ArticleBiochimica et biophysica acta2015
PPARδ activation induces hepatic long-chain acyl-CoA synthetase 4 expression in vivo and in vitro.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- [Role of glutathione in regulating ferroptosis and cuproptosis in metabolic dysfunction-associated steatotic liver disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- PPARδ: An underappreciated tumor accelerator in pancreatic ductal adenocarcinoma.Cancer letters · 2026Review
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Metformin and Placental Ferroptosis in Gestational Diabetes: A Mechanistic Study.Journal of diabetes research · 2026Article
- Comparative evaluation of ferroptosis markers NCOA4, ACSL4, and Nrf2 in periodontitis with and without type 2 diabetes mellitus: a case-control study.Clinical oral investigations · 2025Article
- Schisandrin B Alleviates Lipid Metabolism Disorders and Apoptosis of MAFLD via Modulation of PPARγ-PCK1 and Caspase-3 Signaling Pathways.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Schisandrin B alleviates metabolic associated fatty liver disease by regulating the PPARγ signaling pathway and gut microbiota in mice.Frontiers in pharmacology · 2025Article
- Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia.Cell death & disease · 2024Article
- Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy.Biomedicines · 2024Review
- Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo.Biomedicines · 2023Article
- Hypolipidemic activity of lactic acid bacteria: Adjunct therapy for potential probiotics.PloS one · 2022Article
- Fatty Acids Metabolism: The Bridge Between Ferroptosis and Ionizing Radiation.Frontiers in cell and developmental biology · 2021Review
- Molecular Cloning, Characterization, and Expression Regulation of Acyl-CoA Synthetase 6 Gene and Promoter in Common CarpInternational journal of molecular sciences · 2020Article
- Immunohistochemical staining reveals differential expression of ACSL3 and ACSL4 in hepatocellular carcinoma and hepatic gastrointestinal metastases.Bioscience reports · 2020Article
- 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.American journal of physiology. Endocrinology and metabolism · 2019Article
- Overexpression of Long-Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Oxidation and Free Radical Formation While Attenuating Insulin Signaling in Primary Human Skeletal Myotubes.International journal of environmental research and public health · 2019Article
- Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance.OncoTargets and therapy · 2018Article
- Hypolipidemic effect of XH601 on hamsters of Hyperlipidemia and its potential mechanism.Lipids in health and disease · 2017Article
- Identification of Hepatic Lysophosphatidylcholine Acyltransferase 3 as a Novel Target Gene Regulated by Peroxisome Proliferator-activated Receptor δ.The Journal of biological chemistry · 2017Article
- A novel peroxisome proliferator response element modulates hepatic low-density lipoprotein receptor gene transcription in response to PPARδ activation.The Biochemical journal · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The arachidonic acid preferred long-chain acyl-CoA synthetase 4 (ACSL4) is a key enzyme for fatty acid metabolism in various metabolic tissues. In this study, we utilized hamsters fed a normal chow diet, a high-fat diet or a high cholesterol and high fat diet (HCHFD) as animal models to explore novel transcriptional regulatory mechanisms for ACSL4 expression under hyperlipidemic conditions. Through cloning hamster ACSL4 homolog and tissue profiling ACSL4 mRNA and protein expressions we observed a selective upregulation of ACSL4 in testis and liver of HCHFD fed animals. Examination of transcriptional activators of the ACSL family revealed an increased hepatic expression of PPARδ but not PPARα in HCHFD fed hamsters. To explore a role of PPARδ in dietary cholesterol-mediated upregulation of ACSL4, we administered a PPARδ specific agonist L165041 to normolipidemic and dyslipidemic hamsters. We observed significant increases of hepatic ACSL4 mRNA and protein levels in all L165041-treated hamsters as compared to control animals. The induction of ACSL4 expression by L165041 in liver tissue in vivo was recapitulated in human primary hepatocytes and hepatocytes isolated from hamster and mouse. Moreover, employing the approach of adenovirus-mediated gene knockdown, we showed that depletion of PPARδ in hamster hepatocytes specifically reduced ACSL4 expression. Finally, utilizing HepG2 as a model system, we demonstrate that PPARδ activation leads to increased ACSL4 promoter activity, mRNA and protein expression, and consequently higher arachidonoyl-CoA synthetase activity. Taken together, we have discovered a novel PPARδ-mediated regulatory mechanism for ACSL4 expression in liver tissue and cultured hepatic cells.
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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 Socratic graph.