the AA lipid peroxidation product 4-hydroxynonenal (4-HNE). Additionally, adipocytes from Ad-KO mice fed HFD had reduced p53 activation and increased adipocyte oxygen consumption (OCR), which we demonstrated are direct effects of 4-HNE on adipocytes in vitro.
conclusionThese studies are the first to elucidate ACSL4's in vivo actions to regulate the incorporation of AA into PL and downstream effects on DIO-associated adipocyte dysfunction. By reducing the incorporation of AA into PL and free fatty acid pools in adipocytes, Ad-KO mice were significantly protected against HFD-induced increases in adipose and liver fat accumulation, adipocyte death, gonadal white adipose tissue (gWAT) inflammation, and insulin resistance (IR). Additionally, deficiency of adipocyte ACSL4 expression in mice fed a HFD resulted in increased gWAT adipocyte OCR and whole body energy expenditure (EE).
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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.