ArticleScientific reports2016
Farnesoid X receptor activation promotes cell proliferation via PDK4-controlled metabolic reprogramming.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
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- Single and Multiple Doses of Seladelpar Decrease Diurnal Markers of Bile Acid Synthesis in Mice.PPAR research · 2025Article
- Natural Product 2-Oxokolavenol Is a Novel FXR Agonist.Molecules (Basel, Switzerland) · 2022Article
- CEBPB regulates the bile acid receptor FXR to accelerate colon cancer progression by modulating aerobic glycolysis.Journal of clinical laboratory analysis · 2022Article
- Farnesoid X Receptor Activation Impairs Liver Progenitor Cell-Mediated Liver Regeneration via the PTEN-PI3K-AKT-mTOR Axis in Zebrafish.Hepatology (Baltimore, Md.) · 2021Article
- FXR-Deoxycholic Acid-TNF-α Axis Modulates Acetaminophen-Induced Hepatotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- The effect of Farnesoid X receptor agonist tropifexor on liver damage in rats with experimental obstructive jaundice.Acta cirurgica brasileira · 2021Article
- PDK4-Deficiency Reprograms Intrahepatic Glucose and Lipid Metabolism to Facilitate Liver Regeneration in Mice.Hepatology communications · 2020Article
- SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis.Nature communications · 2020Article
- Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis.Acta pharmaceutica Sinica. B · 2019Article
- Noncanonical farnesoid X receptor signaling inhibits apoptosis and impedes liver fibrosis.EBioMedicine · 2018Article
- Update on FXR Biology: Promising Therapeutic Target?International journal of molecular sciences · 2018Review
- Post-hepatectomy liver regeneration in the context of bile acid homeostasis and the gut-liver signaling axis.Journal of clinical and translational research · 2018Article
- Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis.BMC gastroenterology · 2017Article
- Quantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation.PloS one · 2017Article
- Analysis of Differentially Expressed Genes in Gastrocnemius Muscle between DGAT1 Transgenic Mice and Wild-Type Mice.BioMed research international · 2017Article
- Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Farnesoid X receptor (FXR) plays a pivotal role in the regulation of various metabolic pathways as well as liver regeneration. However, the casual link between cell proliferative effects during liver regeneration and metabolic regulation of FXR was elusive. In this study, we found that FXR activation significantly promotes HepG2 cell proliferation accompanied with metabolic switch towards the excessive accumulation of aerobic glycolytic intermediates including lactic acid, pyruvate and the subsequently increased biosynthesis of glycine. This FXR-induced metabolic switch was found dependent on an up-regulation of pyruvate dehydrogenate kinase 4 (PDK4), a FXR target gene. FXR agonists were found to promote liver regeneration in the murine model of APAP induced liver injury, which was associated with a metabolic switch favoring the accumulation of glycolytic intermediates as precursors for generation of biomass. However, FXR activation has little effect on the glycolytic metabolism in healthy primary hepatocytes in vitro and the liver of healthy mice in vivo. Therefore, we conclude that FXR may promote the proliferation of tumor cells and the hepatocytes in the process of liver regeneration by activating the PDK4-mediated metabolic reprogramming to generate glycolytic intermediates essential for rapid biomass generation, establishing a mechanistic link between cell proliferation and metabolic switch.
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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.