ArticleThe Journal of biological chemistry2019
Glutamate-oxaloacetate transaminase activity promotes palmitate lipotoxicity in rat hepatocytes by enhancing anaplerosis and citric acid cycle flux.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Application of Multivariate Adaptive Regression Splines to Estimate Fatty Liver Index in Healthy Young Taiwanese Men.Diagnostics (Basel, Switzerland) · 2026Article
- Hesperetin Protects from Palmitic-Acid-Induced Lipotoxicity through the Inhibition of Glutaminolysis, mTORC1 Signaling, and Limited Apoptosis.Journal of agricultural and food chemistry · 2025Article
- Effects of glutamate oxaloacetate transaminase on reactive oxygen species in Ganoderma lucidum.Applied microbiology and biotechnology · 2023Article
- Excessive gluconeogenesis causes the hepatic insulin resistance paradox and its sequelae.Heliyon · 2022Review
- The Involvement of Long Non-Coding RNAs in Glutamine-Metabolic Reprogramming and Therapeutic Resistance in Cancer.International journal of molecular sciences · 2022Review
- Article
- Loss of Stearoyl-CoA desaturase 1 leads to cardiac dysfunction and lipotoxicity.The Journal of experimental biology · 2021Article
- Potential attenuation of biochemical parameters and enzymatic functions in Cyprinus carpio fingerlings by Phenthoate 50 EC insecticide exposure.Environmental science and pollution research international · 2020Article
- Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer.Molecules (Basel, Switzerland) · 2020Review
- ATP Production Relies on Fatty Acid Oxidation Rather than Glycolysis in Pancreatic Ductal Adenocarcinoma.Cancers · 2020Article
- Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice.Journal of lipid research · 2020Article
- Tissue-specific analysis of lipid species inJournal of lipid research · 2020Article
- Computational data mining method for isotopomer analysis in the quantitative assessment of metabolic reprogramming.Scientific reports · 2020Article
- Article
- Sodium fluorocitrate having inhibitory effect on fatty acid uptake ameliorates high fat diet-induced non-alcoholic fatty liver disease in C57BL/6J mice.Scientific reports · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hepatocyte lipotoxicity is characterized by aberrant mitochondrial metabolism, which predisposes cells to oxidative stress and apoptosis. Previously, we reported that translocation of calcium from the endoplasmic reticulum to mitochondria of palmitate-treated hepatocytes activates anaplerotic flux from glutamine to α-ketoglutarate (αKG), which subsequently enters the citric acid cycle (CAC) for oxidation. We hypothesized that increased glutamine anaplerosis fuels elevations in CAC flux and oxidative stress following palmitate treatment. To test this hypothesis, primary rat hepatocytes or immortalized H4IIEC3 rat hepatoma cells were treated with lipotoxic levels of palmitate while modulating anaplerotic pathways leading to αKG. We found that culture media supplemented with glutamine, glutamate, or dimethyl-αKG increased palmitate lipotoxicity compared with media that lacked these anaplerotic substrates. Knockdown of glutamate-oxaloacetate transaminase activity significantly reduced the lipotoxic effects of palmitate, whereas knockdown of glutamate dehydrogenase (Glud1) had no effect on palmitate lipotoxicity.
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