ArticleThe Journal of biological chemistry2014
Glucose transporter 8 (GLUT8) mediates fructose-induced de novo lipogenesis and macrosteatosis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 105 citations in OpenAlex.
- Technology-enabled insights into SLC transporters in MAFLD: redefining the multi-hit pathogenesis and therapeutic landscape.Acta pharmacologica Sinica · 2026Review
- Adipose Tissue Inflammation, Oxidative Stress, and Altered Adipogenesis Are Associated With Dyslipidemia in Obesity: A Multiomics Profiling Study.Journal of the American Heart Association · 2026Article
- Testosterone deficiency synergistically exacerbates fructose-induced hepatic steatosis through gut microbiota and pyruvate in mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- Fructose metabolism as an adaptive survival axis in pancreatic cancer: mechanistic insights and therapeutic implications.Frontiers in medicine · 2026Review
- Fructose uptake by brown adipose tissue is independent of carbohydrate response element-binding protein and does not cause elevatedActa biochimica et biophysica Sinica · 2025Article
- Targeting hepatocyte-specific SLC2A8 blocks hepatic steatosis and dissociates TCA cycle flux inhibition from glutamine anaplerosis.Hepatology communications · 2025Article
- Progress in Understanding the Regulation of Glucose and Fructose Metabolism.Annual review of nutrition · 2025Review
- ANGPTL3 orchestrates hepatic fructose sensing and metabolism.Cell reports · 2025Article
- Conceptus Elongation, Implantation, and Early Placental Development in Species with Central Implantation: Pigs, Sheep, and Cows.Biomolecules · 2025Review
- Elucidating neural molecular mechanisms underlying metabolic disorders-induced neuropsychiatric disorders in mice on prolonged high fructose diet.Metabolic brain disease · 2025Article
- The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.Journal of clinical and translational hepatology · 2025Review
- Unraveling the Beneficial Role of Resveratrol in Fructose-Induced Non-Alcoholic Steatohepatitis with a Focus on the AMPK/Nrf2 Signaling Axis.Medicina (Kaunas, Lithuania) · 2025Article
- AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells.Cell death and differentiation · 2024Article
- Mast Cells are Dependent on Glucose Transporter 1 (GLUT1) and GLUT3 for IgE-mediated Activation.Inflammation · 2024Article
- Hepatocyte MMP14 mediates liver and inter-organ inflammatory responses to diet-induced liver injury.PNAS nexus · 2024Article
- Regulation of Fructose Metabolism in Nonalcoholic Fatty Liver Disease.Biomolecules · 2024Review
- Early Embryonic Development in Agriculturally Important Species.Animals : an open access journal from MDPI · 2024Review
- Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective.Metabolites · 2024Review
- Fructose regulates the pentose phosphate pathway and induces an inflammatory and resolution phenotype in Kupffer cells.Scientific reports · 2024Article
- John Yudkin's hypothesis: sugar is a major dietary culprit in the development of cardiovascular disease.Frontiers in nutrition · 2024Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, and it is thought to be the hepatic manifestation of the metabolic syndrome. Excess dietary fructose causes both metabolic syndrome and NAFLD in rodents and humans, but the pathogenic mechanisms of fructose-induced metabolic syndrome and NAFLD are poorly understood. GLUT8 (Slc2A8) is a facilitative glucose and fructose transporter that is highly expressed in liver, heart, and other oxidative tissues. We previously demonstrated that female mice lacking GLUT8 exhibit impaired first-pass hepatic fructose metabolism, suggesting that fructose transport into the hepatocyte, the primary site of fructose metabolism, is in part mediated by GLUT8. Here, we tested the hypothesis that GLUT8 is required for hepatocyte fructose uptake and for the development of fructose-induced NAFLD. We demonstrate that GLUT8 is a cell surface-localized transporter and that GLUT8 overexpression or GLUT8 shRNA-mediated gene silencing significantly induces and blocks radiolabeled fructose uptake in cultured hepatocytes. We further show diminished fructose uptake and de novo lipogenesis in fructose-challenged GLUT8-deficient hepatocytes. Finally, livers from long term high-fructose diet-fed GLUT8-deficient mice exhibited attenuated fructose-induced hepatic triglyceride and cholesterol accumulation without changes in hepatocyte insulin-stimulated Akt phosphorylation. GLUT8 is thus essential for hepatocyte fructose transport and fructose-induced macrosteatosis. Fructose delivery across the hepatocyte membrane is thus a proximal, modifiable disease mechanism that may be exploited to prevent NAFLD.
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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.