ArticleJournal of lipid research2014
Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 126 citations in OpenAlex.
- Plasma lipid profile associates with the improvement of psychological well-being in individuals with perceived stress symptoms.Scientific reports · 2020Trial
- Apical proximal tubule fatty acid uptake-generated ceramides cause endoplasmic reticulum stress from altered membrane fluidity.JCI insight · 2026Article
- Palmitate promotes liver metastases by decreasing neutrophil antitumour behaviour.Nature metabolism · 2026Article
- Palmitoylation-mediated regulation of KAT2A promotes lung metastasis in breast cancer.Nature cell biology · 2026Article
- Involvement of ferroptosis in metabolic dysfunction-associated steatohepatitis-related liver diseases.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Saturated lipid stress attenuates mitochondrial genome synthesis in human cells.bioRxiv : the preprint server for biology · 2025Article
- Application of rapid evaporative ionization mass spectrometry in preclinical and clinical analyses of steatotic liver tissues and cells.Scientific reports · 2025Article
- Article
- MASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives.Molecular oncology · 2025Review
- Article
- ER stress inhibition enhances formation of triacylglcerols and protects endothelial cells from lipotoxicity.Cell communication and signaling : CCS · 2024Article
- Research progress, challenges and perspectives of phospholipids metabolism in the LXR‑LPCAT3 signaling pathway and its relation to NAFLD (Review).International journal of molecular medicine · 2024Review
- Lipid- and phospho-regulation of CTP:Phosphocholine Cytidylyltransferase α association with nuclear lipid droplets.Molecular biology of the cell · 2024Article
- Cell-type specific role of autophagy in the liver and its implications in non-alcoholic fatty liver disease.World journal of hepatology · 2023Article
- Targeted metabolomics reveals plasma biomarkers and metabolic alterations of the aging process in healthy young and older adults.GeroScience · 2023Article
- Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.PLoS genetics · 2023Article
- Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (bioRxiv : the preprint server for biology · 2023Article
- A protein-lipid complex that detoxifies free fatty acids.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.Nature cancer · 2023Article
- Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
High levels of saturated FAs (SFAs) are acutely toxic to a variety of cell types, including hepatocytes, and have been associated with diseases such as type 2 diabetes and nonalcoholic fatty liver disease. SFA accumulation has been previously shown to degrade endoplasmic reticulum (ER) function leading to other manifestations of the lipoapoptotic cascade. We hypothesized that dysfunctional phospholipid (PL) metabolism is an initiating factor in this ER stress response. Treatment of either primary hepatocytes or H4IIEC3 cells with the SFA palmitate resulted in dramatic dilation of the ER membrane, coinciding with other markers of organelle dysfunction. This was accompanied by increased de novo glycerolipid synthesis, significant elevation of dipalmitoyl phosphatidic acid, diacylglycerol, and total PL content in H4IIEC3 cells. Supplementation with oleate (OA) reversed these markers of palmitate (PA)-induced lipotoxicity. OA/PA cotreatment modulated the distribution of PA between lipid classes, increasing the flux toward triacylglycerols while reducing its incorporation into PLs. Similar trends were demonstrated in both primary hepatocytes and the H4IIEC3 hepatoma cell line. Overall, these findings suggest that modifying the FA composition of structural PLs can protect hepatocytes from PA-induced ER stress and associated lipotoxicity.
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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 OpenQuestion graph.