ArticleAmerican journal of physiology. Endocrinology and metabolism2019
Liver-specific knockdown of long-chain acyl-CoA synthetase 4 reveals its key role in VLDL-TG metabolism and phospholipid synthesis in mice fed a high-fat diet.
Article in American journal of physiology. Endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
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- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Gamma oryzanol modulates hepatic lipids expression and regulates integrated pathways in liver disease pathophysiology under a high sugar fat diet.Scientific reports · 2025Article
- Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- The ferroptosis mediator ACSL4 fails to prevent disease progression in mouse models of MASLD.Hepatology communications · 2025Article
- The role of ACSL4 in stroke: mechanisms and potential therapeutic target.Molecular and cellular biochemistry · 2025Review
- From mechanisms to medicine: Ferroptosis as a Therapeutic target in liver disorders.Cell communication and signaling : CCS · 2025Review
- Targeting membrane contact sites to mediate lipid dynamics: innovative cancer therapies.Cell communication and signaling : CCS · 2025Review
- Mapping the future: bibliometric insights into ferroptosis and diabetic nephropathy.Frontiers in physiology · 2025Review
- Lipid metabolism in ferroptosis: mechanistic insights and therapeutic potential.Frontiers in immunology · 2025Review
- Article
- Sperm miR-142-3p Reprogramming Mediates Paternal Pre-Pregnancy Caffeine Exposure-Induced Non-Alcoholic Steatohepatitis in Male Offspring Rats.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanism of Metabolic Dysfunction-associated Steatotic Liver Disease: Important role of lipid metabolism.Journal of clinical and translational hepatology · 2024Review
- MARK4 aggravates cardiac dysfunction in mice with STZ-induced diabetic cardiomyopathy by regulating ACSL4-mediated myocardial lipid metabolism.Scientific reports · 2024Article
- Emerging role of ferroptosis in metabolic dysfunction-associated steatotic liver disease: revisiting hepatic lipid peroxidation.EBioMedicine · 2024Review
- Effect of diet and genotype on the miRNome of mice with altered lipoprotein metabolism.iScience · 2023Article
- Review
- Molecular Characterization, Tissue Distribution Profile, and Nutritional Regulation ofInternational journal of molecular sciences · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Long-chain acyl-CoA synthetase 4 (ACSL4) has a unique substrate specificity for arachidonic acid. Hepatic ACSL4 is coregulated with the phospholipid (PL)-remodeling enzyme lysophosphatidylcholine (LPC) acyltransferase 3 by peroxisome proliferator-activated receptor δ to modulate the plasma triglyceride (TG) metabolism. In this study, we investigated the acute effects of hepatic ACSL4 deficiency on lipid metabolism in adult mice fed a high-fat diet (HFD). Adenovirus-mediated expression of a mouse ACSL4 shRNA (Ad-shAcsl4) in the liver of HFD-fed mice led to a 43% reduction of hepatic arachidonoyl-CoA synthetase activity and a 53% decrease in ACSL4 protein levels compared with mice receiving control adenovirus (Ad-shLacZ). Attenuated ACSL4 expression resulted in a substantial decrease in circulating VLDL-TG levels without affecting plasma cholesterol. Lipidomics profiling revealed that knocking down ACSL4 altered liver PL compositions, with the greatest impact on accumulation of abundant LPC species (LPC 16:0 and LPC 18:0) and lysophosphatidylethanolamine (LPE) species (LPE 16:0 and LPE 18:0). In addition, fasting glucose and insulin levels were higher in Ad-shAcsl4-transduced mice versus control (Ad-shLacZ). Glucose tolerance testing further indicated an insulin-resistant phenotype upon knockdown of ACSL4. These results provide the first in vivo evidence that ACSL4 plays a role in plasma TG and glucose metabolism and hepatic PL synthesis of hyperlipidemic mice.
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