ArticleMolecular pharmacology2015
SLC13A5 is a novel transcriptional target of the pregnane X receptor and sensitizes drug-induced steatosis in human liver.
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Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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53citing papers in PubMed, 1 pooled it
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Conserved hepatic RNA signatures across multiple cohorts reveal novel mechanistic clues for advanced fibrosis in human MASLD.Hepatology communications · 2026Pooled it
- Bempedoic acid within the phase ternary diagram governing biliary cholesterol solubilization and gallstone risk.Journal of lipid research · 2026Review
- Mutation of PXR phosphorylation motif at Ser347 disrupts lipid and bile acid homeostasis in diet-induced metabolic dysfunction-associated steatohepatitis in mice.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Physiological Functions and Pathological Roles of PXR.Journal of the Endocrine Society · 2025Review
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- Insights of direct and indirect regulation of PXR through phosphorylation in fatty liver disease.Molecular pharmacology · 2025Review
- Novel Approaches to Studying SLC13A5 Disease.Metabolites · 2024Review
- The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development.BMC medicine · 2023Article
- Review
- Mapping the Metabolic Niche of Citrate Metabolism andMetabolites · 2023Review
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Atypical functions of xenobiotic receptors in lipid and glucose metabolism.Medical review (2021) · 2022Review
- A Novel and Cross-Species Active Mammalian INDY (NaCT) Inhibitor Ameliorates Hepatic Steatosis in Mice with Diet-Induced Obesity.Metabolites · 2022Article
- Human constitutive androstane receptor represses liver cancer development and hepatoma cell proliferation by inhibiting erythropoietin signaling.The Journal of biological chemistry · 2022Article
- Untargeted Metabolomics of Slc13a5 Deficiency Reveal Critical Liver-Brain Axis for Lipid Homeostasis.Metabolites · 2022Article
- INDY as a Therapeutic Target for Cardio-Metabolic Disease.Metabolites · 2022Review
- The ups and downs of elevator-type di-/tricarboxylate membrane transporters.The FEBS journal · 2022Article
- Phenobarbital Induces SLC13A5 Expression through Activation of PXR but Not CAR in Human Primary Hepatocytes.Cells · 2021Article
- Review
- Review
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Authors and funding
14 authors at 5 institutions in 1 country.
Linhao LiDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Haishan LiDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Brandy GarzelDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Hui YangDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Tatsuya SueyoshiDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Qing LiDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Yan ShuDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Junran ZhangDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Bingfang HuDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Scott HeywardDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Timothy MoellerDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Wen XieDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Masahiko NegishiDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.).
Hongbing WangDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.L., B.G., H.Y., Q.L., Y.S., H.W.); Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental and Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (T.S., M.N.); Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (J.Z.); Bioreclamation In Vitro Technologies, Baltimore, Maryland (S.H., T.M.); and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania (B.H., W.X.) hwang@rx.umaryland.edu.
Case Western Reserve University · USNational Institute of Environmental Health Sciences · USNational Institutes of Health · USUniversity of Pittsburgh · USUniversity of Maryland, Baltimore · US
Funding
Mechanisms and biological consequences of the nuclear receptor CAR activationZIAES080040 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI NEGISHI, MASAHIKO · 2009 to 2020
$35.3MRegulation of CYP2B6 in Human LIverR01DK061652 · NIDDK · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI WANG, HONGBING · 2003 to 2015
$3.7MTHE ROLE OF NEDD4-1 IN IGF-1R SIGNALINGR01CA154625 · NCI · WASHINGTON UNIVERSITY · PI ZHANG, JUNRAN · 2011 to 2016
$1.6MXenobiotic Transporter Regulation and IRIP FunctionR01GM099742 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI SHU, YAN · 2012 to 2016
$1.6MRole of constitutive androstane receptor in cyclophosphamide-based chemotherapyR01GM107058 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI WANG, HONGBING · 2013 to 2016
$1.2MStructural Study Of SulfotransferasesZ01ES071005 · NIEHS · ENVIRONMENTAL HEALTH SCIENCES · PI NEGISHI, MASAHIKO · 1999 to 2007
$388kNCI NIH HHS R01 CA154625NIDDK NIH HHS R01 DK061652NIDDK NIH HHS R01-DK061652NIEHS NIH HHS ZO1ES71005-01NIGMS NIH HHS R01 GM099742NIGMS NIH HHS R01-GM099742NIGMS NIH HHS R01 GM107058NIGMS NIH HHS R01-GM107058
Abstract
The solute carrier family 13 member 5 (SLC13A5) is a sodium-coupled transporter that mediates cellular uptake of citrate, which plays important roles in the synthesis of fatty acids and cholesterol. Recently, the pregnane X receptor (PXR, NR1I2), initially characterized as a xenobiotic sensor, has been functionally linked to the regulation of various physiologic processes that are associated with lipid metabolism and energy homeostasis. Here, we show that the SLC13A5 gene is a novel transcriptional target of PXR, and altered expression of SLC13A5 affects lipid accumulation in human liver cells. The prototypical PXR activator rifampicin markedly induced the mRNA and protein expression of SLC13A5 in human primary hepatocytes. Utilizing cell-based luciferase reporter assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays, we identified and functionally characterized two enhancer modules located upstream of the SLC13A5 gene transcription start site that are associated with regulation of PXR-mediated SLC13A5 induction. Functional analysis further revealed that rifampicin can enhance lipid accumulation in human primary hepatocytes, and knockdown of SLC13A5 expression alone leads to a significant decrease of the lipid content in HepG2 cells. Overall, our results uncover SLC13A5 as a novel target gene of PXR and may contribute to drug-induced steatosis and metabolic disorders in humans.
Indexed as
AnimalsEnhancer Elements, GeneticFatty LiverGene Knockdown TechniquesHepatocytesHep G2 CellsHumansLipid MetabolismLiverMice, TransgenicPregnane X ReceptorReceptors, SteroidResponse ElementsRifampinSymportersTranscriptional ActivationNR1I2 protein, humanNr1i2 protein, mousePregnane X ReceptorReceptors, SteroidRifampinSLC13A5 protein, humanSymporters
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