ArticleOncotarget2015
Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 99 citations in OpenAlex.
- Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis.Lipids in health and disease · 2019Trial
- Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.Nutrients · 2026Review
- Palmitate and oleate differentially regulate oxidative stress and drug resistance markers in steatotic HepG2 cells.Molecular biology reports · 2026Article
- Molecular Biointerface Characterization for an Implanted Medical Device Using Cryogenic Orbitrap Secondary Ion Mass Spectrometry (Cryo-OrbiSIMS).ACS applied materials & interfaces · 2026Article
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- Association Between Blood Free Fatty Acid Concentrations in Midlife and Cerebral Small Vessel Disease.Antioxidants (Basel, Switzerland) · 2025Article
- Resolving fibrosis by stimulating HSC-dependent extracellular matrix degradation.Science translational medicine · 2025Article
- Protection Strategies Against Palmitic Acid-Induced Lipotoxicity in Metabolic Syndrome and Related Diseases.International journal of molecular sciences · 2025Review
- Association Between Circulating Fatty Acids and Blood Pressure: A Review.Current nutrition reports · 2025Review
- Fully hydrogenated vegetable oil-based non-dairy creamer intake impairs athletic performance in mice: serum metabolomics and intestinal microbiota analyses.Frontiers in nutrition · 2025Article
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role ofWorld journal of psychiatry · 2024Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options.International journal of molecular sciences · 2024Review
- Metabolomic Insights into the Mechanisms of Ganoderic Acid: Protection against α-Amanitin-Induced Liver Injury.Metabolites · 2023Article
- Pharmacotherapies of NAFLD: updated opportunities based on metabolic intervention.Nutrition & metabolism · 2023Review
- Change in fatty acid composition of plasma triglyceride caused by a 2 week comprehensive risk management for diabetes: A prospective observational study of type 2 diabetes patients with supercritical fluid chromatography/mass spectrometry-based semi-target lipidomic analysis.Journal of diabetes investigation · 2023Observational
- Differential Immunometabolic Effects of High-Fat Diets Containing Coconut, Sunflower, and Extra Virgin Olive Oils in Female Mice.Molecular nutrition & food research · 2022Article
- Secondary Metabolites with Biomedical Applications from Plants of the Sarraceniaceae Family.International journal of molecular sciences · 2022Review
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Palmitic acid (PA) induces hepatocyte apoptosis and fuels de novo ceramide synthesis in the endoplasmic reticulum (ER). Myristic acid (MA), a free fatty acid highly abundant in copra/palmist oils, is a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Here we investigated the synergism between MA and PA in ceramide synthesis, ER stress, lipotoxicity and NASH. Unlike PA, MA is not lipotoxic but potentiated PA-mediated lipoapoptosis, ER stress, caspase-3 activation and cytochrome c release in primary mouse hepatocytes (PMH). Moreover, MA kinetically sustained PA-induced total ceramide content by stimulating dehydroceramide desaturase and switched the ceramide profile from decreased to increased ceramide 14:0/ceramide16:0, without changing medium and long-chain ceramide species. PMH were more sensitive to equimolar ceramide14:0/ceramide16:0 exposure, which mimics the outcome of PA plus MA treatment on ceramide homeostasis, than to either ceramide alone. Treatment with myriocin to inhibit ceramide synthesis and tauroursodeoxycholic acid to prevent ER stress ameliorated PA plus MA induced apoptosis, similar to the protection afforded by the antioxidant BHA, the pan-caspase inhibitor z-VAD-Fmk and JNK inhibition. Moreover, ruthenium red protected PMH against PA and MA-induced cell death. Recapitulating in vitro findings, mice fed a diet enriched in PA plus MA exhibited lipodystrophy, hepatosplenomegaly, increased liver ceramide content and cholesterol levels, ER stress, liver damage, inflammation and fibrosis compared to mice fed diets enriched in PA or MA alone. The deleterious effects of PA plus MA-enriched diet were largely prevented by in vivo myriocin treatment. These findings indicate a causal link between ceramide synthesis and ER stress in lipotoxicity, and imply that the consumption of diets enriched in MA and PA can cause NASH associated with lipodystrophy.
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Registered trials
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