ArticleJournal of lipid research2024
Lipotoxicity of palmitic acid is associated with DGAT1 downregulation and abolished by PPARα activation in liver cells.
Article in Journal of lipid research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Optical photothermal infrared imaging of fatty acid esterification in the ER of living cells.Science advances · 2026Article
- Physiologically relevant media are associated with overlapping metabolic responses in primary human hepatocytes and Huh7 cells.Physiological reports · 2026Article
- Beyond Glucose: Palmitic Acid Influences VEGFA-VEGFR2 Angiogenic Signaling in Müller Glial Cells.International journal of molecular sciences · 2026Article
- Regulated Cell Death in Fungi, the Role of Metacaspases and Assay Techniques.Methods and protocols · 2026Review
- An Aqueous Extract ofInternational journal of molecular sciences · 2026Article
- Chronic kidney disease induces a distinct lipidomic signature and accelerates atherosclerosis progression in a novel minipig model.Laboratory animal research · 2026Article
- Epithelial-Mesenchymal Transition Shapes the Lipotoxic Response of Colon Cancer Cells to Palmitic Acid.Molecular & cellular proteomics : MCP · 2026Article
- Optical photothermal infrared imaging of fatty acid esterification in the ER of living cells.bioRxiv : the preprint server for biology · 2026Article
- Restoring Mitochondrial Homeostasis: Therapeutic Strategies for Metabolic Dysfunction-Associated Fatty Liver Disease.International journal of molecular sciences · 2026Review
- GLP-1 RAs for Treating Metabolic Dysfunction-Associated Steatosis Liver Disease: From GLP-1 Discovery to FDA Approval: A Comprehensive Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Bioavailable human metabolites from TOTUM-448 (plant-based formulation) maintain liver cell functionality in a hyperlipidic context that drives MASLD onset.Scientific reports · 2025Article
- Neutrophil CD11b is a pivotal PANoptosis marker correlated with disease activity in antineutrophil cytoplasmic antibody-associated vasculitis.Apoptosis : an international journal on programmed cell death · 2025Article
- Concentrated Growth Factor Induces ER Stress and Apoptosis by Increasing Ceramide Generation in Selected Tumour Cell Lines.Journal of cellular and molecular medicine · 2025Article
- Article
- Saturated lipid stress attenuates mitochondrial genome synthesis in human cells.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Role of Oleic Acid in Muscle Cell Differentiation: Mechanisms and Implications for Myogenesis and Metabolic Regulation in C2C12 Myoblasts.Biomedicines · 2025Article
- Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Complement activation at the interface between adipocytes and cancer cells drives tumor progression.JCI insight · 2025Article
- Protective Effect of Carvedilol Against Oxidative Stress Induced by Palmitic Acid in Primary Rat Hepatocytes.Cell biochemistry and function · 2025Article
- A proteome-wide association study reveals novel plasma proteins as potential therapeutic targets for metabolic dysfunction-associated steatotic liver disease.Frontiers in endocrinology · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipotoxicity refers to the harmful effects of excess fatty acids on metabolic health, and it can vary depending on the type of fatty acids involved. Saturated and unsaturated fatty acids exhibit distinct effects, though the precise mechanisms behind these differences remain unclear. Here, we investigated the lipotoxicity of palmitic acid (PA), a saturated fatty acid, compared with oleic acid (OA), a monounsaturated fatty acid, in the hepatic cell line HuH7. Our results demonstrated that PA, unlike OA, induces lipotoxicity, endoplasmic reticulum (ER) stress, and autophagy inhibition. Compared with OA, PA treatment leads to less lipid droplet (LD) accumulation and a significant reduction in the mRNA and protein level of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme of triacylglycerol synthesis. Using modulators of ER stress and autophagy, we established that DGAT1 downregulation by PA is closely linked to these cellular pathways. Notably, the ER stress inhibitor 4-phenylbutyrate can suppress PA-induced DGAT1 downregulation. Furthermore, knockdown of DGAT1 by siRNA or with A922500, a specific DGAT1 inhibitor, resulted in cell death, even with OA. Both PA and OA increased the oxygen consumption rate; however, the increase associated with PA was only partially coupled to ATP synthesis. Importantly, treatment with GW7647 a specific PPARα agonist mitigated the lipotoxic effects of PA, restoring PA-induced ER stress, autophagy block, and DGAT1 suppression. In conclusion, our study highlights the crucial role of DGAT1 in PA-induced lipotoxicity, broadening the knowledge of the mechanisms underlying hepatic lipotoxicity and providing the basis for potential therapeutic interventions.
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