ArticleThe Journal of biological chemistry2009
Effect of anaplerotic fluxes and amino acid availability on hepatic lipoapoptosis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- The insulin-like growth factor 2 mRNA-binding protein 2 affects tumor cell metabolism via mitochondrial transporter activity and lipid alterations.Cell death discovery · 2026Article
- Mechanism of Obesity-Related Lipotoxicity and Clinical Perspective.Advances in experimental medicine and biology · 2024Review
- Applications of Quantitative Systems Pharmacology (QSP) in Drug Development for NAFLD and NASH and Its Regulatory Application.Pharmaceutical research · 2022Article
- Metabolic Flux Analysis-Linking Isotope Labeling and Metabolic Fluxes.Metabolites · 2020Review
- Direct and quantitative analysis of altered metabolic flux distributions and cellular ATP production pathway in fumarate hydratase-diminished cells.Scientific reports · 2020Article
- Glutamate-oxaloacetate transaminase activity promotes palmitate lipotoxicity in rat hepatocytes by enhancing anaplerosis and citric acid cycle flux.The Journal of biological chemistry · 2019Article
- Hepatic lipid homeostasis by peroxisome proliferator-activated receptor gamma 2.Liver research (Beijing, China) · 2018Article
- Transgenic overexpression of CTRP3 prevents alcohol-induced hepatic triglyceride accumulation.American journal of physiology. Endocrinology and metabolism · 2018Article
- The TLR4 Agonist Monophosphoryl Lipid A Drives Broad Resistance to Infection via Dynamic Reprogramming of Macrophage Metabolism.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer.JCI insight · 2016Article
- Knockdown of triglyceride synthesis does not enhance palmitate lipotoxicity or prevent oleate-mediated rescue in rat hepatocytes.Biochimica et biophysica acta · 2016Article
- Pu-erh tea extract ameliorates high-fat diet-induced nonalcoholic steatohepatitis and insulin resistance by modulating hepatic IL-6/STAT3 signaling in mice.Journal of gastroenterology · 2016Article
- RhoC GTPase Is a Potent Regulator of Glutamine Metabolism and N-Acetylaspartate Production in Inflammatory Breast Cancer Cells.The Journal of biological chemistry · 2016Article
- How Inflammation Impinges on NAFLD: A Role for Kupffer Cells.BioMed research international · 2015Review
- OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease.PloS one · 2015Article
- ER calcium release promotes mitochondrial dysfunction and hepatic cell lipotoxicity in response to palmitate overload.Molecular metabolism · 2014Article
- Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells.Journal of lipid research · 2014Article
- Palmitate-induced activation of mitochondrial metabolism promotes oxidative stress and apoptosis in H4IIEC3 rat hepatocytes.Metabolism: clinical and experimental · 2014Article
- Sphingolipid regulators of cellular dysfunction in Type 2 diabetes mellitus: a systems overview.Clinical lipidology · 2014Article
- Nonalcoholic Fatty liver disease: pathogenesis and therapeutics from a mitochondria-centric perspective.Oxidative medicine and cellular longevity · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
To identify metabolic pathways involved in hepatic lipoapoptosis, metabolic flux analysis using [U-(13)C(5)]glutamine as an isotopic tracer was applied to quantify phenotypic changes in H4IIEC3 hepatoma cells treated with either palmitate alone (PA-cells) or both palmitate and oleate in combination (PA/OA-cells). Our results indicate that palmitate inhibited glycolysis and lactate dehydrogenase fluxes while activating citric acid cycle (CAC) flux and glutamine uptake. This decoupling of glycolysis and CAC fluxes occurred during the period following palmitate exposure but preceding the onset of apoptosis. Oleate co-treatment restored most fluxes to their control levels, resulting in steatotic lipid accumulation while preventing apoptosis. In addition, palmitate strongly increased the cytosolic NAD(+)/NADH ratio, whereas oleate co-treatment had the opposite effect on cellular redox. We next examined the influence of amino acids on these free fatty acid-induced phenotypic changes. Increased medium amino acids enhanced reactive oxygen species (ROS) generation and apoptosis in PA-cells but not in PA/OA-cells. Overloading the medium with non-essential amino acids induced apoptosis, but essential amino acid overloading partially ameliorated apoptosis. Glutamate was the most effective single amino acid in promoting ROS. Amino acid overloading also increased cellular palmitoyl-ceramide; however, ceramide synthesis inhibitors had no effect on measurable indicators of apoptosis. Our results indicate that free fatty acid-induced ROS generation and apoptosis are accompanied by the decoupling of glycolysis and CAC fluxes leading to abnormal cytosolic redox states. Amino acids play a modulatory role in these processes via a mechanism that does not involve ceramide accumulation.
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