ArticleJournal of lipid research2017
Chemical chaperone 4-phenyl butyric acid (4-PBA) reduces hepatocellular lipid accumulation and lipotoxicity through induction of autophagy.
Article in Journal of lipid research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 96 citations in OpenAlex.
- Cartilage Intermediate Layer Protein 2 Aggravates Hepatic Lipid Accumulation and Inflammation Through the IRE1α/XBP1 Pathway.International journal of molecular sciences · 2026Article
- Integration of Conjugated Linoleic Acid-Producing Probiotic Strains Having Anti-adipogenic Properties with Honey and Oyster Mushrooms for the Formulation of Non-dairy Probiotic Beverage.Probiotics and antimicrobial proteins · 2026Article
- Crosstalk between Epigenetics and Autophagy in Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of obesity & metabolic syndrome · 2025Review
- Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin.Frontiers in pharmacology · 2025Review
- Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.Molecular metabolism · 2024Article
- ER stress inhibition enhances formation of triacylglcerols and protects endothelial cells from lipotoxicity.Cell communication and signaling : CCS · 2024Article
- HFD-exacerbated Metabolic Side Effects of Olanzapine Are Suppressed by ER Stress Inhibitor.Current medical science · 2023Article
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Influence of the Fatty Acid Metabolism on the Mode of Action of a Cisplatin(IV) Complex with Phenylbutyrate as Axial Ligands.Pharmaceutics · 2023Article
- Review
- Effect of Dietary 4-Phenylbuthyric Acid Supplementation on Acute Heat-Stress-Induced Hyperthermia in Broiler Chickens.Animals : an open access journal from MDPI · 2022Article
- Hepatic Macrophages Express Melanoma Differentiation-Associated Gene 5 in Nonalcoholic Steatohepatitis.Inflammation · 2022Article
- Synthesis and anti-melanoma effect of 3-O-prenyl glycyrrhetinic acid against B16F10 cellsFrontiers in oncology · 2022Article
- A heterozygous p.S143P mutation inFrontiers in cell and developmental biology · 2022Article
- Identification of inflammatory markers in eosinophilic cells of the immune system: fluorescence, Raman and CARS imaging can recognize markers but differently.Cellular and molecular life sciences : CMLS · 2021Article
- Small molecule-mediated induction of endoplasmic reticulum stress in cancer cells.RSC medicinal chemistry · 2021Article
- Neuroprotective Effect of 4-Phenylbutyric Acid against Photo-Stress in the Retina.Antioxidants (Basel, Switzerland) · 2021Article
- Palmitate reduces starvation-induced ER stress by inhibiting ER-phagy in hypothalamic cells.Molecular brain · 2021Article
- 4-phenylbutyric acid promotes hepatocellular carcinoma via initiating cancer stem cells through activation of PPAR-α.Clinical and translational medicine · 2021Article
- Beyond Proteostasis: Lipid Metabolism as a New Player in ER Homeostasis.Metabolites · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective autophagy has been linked to lipotoxicity in several cellular models. We aimed to investigate autophagy in lipid-stimulated hepatoma (Huh7) cells and tested whether 4-phenyl butyric acid (4-PBA), a chemical chaperone, has a beneficial role in hepatic fat accumulation and lipotoxicity. We report that long-term (24 h) exposure of hepatocytes to palmitate block autophagic flux that leads to lipid accumulation and cell death. Western blotting analysis showed increased accumulation of SQSTM1/p62, and decreased expression of Beclin1 and Atg7 in palmitate-treated cells. Autophagy inhibition by 3-methyladenine (3-MA) in palmitate-treated cells neither increased SQSTMI/p62 accumulation nor cell death, thus suggesting complete blockade of autophagy by palmitate. 4-PBA reduced lipid accumulation and cell death that were associated with restoration of autophagy. siRNA-mediated knockdown of Atg7 and presence of autophagy inhibitors, 3-MA and chloroquine, resulted in the decrease in lipid-lowering effect of 4-PBA, suggesting that 4-PBA mediates its lipid-lowering effect via autophagy. Apoptotic parameters, including altered Bcl2:Bax ratio and PARP1 cleavage induced by palmitate, were improved by 4-PBA. Our results indicate that palmitate impairs autophagy and increases lipid accumulation in Huh7 cells, whereas 4-PBA plays a protective role in lipid accumulation and lipotoxicity through activation of autophagy.
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