ArticleBiochimica et biophysica acta2016
Knockdown of triglyceride synthesis does not enhance palmitate lipotoxicity or prevent oleate-mediated rescue in rat hepatocytes.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Red Oranges and Olive Leaf Waste-Derived Bioactive Extracts Promote Adipocyte Functionality In Vitro.Nutrients · 2024Article
- Lipid- and phospho-regulation of CTP:Phosphocholine Cytidylyltransferase α association with nuclear lipid droplets.Molecular biology of the cell · 2024Article
- Isolated and combined impact of dietary olive oil and exercise on markers of health and energy metabolism in female mice.The Journal of nutritional biochemistry · 2022Article
- Heat-KilledFoods (Basel, Switzerland) · 2022Article
- In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver.International journal of molecular sciences · 2021Article
- Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis.Cancer research · 2021Article
- Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets.eLife · 2021Article
- Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice.Journal of lipid research · 2020Article
- DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells.Journal of lipid research · 2019Article
- Lipid Droplets and the Management of Cellular Stress.The Yale journal of biology and medicine · 2019Review
- Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate-induced apoptosis.Molecular oncology · 2018Article
- Lipid Droplets in Cancer: Guardians of Fat in a Stressful World.Molecules (Basel, Switzerland) · 2018Review
- FeedingJournal of lipid research · 2017Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Experiments in a variety of cell types, including hepatocytes, consistently demonstrate the acutely lipotoxic effects of saturated fatty acids, such as palmitate (PA), but not unsaturated fatty acids, such as oleate (OA). PA+OA co-treatment fully prevents PA lipotoxicity through mechanisms that are not well defined but which have been previously attributed to more efficient esterification and sequestration of PA into triglycerides (TGs) when OA is abundant. However, this hypothesis has never been directly tested by experimentally modulating the relative partitioning of PA/OA between TGs and other lipid fates in hepatocytes. In this study, we found that addition of OA to PA-treated hepatocytes enhanced TG synthesis, reduced total PA uptake and PA lipid incorporation, decreased phospholipid saturation and rescued PA-induced ER stress and lipoapoptosis. Knockdown of diacylglycerol acyltransferase (DGAT), the rate-limiting step in TG synthesis, significantly reduced TG accumulation without impairing OA-mediated rescue of PA lipotoxicity. In both wild-type and DGAT-knockdown hepatocytes, OA co-treatment significantly reduced PA lipid incorporation and overall phospholipid saturation compared to PA-treated hepatocytes. These data indicate that OA's protective effects do not require increased conversion of PA into inert TGs, but instead may be due to OA's ability to compete against PA for cellular uptake and/or esterification and, thereby, normalize the composition of cellular lipids in the presence of a toxic PA load.
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